Collagen Induces Maturation of Human Monocyte-Derived Dendritic Cells by Signaling through Osteoclast-Associated Receptor This information is current as of September 29, 2021. Heidi S. Schultz, Louise M. Nitze, Louise H. Zeuthen, Pernille Keller, Albrecht Gruhler, Jesper Pass, Jianhe Chen, Li Guo, Andrew J. Fleetwood, John A. Hamilton, Martin W. Berchtold and Svetlana Panina

J Immunol 2015; 194:3169-3179; Prepublished online 27 Downloaded from February 2015; doi: 10.4049/jimmunol.1402800 http://www.jimmunol.org/content/194/7/3169 http://www.jimmunol.org/

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Collagen Induces Maturation of Human Monocyte-Derived Dendritic Cells by Signaling through Osteoclast-Associated Receptor

Heidi S. Schultz,*,† Louise M. Nitze,*,† Louise H. Zeuthen,* Pernille Keller,* Albrecht Gruhler,* Jesper Pass,* Jianhe Chen,‡ Li Guo,‡ Andrew J. Fleetwood,x John A. Hamilton,x Martin W. Berchtold,† and Svetlana Panina*

Osteoclast-associated receptor (OSCAR) is widely expressed on human myeloid cells. Collagen types (Col)I, II, and III have been described as OSCAR ligands, and ColII peptides can induce costimulatory signaling in receptor activator for NF-kB–dependent osteoclastogenesis. In this study, we isolated collagen as an OSCAR-interacting protein from the membranes of murine osteo- blasts. We have investigated a functional outcome of the OSCAR–collagen interaction in human monocyte-derived dendritic cells Downloaded from (DCs). OSCAR engagement by ColI/II-induced activation/maturation of DCs is characterized by upregulation of cell surface markers and secretion of cytokines. These collagen-matured DCs (Col-DCs) were efficient drivers of allogeneic and autologous naive T cell proliferation. The T cells expanded by Col-DCs secreted cytokines with no clear T cell polarization pattern. Global RNA profiling revealed that multiple proinflammatory mediators, including cytokines and cytokine receptors, components of the stable immune synapse (namely CD40, CD86, CD80, and ICAM-1), as well as components of TNF and TLR signaling, are transcriptional targets of OSCAR in DCs. Our findings indicate the existence of a novel pathway by which extracellular matrix http://www.jimmunol.org/ proteins locally drive maturation of DCs during inflammatory conditions, for example, within synovial tissue of rheumatoid arthritis patients, where collagens become exposed during tissue remodeling and are thus accessible for interaction with infil- trating precursors of DCs. The Journal of Immunology, 2015, 194: 3169–3179.

heumatoid arthritis (RA) is a systemic autoimmune dis- tolerance. Next, a tissue-specific inflammatory response is elicited ease that primarily targets the peripheral diarthrodial in the joints. Activated immune cells accumulate in the synovial joints. It is characterized by the presence of autoanti- tissue and secrete cytokines, chemokines, and matrix-degrading

R by guest on September 29, 2021 bodies, synovial inflammation, pannus formation, cartilage dam- enzymes, causing tissue damage and remodeling. By way of age, and bone erosion. The molecular mechanisms involved in RA a positive feedback loop, the local inflammation is sustained and pathogenesis remain obscure. A multistep mechanism of RA de- finally progresses into a systemic disorder. velopment has been proposed (1, 2). First, unknown environmental The cellular infiltrates in the synovial tissue are mainly com- factors cause alterations in posttranslational protein modifications, posed of blood-derived cells, including T and B cells, as well leading to recognition of autoantigens and the loss of immune as macrophages and dendritic cells (DCs) differentiated from monocytes in the RA synovial microenvironment. Cells of the myeloid lineage are regarded as pivotal regulators of RA. Both *Biopharmaceutical Research Unit, Novo Nordisk A/S, 2760 Ma˚løv, Denmark; immature and mature DC subsets are present in large numbers †Department of Biology, Copenhagen University, Copenhagen 2200, Denmark; x within the RA joint, and strong evidence supports the importance of ‡Novo Nordisk Research Center China, Beijing 102206, China; and Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria DCs in synovial inflammation (3, 4). DCs are professional APCs 3050, Australia that are highly capable of inducing T cell responses. In RA, the Received for publication November 5, 2014. Accepted for publication January 22, DCs are essential for initiation and perpetuation by Ag presenta- 2015. tion as well as for cytokine and chemokine secretion (5, 6). Fur- H.S.S. and L.M.N. received Ph.D. fellowships from the Danish Agency for Science, thermore, DCs are capable of transdifferentiating into osteoclasts, Technology, Innovation and Research. contributing directly to bone erosion (7, 8). The maturation state The microarray dataset presented in this article has been submitted to the Array Express database (http://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-2904/) of the DCs is crucial for determining the balance between toler- under accession number E-MTAB-2904. ance and immunity. Under homeostatic conditions, DCs are Address correspondence and reprint requests to Dr. Svetlana Panina at the current largely immature and are thought to induce tolerance. Changes in address: Novo Nordisk A/S, Hvidkildevej 111, 2400 Copenhagen, Denmark. E-mail the microenvironment stimulate maturation of DCs, which can address: [email protected] promote immunogenicity. The online version of this article contains supplemental material. A human ortholog of murine OSCAR was identified by Merck Abbreviations used in this article: Col, collagen type; Col-DC, collagen-matured DC; et al. (9). OSCAR is expressed on cells of myeloid origin, and it DC, dendritic cell; ECD, extracellular domain; ECM, extracellular matrix; FDR, false discovery rate; iDC, immature DC; LC-MS, liquid chromatography–mass spec- signals through the ITAM-harboring adaptor protein FcRg (9, 10). trometry; MS, mass spectrometry; NP-40, Nonidet P-40; OSCAR, osteoclast- In DCs, cross-linking of OSCAR with specific mAbs enhanced associated receptor; RA, rheumatoid arthritis; SPR, surface plasmon resonance. Ag presentation and promoted a semimature phenotype, causing This article is distributed under The American Association of Immunologists, Inc., chemokine but not proinflammatory cytokine secretion. In synergy Reuse Terms and Conditions for Author Choice articles. with TLR signaling, but not alone, OSCAR cross-linking en- + Copyright Ó 2015 by The American Association of Immunologists, Inc. 0022-1767/15/$25.00 hanced the ability of DCs to induce naive CD4 T cell prolifer- www.jimmunol.org/cgi/doi/10.4049/jimmunol.1402800 3170 OSCAR-DEPENDENT MATURATION OF DCs ation (9, 11, 12). It was concluded that OSCAR can induce Identification of OSCAR ligand a semimatured phenotype in DCs, which is characterized by ex- OSCAR-binding proteins were purified from membranes of MC3T3-E1 pression of costimulatory molecules but an inability to secrete cells by affinity chromatography on an OSCAR–Fc matrix followed by proinflammatory cytokines. Such semimatured DCs are implicated identification of hits using a liquid chromatography–mass spectrometry in the induction of tolerance. (LC-MS) approach. In brief, for extraction of membrane proteins, the cells Recent studies have assessed the role of OSCAR in RA. OSCAR were washed in PBS, scraped with a plastic policeman, and homogenized mechanically using a glass pastel homogenizer in the buffer containing 10 is expressed on mononuclear cells surrounding synovial micro- mM imidazole and 1 mM EDTA (pH 7.4) on ice. The homogenate was vessels and on multinucleated giant cells at the bone resorption spun at 20,000 3 g for 10 min, and the pellet was resuspended in the areas. OSCAR was also found to be upregulated in peripheral blood homogenization buffer. This washing cycle was repeated three times with monocytes from RA patients compared with healthy subjects, and one last time in a buffer containing 2 mM imidazole/1 mM EDTA (pH 7.4). The pellet was then washed twice in 50 mM Tris-HCl/150 mM NaCl its expression correlated to disease activity (13). (pH 8.2), centrifuged, and resuspended in a RIPA buffer (150 mM NaCl, In the present study we aimed to examine OSCAR function in 50 mM Tris-HCl [pH 8.2], 1 mM EDTA, 1% Nonidet P-40 [NP-40], 1 mg/ml DCs with relevance to RA pathogenesis. We identified collagen BSA, protease inhibitor [cOmplete, Roche] and phosphatase inhibitor types (Col)I/II as OSCAR ligands and investigated the func- mixture [Sigma-Aldrich]) for 30 min on ice. The protein extracts were 3 tional outcomes of OSCAR–collagen interaction in DCs. During clarified by centrifugation at 20,000 g. Protein concentration was measured using a bicinchoninic acid protein assay (Pierce). the preparation of this manuscript, Trowsdale and colleagues (14) Preparation of an affinity resin was performed as follows. Human identified ColI, -II and -III to be ligands of OSCAR (14). The OSCAR–Fc IgG4 or Fc IgG4 (control) recombinant proteins were bound to authors showed that within joints collagens are exposed to a protein G–Sepharose 4B Fast Flow affinity matrix (Sigma-Aldrich)

OSCAR-expressing osteoclasts and osteoclast precursors. In vitro, according to the manufacturer’s protocol and then chemically cross- Downloaded from linked as described in Schneider et al. (16). This technique allows opti- OSCAR-binding collagen peptides promoted receptor activator for mal orientation of OSCAR-Fc on the beads and thus efficient binding of NF-kB ligand–induced osteoclast differentiation from blood- interacting proteins with minimal/no leakage of the bait during the elution derived monocytes, indicating that OSCAR is an activating re- process. After cross-linking, the beads were thoroughly washed in 0.1 M ceptor on osteoclast precursor cells. In the present study, we show borate buffer, equilibrated in 5 ml 0.5 M Tris-HCl (pH 8.2), and sedi- that OSCAR–collagen interaction provides an activating signal mented by centrifugation. Cell membrane extracts in RIPA buffer were added to the affinity beads. NaCl concentration was adjusted to final 0.5 M also in monocyte-derived DCs. This indicates an important, yet and the beads were incubated for 3 h at 4˚C with gentle agitation. The http://www.jimmunol.org/ poorly recognized, role of the extracellular matrix (ECM) in the beads were then washed sequentially with three buffers containing 1) 0.5 M arthritic joint, where ColI/II become exposed due to ongoing tis- NaCl, 50 mM Tris-HCl, 1 mM EDTA, and 0.5% NP-40 (pH 8.2); 2) 150 sue remodeling, thus providing activating signals to myeloid cells mM NaCl, 50 mM Tris-HCl, 0.5% NP-40, and 0.1% SDS (pH 8.2); and 3) 150 mM NaCl and 0.5% CHAPS. The latter wash was repeated twice. The to drive a sustained inflammation. Blocking the OSCAR signaling, proteins bound to the affinity matrix were eluted in 50 mM diethylamine/ for example, with a mAb, may be considered as a novel thera- 0.5% CHAPS (pH 11.5) and pH was immediately adjusted to neutral using peutic approach for RA. PBS and borate buffer. The samples were subjected to a 4–12% SDS- PAGE. The gels were stained using a ProteoSilver plus silver stain kit Materials and Methods (Sigma-Aldrich). The bands differentially bound to the OSCAR–Fc matrix were subjected to LC-MS analysis as follows. Bands were excised from the by guest on September 29, 2021 Proteins and Abs for functional assays SDS-PAGE gel, destained with the SilverQuest silver staining kit (Invi- The extracellular domain (ECD) of human OSCAR and OSCAR–Fc fusion trogen), reduced with DTT, alkylated with iodoacetamide, and digested protein were produced by recombinant technique as follows. The fragment with trypsin with a slightly modified version of the method described in encoding ECD (amino acid residues 1–227; sequence ID NP_573399) was Shevchenko et al. (17). amplified by RT-PCR using human universal cDNA (Clontech) as tem- plate, cloned into the pJSV002 expression vector, and sequenced. The LC-MS analysis recombinant protein was expressed in HEK293-6E cells. The purified Peptide mixtures were analyzed by nanoscale liquid chromatography– ∼ recombinant protein is an N-glycosylated monomer of 25 kDa. For ex- electrospray ionization–tandem MS on an Easy-nLC (Proxeon Biosystems) pression of OSCAR–Fc protein, the ECD-encoding cDNA was cloned in- connected to an LTQ Orbitrap mass spectrometer (Thermo Fisher Scien- frame with a sequence encoding the Fc fragment of human IgG4. The tific). Reversed phase chromatography was performed with 0.1% formic sequence was verified and the protein was expressed in HEK293-6E cells. acid (buffer A) and acetonitrile/0.1% formic acid (buffer B). Peptides were ∼ The purified protein is an N-glycosylated dimer of 100 kDa. For cell trapped on a precolumn (Proxeon Biosystems) and separated on a 10-cm binding studies, OSCAR-ECD was labeled using an Alexa Fluor 488 fused-silica column (internal diameter 75 mm) packed with 3-mm protein staining kit (Life Technologies) according to the manufacturer’s ReproSil-Pur C18-AQ (Proxeon Biosystems). MS analysis was performed protocol. on the LTQ Orbitrap in data-dependent mode, where one MS survey scan A panel of murine mAbs against OSCAR-ECD and isotype controls was followed by MS fragmentation spectra of the four most intense ions. were generated using hybridoma technology and then humanized using Analysis of the MS data were performed with Proteome Discoverer 1.4 recombinant technology. The CDR of the generated mAb was grafted on (Thermo Fisher Scientific). Peak lists of the MS fragmentation spectra were a germline-encoded, human-mutated IgG1 Fc part, Fc-hIgG1.1 (15, 16). generated and searched in MASCOT against the mammalian part of the Five point mutations introduced in the Fc-hIgG1.1 hinder its binding to SwissProt database with oxidation (P), oxidation (M), and deamidated (NQ) high-affinity Fc receptors. As isotype controls, an anti-OSCAR non- as dynamic modifications and carbamidomethyl (C) as fixed modification. blocking high-affinity mAb as well as anti-TNP hIgG1.1 were used. Most Results were filtered for a false discovery rate (FDR) of 0.01 and a minimum blocking experiments were performed with the use of several different MASCOT peptide score of 25. high-affinity anti-OSCAR–blocking mAbs and the two above-mentioned isotype controls with identical results. For simplicity, data are shown Binding of OSCAR to collagen only for 1 mg/ml mAb unless specified otherwise. For functional assays, the following commercially available mAbs were used: anti-CD3 mAb Binding of the soluble extracellular domain of OSCAR to human collagens (clone OKT3; eBioscience), anti-CD3/CD28 expander beads (Dynal), was tested by surface plasmon resonance (SPR) on a ProteOn instrument and anti–integrin a2b1 mAb (clone BHA2.1; Millipore). ColI purified (Bio-Rad). Human collagens were immobilized on a GLC sensor chip using from human skin was purchased from Sigma-Aldrich. ColII purified the amine coupling kit (Bio-Rad). The experiment was performed at 15˚C from human cartilage was purchased from Millipore. ColIII purified from using HBS-EP+ (GE Healthcare) as running buffer for the immobilization human placenta was purchased from Millipore. ColIV from human and HBS-EP+/0.1% BSA for binding analysis. The chip was activated with placenta was purchased from Sigma-Aldrich. Endotoxin level in the 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride/normal protein solutions was measured using the turbidimetric kinetic Limulus human serum (diluted 2:1 with H2O) according to instructions. Collagens amebocyte lysate assay (reagents supplied by Charles River Laborato- were diluted in 10 mM NaAc buffer (pH 4.5) to 25 mg/ml and injected for ries). All proteins used for functional assays in this study were essen- 200 s followed by quenching with ethanolamine. OSCAR-ECD was tially endotoxin-free. injected at 2 mM, 1 mM, 500 nM, 250 nM, and 125 nM for 200 s at a flow The Journal of Immunology 3171 of 60 ml/min followed by regeneration with 10 mM glycine (pH 2.0) for cific Blue–conjugated anti-human CD3 (BD Pharmingen). Cells were 30 s. Binding curves were double referenced by subtraction of the signals washed twice in PBS with 2% FCS and then stained for 30 min at 37˚C in from reference cells and a buffer injection using the ProteOn Manager PBS with 2% FCS in the presence of 1% human serum albumin to block software. unspecific binding. Cells were rinsed three times in PBS with 2% FCS prior to flow cytometry analysis. Data acquisition was done using Competition of OSCAR binding to collagen a FACSFortessa (BD Biosciences). Only live cells, that is, negative for Competition of anti-OSCAR mAb with OSCAR binding to collagen was allophycocyanin-H7 dead cell stain (Invitrogen/Life Technologies) were measured by SPR on a Biacore T100 instrument using the same buffers as analyzed. For compensation single stain was used with one drop of neg- described above. ative control beads and anti-mouse IgG beads (BD Biosciences). For the dead cell marker compensation, amine reactive compensation beads were Human ColI was diluted with 10 mM NaAc (pH 4.5) to a final con- used (Invitrogen/Life Technologies). Data analysis was performed using centration of 2.5 mg/ml and immobilized on a CM5 sensor chip (GE Healthcare) using the amine coupling kit (GE Healthcare). Immobilization Kaluza software version 1.2 (Beckman Coulter). was carried out at 4˚C with HBS-EP+ as buffer using 200 resonance units Microarray analysis as a target level for the immobilized ligand. OSCAR was diluted to 25 nM in HBS-EP+ buffer containing 0.1% serum albumin and increasing con- Total RNAwas obtained 4 and 20 h after stimulating DCs with ColI/II in the centrations of the anti-OSCAR Abs from 0 to 20 mg/ml. The OSCAR/mAb absence or presence of anti-OSCAR mAb or isotype control mAb. RNAwas solutions were injected for 240 s followed by 200 s dissociation at a flow extracted using TRIzol (Invitrogen/Life Technologies) followed by puri- rate of 50 ml/min at 4˚C followed by regeneration with 10 mM glycine (pH fication with an RNeasy MinElute cleanup kit (Qiagen). The RNA integrity 2.0). Binding curves were double referenced by subtraction of the signals was evaluated on an Agilent 2100 bioanalyzer using Agilent RNA 6000 from reference cells and a buffer injection and further analyzed using the Nano Kit chips (Agilent Technologies), with RNA integrity number scores Biacore T100 evaluation software. of $9.9. Microarray experiments were performed according to the pro- tocols supplied by Affymetrix and run on the HT HG-U133+ PM chip Cells from Affymetrix using an Affymetrix GeneTitan machine in a 96-well Downloaded from Buffy coats from healthy individuals were obtained anonymously from the layout. Array data were normalized using the robust multiarray average Blood Bank, Rigshospitalet, Copenhagen, Denmark. All donors gave in- algorithm with a custom chip definition file obtained from BrainArray formed consent according to the protocol approved by the Ethics Committee (University of Michigan) based on Ensembl gene annotations (ENSG). for Copenhagen, Denmark, for research use (approval no. H-D-2008-113). Microarray data were analyzed for significant differences using Qlucore Omics Explorer (v2.2) software. A paired two-group comparison was PBMCs were freshly purified by Ficoll-Plaque density centrifugation. performed with Benjamini–Hochberg correction for multiple testing ap- Monocytes were purified from PBMCs using the CD14 MicroBeads positive

. http://www.jimmunol.org/ selection kit (Miltenyi Biotec). To induce DC differentiation, monocytes plying a FDR of 5% and a biological threshold of 2-fold regulation. were cultured in RPMI 1640/10% FCS in the presence of 50 ng/ml Differentially expressed genes were subjected to gene ontology analysis recombinant human GM-CSF and 50 ng/ml recombinant human IL-4 for biological processes using Ingenuity Pathway Analysis. The dataset (Novo Nordisk) for 6 d. These cells are referred to as immature DCs and technical information compliant with minimum information about + + a microarray experiment can be found at the EMBL-EBI ArrayExpress (iDCs). Naive CD4 RA cells were purified from PBMCs using a human + depository, accession no. E-MTAB-2904 (http://www.ebi.ac.uk/arrayexpress/ naive CD4 T cell enrichment kit (StemCell Technologies). For freezing, T cells were resuspended at a density of 7 3 106/ml in RPMI 1640/50% experiments/E-MTAB-2904/). FBS/10% DMSO, and cryovials were placed in a Mr. Frosty container Statistical analysis (Thermo Fisher Scientific) at 280˚C overnight and then transferred into a 2140˚C freezer. Viability of the thawed cells was ∼95% as measured Statistical analyses were performed in GraphPad Prism 5 using Student two- , using a NucleoCounter (ChemoMetec). tailed t tests. A p value 0.05 was considered statistically significant. by guest on September 29, 2021 Unless otherwise indicated, means and SD are shown. DC culture on collagen Untreated virgin polystyrene 24-well plates were coated with ColI or ColII Results ∼ 2 3 6 in PBS at 3 mg/cm overnight at 4˚C. iDCs (1 10 ) were added per well Identification of OSCAR ligand after being preincubated for 20 min with indicated mAb. The cells were cultured for 20 h unless otherwise specified. ColI and ColII had similar It was previously shown that a putative ligand for murine OSCAR is effects in all experiments. ColII was always slightly more potent than ColI. expressed on the cell surface of osteoblasts (18). In the present Functional data in the manuscript are shown for ColII only unless other- wise specified. study, we screened a panel of cell lines for expression of a putative ligand for human OSCAR by monitoring binding of fluorescently Allogeneic and autologous MLR labeled OSCAR-ECD to the surface of live cells. A murine For allogeneic MLRs freshly purified cells were used. For autologous MC3T3-E1 preosteoblast cell line was selected for purification of reactions, T cells were kept frozen in RPMI 1640/50% FBS/10% DMSO the OSCAR ligand. Using affinity chromatography followed by 5 until the autologous DCs became matured. T cells (1 3 10 ) were liquid chromatography–tandem MS analysis of eluted proteins, we 3 3 cocultured in triplicate wells with 1 10 DCs in RPMI 1640/10% FCS have identified a1 ColI as OSCAR-interacting protein. Direct growth medium. No live DCs were detected in the coculture at the time of termination of the experiment. To assess T cell proliferation pulse labeling interaction of OSCAR with native human ColI an ColII was of cells with [3H]thymidine was used to monitor DNA synthesis. Briefly, at confirmed by SPR, whereas no binding was detected to ColIII or day 4 of coculture the cells were pulsed with 0.5 mCi [3H]thymidine ColIV (Supplemental Fig. 1). Thus, ColI and ColII serve as nat- 3 (PerkinElmer) for 18 h. [ H]thymidine incorporation was measured by urally occurring OSCAR ligands. liquid scintillation counting using a TopCount NXT (PerkinElmer). Anti-OSCAR mAb capable of blocking OSCAR–collagen in- Cytokine secretion teraction as well as nonblocking mAb were selected for further functional assays using SPR (Supplemental Fig. 2). Multiplex analysis of cytokines was performed using the BioPlex 200 cytokine assay platform (Bio-Rad). IL-23 (p19/p40) was detected using the OSCAR–collagen signaling promotes DC survival Platinum ELISA kit (eBioscience). It has previously been found that cross-linking of OSCAR with an Expression of cell surface markers mAb promoted survival of monocyte-derived DCs (11). In the For analysis of cell surface marker expression, the following Abs were used: present study, we tested whether the naturally occurring OSCAR BD multicolor PE-conjugated mouse monoclonal anti-human CD86, ligands, namely ColI/II, could promote DC survival. We differ- PerCP-Cy5.5–conjugated mouse anti-human CD209, allophycocyanin- entiated iDCs from peripheral blood monocytes in the presence of conjugated mouse anti-human CD83 (BD Biosciences), FITC-conju- gated mouse anti-human HLA-DR (BD Pharmingen), allophycocyanin- GM-CSF and IL-4. This method allows generation of cells phe- conjugated mouse anti-human CD14 (BD Pharmingen), PE-conjugated notypically resembling “inflammatory” DCs, which differentiate mouse anti-human OSCAR (clone 11.1CN5; Beckman Coulter), and Pa- in vivo from blood-derived precursors during inflammation (19). 3172 OSCAR-DEPENDENT MATURATION OF DCs

The iDCs were plated onto either uncoated plates with or without DCs (Col-DCs). Thus, OSCAR signaling leads to activation of GM-CSF, or onto collagen-coated plates without GM-CSF in the DCs characterized by production of a broad range of cytokines absence or presence of anti-OSCAR–blocking mAb or an isotype and chemokines, mainly of a proinflammatory type. control mAb. We assessed cell viability by monitoring the intra- cellular reducing environment (an indicator of cellular well-being) Collagen promotes maturation of monocyte-derived DCs with alamarBlue and by detecting cell death using annexin ColI has been shown to induce maturation of monocyte-derived V/propidium iodine staining. After 7 d of incubation, the reducing DCs, but the receptors mediating this effect were not identified potential was significantly decreased in DCs cultured on plastic (21). Cross-linking of OSCAR with specific Abs induced semi- without GM-CSF and in collagen-coated plates in the presence of maturation of DCs (11). We therefore tested whether collagen- anti-OSCAR mAb. In contrast, the cells maintained the reducing induced DC maturation is mediated by OSCAR. iDCs were gen- environment upon culturing with GM-CSF or on collagen (Fig. 1). erated as described above. The phenotype of these cells (CD142 Already after 3 d, a large percentage of annexin V+ apoptotic cells CD209+) was confirmed by flow cytometry. Treatment with anti- was detected in cultures lacking GM-CSF, whereas most cells OSCAR mAb did not have an effect on differentiation of iDCs cultured on collagen were alive (Table I). The latter effect was under the conditions used (data not shown). The iDCs were plated completely abolished by treatment of cells with anti-OSCAR onto ColI- (data not shown) or ColII-coated plates and cultured for mAb. As control, treatment with Enbrel (etanercept, the p75TNFR- 1–2 d. The cell surface markers were analyzed by flow cytometry Fc fusion protein), a drug currentlyusedfortreatmentofRA,was (Fig. 2A). We found that collagen drastically upregulated ex- used, as it has been shown that TNF-a signaling supports DC sur- pression of the maturation markers CD83 and CD86. HLA-DR vival (20). We show that Enbrel treatment partially inhibits collagen- was upregulated only in donors that had a relatively low basal Downloaded from induced survival of DCs. Our data indicate that OSCAR–collagen expression of this marker (Fig. 2B). This effect was completely signaling can promote DC survival under the conditions of growth abolished by anti-OSCAR–blocking mAb in a dose-dependent factor withdrawal. manner (Fig. 2C), indicating that collagen-induced DC matura- tion is mediated by OSCAR signaling. A mAb against integrin Collagen induces secretion of cytokines and chemokines by a b , another known collagen receptor, had no inhibitory effect monocyte-derived DCs 2 1

(data not shown), which is in agreement with the data published http://www.jimmunol.org/ Cross-linking of OSCAR in iDCs has been shown to induce se- by Brand et al. (21). LPS, which was used in some experiments as cretion of IL-8, IL-12p40, M-CSF, MCP-1/CCL2, and MDC/ positive control, showed a level of upregulation of the cell surface CCL22, whereas no secretion of IL-1b, IL-6, IL-10, GM-CSF, markers that was comparable to collagen (data not shown). Mat- IL-12p70, IP-10/CXCL10, and TNF-a was detected (9, 11). We uration of DCs can be induced by TNF-a (19). Because we have tested whether collagen can induce secretion of cytokines via shown that collagen induces TNF-a release from DCs, we tested OSCAR signaling. Culturing of iDCs on ColII-coated plates whether blocking TNF-a would inhibit ColII-induced DC matu- caused a profound induction of multiple cytokines secretion, in- ration. Treatment of the cells with Enbrel only partially inhibited cluding TNF-a, IL-6, IL-8, IL-10, IL-13, IL-23, and RANTES DC maturation in two of four donors tested (Fig. 2D). Thus, (CCL5). This activation of DCs was completely abolished by anti- autocrine TNF-a does not seem to be the major contributor to the by guest on September 29, 2021 OSCAR–blocking mAb (Table II). Meanwhile, anti-OSCAR mAb collagen-induced DC maturation. did not show any effect on the LPS-stimulated cytokine release (data not shown). In contrast to the positive control, namely LPS- Col-DCs are efficient inducers of T cell proliferation matured DCs, IL-12p70 was not secreted by collagen-matured Triggering of OSCAR with cross-linking mAb was found to potentiate effects of TLR ligands on DC maturation and, as a consequence, to enhance the ability of TLR-matured DCs to induce proliferation of allogeneic naive T cells. In the absence of TLR ligands, the DCs treated with anti-OSCAR cross-linking mAb completely failed to induce T cell proliferation (11). In the present study, we tested whether the Col-DCs can promote proliferation of allogeneic naive CD4+CD45RA+ Tcells.The Col-DCs were very efficient in promoting T cell proliferation as monitored either by [3H]thymidine incorporation (Fig. 3A) or by the expression of a proliferation marker, Ki67 (not shown). When the Col-DCs were matured in the presence of anti-OSCAR mAb, this proliferative effect was abolished in a dose-dependent manner. Cytokines secreted by T cells, which had been expanded by Col- DCs, were analyzed (Table III). Noticeably, a strong induction of a number of cytokines, including Th2-specific IL-5 and IL-13, as well as proinflammatory IL-6, IL-8, TNF-a, and RANTES FIGURE 1. OSCAR–collagen signaling promotes DC survival. Human (CCL5), was evident in the Col-DC/T cell cocultures, which was monocytes were purified and differentiated into iDCs by GM-CSF and IL-4 not the case when DCs were treated with anti-OSCAR mAb 3 6 (50 ng/ml each) for 6 d. Then, 1 10 iDCs/ml were cultured on either during the maturation step. uncoated or ColII-coated plates. To the ColII-coated wells, OSCAR- We further tested the ability of Col-DCs to induce proliferation blocking Ab (1 mg/ml) or control Ab (1 mg/ml) was added. GM-CSF (50 ng/ml) was added as a positive control of survival. As a negative control, of autologous naive T cells. In this setting also, Col-DCs were iDCs were left in growth factor–free medium. After 7 d, cell viability was efficient inducers of T cell proliferation (Fig. 3B). The secretion of assessed using alamarBlue. Data are expressed as mean of biological trip- cytokines was analyzed as above (Table IV). We detected high licates 6 SD. Data shown are from one representative donor out of five levels of IL-13 and IL-5, the cytokines that polarize T cells toward analyzed. the Th2 lineage. However, the proinflammatory cytokines IL-6, The Journal of Immunology 3173

Table I. DC viability analyzed by flow cytometry

Alive (PI2/Annexin V2) Early Apoptotic (PI2/Annexin V+) Necrotic (PI+/Annexin V2) Late Apoptotic (PI+/Annexin V+) Untreated 18.1 6 1.3 30.6 6 0.5 11.8 6 1.2 39.7 6 1.9 GM-CSF 65.0 6 5.6** 17.4 6 1.7** 2.7 6 1.3* 14.9 6 3.0 *** ColII 83.9 6 1.4*** 9.1 6 0.3*** 0.4 6 0.1** 6.6 6 1.1** ColII + anti-OSCAR 13.4 6 1.1* 31.0 6 0.3 14.2 6 3.5 41.5 6 4.1 ColII + isotype 80.6 6 3.8** 10.4 6 1.6** 0.3 6 0.1** 8.7 6 2.1** ColII + Enbrel 59.3 6 4.4** 20.7 6 2.0* 0.8 6 0.1** 19.1 6 2.6* iDCs were cultured on ColII-coated plates. Cells were untreated or treated with either 50 ng/ml GM-CSF, 1 mg/ml anti-OSCAR, 1 mg/ml isotype control, or 10 mg/ml Enbrel. After 3 d of culture cells were stained for annexin V and propidium iodide (PI) and analyzed via flow cytometry. For flow cytometry analysis, single cells were gated on with side scatter (SSC) height versus SSC width, followed by SSC versus forward scatter where debris was gated out. The percentages of cell populations were analyzed based on a dot plot (annexin V versus PI). Data are expressed as means 6 SD of triplicate wells treated independently. Data are shown for one representative donor out of four analyzed. *p , 0.05, **p , 0.01, ***p , 0.001 versus untreated.

IL-8, and TNF-a as well as Th1-polarizing INF-g were also in- gets of the OSCAR–collagen signaling pathway (Supplemental duced in an OSCAR-dependent manner. Thus, no clear pattern of Table IC). Using Ingenuity Pathway Analysis, the OSCAR- T cell polarization was evident. regulated genes were clustered into several different functional pathways. The top 20 canonical pathways are listed in Table V.

Signaling by OSCAR–collagen regulates gene expression in Downloaded from The OSCAR-dependent genes were mainly associated with im- DCs mune regulation, maturation, adhesion, apoptosis, and various The overall gene expression profile resulting from the OSCAR– signal transduction pathways. The data show that OSCAR reg- collagen interaction in DCs was characterized by Affymetrix gene ulates expression of the major components of the stable immune chip analysis. iDCs were exposed to ColI or ColII for 4 or 20 h in synapse such as CD40, CD80, CD86, CD83, and ICAM-1. Fur- the presence or absence of antagonistic anti-OSCAR mAb or thermore, OSCAR signaling induced proinflammatory cytokine isotype control mAb. The effects of ColI and ColII were very and chemokine gene expression as well as the genes encoding http://www.jimmunol.org/ similar (.90% of genes regulated by ColI were also regulated by cytokine and chemokine receptors. The gene encoding CCL20, ColII). Only data for the 4-h ColII treatment are discussed in this a chemokine attracting iDCs, was noticeably the most upregulated section, as it more closely represents the primary response to gene with a fold change of .150. Of note, chemoattractants for OSCAR stimulation without following amplification (secondary precursors of endothelial cell CXCL1, -2, and -3 mRNA levels response). LPS was included as a positive control for DC matu- were drastically induced (.25-fold) at a transcriptional level ration, and there was a good overlap (∼70%) in gene expression (Supplemental Table IC), indicating possible involvement of the changes in cells treated with LPS and ColI/II. Raw data files for all OSCAR pathway in the regulation of neoangiogenesis. OSCAR– treatments can be downloaded from the ArrayExpress depository collagen signaling upregulated genes encoding components of (accession no. E-MTAB-2904). TLR, TREM-1, and uPA/MMP-9 pathways highly relevant for by guest on September 29, 2021 A marked change in the gene expression level was observed pathogenesis of RA and other autoimmune diseases (22). Of in- for 709 genes in cells treated with ColII for 4 h (Supplemental terest is also the downregulation of the Wnt/fzd pathway that Table IA). When comparing the effect of preincubating the iDCs programs DCs to induce tolerogenic responses (23). We observed with anti-OSCAR mAb or isotype control mAb prior to plating on that ColII decreased FZD2 gene expression by 18-fold, which was ColII, the expression level of 546 genes was significantly different abrogated by treatment with anti-OSCAR mAb. Taken together, between the two treatments (Supplemental Table IB). No signif- our data indicate that OSCAR signaling in DCs has a profound icant differences (FDR of 10%) were found for treatments with effect on the induction/maintenance of proinflammatory responses ColII in the presence or absence of isotype mAb, negating an effect at multiple levels. of the isotype control mAb on OSCAR biology. When comparing the ColII-regulated genes and genes regulated Discussion in the presence of anti-OSCAR mAb, 472 genes were overlapping. Until recently, the naturally occurring ligand for OSCAR remained Thus, these genes are thought to be the true transcriptional tar- unknown. In the present study we have identified OSCAR ligand

Table II. Cytokines and chemokines secreted by DCs

iDCs Col-DCs Col-DCs + Anti-OSCAR Col-DCs + Isotype mAb LPS-DCs IL-6 2,428.0 6 1.5 8,565.0 6 175.8* 1,729.0 6 97.7** 6,750.0 6 501.1ns 22,547.0 6 364.4** IL-8 11,406.0 6 485.5 20,167.0 6 523.4** 11,809.0 6 457.6** 19,911.0 6 699 ns 20,286.0 6 508.0** IL-10 239.5 6 48.4 2,801.0 6 188.0* 85.5 6 11.0* 2,330.0 6 48.4ns 12,049.0 6 126.4** IL-12p40 536.2 6 35.0 46,361.0 6 406.0** 595.6 6 49.0** 46,937.0 6 2,298.0ns 39,407.0 6 1771.0* IL-12p70 71.5 6 33.7 99.7 6 6.1ns 40.1 6 1.5* 86.7 6 0.0ns 14,287.0 6 315.8** IL-13 21.2 6 11.2 1,034.0 6 34.3* 11.5 6 0.0* 1,039.0 6 34.7ns 1,658.0 6 6.9** RANTES 64.0 6 15.4 2,201.0 6 132.1* 54.8 6 0.5* 2,131.0 6 52.9ns 44,79.0 6 193.4* TNF-a 366.6 6 101.2 44,763.0 6 1881.0* 78.1 6 0.0* 28,719.0 6 2669.0ns 31,108.0 6 1961.0* IL-23 0.4 6 0.4 272.2 6 6.5*** 0.8 6 3.4*** 289.3 6 40.1ns 696.3 6 8.6*** Multiple cytokines were measured in the supernatants from DCs cultured at the indicated conditions using Luminex technology. Values are shown in pg/ml. Data represent means 6 SD of triplicate wells treated independently. Data are shown for 1 representative donor out of .20 donors analyzed with similar results. IL-23 was measured using a sandwich ELISA. nsnonsignificant. *p , 0.05, **p , 0.01, ***p , 0.001 by t test for the following conditions: iDCs versus Col-DCs and for Col-DCs versus Col-DCs plus anti-OSCAR. LPS-DCs, LPS-matured DCs. 3174 OSCAR-DEPENDENT MATURATION OF DCs Downloaded from http://www.jimmunol.org/ by guest on September 29, 2021

FIGURE 2. Expression of cell surface markers on DCs analyzed by flow cytometry. Initially, 1 3 106 iDCs/ml were cultured on either uncoated or ColII- coated plates for 18 h. At these conditions, DCs upregulated expression of maturation markers when cultured on collagen. (A) Top panel, Gating strategy for flow cytometry analysis. Only cells negative for the dead cell marker Near-IR were used in the analysis (gate a). Single cells from gate a were further gated on with side scatter height (SSC-H) versus SSC width (SSC-W) (gate b), followed by gating out cell debris with SSC versus forward scatter (FSC) (gate c). Hierarchy of gating is indicated with arrows. Only cells from gate c were further analyzed. Lower panel, Representative histograms are shown for the in- dicated surface markers. Open histograms represent unstained cells. Gray and black histograms represent iDCs and Col-DCs, respectively. (B) Combined data are shown for 16 donors. (C) ColII-induced expression of maturation markers is downregulated by anti-OSCAR mAb in a dose-dependent manner; 0.01, 0.1, and 1 mg/ml anti-OSCAR mAb or 1 mg/ml isotype control mAb was used. Data are expressed as mean of independently treated triplicate wells 6 SD. Data are shown for 1 representative donor out of 10. (D) DCs treated with 10 mg/ml Enbrel or 1 mg/ml isotype control mAb. Data for four donors are shown. The Journal of Immunology 3175

FIGURE 3. ColII-matured DCs induce proliferation of T cells. (A) Allogeneic MLR. Proliferation of CD3+CD4+CD45+RA+ T cells was estimated by [3H]thymidine incorporation. T cells were incubated for 4 d with the indicated allogeneic DCs: iDCs, ColII-matured DCs, or DCs that were maintained on collagen in the presence of anti-OSCAR mAb (data shown for 0.01, 0.1, and 1 mg/ml mAb) or isotype control mAb (1 mg/ml), as well as T cells alone (no DCs) as negative control and T cells stimulated with CD3/CD28 beads as positive control. (B) Proliferation of autologous CD3+CD4+CD45+RA+ T cells in Downloaded from the presence of the indicated DCs; costimulation of TCR was achieved by treatment with an agonistic OKT-3 mAb; all treatments and controls are as in (A). Data are mean 6 SD of triplicate wells from one representative experiment out of seven (allogeneic) or three (autologous) performed with similar results. expressed on murine preosteoblasts as being a1 ColI. OSCAR that was shown to be specific for this cell type (28). CD1a+ cells

interaction with native human ColI and ColII was confirmed by were found in RA synovial tissue, where they are thought to be http://www.jimmunol.org/ the SPR technique. While we were conducting our experiments, functional (29). In the present study, we chose to focus on this the Trowsdale et al. (14) published their discovery of collagens as population of inflammatory DCs to mechanistically address the ligands of OSCAR. In this study, the authors used a synthetic outcome of OSCAR–collagen signaling with relevance to the RA ColII peptide library and identified a number of peptides showing pathogenesis, although we cannot exclude an impact of the direct binding to human OSCAR. Some of these peptides were OSCAR–collagen interaction on the Ag-presenting function in efficient stimulators of receptor activator for NF-kB ligand–de- subpopulations of the CD11c+ cells, which should further be pendent osteoclastogenesis. The authors confirmed binding of addressed in clinical studies. OSCAR to native human ColI, ColII, and ColIII. We neither saw Merck et al. (9, 11) have shown that cross-linking of OSCAR a binding to native ColIII using SPR analysis nor a biological with the receptor-specific Abs can provide survival, activation, and by guest on September 29, 2021 effect on DCs, which might be attributed to differences in qualities maturation signals to human monocyte-derived DCs. The use of of the native protein preparations used in the two studies. cross-linking mAbs to stimulate the ITAM-bearing receptors via Collagens are broadly distributed in the human and, in addition aggregation is an efficient way to address the signaling potential of to their structural function, they play an important role in cell a receptor when its natural ligand is unknown. However, an en- adhesion, migration, proliferation, differentiation, and survival dogenous ligand may induce a signal of different magnitude and (24). These multiple and diverse effects are highly dependent on quality, depending on the affinity of interaction and cross-talking the ECM structure and remodeling (25). ColI is the main protein signaling pathways modulating the ITAM signal. Therefore, it is constituent of bone, whereas ColII is the major protein component essential to investigate the outcome of the OSCAR signaling in the of cartilage. Under pathological conditions, such as, for example, presence of the native ligand in the cells where other collagen RA, the ECM undergoes excessive remodeling with drastic up- receptors are coexpressed. regulation of the ColI–III turnover within the joints (26). We OSCAR expression in human monocyte-derived DCs (11) and suggest that under such conditions, collagens of bone and cartilage monocytes (30) was suggested to support cell survival in the ab- may become available for interaction with infiltrating immune sence of growth factors via induction of antiapoptotic molecules cells and may considerably influence their activation status and Bcl-2 and Bcl-xL through PI3K and ERK signaling. In our study, viability within RA joints. Indeed, it has been shown that OSCAR- the DCs plated on ColI/II showed prolonged viability in the ab- expressing mononuclear cells are in contact with collagens in the sence of the essential growth factor, GM-CSF, indicating that joints and the OSCAR-binding sites are expected to be on the OSCAR could play an important role in cell survival. Expression surface of collagens exposed to the infiltrating cells (14). of genes encoding multiple components of the ERK pathway Among the cells expressing the OSCAR protein and potentially (including MAP3K1 and MAP3K8), as well as BCL2A1 encoding capable of entering synovial tissue upon inflammation are a Bcl-2 related protein, was strongly upregulated by the OSCAR– monocytes, monocyte-derived DCs, and lineage-negative CD11c+ Col signaling. Autocrine TNF-a was previously shown to provide DC (9). Whereas the latter are thought to represent a rare het- survival signals to DCs (20). Blocking of TNF-a with either erogeneous population of cells found in health and disease, soluble p55TNFR-Fc or anti–TNF-a mAb (infliximab) signifi- monocytes may serve as precursors of inflammatory DCs, which cantly reduced survival of LPS-matured DCs (31). We show in the are only generated in pathological conditions, such as, for ex- present study that survival of Col-DCs was impaired by treatment ample, RA (27). Development of such inflammatory, fully func- with Enbrel, although to a much lower degree than by treatment tional DCs is commonly modeled in vitro by treatment of with anti-OSCAR mAb. These data indicate that collagen supports peripheral blood monocytes with GM-CSF and IL-4 (19). The survival of DCs at least in part via an autocrine TNF-a signaling. monocyte-derived DCs are potent APCs, which secrete multiple DCs plated on ColI/II secreted a number of cytokines with proinflammatory cytokines and express CD1a, a surface marker a proinflammatory function. In contrast to the OSCAR cross- 3176 OSCAR-DEPENDENT MATURATION OF DCs

Table III. Cytokines and chemokines secreted by T cells cocultured with allogeneic DCs

Col-DCs + Col-DCs + iDCs Col-DCs Anti-OSCAR Isotype mAb IL-2 38.4 6 13.2 3,135.0 6 463.0** 35.8 6 18.0** 2,666.0 6 543.0ns IL-3 811.8 6 16.4 771.7 6 6.1* 782.3 6 62.0ns 751.7 6 65.5ns IL-5 1.4 6 0.2 2,087.0 6 234.0** 1.3 6 0.0** 1,919.0 6 598.9ns IL-6 12.0 6 3.7 1,414.0 6 329.5* 20.0 6 10.8* 1,569.0 6 163.7ns IL-8 1,035.0 6 761.8 10,852.0 6 859.8** 1,352.0 6 458.4** 10,936.0 6 274.1ns IL-10 13.9 6 1.4 99.0 6 65.2ns 14.2 6 2.5ns 147.2 6 54.8ns IL-12p40 1,339.0 6 65.4 10,083.0 6 292.1** 1,349.0 6 56.5*** 13,601.0 6 403.8ns IL-12p70 10.4 6 0.0 13.0 6 0.0ns 11.3 6 1.5ns 14.3 6 1.3ns IL-13 2.5 6 0.8 3,547.0 6 142.3*** 2.5 6 0.2*** 3,609.0 6 321.5ns IL-17 46.1 6 3.2 48.9 6 3.2ns 48.9 6 3.2ns 49.4 6 5.6ns IL-18 25.8 6 2.5 25.2 6 1.4ns 24.2 6 0.7ns 26.4 6 1.6ns GM-CSF 26.1 6 3.9 1,402.0 6 217.4** 23.9 6 2.5** 1,581.0 6 135.2ns IFN-g 24.5 6 2.0 254.9 6 69.4* 23.1 6 2.4* 514.0 6 195.1ns MCP-1 992.4 6 549.3 85.6 6 2.3ns 1,505.0 6 654.3ns 86.0 6 8.8ns M-CSF 268.5 6 12.0 347.6 6 20.0* 248.4 6 6.4** 357.1 6 30.7ns RANTES 14.6 6 6.3 2,180.0 6 230.4** 18.4 6 9.6** 2,287.0 6 152.2ns TNF-a 104.3 6 56.4 3,830.0 6 168.4*** 101.9 6 18.1*** 3,575.0 6 567.1ns Downloaded from Multiple cytokines were measured in the supernatants of T cells cultured with the indicated allogeneic DCs. Supernatants were collected at day 4 of coculture. Anti-OSCAR mAbs or isotype control mAbs were used at 1 mg/ml. Values are shown in pg/ml. Data represent means 6 SD of triplicate wells treated independently. Data are shown for one representative experiment out of four independent experiments with similar results. nsnonsignificant. p , 0.05, **p , 0.01, ***p , 0.001 by t test for the following conditions: iDCs versus Col-DCs, Col-DCs versus Col- DCs + anti-OSCAR, and Col-DCs versus Col-DCs + isotype. http://www.jimmunol.org/ linking data (9, 11), we observed a profound induction of IL-6, IL- NF-kB pathway members, STAT pathway members, MAPKs) 1b, and TNF-a by ColI/II. The discrepancy might be due to werealsoupregulatedbycollageninanOSCAR-dependent a higher sensitivity of the detection method used in the present manner at the transcriptional level. Merck et al. (11) have study (Luminex versus ELISA) or due to the differences in bio- shown potentiation of TLR signaling by OSCAR cross-linking logical set-up, where exposure to ColI/II may provide additional characterized by secretion of proinflammatory cytokines and signals necessary for more efficient performance of the OSCAR maturation of DCs. In the present study, we provide evidence that pathway. Most of the cytokines and their receptors were found to the OSCAR signaling pathway upregulates transcription of the be transcriptional targets of OSCAR based on the microarray genes encoding receptors and multiple components of the TLR by guest on September 29, 2021 analysis. A number of chemokines were also induced by OSCAR– signaling machinery. collagen signaling, including CCL20 (recruiting iDCs), IL-8 Earlier studies indicated that ColI can stimulate maturation of (chemoattractant for granulocytes), and RANTES (CCL5, che- human monocyte-derived DCs in an integrin-independent manner moattractant for T cells) as well as attractants for endothelial cell (21), the mechanism for which so far remained undiscovered. Our precursors CXCL1, -2, and -3. The components of the pathways data show that the OSCAR signaling pathway controls Col- regulating expression of these proinflammatory mediators (e.g., induced DC maturation. The iDCs plated on ColI/II showed fast

Table IV. Cytokines and chemokines secreted by T cells cocultured with autologous DCs

iDCs Col-DCs Col-DCs + Anti-OSCAR Col-DCs + Isotype mAb IL-2 16.2 6 0.9 18.0 6 0.6ns 14.0 6 1.7ns 15.6 6 0.6ns IL-3 2397.0 6 140.9 2,399.0 6 85.2ns 2,225.0 6 186.1ns 2,456.0 6 47.0ns IL-5 52.8 6 23.9 377.9 6 67.0* 45.3 6 22.1* 302.7 6 19.4ns IL-6 894.0 6 97.4 2,595.0 6 202.3** 395.1 6 88.3** 3,052.0 6 1,125.0ns IL-8 2,1579.0 6 17.9 22,683.0 6 270.7* 18,465.0 6 1,058* 21,496.0 6 328.1ns IL-10 213.8 6 9.0 430.7 6 10.6** 188.2 6 23.1** 419.7 6 16.1ns IL-12p40 20,956.0 6 3,700.0 38,572.0 6 732.8* 10,840.0 6 1,641** 43,733.0 6 3518ns IL-12p70 28.9 6 2.7 19.3 6 0.0ns 16.4 6 1.4ns 20.2 6 2.7ns IL-13 207.4 6 0.2 966.1 6 28.3*** 158.5 6 18.4*** 884.3 6 114.4ns IL-17 52.3 6 5.5 67.8 6 11.0ns 42.1 6 4.8ns 55.2 6 1.4ns IL-18 20.5 6 2.5 21.0 6 0.8ns 20.5 6 0.8ns 21.6 6 2.5ns GM-CSF 227.5 6 4.2 495.0 6 58.6* 230.3 6 11.0* 472.3 6 83.2ns IFN-g 1,429.0 6 352.4 3,236.0 6 954.6ns 213.3 6 166.2* 3,704.0 6 1,330.0ns MCP-1 234.7 6 52.8 8.0 6 1.1* 372.9 6 35.4** 8.1 6 1.8ns M-CSF 893.7 6 6.0 1,873.0 6 82.6** 908.0 6 38.3** 2,163.0 6 3.0* RANTES 1,416.0 6 0.9 1,262.0 6 85.3ns 2,408.0 6 63.6** 15,12.0 6 182.8ns TNF-a 1,706.0 6 305.0 8,297.0 6 507.3** 2,016.0 6 377.2** 9251.0 6 855.6ns Multiple cytokines were measured in the supernatants of T cells cultured with the indicated autologous DCs. Supernatants were collected at day 4 of coculture. Anti-OSCAR mAbs or isotype control mAbs were used at 1 mg/ml. Values are shown in pg/ml. Data represent means 6 SD of triplicate wells treated independently. Data are shown for one representative experiment out of four independent experiments with similar results. nsnonsignificant. *p , 0.05, **p , 0.01, ***p , 0.001 by t test for the following conditions: iDCs versus Col-DCs, Col-DCs versus Col-DCs + anti-OSCAR, and Col-DCs versus Col-DCs + isotype. The Journal of Immunology 3177

Table V. Top 20 canonical pathways regulated by ColII and reversed by anti-OSCAR

Ingenuity Canonical Pathways Molecules 2Log (p Value) TLR signaling MAP3K14, IL1A, MAP3K1, TLR8, TNFAIP3, MAPK13, NFKB1, 1.05E+01 TLR2, NFKBIA, IL1RN, IL1B, MAP2K3, TNF, TRAF1, IRAK2 Hepatic fibrosis/hepatic stellate cell activation IL4R, IL1A, ICA, VEGFA, CXCL3, CCL2, CD40, EDN1, CSF1, 1.04E+01 TNFSF8, IL1B, SERPINE1, IL1RAP, TNF, MMP9, TNFSF14 Atherosclerosis signaling IL1A, ICAM1, PDGFA, NFKB1, F3, TNFRSF12A, SELPLG, 9.06E+00 CD40, CCL2, CSF1, IL1RN, LPL, IL1B, SERPINA1, TNF, MMP9, TNFSF14 Type I diabetes mellitus signaling SOCS3, MAP3K14, IFNGR1, MAPK13, MAP3K5, JAK2, NFKB1, 8.89E+00 NFKBIA, CD80, IL1B, CD86, BID, MAP2K3, CASP8, IL1RAP, TNF Role of macrophages, fibroblasts, and SOCS3, IL1A, ICAM1, PDGFA, TLR8, JAK2, NFKB1, VEGFA, 8.86E+00 endothelial cells in RA NFAT5, NFKBIA, CCL2, OSM, MAPKAPK2, IL1RAP, FZD2, TRAF1, MAP3K14, C5AR1, CREB3, TLR2, CSF1, IL1RN, IL1B, MAP2K3, TNF, IRAK2 Acute phase response signaling SOCS3, MAP3K14, IL1A, C3, MAP3K1, JAK2, MAPK13, 8.48E+00 MAP3K5, NFKB1, NFKBIA, SOD2, IL1RN, OSM, IL1B, SERPINA1, MAP2K3, SERPINE1, IL1RAP, TNF Granulocyte adhesion and diapedesis IL1A, C5AR1, ICAM1, CCL20, CCL22, SDC4, SELPLG, CXCL3, 8.14E+00 CLDN12, CCL2, CLDN1, IL1RN, IL1B, CXCL1, CXCL2, Downloaded from IL1RAP, TNF, MMP9, CCL1 IL-6 signaling SOCS3, MAP3K14, IL1A, MAPK13, JAK2, NFKB1, VEGFA, 7.71E+00 NFKBIA, IL1RN, IL1B, MAP2K3, MAPKAPK2, IL1RAP, TNF, MCL1 IL-10 signaling SOCS3, MAP3K14, IL1A, IL4R, NFKBIA, IL1RN, IL1B, 7.54E+00 MAP2K3, MAPK13, NFKB1, TNF, IL1RAP Altered T cell and B cell signaling in RA MAP3K14, IL1A, SLAMF1, TLR8, NFKB1, TLR2, CD80, CD40, 7.46E+00 http://www.jimmunol.org/ CSF1, IL1RN, CD86, IL1B, TNF TREM1 signaling TLR2, CXCL3, TREM1, ICAM1, CCL2, CD40, TLR8, CD86, 7.27E+00 IL1B, JAK2, NFKB1, TNF CD40 signaling MAP3K14, ICAM1, NFKBIA, CD40, TNFAIP3, MAP2K3, 7.03E+00 MAPK13, PTGS2, MAPKAPK2, NFKB1, TRAF1 CD27 signaling in lymphocytes MAP3K14, NFKBIA, MAP3K1, BID, MAP3K8, MAP2K3, 6.99E+00 MAP3K5, CASP8, NFKB1, MAP3K2 Agranulocyte adhesion and diapedesis IL1A, C5AR1, ICAM1, CCL20, CCL22, SDC4, SELPLG, CXCL3, 6.98E+00 CLDN12, CCL2, CLDN1, IL1RN, IL1B, CXCL1, CXCL2, TNF, MMP9, CCL1

NF-kB signaling MAP3K14, IL1A, FLT1, MAP3K1, TLR8, TNFAIP3, MALT1, 6.86E+00 by guest on September 29, 2021 NFKB1, TGFBR2, TLR2, NFKBIA, CD40, IL1RN, IL1B, MAP3K8, CASP8, TNF Role of IL-17A in arthritis CXCL3, NFKBIA, CCL2, CCL20, MAP2K3, CXCL1, MAPK13, 6.67E+00 PTGS2, MAPKAPK2, NFKB1 DC maturation MAP3K14, IL1A, ICAM1, CREB3, MAPK13, JAK2, NFKB1, 6.64E+00 STAT4, TLR2, NFKBIA, CD40, CD80, IL1RN, CD86, IL1B, IRF8, TNF BCR signaling BLNK, MAP3K14, CREB3, MAP3K1, MAPK13, MALT1, 6.57E+00 MAP3K5, NFKB1, INPP5D, NFKBIA, NFAT5, SYK, MAP2K3, MAP3K8, RASSF5, BCL2A1, MAP3K2 TWEAK signaling CASP6, MAP3K14, NFKBIA, BID, CASP8, NFKB1, 6.42E+00 TNFRSF12A, TRAF1 TNFR1 signaling CASP6, MAP3K14, NFKBIA, MAP3K1, TNFAIP3, BID, CASP8, 6.17E+00 NFKB1, TNF iDCs were cultured on ColII for 4 h in the presence or absence of GM-CSF (50 ng/ml), anti-OSCAR mAb (1 mg/ml), or isotype control (1 mg/ml). Total cellular RNA was isolated, and genome-wide mRNA levels were determined using Affymetrix GeneChip microarray analysis. The table shows canonical pathways for OSCAR-ColII–regulated genes at an FDR of 5% and a biological criterion of minimum 2-fold change. A complete list of all genes regulated by the OSCAR-ColII signaling at 4 h time point is provided in Supplemental Table IC. Samples from six independent experiments were analyzed. and drastic upregulation of maturation markers. Microarray In contrast to the OSCAR cross-linking data (11), in our study analysis has shown that most of the major components of the triggering of the OSCAR signaling in DCs with a native ligand led stable immune synapse, including CD40, CD80, CD86, and to formation of matured cells, which efficiently stimulated pro- ICAM-1, are transcriptional targets of the OSCAR–collagen sig- liferation of allogeneic and autologous naive T cells. Thus, even in naling. Treatment of cells with anti-OSCAR mAb completely the absence of microbial or inflammatory stimulation, OSCAR blocked this collagen-induced maturation process. The cell engagement by collagen was sufficient to induce a full DC mat- surface expression of HLA-DR was upregulated in an OSCAR- uration program. The T cells expanded by Col-DCs produced dependent manner. However, expression of the MHC class II multiple cytokines mainly of the proinflammatory type, but with genes was not influenced by collagen exposure, indicating reg- no clear signs of T cell polarization. Additional studies on phe- ulation at a posttranscriptional level. These results are in line notyping of these cells (e.g., microarray and transcription factor with the previously published studies showing posttranscrip- profiling) are needed to fully understand the T cell polarizing tional regulation of the surface expression of MHC class II (32), effect of the Col-DCs. particularly via protein recycling/trafficking to and from the Upregulation of OSCAR expression on the surface of blood plasma membrane (33, 34). monocytes was found in RA patients with active disease, and 3178 OSCAR-DEPENDENT MATURATION OF DCs

OSCAR-expressing mononuclear cells were detected in peri- 11. Merck, E., B. de Saint-Vis, M. Scuiller, C. Gaillard, C. Caux, G. Trinchieri, and E. E. Bates. 2005. Fc receptor g-chain activation via hOSCAR induces survival vascular areas of the synovium (13). The RA synovium is con- and maturation of dendritic cells and modulates Toll-like receptor responses. sidered an ectopic lymphoid organ (35). Both immature and Blood 105: 3623–3632. mature DCs are present in the RA synovium in about a 1:1 ratio. 12. Tenca, C., A. Merlo, E. Merck, E. E. Bates, D. Saverino, R. Simone, D. Zarcone, G. Trinchieri, C. E. Grossi, and E. Ciccone. 2005. CD85j (leukocyte Ig-like The immature cells are primarily located in the sublining or lining receptor-1/Ig-like transcript 2) inhibits human osteoclast-associated receptor- layer of the synovium and in the perivascular infiltrates, whereas mediated activation of human dendritic cells. J. Immunol. 174: 6757–6763. mature DCs are associated with perivascular lymphocytic infil- 13. Herman, S., R. B. Muller,€ G. Kro¨nke, J. Zwerina, K. Redlich, A. J. Hueber, H. Gelse, E. Neumann, U. Muller-Ladner,€ and G. Schett. 2008. Induction of trates (36, 37). These perivascular DCs were suggested to origi- osteoclast-associated receptor, a key osteoclast costimulation molecule, in nate from blood-derived precursors that migrated through the rheumatoid arthritis. Arthritis Rheum. 58: 3041–3050. activated endothelium and received differentiation signals, such as 14. Barrow, A. D., N. Raynal, T. L. Andersen, D. A. Slatter, D. Bihan, N. Pugh, M. Cella, T. Kim, J. Rho, T. Negishi-Koga, et al. 2011. OSCAR is a collagen GM-CSF and IL-13, within the joint (reviewed in Ref. 38). It is receptor that costimulates osteoclastogenesis in DAP12-deficient humans and thought that functional DC/T cell interaction can take place lo- mice. J. Clin. Invest. 121: 3505–3516. cally (39, 40), and the perivascular region may act as a site for cell 15. Canfield, S. M., and S. L. Morrison. 1991. The binding affinity of human IgG for its high affinity Fc receptor is determined by multiple amino acids in the CH2 activation (41). Intriguingly, surgical removal of cartilage in RA domain and is modulated by the hinge region. J. Exp. Med. 173: 1483–1491. patients led to reduced inflammation and suppression of functional 16. Schneider, C., R. A. Newman, D. R. Sutherland, U. Asser, and M. F. Greaves. 1982. A one-step purification of membrane proteins using a high efficiency differentiation of DCs in the synovium (42). Because ColII makes immunomatrix. J. Biol. Chem. 257: 10766–10769. up to 60% of dry weight of articular cartilage (43), we speculate 17. Shevchenko, A., M. Wilm, O. Vorm, and M. Mann. 1996. Mass spectrometric se- that this observed effect might at least partially be attributed to quencing of proteins silver-stained polyacrylamide gels. Anal. Chem. 68: 850–858. 18. Kim, N., M. Takami, J. Rho, R. Josien, and Y. Choi. 2002. A novel member of interference with the OSCAR signaling in DCs. the leukocyte receptor complex regulates osteoclast differentiation. J. Exp. Med. Downloaded from Taken together, our data indicate that the principal role of 195: 201–209. OSCAR in DCs is proinflammatory. Although OSCAR is expressed 19. Sallusto, F., and A. Lanzavecchia. 1994. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage in resting myeloid cells (9, 13), it may not be functional because colony-stimulating factor plus interleukin 4 and downregulated by tumor ne- the ligand accessibility is limited. We hypothesize that the crosis factor alpha. J. Exp. Med. 179: 1109–1118. OSCAR–collagen signaling plays a pivotal role in pathology, such as 20. Ludewig, B., D. Graf, H. R. Gelderblom, Y. Becker, R. A. Kroczek, and G. Pauli. 1995. Spontaneous apoptosis of dendritic cells is efficiently inhibited by TRAP in RA, where ligands become available due to ongoing tissue (CD40-ligand) and TNF-a, but strongly enhanced by interleukin-10. Eur. J. http://www.jimmunol.org/ remodeling. OSCAR may act at multiple levels contributing to Immunol. 25: 1943–1950. 21. Brand, U., I. Bellinghausen, A. H. Enk, H. Jonuleit, D. Becker, J. Knop, and perpetuation of local synovial inflammation and may impact J. Saloga. 1998. Influence of extracellular matrix proteins on the development of systemic inflammation in RA via expansion of proinflammatory cultured human dendritic cells. Eur. J. Immunol. 28: 1673–1680. T cells. 22. Liu, Z., N. Li, L. A. Diaz, M. Shipley, R. M. Senior, and Z. Werb. 2005. Synergy between a plasminogen cascade and MMP-9 in autoimmune disease. J. Clin. Invest. 115: 879–887. Acknowledgments 23. Pulendran, B., H. Tang, and S. Manicassamy. 2010. Programming dendritic cells to induce TH2 and tolerogenic responses. Nat. Immunol. 11: 647–655. We thank Lise F. W. Jensen, Jette W. Platou, Jing Wang, Bing Zhang, Helene 24. Hynes, R. O. 2009. The extracellular matrix: not just pretty fibrils. Science 326: Bregnbak, Jian Zhou, Wenjuan Xia, Xiaoai Wu, Li Yang, and Chunyan Ma 1216–1219. for excellent technical assistance. 25. Daley, W. P., S. B. Peters, and M. Larsen. 2008. Extracellular matrix dynamics in by guest on September 29, 2021 development and regenerative medicine. J. Cell Sci. 121: 255–264. 26. Karsdal, M. A., T. Woodworth, K. Henriksen, W. P. Maksymowych, H. Genant, Disclosures P. Vergnaud, C. Christiansen, T. Schubert, P. Qvist, G. Schett, et al. 2011. Bio- The authors have no financial conflicts of interest. chemical markers of ongoing joint damage in rheumatoid arthritis—current and future applications, limitations and opportunities. Arthritis Res. Ther. 13: 215. 27. Shortman, K., and S. H. Naik. 2007. Steady-state and inflammatory dendritic- cell development. Nat. Rev. Immunol. 7: 19–30. References 28. Leo´n, B., M. Lo´pez-Bravo, and C. Ardavı´n. 2005. Monocyte-derived dendritic 1. McInnes, I. B., and G. Schett. 2011. The pathogenesis of rheumatoid arthritis. N. cells. Semin. Immunol. 17: 313–318. Engl. J. Med. 365: 2205–2219. 29. Steenbakkers,P.G.,D.Baeten,E.Rovers,E.M.Veys,A.W.Rijnders,J.Meijerink, 2. Holmdahl, R., V. Malmstro¨m, and H. Burkhardt. 2014. Autoimmune priming, F. De Keyser, and A. M. Boots. 2003. Localization of MHC class II/human cartilage tissue attack and chronic inflammation—the three stages of rheumatoid arthritis. glycoprotein-39 complexes in synovia of rheumatoid arthritis patients using Eur. J. Immunol. 44: 1593–1599. complex-specific monoclonal antibodies. J. Immunol. 170: 5719–5727. 3. Thomas, R., L. S. Davis, and P. E. Lipsky. 1994. Rheumatoid synovium is enriched 30. Merck, E., C. Gaillard, M. Scuiller, P. Scapini, M. A. Cassatella, G. Trinchieri, in mature antigen-presenting dendritic cells. J. Immunol. 152: 2613–2623. and E. E. Bates. 2006. Ligation of the FcRg chain-associated human osteoclast- 4. Radstake, T. R., A. W. van Lieshout, P. L. van Riel, W. B. van den Berg, and associated receptor enhances the proinflammatory responses of human mono- G. J. Adema. 2005. Dendritic cells, Fcg receptors, and Toll-like receptors: po- cytes and neutrophils. J. Immunol. 176: 3149–3156. tential allies in the battle against rheumatoid arthritis. Ann. Rheum. Dis. 64: 31. Baldwin, H. M., T. Ito-Ihara, J. D. Isaacs, and C. M. Hilkens. 2010. Tumour 1532–1538. necrosis factor alpha blockade impairs dendritic cell survival and function in 5. Lebre, M. C., and P. P. Tak. 2008. Dendritic cell subsets: their roles in rheu- rheumatoid arthritis. Ann. Rheum. Dis. 69: 1200–1207. matoid arthritis. Acta Reumatol. Port. 33: 35–45. 32. Pai, R. K., D. Askew, W. H. Boom, and C. V. Harding. 2002. Regulation of class 6. Radstake, T. R., R. van der Voort, M. ten Brummelhuis, M. de Waal Malefijt, II MHC expression in APCs: roles of types I, III, and IV class II transactivator. J. M. Looman, C. G. Figdor, W. B. van den Berg, P. Barrera, and G. J. Adema. Immunol. 169: 1326–1333. 2005. Increased expression of CCL18, CCL19, and CCL17 by dendritic cells 33. Shin, J. S., M. Ebersold, M. Pypaert, L. Delamarre, A. Hartley, and I. Mellman. from patients with rheumatoid arthritis, and regulation by Fcg receptors. Ann. 2006. Surface expression of MHC class II in dendritic cells is controlled by Rheum. Dis. 64: 359–367. regulated ubiquitination. Nature 444: 115–118. 7. Rivollier, A., M. Mazzorana, J. Tebib, M. Piperno, T. Aitsiselmi, C. Rabourdin- 34. Chow, A., D. Toomre, W. Garrett, and I. Mellman. 2002. Dendritic cell matu- Combe, P. Jurdic, and C. Servet-Delprat. 2004. Immature dendritic cell trans- ration triggers retrograde MHC class II transport from lysosomes to the plasma differentiation into osteoclasts: a novel pathway sustained by the rheumatoid membrane. Nature 418: 988–994. arthritis microenvironment. Blood 104: 4029–4037. 35.Kratz,A.,A.Campos-Neto,M.S.Hanson,andN.H.Ruddle.1996.Chronicinflam- 8. Alnaeeli, M., J. M. Penninger, and Y. T. Teng. 2006. Immune interactions with mation caused by lymphotoxin is lymphoid neogenesis. J. Exp. Med. 183: 1461–1472. CD4+ T cells promote the development of functional osteoclasts from murine 36. Page, G., S. Lebecque, and P. Miossec. 2002. Anatomic localization of immature CD11c+ dendritic cells. J. Immunol. 177: 3314–3326. and mature dendritic cells in an ectopic lymphoid organ: correlation with selective 9. Merck, E., C. Gaillard, D. M. Gorman, F. Montero-Julian, I. Durand, chemokine expression in rheumatoid synovium. J. Immunol. 168: 5333–5341. S. M. Zurawski, C. Menetrier-Caux, G. Carra, S. Lebecque, G. Trinchieri, and 37. Manzo, A., S. Bugatti, R. Caporali, R. Prevo, D. G. Jackson, M. Uguccioni, E. E. Bates. 2004. OSCAR is an FcRg-associated receptor that is expressed by C. D. Buckley, C. Montecucco, and C. Pitzalis. 2007. CCL21 expression pattern myeloid cells and is involved in antigen presentation and activation of human of human secondary lymphoid organ stroma is conserved in inflammatory dendritic cells. Blood 104: 1386–1395. lesions with lymphoid neogenesis. Am. J. Pathol. 171: 1549–1562. 10. Ishikawa, S., N. Arase, T. Suenaga, Y. Saita, M. Noda, T. Kuriyama, H. Arase, 38. Thomas, R., K. P. MacDonald, A. R. Pettit, L. L. Cavanagh, J. Padmanabha, and and T. Saito. 2004. Involvement of FcRg in signal transduction of osteoclast- S. Zehntner. 1999. Dendritic cells and the pathogenesis of rheumatoid arthritis. associated receptor (OSCAR). Int. Immunol. 16: 1019–1025. J. Leukoc. Biol. 66: 286–292. The Journal of Immunology 3179

39. Baeten, D., P. G. Steenbakkers, A. M. Rijnders, A. M. Boots, E. M. Veys, and 41. Krenn, V., N. Schalhorn, A. Greiner, R. Molitoris, A. Ko¨nig, F. Gohlke, and F. De Keyser. 2004. Detection of major histocompatibility complex/human H. K. Muller-Hermelink.€ 1996. Immunohistochemical analysis of proliferating and cartilage gp-39 complexes in rheumatoid arthritis synovitis as a specific and antigen-presenting cells in rheumatoid synovial tissue. Rheumatol. Int. 15: 239–247. independent histologic marker. Arthritis Rheum. 50: 444–451. 42. Li, T. F., J. Mandelin, M. Hukkanen, J. Lassus, J. Sandelin, S. Santavirta, 40. Timmer, T. C., B. Baltus, M. Vondenhoff, T. W. Huizinga, P. P. Tak, I. Virtanen, and Y. T. Konttinen. 2002. Dendritic cells in rheumatoid synovial C. L. Verweij, R. E. Mebius, and T. C. van der Pouw Kraan. 2007. Inflammation membrane after total removal of the hyaline articular cartilage. Rheumatology and ectopic lymphoid structures in rheumatoid arthritis synovial tissues dissected (Oxford) 41: 319–323. by genomics technology: identification of the interleukin-7 signaling pathway in 43. Sophia Fox, A. J., A. Bedi, and S. A. Rodeo. 2009. The basic science of articular tissues with lymphoid neogenesis. Arthritis Rheum. 56: 2492–2502. cartilage: structure, composition, and function. Sports Health 1: 461–468. Downloaded from http://www.jimmunol.org/ by guest on September 29, 2021 Collagen I Collagen II

Collagen III Collagen IV

Figure S1

Figure S1. Identification of OSCAR ligand

(A) Binding of Alexa488-labelled OSCAR-ECD to the surface of live cells was analyzed by flow cytometry. A murine MC3T3-E1 pre-osteoblast cell line expressed OSCAR-binding moieties on the cell surface and therefore was selected for purification of the OSCAR ligand. Open histograms – fluorescence in the presence of the Alexa488-conjugated protein, black histograms - untreated cells; (B). Proteins extracted from the membranes of the MC3T3-E1 cells were incubated with either Protein G/OSCAR-Fc affinity matrix or control Protein G/Fc matrix. The bound proteins were eluted and analyzed by SDS-PAGE. The proteins which were differentially bound to the OSCAR-Fc and not to the Protein G/Fc matrix were further analyzed. The major diffuse protein band with an approx. electrophoretic mobility of 170-200 kD was subjected to in-gel tryptic digest and the peptides analyzed by LCMSMS. Peak lists were generated and searched with MASCOT against the mammalian part of the Swissprot database. The top hit was mouse alpha 1 type I Collagen (accession number P11087) with a MASCOT score of 2241 and a sequence coverage of 49%. In addition, mouse alpha 1 Collagen type III (accession number P08121) was identified with a lower score of 471 and a sequence coverage of 15%. SDS-PAGE analysis of proteins from MC3T3-E1 bound to the OSCAR-Fc (lane 1) and to the Fc control (lane 2) affinity matrix. The arrow is indicating a band which was identified by LC-MS MS as Collagen alpha 1 type I and Collagen alpha 1 type III chains; (C). Interaction of OSCAR-ECD with native human Collagens was further verified using surface plasmon resonance technique (SPR). Human ColI-IV proteins were immobilized to a sensor chip followed by injection of OSCAR-ECD. Binding of OSCAR-ECD was observed to ColI and II, but not to ColIII and IV. Thus, ColI and II appear to be natural ligands for OSCAR.

Blocking mAb

Non-blocking mAb

Time (s)

Figure S2 Figure S2. SPR analysis of OSCAR binding to ColI in the presence of anti- OSCAR mAb

A panel of mAb against OSCAR was generated and tested for their ability to block the interaction between OSCAR-ECD and ColI. For this purpose, ColI was immobilized on a SPR sensor chip. Binding of a constant amount of OSCAR-ECD to ColI was measured in the presence of increasing concentrations of anti-OSCAR mAb. In cases where the antibody did not inhibit the interaction between OSCAR and Collagen, the SPR signal increased with increasing amounts of antibody, due to the higher mass of the OSCAR-ECD/mAb complex. In contrast, several mAb prevented the binding of OSCAR to Collagen thereby leading to a concentration dependent decrease of the SPR signal. The mAb from these two groups were used in this study as control and a function-blocking mAb, respectively. Supplementary Table 1A. Genes regulated by ColII ColII vs iDC at 4 hours name gene title gene symbol q-value Fold change ENSG00000115009 chemokine (C-C motif) ligand 20 CCL20 0,002 158,54 ENSG00000073756 prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) PTGS2 0,003 56,05 ENSG00000115008 interleukin 1, alpha IL1A 0,010 43,04 ENSG00000153234 nuclear receptor subfamily 4, group A, member 2 NR4A2 0,003 39,00 ENSG00000164949 GTP binding protein overexpressed in skeletal muscle GEM 0,003 36,00 ENSG00000234883 MIR155 host gene (non-protein coding) MIR155HG 0,005 32,15 ENSG00000078401 endothelin 1 EDN1 0,011 26,45 ENSG00000163734 chemokine (C-X-C motif) ligand 3 CXCL3 0,011 26,13 ENSG00000081041 chemokine (C-X-C motif) ligand 2 CXCL2 0,010 24,83 ENSG00000123689 G0/G1switch 2 G0S2 0,004 24,05 ENSG00000232810 tumor necrosis factor TNF 0,003 23,13 ENSG00000125538 interleukin 1, beta IL1B 0,007 23,07 ENSG00000158050 dual specificity phosphatase 2 DUSP2 0,003 22,23 ENSG00000163739 chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha) CXCL1 0,011 21,49 ENSG00000120875 dual specificity phosphatase 4 DUSP4 0,004 20,84 ENSG00000178726 thrombomodulin THBD 0,008 19,30 ENSG00000101187 solute carrier organic anion transporter family, member 4A1 SLCO4A1 0,003 18,32 ENSG00000041982 tenascin C TNC 0,008 17,85 ENSG00000117525 coagulation factor III (thromboplastin, tissue factor) F3 0,003 17,12 ENSG00000164181 ELOVL family member 7, elongation of long chain fatty acids (yeast) ELOVL7 0,004 15,63 ENSG00000179388 early growth response 3 EGR3 0,008 15,18 ENSG00000113070 heparin-binding EGF-like growth factor HBEGF 0,005 15,14 ENSG00000108691 chemokine (C-C motif) ligand 2 CCL2 0,010 14,11 ENSG00000153162 bone morphogenetic protein 6 BMP6 0,004 13,46 ENSG00000013619 mastermind-like domain containing 1 MAMLD1 0,004 12,79 ENSG00000140379 BCL2-related protein A1 BCL2A1 0,007 12,23 ENSG00000232956 chromosome 7 open reading frame 40 C7orf40 0,005 11,74 ENSG00000116717 growth arrest and DNA-damage-inducible, alpha GADD45A 0,005 11,17 ENSG00000186827 tumor necrosis factor receptor superfamily, member 4 TNFRSF4 0,004 11,15 ENSG00000180758 G protein-coupled receptor 157 GPR157 0,011 11,14 ENSG00000149289 zinc finger CCCH-type containing 12C ZC3H12C 0,003 11,11 ENSG00000163661 pentraxin 3, long PTX3 0,012 11,06 ENSG00000056558 TNF receptor-associated factor 1 TRAF1 0,004 10,51 ENSG00000099985 oncostatin M OSM 0,002 10,47 ENSG00000157557 v-ets erythroblastosis virus E26 oncogene homolog 2 (avian) ETS2 0,006 10,15 ENSG00000112394 solute carrier family 16, member 10 (aromatic amino acid transporter) SLC16A10 0,010 10,06 ENSG00000144802 nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, zeta NFKBIZ 0,004 9,42 ENSG00000108702 chemokine (C-C motif) ligand 1 CCL1 0,011 8,91 ENSG00000170542 serpin peptidase inhibitor, clade B (ovalbumin), member 9 SERPINB9 0,008 8,63 ENSG00000132510 lysine (K)-specific demethylase 6B KDM6B 0,002 8,55 ENSG00000125735 tumor necrosis factor (ligand) superfamily, member 14 TNFSF14 0,002 8,54 ENSG00000110047 EH-domain containing 1 EHD1 0,008 8,48 ENSG00000173846 polo-like kinase 3 PLK3 0,003 8,37 ENSG00000167604 nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, delta NFKBID 0,004 8,27 ENSG00000116285 ERBB receptor feedback inhibitor 1 ERRFI1 0,007 8,04 ENSG00000099860 growth arrest and DNA-damage-inducible, beta GADD45B 0,002 7,92 ENSG00000118503 tumor necrosis factor, alpha-induced protein 3 TNFAIP3 0,006 7,87 ENSG00000120738 early growth response 1 EGR1 0,009 7,70 ENSG00000134070 interleukin-1 receptor-associated kinase 2 IRAK2 0,003 7,65 ENSG00000135476 extra spindle pole bodies homolog 1 (S. cerevisiae) ESPL1 0,020 7,49 ENSG00000114473 IQ motif containing G IQCG 0,006 7,31 ENSG00000253522 microRNA 146a (MIR146A), microRNA CTC-231O11.1 0,010 7,19 ENSG00000112096 superoxide dismutase 2, mitochondrial SOD2 0,004 7,13 ENSG00000065809 family with sequence similarity 107, member B FAM107B 0,003 7,02 ENSG00000103257 solute carrier family 7 (cationic amino acid transporter, y+ system), member 5 SLC7A5 0,008 6,94 ENSG00000152413 homer homolog 1 (Drosophila) HOMER1 0,006 6,93 ENSG00000010810 FYN oncogene related to SRC, FGR, YES FYN 0,011 6,83 ENSG00000185022 v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (avian) MAFF 0,008 6,81 ENSG00000124145 syndecan 4 SDC4 0,003 6,60 ENSG00000023445 baculoviral IAP repeat containing 3 BIRC3 0,015 6,57 ENSG00000184371 colony stimulating factor 1 (macrophage) CSF1 0,003 6,33 ENSG00000123610 tumor necrosis factor, alpha-induced protein 6 TNFAIP6 0,028 6,22 ENSG00000167772 angiopoietin-like 4 ANGPTL4 0,022 6,22 ENSG00000124882 epiregulin EREG 0,017 6,21 ENSG00000034152 mitogen-activated protein kinase kinase 3 MAP2K3 0,002 6,17 ENSG00000249992 transmembrane protein 158 (gene/pseudogene) TMEM158 0,013 6,04 ENSG00000162645 guanylate binding protein 2, interferon-inducible GBP2 0,003 6,02 ENSG00000186665 chromosome 17 open reading frame 58 C17orf58 0,005 5,96 ENSG00000154640 BTG family, member 3 BTG3 0,006 5,94 ENSG00000125384 prostaglandin E receptor 2 (subtype EP2), 53kDa PTGER2 0,005 5,92 ENSG00000119508 nuclear receptor subfamily 4, group A, member 3 NR4A3 0,014 5,85 ENSG00000179294 chromosome 17 open reading frame 96 C17orf96 0,008 5,59 ENSG00000167695 family with sequence similarity 57, member A FAM57A 0,015 5,57 ENSG00000112715 vascular endothelial growth factor A VEGFA 0,007 5,57 ENSG00000131016 A kinase (PRKA) anchor protein 12 AKAP12 0,014 5,52 ENSG00000136158 sprouty homolog 2 (Drosophila) SPRY2 0,007 5,51 ENSG00000136689 interleukin 1 receptor antagonist IL1RN 0,005 5,48 ENSG00000106366 serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 SERPINE1 0,009 5,47 ENSG00000165997 ADP-ribosylation factor-like 5B ARL5B 0,004 5,38 ENSG00000258227 C-type lectin domain family 5 member A AC073647.10 0,007 5,35 ENSG00000121797 chemokine (C-C motif) receptor-like 2 CCRL2 0,004 5,35 ENSG00000162924 v-rel reticuloendotheliosis viral oncogene homolog (avian) REL 0,011 5,14 ENSG00000090339 intercellular adhesion molecule 1 ICAM1 0,010 5,13 ENSG00000138670 RasGEF domain family, member 1B RASGEF1B 0,003 5,13 ENSG00000186891 tumor necrosis factor receptor superfamily, member 18 TNFRSF18 0,002 4,95 ENSG00000169429 interleukin 8 IL8 0,015 4,94 ENSG00000108179 peptidylprolyl isomerase F PPIF 0,006 4,91 ENSG00000139289 pleckstrin homology-like domain, family A, member 1 PHLDA1 0,013 4,90 ENSG00000117090 signaling lymphocytic activation molecule family member 1 SLAMF1 0,022 4,88 ENSG00000139318 dual specificity phosphatase 6 DUSP6 0,007 4,85 ENSG00000159200 regulator of calcineurin 1 RCAN1 0,004 4,83 ENSG00000117009 kynurenine 3-monooxygenase (kynurenine 3-hydroxylase) KMO 0,017 4,82 ENSG00000145777 thymic stromal lymphopoietin TSLP 0,047 4,82 ENSG00000163347 claudin 1 CLDN1 0,003 4,76 ENSG00000214900 chromosome 14 open reading frame 182 C14orf182 0,009 4,75 ENSG00000172175 mucosa associated lymphoid tissue lymphoma translocation gene 1 MALT1 0,003 4,72 ENSG00000163082 sphingosine-1-phosphate phosphatase 2 SGPP2 0,018 4,71 ENSG00000121594 CD80 molecule CD80 0,011 4,67 ENSG00000127824 tubulin, alpha 4a TUBA4A 0,010 4,60 ENSG00000144655 cysteine-serine-rich nuclear protein 1 CSRNP1 0,004 4,57 ENSG00000109320 nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 NFKB1 0,007 4,56 ENSG00000198355 pim-3 oncogene PIM3 0,006 4,53 ENSG00000175040 carbohydrate (N-acetylglucosamine-6-O) sulfotransferase 2 CHST2 0,025 4,51 ENSG00000198369 sprouty-related, EVH1 domain containing 2 SPRED2 0,008 4,49 ENSG00000138378 signal transducer and activator of transcription 4 STAT4 0,012 4,48 ENSG00000011422 plasminogen activator, urokinase receptor PLAUR 0,005 4,47 ENSG00000100985 matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) MMP9 0,014 4,46 ENSG00000145990 glucose-fructose oxidoreductase domain containing 1 GFOD1 0,013 4,44 ENSG00000110042 deltex homolog 4 (Drosophila) DTX4 0,018 4,43 ENSG00000137267 tubulin, beta 2A TUBB2A 0,011 4,42 ENSG00000168685 interleukin 7 receptor IL7R 0,013 4,40 ENSG00000143067 zinc finger protein 697 ZNF697 0,007 4,40 ENSG00000165474 gap junction protein, beta 2, 26kDa GJB2 0,007 4,39 ENSG00000148841 inositol 1,4,5-trisphosphate receptor interacting protein ITPRIP 0,003 4,39 ENSG00000123358 nuclear receptor subfamily 4, group A, member 1 NR4A1 0,002 4,36 ENSG00000185245 glycoprotein Ib (platelet), alpha polypeptide GP1BA 0,031 4,36 ENSG00000136048 DNA-damage regulated autophagy modulator 1 DRAM1 0,008 4,31 ENSG00000148339 solute carrier family 25 (mitochondrial carrier; phosphate carrier), member 25 SLC25A25 0,027 4,27 ENSG00000159388 BTG family, member 2 BTG2 0,008 4,27 ENSG00000150977 Rab interacting lysosomal protein-like 2 RILPL2 0,004 4,26 ENSG00000154127 ubiquitin associated and SH3 domain containing B UBASH3B 0,007 4,23 ENSG00000236700 N/A RP11-557H15.2 0,015 4,21 ENSG00000166592 Ras-related associated with diabetes RRAD 0,007 4,19 ENSG00000166881 transmembrane protein 194A TMEM194A 0,008 4,18 ENSG00000172738 transmembrane protein 217 TMEM217 0,018 4,17 ENSG00000153721 CNKSR family member 3 CNKSR3 0,016 4,16 ENSG00000120129 dual specificity phosphatase 1 DUSP1 0,005 4,07 ENSG00000163171 CDC42 effector protein (Rho GTPase binding) 3 CDC42EP3 0,003 4,07 ENSG00000172071 eukaryotic translation initiation factor 2-alpha kinase 3 EIF2AK3 0,003 4,06 ENSG00000153898 mucolipin 2 MCOLN2 0,010 4,03 ENSG00000261005 na na 0,004 4,01 ENSG00000186480 insulin induced gene 1 INSIG1 0,003 4,01 ENSG00000260196 na na 0,005 3,99 ENSG00000164211 StAR-related lipid transfer (START) domain containing 4 STARD4 0,016 3,99 ENSG00000182224 cytochrome b5 domain containing 1 CYB5D1 0,008 3,96 ENSG00000090104 regulator of G-protein signaling 1 RGS1 0,008 3,95 ENSG00000164023 sphingomyelin synthase 2 SGMS2 0,008 3,94 ENSG00000137331 immediate early response 3 IER3 0,023 3,92 ENSG00000124731 triggering receptor expressed on myeloid cells 1 TREM1 0,010 3,91 ENSG00000168906 methionine adenosyltransferase II, alpha MAT2A 0,015 3,90 ENSG00000131873 chondroitin sulfate synthase 1 CHSY1 0,005 3,85 ENSG00000060982 branched chain amino-acid transaminase 1, cytosolic BCAT1 0,006 3,85 ENSG00000054523 kinesin family member 1B KIF1B 0,006 3,81 ENSG00000125740 FBJ murine osteosarcoma viral oncogene homolog B FOSB 0,021 3,78 ENSG00000135604 syntaxin 11 STX11 0,008 3,77 ENSG00000131669 ninjurin 1 NINJ1 0,008 3,77 ENSG00000007264 megakaryocyte-associated tyrosine kinase MATK 0,036 3,71 ENSG00000197405 complement component 5a receptor 1 C5AR1 0,023 3,69 ENSG00000168389 major facilitator superfamily domain containing 2A MFSD2A 0,034 3,69 ENSG00000133639 B-cell translocation gene 1, anti-proliferative BTG1 0,005 3,67 ENSG00000168884 TNFAIP3 interacting protein 2 TNIP2 0,004 3,66 ENSG00000175556 LON peptidase N-terminal domain and ring finger 3 LONRF3 0,010 3,66 ENSG00000139725 na na 0,007 3,66 ENSG00000137449 cytoplasmic polyadenylation element binding protein 2 CPEB2 0,003 3,63 ENSG00000118985 elongation factor, RNA polymerase II, 2 ELL2 0,007 3,62 ENSG00000112149 CD83 molecule CD83 0,023 3,62 ENSG00000095794 cAMP responsive element modulator CREM 0,011 3,61 ENSG00000160888 immediate early response 2 IER2 0,005 3,61 ENSG00000135919 serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 2 SERPINE2 0,018 3,58 ENSG00000166920 chromosome 15 open reading frame 48 C15orf48 0,014 3,57 ENSG00000123342 matrix metallopeptidase 19 MMP19 0,015 3,54 ENSG00000183696 uridine phosphorylase 1 UPP1 0,003 3,49 ENSG00000175592 FOS-like antigen 1 FOSL1 0,005 3,49 ENSG00000102755 fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)FLT1 0,008 3,49 ENSG00000125730 complement component 3 C3 0,028 3,47 ENSG00000106952 tumor necrosis factor (ligand) superfamily, member 8 TNFSF8 0,021 3,46 ENSG00000117228 guanylate binding protein 1, interferon-inducible GBP1 0,015 3,46 ENSG00000117036 ets variant 3 ETV3 0,007 3,45 ENSG00000163874 zinc finger CCCH-type containing 12A ZC3H12A 0,005 3,44 ENSG00000142178 salt-inducible kinase 1 SIK1 0,011 3,40 ENSG00000188001 tumor protein p63 regulated 1 TPRG1 0,011 3,40 ENSG00000138166 dual specificity phosphatase 5 DUSP5 0,004 3,36 ENSG00000141682 phorbol-12-myristate-13-acetate-induced protein 1 PMAIP1 0,017 3,34 ENSG00000229644 nicotinamide phosphoribosyltransferase-like NAMPTL 0,007 3,34 ENSG00000105835 nicotinamide phosphoribosyltransferase NAMPT 0,004 3,34 ENSG00000164935 transmembrane 7 superfamily member 4 TM7SF4 0,019 3,31 ENSG00000104312 receptor-interacting serine-threonine kinase 2 RIPK2 0,002 3,29 ENSG00000176845 meteorin, glial cell differentiation regulator-like METRNL 0,006 3,25 ENSG00000077984 cystatin F (leukocystatin) CST7 0,013 3,20 ENSG00000134242 protein tyrosine phosphatase, non-receptor type 22 (lymphoid) PTPN22 0,007 3,19 ENSG00000134830 G protein-coupled receptor 77 GPR77 0,008 3,19 ENSG00000223749 N/A AC004383.4 0,007 3,19 ENSG00000156711 mitogen-activated protein kinase 13 MAPK13 0,010 3,18 ENSG00000010818 human immunodeficiency virus type I enhancer binding protein 2 HIVEP2 0,046 3,17 ENSG00000107968 mitogen-activated protein kinase kinase kinase 8 MAP3K8 0,005 3,17 ENSG00000100906 nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha NFKBIA 0,008 3,17 ENSG00000163399 ATPase, Na+/K+ transporting, alpha 1 polypeptide ATP1A1 0,003 3,16 ENSG00000101017 CD40 molecule, TNF receptor superfamily member 5 CD40 0,008 3,15 ENSG00000224818 N/A RP11-134G8.8 0,008 3,14 ENSG00000178860 musculin MSC 0,015 3,14 ENSG00000087074 protein phosphatase 1, regulatory (inhibitor) subunit 15A PPP1R15A 0,004 3,12 ENSG00000179241 low density lipoprotein receptor class A domain containing 3 LDLRAD3 0,003 3,11 ENSG00000005513 SRY (sex determining region Y)-box 8 SOX8 0,034 3,11 ENSG00000172818 ovo-like 1(Drosophila) OVOL1 0,015 3,10 ENSG00000122861 plasminogen activator, urokinase PLAU 0,039 3,10 ENSG00000102760 chromosome 13 open reading frame 15 C13orf15 0,008 3,09 ENSG00000006062 mitogen-activated protein kinase kinase kinase 14 MAP3K14 0,003 3,09 ENSG00000173517 Pseudopodium-enriched atypical kinase 1 AC087465.1 0,005 3,08 ENSG00000182022 carbohydrate (N-acetylgalactosamine 4-sulfate 6-O) sulfotransferase 15 CHST15 0,015 3,08 ENSG00000176170 sphingosine kinase 1 SPHK1 0,031 3,05 ENSG00000110218 pannexin 1 PANX1 0,012 3,05 ENSG00000165312 OTU domain containing 1 OTUD1 0,007 3,04 ENSG00000151247 eukaryotic translation initiation factor 4E EIF4E 0,008 3,02 ENSG00000137094 DnaJ (Hsp40) homolog, subfamily B, member 5 DNAJB5 0,014 3,01 ENSG00000146676 purine-rich element binding protein B PURB 0,004 3,00 ENSG00000115956 pleckstrin PLEK 0,008 2,98 ENSG00000104783 potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4 KCNN4 0,011 2,98 ENSG00000123908 eukaryotic translation initiation factor 2C, 2 EIF2C2 0,007 2,97 ENSG00000184557 suppressor of cytokine signaling 3 SOCS3 0,009 2,96 ENSG00000167874 transmembrane protein 88 TMEM88 0,010 2,96 ENSG00000113811 Selenoprotein K RP11-884K10.5 0,006 2,96 ENSG00000173166 Ras association (RalGDS/AF-6) and pleckstrin homology domains 1 RAPH1 0,004 2,95 ENSG00000136891 testis expressed 10 TEX10 0,011 2,94 ENSG00000133657 ATPase type 13A3 ATP13A3 0,007 2,93 ENSG00000140406 mesoderm development candidate 1 MESDC1 0,030 2,91 ENSG00000116741 regulator of G-protein signaling 2, 24kDa RGS2 0,008 2,91 ENSG00000137193 pim-1 oncogene PIM1 0,008 2,90 ENSG00000125810 CD93 molecule CD93 0,024 2,89 ENSG00000003402 CASP8 and FADD-like apoptosis regulator CFLAR 0,005 2,89 ENSG00000163376 kelch repeat and BTB (POZ) domain containing 8 KBTBD8 0,015 2,89 ENSG00000118785 secreted phosphoprotein 1 SPP1 0,020 2,88 ENSG00000136653 Ras association (RalGDS/AF-6) domain family member 5 RASSF5 0,003 2,88 ENSG00000138119 myoferlin MYOF 0,004 2,87 ENSG00000175352 nuclear receptor interacting protein 3 NRIP3 0,006 2,84 ENSG00000008083 jumonji, AT rich interactive domain 2 JARID2 0,018 2,83 ENSG00000095951 human immunodeficiency virus type I enhancer binding protein 1 HIVEP1 0,008 2,81 ENSG00000125430 heparan sulfate (glucosamine) 3-O-sulfotransferase 3B1 HS3ST3B1 0,023 2,80 ENSG00000213859 potassium channel tetramerisation domain containing 11 KCTD11 0,013 2,79 ENSG00000175445 lipoprotein lipase LPL 0,008 2,77 ENSG00000163389 protein O-glucosyltransferase 1 POGLUT1 0,013 2,76 ENSG00000100221 Josephin domain containing 1 JOSD1 0,004 2,76 ENSG00000120539 microtubule associated serine/threonine kinase-like MASTL 0,007 2,74 ENSG00000121769 fatty acid binding protein 3, muscle and heart (mammary-derived growth inhibitor) FABP3 0,003 2,73 ENSG00000168994 chromosome 6 open reading frame 145 C6orf145 0,004 2,72 ENSG00000196083 interleukin 1 receptor accessory protein IL1RAP 0,008 2,72 ENSG00000115738 inhibitor of DNA binding 2, dominant negative helix-loop-helix protein ID2 0,013 2,71 ENSG00000183484 G protein-coupled receptor 132 GPR132 0,015 2,71 ENSG00000108932 solute carrier family 16, member 6 (monocarboxylic acid transporter 7) SLC16A6 0,024 2,71 ENSG00000176142 transmembrane protein 39A TMEM39A 0,005 2,70 ENSG00000196396 protein tyrosine phosphatase, non-receptor type 1 PTPN1 0,010 2,69 ENSG00000138678 1-acylglycerol-3-phosphate O-acyltransferase 9 AGPAT9 0,016 2,69 ENSG00000160883 hexokinase 3 (white cell) HK3 0,007 2,69 ENSG00000151689 inositol polyphosphate-1-phosphatase INPP1 0,008 2,68 ENSG00000124225 prostate transmembrane protein, androgen induced 1 PMEPA1 0,008 2,67 ENSG00000260231 na na 0,016 2,67 ENSG00000101665 SMAD family member 7 SMAD7 0,007 2,67 ENSG00000139722 vacuolar protein sorting 37 homolog B (S. cerevisiae) VPS37B 0,007 2,66 ENSG00000114013 CD86 molecule CD86 0,005 2,65 ENSG00000161091 chromosome 19 open reading frame 28 C19orf28 0,004 2,65 ENSG00000178623 G protein-coupled receptor 35 GPR35 0,007 2,64 ENSG00000156535 CD109 molecule CD109 0,013 2,64 ENSG00000102226 ubiquitin specific peptidase 11 USP11 0,005 2,63 ENSG00000034677 ring finger protein 19A RNF19A 0,003 2,62 ENSG00000197696 neuromedin B NMB 0,005 2,61 ENSG00000181649 pleckstrin homology-like domain, family A, member 2 PHLDA2 0,006 2,60 ENSG00000162772 activating transcription factor 3 ATF3 0,044 2,59 ENSG00000131370 SH3-domain binding protein 5 (BTK-associated) SH3BP5 0,009 2,56 ENSG00000006327 tumor necrosis factor receptor superfamily, member 12A TNFRSF12A 0,011 2,56 ENSG00000117479 solute carrier family 19 (thiamine transporter), member 2 SLC19A2 0,007 2,56 ENSG00000146457 Wilms tumor 1 associated protein WTAP 0,015 2,55 ENSG00000139832 RAB20, member RAS oncogene family RAB20 0,029 2,55 ENSG00000089041 purinergic receptor P2X, ligand-gated ion channel, 7 P2RX7 0,010 2,54 ENSG00000196449 yrdC domain containing (E. coli) YRDC 0,007 2,54 ENSG00000008405 cryptochrome 1 (photolyase-like) CRY1 0,012 2,53 ENSG00000162711 NLR family, pyrin domain containing 3 NLRP3 0,026 2,52 ENSG00000151726 acyl-CoA synthetase long-chain family member 1 ACSL1 0,007 2,52 ENSG00000126003 pleiomorphic adenoma gene-like 2 PLAGL2 0,013 2,50 ENSG00000165195 phosphatidylinositol glycan anchor biosynthesis, class A PIGA 0,014 2,50 ENSG00000137462 toll-like receptor 2 TLR2 0,022 2,50 ENSG00000259758 N/A N/A 0,007 2,49 ENSG00000171522 prostaglandin E receptor 4 (subtype EP4) PTGER4 0,016 2,49 ENSG00000141540 tweety homolog 2 (Drosophila) TTYH2 0,006 2,49 ENSG00000151092 N-glycanase 1 NGLY1 0,007 2,48 ENSG00000170779 cell division cycle associated 4 CDCA4 0,013 2,47 ENSG00000107104 KN motif and ankyrin repeat domains 1 KANK1 0,007 2,47 ENSG00000103855 CD276 molecule CD276 0,017 2,47 ENSG00000138623 semaphorin 7A, GPI membrane anchor (John Milton Hagen blood group) SEMA7A 0,003 2,47 ENSG00000137507 leucine rich repeat containing 32 LRRC32 0,024 2,44 ENSG00000129667 rhomboid 5 homolog 2 (Drosophila) RHBDF2 0,018 2,43 ENSG00000144136 solute carrier family 20 (phosphate transporter), member 1 SLC20A1 0,008 2,42 ENSG00000181788 seven in absentia homolog 2 (Drosophila) SIAH2 0,009 2,41 ENSG00000102908 nuclear factor of activated T-cells 5, tonicity-responsive NFAT5 0,011 2,40 ENSG00000184292 tumor-associated calcium signal transducer 2 TACSTD2 0,045 2,40 ENSG00000242247 ADP-ribosylation factor GTPase activating protein 3 ARFGAP3 0,004 2,40 ENSG00000135625 early growth response 4 EGR4 0,008 2,40 ENSG00000158470 UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase, polypeptide 5 B4GALT5 0,021 2,39 ENSG00000197147 leucine rich repeat containing 8 family, member B LRRC8B 0,019 2,39 ENSG00000197249 serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1 SERPINA1 0,004 2,37 ENSG00000143384 myeloid cell leukemia sequence 1 (BCL2-related) MCL1 0,003 2,37 ENSG00000260006 na na 0,031 2,36 ENSG00000102962 chemokine (C-C motif) ligand 22 CCL22 0,011 2,36 ENSG00000074660 scavenger receptor class F, member 1 SCARF1 0,004 2,36 ENSG00000169508 G protein-coupled receptor 183 GPR183 0,008 2,34 ENSG00000263899 na na 0,027 2,34 ENSG00000155366 ras homolog gene family, member C RHOC 0,006 2,32 ENSG00000119280 chromosome 1 open reading frame 198 C1orf198 0,008 2,32 ENSG00000147650 low density lipoprotein receptor-related protein 12 LRP12 0,006 2,32 ENSG00000115339 UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GalNAc-T3)GALNT3 0,014 2,32 ENSG00000261827 na na 0,010 2,32 ENSG00000015475 BH3 interacting domain death agonist BID 0,007 2,32 ENSG00000107175 cAMP responsive element binding protein 3 CREB3 0,004 2,32 ENSG00000145901 TNFAIP3 interacting protein 1 TNIP1 0,036 2,31 ENSG00000117143 UDP-N-acteylglucosamine pyrophosphorylase 1 UAP1 0,012 2,31 ENSG00000140968 interferon regulatory factor 8 IRF8 0,005 2,30 ENSG00000115641 four and a half LIM domains 2 FHL2 0,018 2,28 ENSG00000104450 sperm associated antigen 1 SPAG1 0,016 2,27 ENSG00000127124 human immunodeficiency virus type I enhancer binding protein 3 HIVEP3 0,005 2,27 ENSG00000173548 sorting nexin 33 SNX33 0,015 2,27 ENSG00000197461 platelet-derived growth factor alpha polypeptide PDGFA 0,018 2,26 ENSG00000132661 NTF2-like export factor 1 NXT1 0,011 2,25 ENSG00000023330 aminolevulinate, delta-, synthase 1 ALAS1 0,018 2,25 ENSG00000077238 interleukin 4 receptor IL4R 0,007 2,24 ENSG00000172530 BTG3 associated nuclear protein BANP 0,007 2,24 ENSG00000155926 Src-like-adaptor SLA 0,043 2,23 ENSG00000117868 extended synaptotagmin-like protein 2 ESYT2 0,004 2,23 ENSG00000130340 sorting nexin 9 SNX9 0,003 2,23 ENSG00000113742 cytoplasmic polyadenylation element binding protein 4 CPEB4 0,013 2,23 ENSG00000157224 claudin 12 CLDN12 0,015 2,22 ENSG00000026751 SLAM family member 7 SLAMF7 0,015 2,21 ENSG00000167487 kelch-like 26 (Drosophila) KLHL26 0,016 2,21 ENSG00000170425 adenosine A2b receptor ADORA2B 0,010 2,21 ENSG00000064225 ST3 beta-galactoside alpha-2,3-sialyltransferase 6 ST3GAL6 0,003 2,21 ENSG00000188786 metal-regulatory transcription factor 1 MTF1 0,019 2,21 ENSG00000177150 chromosome 18 open reading frame 19 C18orf19 0,003 2,21 ENSG00000186594 chromosome 17 open reading frame 91 C17orf91 0,017 2,21 ENSG00000136205 tensin 3 TNS3 0,008 2,20 ENSG00000155090 Kruppel-like factor 10 KLF10 0,035 2,20 ENSG00000139637 chromosome 12 open reading frame 10 C12orf10 0,014 2,20 ENSG00000101384 jagged 1 JAG1 0,004 2,20 ENSG00000169504 chloride intracellular channel 4 CLIC4 0,003 2,20 ENSG00000104447 trichorhinophalangeal syndrome I TRPS1 0,005 2,19 ENSG00000115758 ornithine decarboxylase 1 ODC1 0,004 2,19 ENSG00000265148 na na 0,011 2,19 ENSG00000225968 na na 0,044 2,18 ENSG00000173559 oligonucleotide/oligosaccharide-binding fold containing 2A OBFC2A 0,016 2,18 ENSG00000128016 zinc finger protein 36, C3H type, homolog (mouse) ZFP36 0,027 2,18 ENSG00000138606 Src homology 2 domain containing F SHF 0,009 2,18 ENSG00000100139 MICAL-like 1 MICALL1 0,026 2,17 ENSG00000179820 myeloid-associated differentiation marker MYADM 0,022 2,17 ENSG00000025772 translocase of outer mitochondrial membrane 34 TOMM34 0,028 2,17 ENSG00000142871 cysteine-rich, angiogenic inducer, 61 CYR61 0,023 2,17 ENSG00000037897 methyltransferase like 1 METTL1 0,017 2,16 ENSG00000119866 B-cell CLL/lymphoma 11A (zinc finger protein) BCL11A 0,047 2,16 ENSG00000160326 solute carrier family 2 (facilitated glucose transporter), member 6 SLC2A6 0,037 2,16 ENSG00000143153 ATPase, Na+/K+ transporting, beta 1 polypeptide ATP1B1 0,012 2,16 ENSG00000196843 AT rich interactive domain 5A (MRF1-like) ARID5A 0,005 2,15 ENSG00000251136 N/A RP11-37B2.1 0,023 2,14 ENSG00000112941 PAP associated domain containing 7 PAPD7 0,007 2,14 ENSG00000170776 A kinase (PRKA) anchor protein 13 AKAP13 0,012 2,14 ENSG00000120063 guanine nucleotide binding protein (G protein), alpha 13 GNA13 0,006 2,14 ENSG00000162723 SLAM family member 9 SLAMF9 0,018 2,14 ENSG00000102119 emerin EMD 0,003 2,13 ENSG00000182853 vitelline membrane outer layer 1 homolog (chicken) VMO1 0,036 2,13 ENSG00000179362 na na 0,031 2,13 ENSG00000132170 peroxisome proliferator-activated receptor gamma PPARG 0,021 2,13 ENSG00000162889 mitogen-activated protein kinase-activated protein kinase 2 MAPKAPK2 0,004 2,12 ENSG00000143393 phosphatidylinositol 4-kinase, catalytic, beta PI4KB 0,002 2,11 ENSG00000104951 interleukin 4 induced 1 IL4I1 0,028 2,11 ENSG00000087008 acyl-CoA oxidase 3, pristanoyl ACOX3 0,005 2,10 ENSG00000139496 nucleoporin like 1 NUPL1 0,008 2,10 ENSG00000196781 transducin-like enhancer of split 1 (E(sp1) homolog, Drosophila) TLE1 0,038 2,10 ENSG00000011132 amyloid beta (A4) precursor protein-binding, family A, member 3 APBA3 0,004 2,09 ENSG00000171617 ectodermal-neural cortex 1 (with BTB-like domain) ENC1 0,043 2,09 ENSG00000183624 chromosome 3 open reading frame 37 C3orf37 0,047 2,08 ENSG00000104885 DOT1-like, histone H3 methyltransferase (S. cerevisiae) DOT1L 0,009 2,07 ENSG00000078081 lysosomal-associated membrane protein 3 LAMP3 0,021 2,07 ENSG00000206560 ankyrin repeat domain 28 ANKRD28 0,015 2,07 ENSG00000180611 Mab-21 domain containing 2 MB21D2 0,018 2,07 ENSG00000154122 ankylosis, progressive homolog (mouse) ANKH 0,021 2,06 ENSG00000118971 cyclin D2 CCND2 0,041 2,06 ENSG00000129450 sialic acid binding Ig-like lectin 9 SIGLEC9 0,006 2,05 ENSG00000085117 CD82 molecule CD82 0,011 2,05 ENSG00000136802 leucine rich repeat containing 8 family, member A LRRC8A 0,015 2,05 ENSG00000125657 tumor necrosis factor (ligand) superfamily, member 9 TNFSF9 0,046 2,04 ENSG00000136286 myosin IG MYO1G 0,014 2,04 ENSG00000205189 zinc finger and BTB domain containing 10 ZBTB10 0,041 2,04 ENSG00000246731 N/A CTD-2514K5.2 0,007 2,03 ENSG00000173334 tribbles homolog 1 (Drosophila) TRIB1 0,019 2,03 ENSG00000161835 GRP1 (general receptor for phosphoinositides 1)-associated scaffold protein GRASP 0,011 2,03 ENSG00000008294 sperm associated antigen 9 SPAG9 0,011 2,02 ENSG00000086062 UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase, polypeptide 1 B4GALT1 0,006 2,02 ENSG00000062582 mitochondrial ribosomal protein S24 MRPS24 0,007 2,01 ENSG00000103569 aquaporin 9 AQP9 0,007 2,01 ENSG00000120217 CD274 molecule CD274 0,024 2,00 ENSG00000136052 solute carrier family 41, member 2 SLC41A2 0,009 2,00 ENSG00000197798 family with sequence similarity 118, member B FAM118B 0,003 -2,00 ENSG00000173801 junction plakoglobin JUP 0,024 -2,00 ENSG00000139687 retinoblastoma 1 RB1 0,010 -2,00 ENSG00000064012 caspase 8, apoptosis-related cysteine peptidase CASP8 0,027 -2,00 ENSG00000135972 mitochondrial ribosomal protein S9 MRPS9 0,018 -2,00 ENSG00000198824 zinc finger protein 828 ZNF828 0,009 -2,01 ENSG00000167333 tripartite motif containing 68 TRIM68 0,031 -2,01 ENSG00000066135 lysine (K)-specific demethylase 4A KDM4A 0,014 -2,01 ENSG00000123933 MAX dimerization protein 4 MXD4 0,014 -2,01 ENSG00000152359 POC5 centriolar protein homolog (Chlamydomonas) POC5 0,036 -2,01 ENSG00000163918 replication factor C (activator 1) 4, 37kDa RFC4 0,011 -2,01 ENSG00000108055 structural maintenance of chromosomes 3 SMC3 0,021 -2,02 ENSG00000127337 YEATS domain containing 4 YEATS4 0,006 -2,02 ENSG00000084090 StAR-related lipid transfer (START) domain containing 7 STARD7 0,009 -2,02 ENSG00000165406 membrane-associated ring finger (C3HC4) 8 MARCH8 0,011 -2,02 ENSG00000168291 pyruvate dehydrogenase (lipoamide) beta PDHB 0,007 -2,02 ENSG00000179933 chromosome 14 open reading frame 119 C14orf119 0,013 -2,02 ENSG00000103174 N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase NAGPA 0,014 -2,02 ENSG00000134755 desmocollin 2 DSC2 0,008 -2,03 ENSG00000197050 zinc finger protein 420 ZNF420 0,017 -2,03 ENSG00000138764 cyclin G2 CCNG2 0,033 -2,03 ENSG00000171700 regulator of G-protein signaling 19 RGS19 0,014 -2,04 ENSG00000111276 cyclin-dependent kinase inhibitor 1B (p27, Kip1) CDKN1B 0,015 -2,04 ENSG00000182319 Tyrosine-protein kinase SgK223 AC068353.1 0,017 -2,04 ENSG00000170915 progestin and adipoQ receptor family member VIII PAQR8 0,012 -2,04 ENSG00000115548 lysine (K)-specific demethylase 3A KDM3A 0,006 -2,05 ENSG00000187796 caspase recruitment domain family, member 9 CARD9 0,006 -2,05 ENSG00000175643 chromosome 16 open reading frame 75 C16orf75 0,015 -2,05 ENSG00000131401 napsin B aspartic peptidase pseudogene NAPSB 0,022 -2,05 ENSG00000170846 N/A AC093323.3 0,018 -2,06 ENSG00000146376 Rho GTPase activating protein 18 ARHGAP18 0,008 -2,06 ENSG00000181192 dehydrogenase E1 and transketolase domain containing 1 DHTKD1 0,004 -2,06 ENSG00000145332 kelch-like 8 (Drosophila) KLHL8 0,016 -2,06 ENSG00000163535 shugoshin-like 2 (S. pombe) SGOL2 0,012 -2,06 ENSG00000121486 TRM1 tRNA methyltransferase 1-like TRMT1L 0,008 -2,06 ENSG00000116497 S100P binding protein S100PBP 0,007 -2,06 ENSG00000169249 zinc finger (CCCH type), RNA-binding motif and serine/arginine rich 2 ZRSR2 0,039 -2,06 ENSG00000144228 speckle-type POZ protein-like SPOPL 0,006 -2,07 ENSG00000147382 family with sequence similarity 58, member A FAM58A 0,019 -2,07 ENSG00000170836 protein phosphatase, Mg2+/Mn2+ dependent, 1D PPM1D 0,012 -2,07 ENSG00000150048 C-type lectin domain family 1, member A CLEC1A 0,023 -2,07 ENSG00000168918 inositol polyphosphate-5-phosphatase, 145kDa INPP5D 0,024 -2,07 ENSG00000166855 ClpX caseinolytic peptidase X homolog (E. coli) CLPX 0,008 -2,07 ENSG00000138496 poly (ADP-ribose) polymerase family, member 9 PARP9 0,009 -2,07 ENSG00000014123 KIAA0776 KIAA0776 0,011 -2,07 ENSG00000130021 haloacid dehalogenase-like hydrolase domain containing 1 HDHD1 0,027 -2,08 ENSG00000106799 transforming growth factor, beta receptor 1 TGFBR1 0,003 -2,08 ENSG00000064102 chromosome 12 open reading frame 11 C12orf11 0,008 -2,08 ENSG00000105383 CD33 molecule CD33 0,032 -2,08 ENSG00000107738 chromosome 10 open reading frame 54 C10orf54 0,014 -2,08 ENSG00000006007 glycerophosphodiester phosphodiesterase 1 GDE1 0,011 -2,08 ENSG00000125843 chromosome 20 open reading frame 29 C20orf29 0,012 -2,08 ENSG00000196290 NIF3 NGG1 interacting factor 3-like 1 (S. pombe) NIF3L1 0,025 -2,08 ENSG00000189190 zinc finger protein 600 ZNF600 0,013 -2,09 ENSG00000084092 chromosome 4 open reading frame 14 C4orf14 0,009 -2,09 ENSG00000175073 valosin containing protein (p97)/p47 complex interacting protein 1 VCPIP1 0,007 -2,09 ENSG00000136193 secernin 1 SCRN1 0,022 -2,09 ENSG00000063438 aryl-hydrocarbon receptor repressor AHRR 0,019 -2,09 ENSG00000090989 exocyst complex component 1 EXOC1 0,008 -2,10 ENSG00000170085 chromosome 5 open reading frame 25 C5orf25 0,009 -2,10 ENSG00000198331 hydrolethalus syndrome 1 HYLS1 0,018 -2,10 ENSG00000240024 N/A RP11-393B14.1 0,021 -2,11 ENSG00000121749 TBC1 domain family, member 15 TBC1D15 0,008 -2,11 ENSG00000075188 nucleoporin 37kDa NUP37 0,014 -2,11 ENSG00000108389 myotubularin related protein 4 MTMR4 0,012 -2,11 ENSG00000152240 HAUS augmin-like complex, subunit 1 HAUS1 0,040 -2,12 ENSG00000152642 glycerol-3-phosphate dehydrogenase 1-like GPD1L 0,012 -2,12 ENSG00000169967 mitogen-activated protein kinase kinase kinase 2 MAP3K2 0,010 -2,12 ENSG00000121858 tumor necrosis factor (ligand) superfamily, member 10 TNFSF10 0,040 -2,13 ENSG00000121152 non-SMC condensin I complex, subunit H NCAPH 0,017 -2,13 ENSG00000023287 RB1-inducible coiled-coil 1 RB1CC1 0,013 -2,13 ENSG00000151500 thymocyte nuclear protein 1 THYN1 0,030 -2,13 ENSG00000251442 N/A RP11-792D21.2 0,018 -2,13 ENSG00000109689 stromal interaction molecule 2 STIM2 0,014 -2,13 ENSG00000121897 lipoic acid synthetase LIAS 0,029 -2,13 ENSG00000080200 beta-gamma crystallin domain containing 3 CRYBG3 0,015 -2,14 ENSG00000048392 ribonucleotide reductase M2 B (TP53 inducible) RRM2B 0,005 -2,14 ENSG00000008869 HEAT repeat containing 5B HEATR5B 0,006 -2,14 ENSG00000260539 na na 0,018 -2,14 ENSG00000123405 nuclear factor (erythroid-derived 2), 45kDa NFE2 0,016 -2,15 ENSG00000170293 CKLF-like MARVEL transmembrane domain containing 8 CMTM8 0,012 -2,16 ENSG00000238113 N/A RP11-262H14.1 0,011 -2,16 ENSG00000158109 tumor protein p63 regulated 1-like TPRG1L 0,020 -2,17 ENSG00000110583 N(alpha)-acetyltransferase 40, NatD catalytic subunit, homolog (S. cerevisiae) NAA40 0,007 -2,18 ENSG00000168297 PX domain containing serine/threonine kinase PXK 0,010 -2,18 ENSG00000163946 chromosome 3 open reading frame 63 C3orf63 0,011 -2,18 ENSG00000112312 geminin, DNA replication inhibitor GMNN 0,016 -2,18 ENSG00000170558 cadherin 2, type 1, N-cadherin (neuronal) CDH2 0,005 -2,19 ENSG00000013503 polymerase (RNA) III (DNA directed) polypeptide B POLR3B 0,018 -2,19 ENSG00000144567 family with sequence similarity 134, member A FAM134A 0,009 -2,19 ENSG00000147854 ubiquitin-like with PHD and ring finger domains 2 UHRF2 0,035 -2,20 ENSG00000257093 protein LCHN AC004918.4 0,027 -2,20 ENSG00000125871 chromosome 20 open reading frame 72 C20orf72 0,019 -2,21 ENSG00000123609 N-myc (and STAT) interactor NMI 0,009 -2,21 ENSG00000034533 asteroid homolog 1 (Drosophila) ASTE1 0,012 -2,21 ENSG00000205730 inositol 1,4,5-trisphosphate receptor interacting protein-like 2 ITPRIPL2 0,006 -2,21 ENSG00000166938 DIS3 mitotic control homolog (S. cerevisiae)-like DIS3L 0,013 -2,22 ENSG00000115718 protein C (inactivator of coagulation factors Va and VIIIa) PROC 0,031 -2,22 ENSG00000164221 coiled-coil domain containing 112 CCDC112 0,018 -2,23 ENSG00000187147 ring finger protein 220 RNF220 0,016 -2,23 ENSG00000133574 GTPase, IMAP family member 4 GIMAP4 0,048 -2,23 ENSG00000138604 glucuronic acid epimerase GLCE 0,004 -2,23 ENSG00000140450 arrestin domain containing 4 ARRDC4 0,010 -2,23 ENSG00000135828 ribonuclease L (2',5'-oligoisoadenylate synthetase-dependent) RNASEL 0,013 -2,23 ENSG00000185862 ecotropic viral integration site 2B EVI2B 0,016 -2,24 ENSG00000151461 UPF2 regulator of nonsense transcripts homolog (yeast) UPF2 0,012 -2,24 ENSG00000144635 dynein, cytoplasmic 1, light intermediate chain 1 DYNC1LI1 0,007 -2,24 ENSG00000112079 serine/threonine kinase 38 STK38 0,005 -2,24 ENSG00000148835 TAF5 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 100kDa TAF5 0,010 -2,24 ENSG00000121067 speckle-type POZ protein SPOP 0,009 -2,25 ENSG00000068724 tetratricopeptide repeat domain 7A TTC7A 0,002 -2,25 ENSG00000107897 acyl-CoA binding domain containing 5 ACBD5 0,003 -2,26 ENSG00000136869 toll-like receptor 4 TLR4 0,015 -2,26 ENSG00000114541 FERM domain containing 4B FRMD4B 0,008 -2,26 ENSG00000171940 zinc finger protein 217 ZNF217 0,018 -2,26 ENSG00000082074 FYN binding protein FYB 0,015 -2,27 ENSG00000164331 ankyrin repeat, family A (RFXANK-like), 2 ANKRA2 0,014 -2,27 ENSG00000125779 pantothenate kinase 2 PANK2 0,006 -2,27 ENSG00000163513 transforming growth factor, beta receptor II (70/80kDa) TGFBR2 0,005 -2,28 ENSG00000165983 phosphotriesterase related PTER 0,007 -2,28 ENSG00000165025 spleen tyrosine kinase SYK 0,010 -2,28 ENSG00000099337 potassium channel, subfamily K, member 6 KCNK6 0,026 -2,29 ENSG00000143337 torsin A interacting protein 1 TOR1AIP1 0,010 -2,29 ENSG00000156136 deoxycytidine kinase DCK 0,009 -2,29 ENSG00000181004 Bardet-Biedl syndrome 12 BBS12 0,020 -2,30 ENSG00000248791 N/A CTD-2165H16.3 0,007 -2,30 ENSG00000148090 AU RNA binding protein/enoyl-CoA hydratase AUH 0,005 -2,30 ENSG00000174197 MAX gene associated MGA 0,009 -2,30 ENSG00000113851 cereblon CRBN 0,005 -2,30 ENSG00000111727 host cell factor C2 HCFC2 0,007 -2,30 ENSG00000197321 supervillin SVIL 0,008 -2,31 ENSG00000169926 na na 0,006 -2,31 ENSG00000088451 TDP-glucose 4,6-dehydratase TGDS 0,011 -2,32 ENSG00000157107 FCH domain only 2 FCHO2 0,004 -2,32 ENSG00000115271 grancalcin, EF-hand calcium binding protein GCA 0,003 -2,32 ENSG00000126775 ATG14 autophagy related 14 homolog (S. cerevisiae) ATG14 0,006 -2,32 ENSG00000241732 N/A RP11-38P22.2 0,035 -2,32 ENSG00000153140 centrin, EF-hand protein, 3 CETN3 0,007 -2,32 ENSG00000068024 histone deacetylase 4 HDAC4 0,030 -2,33 ENSG00000096654 zinc finger protein 184 ZNF184 0,006 -2,33 ENSG00000172086 lysine-rich coiled-coil 1 KRCC1 0,005 -2,33 ENSG00000117226 guanylate binding protein 3 GBP3 0,007 -2,34 ENSG00000124659 tubulin folding cofactor C TBCC 0,014 -2,34 ENSG00000139354 growth arrest-specific 2 like 3 GAS2L3 0,026 -2,35 ENSG00000164414 solute carrier family 35 (CMP-sialic acid transporter), member A1 SLC35A1 0,010 -2,36 ENSG00000154642 chromosome 21 open reading frame 91 C21orf91 0,029 -2,36 ENSG00000170854 MYC induced nuclear antigen MINA 0,025 -2,36 ENSG00000152457 DNA cross-link repair 1C DCLRE1C 0,007 -2,37 ENSG00000170365 SMAD family member 1 SMAD1 0,007 -2,37 ENSG00000165516 kelch domain containing 2 KLHDC2 0,014 -2,37 ENSG00000134899 excision repair cross-complementing rodent repair deficiency, complementation group 5 ERCC5 0,005 -2,37 ENSG00000169019 COMM domain containing 8 COMMD8 0,008 -2,38 ENSG00000079950 syntaxin 7 STX7 0,008 -2,38 ENSG00000162073 progestin and adipoQ receptor family member IV PAQR4 0,003 -2,38 ENSG00000136044 adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 2 APPL2 0,017 -2,39 ENSG00000165533 tetratricopeptide repeat domain 8 TTC8 0,027 -2,39 ENSG00000204264 proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7) PSMB8 0,011 -2,39 ENSG00000205269 transmembrane protein 170B TMEM170B 0,012 -2,39 ENSG00000023516 A kinase (PRKA) anchor protein 11 AKAP11 0,009 -2,39 ENSG00000080819 coproporphyrinogen oxidase CPOX 0,009 -2,40 ENSG00000137414 family with sequence similarity 8, member A1 FAM8A1 0,008 -2,40 ENSG00000138794 caspase 6, apoptosis-related cysteine peptidase CASP6 0,014 -2,41 ENSG00000180917 FtsJ methyltransferase domain containing 1 FTSJD1 0,028 -2,42 ENSG00000146476 chromosome 6 open reading frame 211 C6orf211 0,007 -2,42 ENSG00000112234 F-box and leucine-rich repeat protein 4 FBXL4 0,002 -2,43 ENSG00000239213 N/A RP11-85F14.5 0,013 -2,43 ENSG00000169220 regulator of G-protein signaling 14 RGS14 0,011 -2,43 ENSG00000198736 selenoprotein X, 1 SEPX1 0,014 -2,43 ENSG00000174749 chromosome 4 open reading frame 32 C4orf32 0,020 -2,44 ENSG00000171681 activating transcription factor 7 interacting protein ATF7IP 0,010 -2,45 ENSG00000174946 G protein-coupled receptor 171 GPR171 0,032 -2,46 ENSG00000005175 RNA polymerase II associated protein 3 RPAP3 0,009 -2,46 ENSG00000110876 selectin P ligand SELPLG 0,008 -2,46 ENSG00000213689 three prime repair exonuclease 1 TREX1 0,008 -2,47 ENSG00000164244 proline-rich coiled-coil 1 PRRC1 0,007 -2,47 ENSG00000132357 caspase recruitment domain family, member 6 CARD6 0,019 -2,47 ENSG00000162378 zyg-11 homolog B (C. elegans) ZYG11B 0,005 -2,47 ENSG00000167912 N/A RP11-25K19.1 0,012 -2,47 ENSG00000169403 platelet-activating factor receptor PTAFR 0,027 -2,48 ENSG00000143457 golgi phosphoprotein 3-like GOLPH3L 0,015 -2,49 ENSG00000215256 Full-length cDNA clone CS0DF029YN24 of Fetal brain of Homo sapiens (human) AL136419.1 0,006 -2,49 ENSG00000125703 ATG4 autophagy related 4 homolog C (S. cerevisiae) ATG4C 0,018 -2,49 ENSG00000127720 chromosome 12 open reading frame 26 C12orf26 0,007 -2,50 ENSG00000145569 family with sequence similarity 105, member A FAM105A 0,007 -2,51 ENSG00000170385 solute carrier family 30 (zinc transporter), member 1 SLC30A1 0,018 -2,51 ENSG00000180573 histone cluster 1, H2ac HIST1H2AC 0,026 -2,51 ENSG00000096968 Janus kinase 2 JAK2 0,003 -2,53 ENSG00000198382 UV radiation resistance associated gene UVRAG 0,006 -2,53 ENSG00000164649 cell division cycle associated 7-like CDCA7L 0,013 -2,53 ENSG00000096717 sirtuin 1 SIRT1 0,013 -2,54 ENSG00000144681 SH3 and cysteine rich domain STAC 0,005 -2,54 ENSG00000156853 zinc finger protein 689 ZNF689 0,008 -2,54 ENSG00000146083 ring finger protein 44 RNF44 0,007 -2,54 ENSG00000174718 chromosome 12 open reading frame 35 C12orf35 0,018 -2,55 ENSG00000184992 BRI3 binding protein BRI3BP 0,015 -2,56 ENSG00000117616 chromosome 1 open reading frame 63 C1orf63 0,012 -2,56 ENSG00000107719 KIAA1274 KIAA1274 0,047 -2,56 ENSG00000080546 sestrin 1 SESN1 0,014 -2,57 ENSG00000174738 nuclear receptor subfamily 1, group D, member 2 NR1D2 0,022 -2,57 ENSG00000120162 MOB1, Mps One Binder kinase activator-like 2B (yeast) MOBKL2B 0,016 -2,57 ENSG00000196323 zinc finger and BTB domain containing 44 ZBTB44 0,007 -2,58 ENSG00000055917 pumilio homolog 2 (Drosophila) PUM2 0,007 -2,59 ENSG00000145246 ATPase, class V, type 10D ATP10D 0,013 -2,60 ENSG00000164117 F-box protein 8 FBXO8 0,009 -2,61 ENSG00000038274 methionine adenosyltransferase II, beta MAT2B 0,005 -2,61 ENSG00000072121 zinc finger, FYVE domain containing 26 ZFYVE26 0,006 -2,61 ENSG00000160179 na na 0,003 -2,61 ENSG00000001084 glutamate-cysteine ligase, catalytic subunit GCLC 0,008 -2,61 ENSG00000189144 zinc finger protein 573 ZNF573 0,011 -2,62 ENSG00000266753 na na 0,006 -2,63 ENSG00000136643 ribosomal protein S6 kinase, 52kDa, polypeptide 1 RPS6KC1 0,049 -2,63 ENSG00000118482 PHD finger protein 3 PHF3 0,005 -2,63 ENSG00000119950 MAX interactor 1 MXI1 0,003 -2,63 ENSG00000106780 multiple EGF-like-domains 9 MEGF9 0,007 -2,63 ENSG00000134294 solute carrier family 38, member 2 SLC38A2 0,010 -2,64 ENSG00000181481 ring finger protein 135 RNF135 0,015 -2,64 ENSG00000138433 corepressor interacting with RBPJ, 1 CIR1 0,010 -2,65 ENSG00000185950 insulin receptor substrate 2 IRS2 0,015 -2,66 ENSG00000112773 family with sequence similarity 46, member A FAM46A 0,003 -2,66 ENSG00000261799 na na 0,024 -2,66 ENSG00000155508 CCR4-NOT transcription complex, subunit 8 CNOT8 0,004 -2,66 ENSG00000188906 leucine-rich repeat kinase 2 LRRK2 0,033 -2,67 ENSG00000125249 RAP2A, member of RAS oncogene family RAP2A 0,004 -2,67 ENSG00000163154 tumor necrosis factor, alpha-induced protein 8-like 2 TNFAIP8L2 0,006 -2,68 ENSG00000124496 transcriptional regulating factor 1 TRERF1 0,007 -2,68 ENSG00000080503 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, memberSMARCA2 2 0,003 -2,68 ENSG00000111231 GPN-loop GTPase 3 GPN3 0,016 -2,70 ENSG00000178966 RMI1, RecQ mediated genome instability 1, homolog (S. cerevisiae) RMI1 0,004 -2,70 ENSG00000172123 schlafen family member 12 SLFN12 0,026 -2,71 ENSG00000100354 trinucleotide repeat containing 6B TNRC6B 0,007 -2,72 ENSG00000109861 cathepsin C CTSC 0,002 -2,72 ENSG00000021574 spastin SPAST 0,007 -2,72 ENSG00000158092 NCK adaptor protein 1 NCK1 0,010 -2,72 ENSG00000205302 sorting nexin 2 SNX2 0,002 -2,72 ENSG00000144909 oxysterol binding protein-like 11 OSBPL11 0,013 -2,73 ENSG00000165490 chromosome 11 open reading frame 82 C11orf82 0,007 -2,73 ENSG00000007944 myosin regulatory light chain interacting protein MYLIP 0,015 -2,74 ENSG00000150593 programmed cell death 4 (neoplastic transformation inhibitor) PDCD4 0,008 -2,74 ENSG00000164938 tumor protein p53 inducible nuclear protein 1 TP53INP1 0,013 -2,75 ENSG00000163947 Rho guanine nucleotide exchange factor (GEF) 3 ARHGEF3 0,041 -2,76 ENSG00000232941 N/A AC090186.1 0,008 -2,77 ENSG00000187626 zinc finger with KRAB and SCAN domains 4 ZKSCAN4 0,011 -2,77 ENSG00000180871 chemokine (C-X-C motif) receptor 2 CXCR2 0,022 -2,78 ENSG00000145241 centromere protein C 1 CENPC1 0,023 -2,79 ENSG00000135999 enhancer of polycomb homolog 2 (Drosophila) EPC2 0,008 -2,79 ENSG00000132405 TBC1 domain family, member 14 TBC1D14 0,030 -2,80 ENSG00000204103 v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (avian) MAFB 0,008 -2,80 ENSG00000172716 schlafen family member 11 SLFN11 0,011 -2,84 ENSG00000203880 protein-L-isoaspartate (D-aspartate) O-methyltransferase domain containing 2 PCMTD2 0,007 -2,85 ENSG00000121281 adenylate cyclase 7 ADCY7 0,022 -2,87 ENSG00000221869 CCAAT/enhancer binding protein (C/EBP), delta CEBPD 0,047 -2,87 ENSG00000168061 SAC3 domain containing 1 SAC3D1 0,009 -2,89 ENSG00000011258 mbt domain containing 1 MBTD1 0,006 -2,90 ENSG00000186188 omega-3 fatty acid receptor 1 O3FAR1 0,007 -2,90 ENSG00000166387 PTPRF interacting protein, binding protein 2 (liprin beta 2) PPFIBP2 0,010 -2,92 ENSG00000114737 cytokine inducible SH2-containing protein CISH 0,007 -2,93 ENSG00000167716 WD repeat domain 81 WDR81 0,022 -2,95 ENSG00000117289 thioredoxin interacting protein TXNIP 0,025 -2,96 ENSG00000197442 mitogen-activated protein kinase kinase kinase 5 MAP3K5 0,006 -2,97 ENSG00000106100 nucleotide-binding oligomerization domain containing 1 NOD1 0,008 -3,00 ENSG00000167528 zinc finger protein 641 ZNF641 0,007 -3,06 ENSG00000047346 KIAA1370 KIAA1370 0,006 -3,06 ENSG00000177409 sterile alpha motif domain containing 9-like SAMD9L 0,018 -3,07 ENSG00000134326 cytidine monophosphate (UMP-CMP) kinase 2, mitochondrial CMPK2 0,023 -3,10 ENSG00000138463 disrupted in renal carcinoma 2 DIRC2 0,007 -3,14 ENSG00000205413 sterile alpha motif domain containing 9 SAMD9 0,014 -3,14 ENSG00000133111 regulatory factor X-associated protein RFXAP 0,016 -3,15 ENSG00000198829 succinate receptor 1 SUCNR1 0,007 -3,15 ENSG00000027697 interferon gamma receptor 1 IFNGR1 0,013 -3,16 ENSG00000101916 toll-like receptor 8 TLR8 0,012 -3,18 ENSG00000198740 zinc finger protein 652 ZNF652 0,006 -3,28 ENSG00000165272 aquaporin 3 (Gill blood group) AQP3 0,004 -3,31 ENSG00000104205 serum/glucocorticoid regulated kinase family, member 3 SGK3 0,009 -3,37 ENSG00000075643 molybdenum cofactor sulfurase MOCOS 0,006 -3,38 ENSG00000182511 feline sarcoma oncogene FES 0,003 -3,40 ENSG00000117643 mannosidase, alpha, class 1C, member 1 MAN1C1 0,003 -3,43 ENSG00000196227 chromosome 20 open reading frame 177 C20orf177 0,008 -3,47 ENSG00000175155 yippee-like 2 (Drosophila) YPEL2 0,007 -3,48 ENSG00000136161 regulator of chromosome condensation (RCC1) and BTB (POZ) domain containing protein 2 RCBTB2 0,008 -3,48 ENSG00000130816 DNA (cytosine-5-)-methyltransferase 1 DNMT1 0,005 -3,50 ENSG00000138172 calcium homeostasis modulator 2 CALHM2 0,009 -3,53 ENSG00000178199 zinc finger CCCH-type containing 12D ZC3H12D 0,004 -3,57 ENSG00000095015 mitogen-activated protein kinase kinase kinase 1 MAP3K1 0,003 -3,62 ENSG00000071073 mannosyl (alpha-1,3-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferase, isozyme A MGAT4A 0,004 -3,62 ENSG00000189227 chromosome 15 open reading frame 61 C15orf61 0,017 -3,68 ENSG00000129518 E2F-associated phosphoprotein EAPP 0,006 -3,74 ENSG00000163606 CD200 receptor 1 CD200R1 0,019 -3,79 ENSG00000178977 non-protein coding RNA 324 NCRNA00324 0,011 -3,84 ENSG00000148158 sorting nexin family member 30 SNX30 0,013 -3,89 ENSG00000163563 myeloid cell nuclear differentiation antigen MNDA 0,017 -3,94 ENSG00000164104 high mobility group box 2 HMGB2 0,003 -3,96 ENSG00000140416 tropomyosin 1 (alpha) TPM1 0,009 -4,03 ENSG00000114796 kelch-like 24 (Drosophila) KLHL24 0,007 -4,09 ENSG00000181274 frequently rearranged in advanced T-cell lymphomas 2 FRAT2 0,012 -4,15 ENSG00000105851 phosphoinositide-3-kinase, catalytic, gamma polypeptide PIK3CG 0,010 -4,16 ENSG00000077063 cortactin binding protein 2 CTTNBP2 0,011 -4,27 ENSG00000186767 spindlin family, member 4 SPIN4 0,004 -4,33 ENSG00000187210 glucosaminyl (N-acetyl) transferase 1, core 2 GCNT1 0,044 -4,34 ENSG00000101236 ring finger protein 24 RNF24 0,006 -4,36 ENSG00000176046 nuclear protein, transcriptional regulator, 1 NUPR1 0,022 -4,36 ENSG00000178573 v-maf musculoaponeurotic fibrosarcoma oncogene homolog (avian) MAF 0,019 -4,44 ENSG00000164442 Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2 CITED2 0,013 -4,47 ENSG00000132646 proliferating cell nuclear antigen PCNA 0,023 -4,57 ENSG00000152804 hematopoietically expressed homeobox HHEX 0,010 -4,58 ENSG00000095585 B-cell linker BLNK 0,023 -4,58 ENSG00000171631 pyrimidinergic receptor P2Y, G-protein coupled, 6 P2RY6 0,008 -4,67 ENSG00000145416 membrane-associated ring finger (C3HC4) 1 MARCH1 0,011 -4,74 ENSG00000110852 C-type lectin domain family 2, member B CLEC2B 0,003 -4,89 ENSG00000164463 chromosome 5 open reading frame 41 C5orf41 0,005 -4,92 ENSG00000118308 lymphoid-restricted membrane protein LRMP 0,014 -4,96 ENSG00000121933 adenosine A3 receptor ADORA3 0,010 -5,11 ENSG00000129534 MIS18 binding protein 1 MIS18BP1 0,010 -5,19 ENSG00000167851 CD300a molecule CD300A 0,003 -5,29 ENSG00000163565 interferon, gamma-inducible protein 16 IFI16 0,007 -5,53 ENSG00000136826 Kruppel-like factor 4 (gut) KLF4 0,004 -5,93 ENSG00000170448 nuclear transcription factor, X-box binding-like 1 NFXL1 0,013 -6,63 ENSG00000174944 purinergic receptor P2Y, G-protein coupled, 14 P2RY14 0,003 -6,69 ENSG00000117318 inhibitor of DNA binding 3, dominant negative helix-loop-helix protein ID3 0,038 -6,76 ENSG00000106560 GTPase, IMAP family member 2 GIMAP2 0,007 -7,01 ENSG00000139679 lysophosphatidic acid receptor 6 LPAR6 0,014 -7,29 ENSG00000180340 frizzled homolog 2 (Drosophila) FZD2 0,009 -8,89 ENSG00000169087 HSPB (heat shock 27kDa) associated protein 1 HSPBAP1 0,012 -9,66 ENSG00000150681 regulator of G-protein signaling 18 RGS18 0,007 -9,76 ENSG00000164379 forkhead box Q1 FOXQ1 0,004 -23,52 Supplementary Table 1B. Genes regulated by OSCAR ColII+anti-OSCAR mAb vs ColII+isotype mAb at 4 hours name gene title gene symbol q-value Fold change ENSG00000115009 chemokine (C-C motif) ligand 20 CCL20 0,018 -102,55 ENSG00000115008 interleukin 1, alpha IL1A 0,028 -36,58 ENSG00000073756 prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)PTGS2 0,026 -35,61 ENSG00000234883 MIR155 host gene (non-protein coding) MIR155HG 0,012 -31,22 ENSG00000232810 tumor necrosis factor TNF 0,022 -27,14 ENSG00000164949 GTP binding protein overexpressed in skeletal muscle GEM 0,019 -26,49 ENSG00000125538 interleukin 1, beta IL1B 0,049 -21,71 ENSG00000153234 nuclear receptor subfamily 4, group A, member 2 NR4A2 0,048 -20,68 ENSG00000163734 chemokine (C-X-C motif) ligand 3 CXCL3 0,028 -19,65 ENSG00000123689 G0/G1switch 2 G0S2 0,027 -18,43 ENSG00000178726 thrombomodulin THBD 0,032 -18,39 ENSG00000078401 endothelin 1 EDN1 0,017 -17,90 ENSG00000081041 chemokine (C-X-C motif) ligand 2 CXCL2 0,036 -17,15 ENSG00000163739 chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha) CXCL1 0,031 -16,79 ENSG00000158050 dual specificity phosphatase 2 DUSP2 0,032 -15,65 ENSG00000108691 chemokine (C-C motif) ligand 2 CCL2 0,039 -15,36 ENSG00000120875 dual specificity phosphatase 4 DUSP4 0,017 -15,21 ENSG00000099985 oncostatin M OSM 0,023 -15,19 ENSG00000113070 heparin-binding EGF-like growth factor HBEGF 0,019 -14,78 ENSG00000117525 coagulation factor III (thromboplastin, tissue factor) F3 0,048 -14,66 ENSG00000101187 solute carrier organic anion transporter family, member 4A1 SLCO4A1 0,012 -13,48 ENSG00000140379 BCL2-related protein A1 BCL2A1 0,019 -13,16 ENSG00000232956 chromosome 7 open reading frame 40 C7orf40 0,022 -12,98 ENSG00000164181 ELOVL family member 7, elongation of long chain fatty acids (yeast) ELOVL7 0,015 -12,92 ENSG00000013619 mastermind-like domain containing 1 MAMLD1 0,018 -12,11 ENSG00000041982 tenascin C TNC 0,022 -11,82 ENSG00000153162 bone morphogenetic protein 6 BMP6 0,018 -11,47 ENSG00000157557 v-ets erythroblastosis virus E26 oncogene homolog 2 (avian) ETS2 0,023 -10,25 ENSG00000144802 nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, zeta NFKBIZ 0,028 -9,58 ENSG00000112394 solute carrier family 16, member 10 (aromatic amino acid transporter) SLC16A10 0,025 -9,29 ENSG00000108702 chemokine (C-C motif) ligand 1 CCL1 0,021 -9,11 ENSG00000253522 microRNA 146a (MIR146A), microRNA CTC-231O11.1 0,013 -8,77 ENSG00000149289 zinc finger CCCH-type containing 12C ZC3H12C 0,046 -8,75 ENSG00000056558 TNF receptor-associated factor 1 TRAF1 0,031 -8,55 ENSG00000186827 tumor necrosis factor receptor superfamily, member 4 TNFRSF4 0,037 -8,52 ENSG00000170542 serpin peptidase inhibitor, clade B (ovalbumin), member 9 SERPINB9 0,023 -8,10 ENSG00000138135 cholesterol 25-hydroxylase CH25H 0,026 -7,90 ENSG00000152413 homer homolog 1 (Drosophila) HOMER1 0,028 -7,83 ENSG00000116285 ERBB receptor feedback inhibitor 1 ERRFI1 0,019 -7,76 ENSG00000173846 polo-like kinase 3 PLK3 0,019 -7,72 ENSG00000110047 EH-domain containing 1 EHD1 0,024 -7,68 ENSG00000125735 tumor necrosis factor (ligand) superfamily, member 14 TNFSF14 0,018 -7,64 ENSG00000121594 CD80 molecule CD80 0,024 -7,62 ENSG00000180758 G protein-coupled receptor 157 GPR157 0,032 -7,58 ENSG00000167604 nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, delta NFKBID 0,015 -7,52 ENSG00000099860 growth arrest and DNA-damage-inducible, beta GADD45B 0,025 -7,41 ENSG00000124145 syndecan 4 SDC4 0,030 -7,40 ENSG00000103257 solute carrier family 7 (cationic amino acid transporter, y+ system), member 5 SLC7A5 0,014 -7,30 ENSG00000114473 IQ motif containing G IQCG 0,018 -7,10 ENSG00000136158 sprouty homolog 2 (Drosophila) SPRY2 0,027 -7,00 ENSG00000116717 growth arrest and DNA-damage-inducible, alpha GADD45A 0,049 -6,78 ENSG00000132510 lysine (K)-specific demethylase 6B KDM6B 0,031 -6,74 ENSG00000136689 interleukin 1 receptor antagonist IL1RN 0,022 -6,72 ENSG00000090339 intercellular adhesion molecule 1 ICAM1 0,022 -6,71 ENSG00000135476 extra spindle pole bodies homolog 1 (S. cerevisiae) ESPL1 0,048 -6,61 ENSG00000139289 pleckstrin homology-like domain, family A, member 1 PHLDA1 0,022 -6,55 ENSG00000168685 interleukin 7 receptor IL7R 0,042 -6,52 ENSG00000167772 angiopoietin-like 4 ANGPTL4 0,035 -6,32 ENSG00000138166 dual specificity phosphatase 5 DUSP5 0,019 -6,13 ENSG00000249992 transmembrane protein 158 (gene/pseudogene) TMEM158 0,026 -6,09 ENSG00000118503 tumor necrosis factor, alpha-induced protein 3 TNFAIP3 0,031 -6,06 ENSG00000139318 dual specificity phosphatase 6 DUSP6 0,026 -6,01 ENSG00000184371 colony stimulating factor 1 (macrophage) CSF1 0,010 -5,95 ENSG00000112096 superoxide dismutase 2, mitochondrial SOD2 0,025 -5,85 ENSG00000186665 chromosome 17 open reading frame 58 C17orf58 0,016 -5,68 ENSG00000131016 A kinase (PRKA) anchor protein 12 AKAP12 0,017 -5,62 ENSG00000166881 transmembrane protein 194A TMEM194A 0,023 -5,60 ENSG00000185022 v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (avian) MAFF 0,042 -5,58 ENSG00000154640 BTG family, member 3 BTG3 0,031 -5,39 ENSG00000163347 claudin 1 CLDN1 0,023 -5,39 ENSG00000117090 signaling lymphocytic activation molecule family member 1 SLAMF1 0,027 -5,35 ENSG00000108179 peptidylprolyl isomerase F PPIF 0,026 -5,31 ENSG00000134070 interleukin-1 receptor-associated kinase 2 IRAK2 0,028 -5,21 ENSG00000179294 chromosome 17 open reading frame 96 C17orf96 0,037 -5,21 ENSG00000034152 mitogen-activated protein kinase kinase 3 MAP2K3 0,020 -5,20 ENSG00000010810 FYN oncogene related to SRC, FGR, YES FYN 0,030 -5,15 ENSG00000167695 family with sequence similarity 57, member A FAM57A 0,026 -5,12 ENSG00000065809 family with sequence similarity 107, member B FAM107B 0,021 -5,10 ENSG00000198355 pim-3 oncogene PIM3 0,031 -5,05 ENSG00000121797 chemokine (C-C motif) receptor-like 2 CCRL2 0,025 -5,03 ENSG00000164211 StAR-related lipid transfer (START) domain containing 4 STARD4 0,034 -5,03 ENSG00000138378 signal transducer and activator of transcription 4 STAT4 0,025 -4,98 ENSG00000162924 v-rel reticuloendotheliosis viral oncogene homolog (avian) REL 0,034 -4,96 ENSG00000154127 ubiquitin associated and SH3 domain containing B UBASH3B 0,019 -4,91 ENSG00000145777 thymic stromal lymphopoietin TSLP 0,042 -4,91 ENSG00000137193 pim-1 oncogene PIM1 0,039 -4,89 ENSG00000162645 guanylate binding protein 2, interferon-inducible GBP2 0,018 -4,83 ENSG00000186891 tumor necrosis factor receptor superfamily, member 18 TNFRSF18 0,018 -4,82 ENSG00000183696 uridine phosphorylase 1 UPP1 0,021 -4,79 ENSG00000198369 sprouty-related, EVH1 domain containing 2 SPRED2 0,025 -4,67 ENSG00000102755 fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factorFLT1 receptor) 0,013 -4,57 ENSG00000101017 CD40 molecule, TNF receptor superfamily member 5 CD40 0,026 -4,55 ENSG00000137267 tubulin, beta 2A TUBB2A 0,021 -4,53 ENSG00000011422 plasminogen activator, urokinase receptor PLAUR 0,032 -4,52 ENSG00000172175 mucosa associated lymphoid tissue lymphoma translocation gene 1 MALT1 0,017 -4,46 ENSG00000112715 vascular endothelial growth factor A VEGFA 0,031 -4,44 ENSG00000007264 megakaryocyte-associated tyrosine kinase MATK 0,036 -4,41 ENSG00000140406 mesoderm development candidate 1 MESDC1 0,047 -4,40 ENSG00000165997 ADP-ribosylation factor-like 5B ARL5B 0,038 -4,40 ENSG00000175040 carbohydrate (N-acetylglucosamine-6-O) sulfotransferase 2 CHST2 0,047 -4,37 ENSG00000153721 CNKSR family member 3 CNKSR3 0,025 -4,32 ENSG00000109320 nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 NFKB1 0,042 -4,28 ENSG00000143067 zinc finger protein 697 ZNF697 0,039 -4,23 ENSG00000188001 tumor protein p63 regulated 1 TPRG1 0,028 -4,20 ENSG00000196083 interleukin 1 receptor accessory protein IL1RAP 0,024 -4,15 ENSG00000166592 Ras-related associated with diabetes RRAD 0,012 -4,14 ENSG00000120129 dual specificity phosphatase 1 DUSP1 0,038 -4,12 ENSG00000100985 matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) MMP9 0,033 -4,12 ENSG00000198142 ankyrin repeat domain 57 ANKRD57 0,029 -4,10 ENSG00000144655 cysteine-serine-rich nuclear protein 1 CSRNP1 0,031 -4,08 ENSG00000214900 chromosome 14 open reading frame 182 C14orf182 0,015 -4,08 ENSG00000137449 cytoplasmic polyadenylation element binding protein 2 CPEB2 0,026 -4,05 ENSG00000148841 inositol 1,4,5-trisphosphate receptor interacting protein ITPRIP 0,032 -4,03 ENSG00000060982 branched chain amino-acid transaminase 1, cytosolic BCAT1 0,023 -4,02 ENSG00000168906 methionine adenosyltransferase II, alpha MAT2A 0,027 -3,99 ENSG00000184557 suppressor of cytokine signaling 3 SOCS3 0,019 -3,97 ENSG00000182224 cytochrome b5 domain containing 1 CYB5D1 0,030 -3,91 ENSG00000159200 regulator of calcineurin 1 RCAN1 0,036 -3,81 ENSG00000236700 N/A RP11-557H15.2 0,032 -3,76 ENSG00000131669 ninjurin 1 NINJ1 0,030 -3,73 ENSG00000168884 TNFAIP3 interacting protein 2 TNIP2 0,024 -3,71 ENSG00000125730 complement component 3 C3 0,027 -3,68 ENSG00000106366 serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), memberSERPINE1 1 0,024 -3,67 ENSG00000150977 Rab interacting lysosomal protein-like 2 RILPL2 0,025 -3,66 ENSG00000095794 cAMP responsive element modulator CREM 0,033 -3,66 ENSG00000172071 eukaryotic translation initiation factor 2-alpha kinase 3 EIF2AK3 0,017 -3,64 ENSG00000131873 chondroitin sulfate synthase 1 CHSY1 0,017 -3,50 ENSG00000138670 RasGEF domain family, member 1B RASGEF1B 0,028 -3,48 ENSG00000118985 elongation factor, RNA polymerase II, 2 ELL2 0,017 -3,48 ENSG00000224818 N/A RP11-134G8.8 0,027 -3,47 ENSG00000123358 nuclear receptor subfamily 4, group A, member 1 NR4A1 0,028 -3,45 ENSG00000260196 na na 0,022 -3,44 ENSG00000156711 mitogen-activated protein kinase 13 MAPK13 0,012 -3,44 ENSG00000163874 zinc finger CCCH-type containing 12A ZC3H12A 0,018 -3,40 ENSG00000124731 triggering receptor expressed on myeloid cells 1 TREM1 0,047 -3,39 ENSG00000186480 insulin induced gene 1 INSIG1 0,032 -3,36 ENSG00000008083 jumonji, AT rich interactive domain 2 JARID2 0,020 -3,36 ENSG00000164935 transmembrane 7 superfamily member 4 TM7SF4 0,015 -3,35 ENSG00000106952 tumor necrosis factor (ligand) superfamily, member 8 TNFSF8 0,021 -3,35 ENSG00000145990 glucose-fructose oxidoreductase domain containing 1 GFOD1 0,025 -3,34 ENSG00000104312 receptor-interacting serine-threonine kinase 2 RIPK2 0,022 -3,33 ENSG00000197405 complement component 5a receptor 1 C5AR1 0,037 -3,33 ENSG00000139725 na na 0,017 -3,30 ENSG00000123908 eukaryotic translation initiation factor 2C, 2 EIF2C2 0,012 -3,27 ENSG00000101665 SMAD family member 7 SMAD7 0,012 -3,26 ENSG00000054523 kinesin family member 1B KIF1B 0,046 -3,26 ENSG00000163171 CDC42 effector protein (Rho GTPase binding) 3 CDC42EP3 0,040 -3,25 ENSG00000176845 meteorin, glial cell differentiation regulator-like METRNL 0,033 -3,19 ENSG00000125740 FBJ murine osteosarcoma viral oncogene homolog B FOSB 0,028 -3,18 ENSG00000006062 mitogen-activated protein kinase kinase kinase 14 MAP3K14 0,019 -3,14 ENSG00000107968 mitogen-activated protein kinase kinase kinase 8 MAP3K8 0,018 -3,13 ENSG00000077984 cystatin F (leukocystatin) CST7 0,023 -3,12 ENSG00000117036 ets variant 3 ETV3 0,036 -3,08 ENSG00000135919 serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), memberSERPINE2 2 0,047 -3,05 ENSG00000003402 CASP8 and FADD-like apoptosis regulator CFLAR 0,034 -3,05 ENSG00000118971 cyclin D2 CCND2 0,023 -3,03 ENSG00000163399 ATPase, Na+/K+ transporting, alpha 1 polypeptide ATP1A1 0,016 -3,02 ENSG00000158792 spermatogenesis associated 2-like SPATA2L 0,040 -3,01 ENSG00000223749 N/A AC004383.4 0,022 -3,00 ENSG00000175445 lipoprotein lipase LPL 0,025 -3,00 ENSG00000087074 protein phosphatase 1, regulatory (inhibitor) subunit 15A PPP1R15A 0,023 -2,96 ENSG00000120217 CD274 molecule CD274 0,023 -2,96 ENSG00000146676 purine-rich element binding protein B PURB 0,030 -2,96 ENSG00000136653 Ras association (RalGDS/AF-6) domain family member 5 RASSF5 0,030 -2,95 ENSG00000179241 low density lipoprotein receptor class A domain containing 3 LDLRAD3 0,015 -2,95 ENSG00000124225 prostate transmembrane protein, androgen induced 1 PMEPA1 0,018 -2,93 ENSG00000100906 nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha NFKBIA 0,047 -2,92 ENSG00000115738 inhibitor of DNA binding 2, dominant negative helix-loop-helix protein ID2 0,036 -2,91 ENSG00000165195 phosphatidylinositol glycan anchor biosynthesis, class A PIGA 0,042 -2,90 ENSG00000133657 ATPase type 13A3 ATP13A3 0,027 -2,90 ENSG00000173166 Ras association (RalGDS/AF-6) and pleckstrin homology domains 1 RAPH1 0,033 -2,90 ENSG00000151247 eukaryotic translation initiation factor 4E EIF4E 0,015 -2,89 ENSG00000104783 potassium intermediate/small conductance calcium-activated channel, subfamily N, memberKCNN4 4 0,025 -2,88 ENSG00000140968 interferon regulatory factor 8 IRF8 0,025 -2,85 ENSG00000181649 pleckstrin homology-like domain, family A, member 2 PHLDA2 0,033 -2,84 ENSG00000099377 hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7 HSD3B7 0,034 -2,84 ENSG00000197147 leucine rich repeat containing 8 family, member B LRRC8B 0,033 -2,82 ENSG00000147650 low density lipoprotein receptor-related protein 12 LRP12 0,017 -2,82 ENSG00000133639 B-cell translocation gene 1, anti-proliferative BTG1 0,025 -2,81 ENSG00000121769 fatty acid binding protein 3, muscle and heart (mammary-derived growth inhibitor) FABP3 0,019 -2,78 ENSG00000138119 myoferlin MYOF 0,044 -2,76 ENSG00000113811 Selenoprotein K RP11-884K10.5 0,029 -2,76 ENSG00000175352 nuclear receptor interacting protein 3 NRIP3 0,019 -2,75 ENSG00000196449 yrdC domain containing (E. coli) YRDC 0,027 -2,74 ENSG00000132170 peroxisome proliferator-activated receptor gamma PPARG 0,046 -2,74 ENSG00000103855 CD276 molecule CD276 0,023 -2,74 ENSG00000115956 pleckstrin PLEK 0,048 -2,74 ENSG00000102760 chromosome 13 open reading frame 15 C13orf15 0,025 -2,73 ENSG00000260231 na na 0,028 -2,73 ENSG00000155366 ras homolog gene family, member C RHOC 0,022 -2,72 ENSG00000168994 chromosome 6 open reading frame 145 C6orf145 0,030 -2,71 ENSG00000137094 DnaJ (Hsp40) homolog, subfamily B, member 5 DNAJB5 0,030 -2,71 ENSG00000186594 chromosome 17 open reading frame 91 C17orf91 0,035 -2,70 ENSG00000173517 Pseudopodium-enriched atypical kinase 1 AC087465.1 0,025 -2,70 ENSG00000006327 tumor necrosis factor receptor superfamily, member 12A TNFRSF12A 0,031 -2,68 ENSG00000134954 v-ets erythroblastosis virus E26 oncogene homolog 1 (avian) ETS1 0,023 -2,68 ENSG00000100221 Josephin domain containing 1 JOSD1 0,023 -2,68 ENSG00000213859 potassium channel tetramerisation domain containing 11 KCTD11 0,034 -2,68 ENSG00000197461 platelet-derived growth factor alpha polypeptide PDGFA 0,017 -2,67 ENSG00000180611 Mab-21 domain containing 2 MB21D2 0,030 -2,66 ENSG00000114013 CD86 molecule CD86 0,019 -2,66 ENSG00000139722 vacuolar protein sorting 37 homolog B (S. cerevisiae) VPS37B 0,025 -2,61 ENSG00000144136 solute carrier family 20 (phosphate transporter), member 1 SLC20A1 0,023 -2,61 ENSG00000102962 chemokine (C-C motif) ligand 22 CCL22 0,032 -2,61 ENSG00000165312 OTU domain containing 1 OTUD1 0,047 -2,60 ENSG00000142178 salt-inducible kinase 1 SIK1 0,030 -2,59 ENSG00000102908 nuclear factor of activated T-cells 5, tonicity-responsive NFAT5 0,034 -2,59 ENSG00000137462 toll-like receptor 2 TLR2 0,047 -2,58 ENSG00000152484 ubiquitin specific peptidase 12 USP12 0,023 -2,58 ENSG00000181788 seven in absentia homolog 2 (Drosophila) SIAH2 0,029 -2,57 ENSG00000008405 cryptochrome 1 (photolyase-like) CRY1 0,015 -2,56 ENSG00000095951 human immunodeficiency virus type I enhancer binding protein 1 HIVEP1 0,028 -2,56 ENSG00000023330 aminolevulinate, delta-, synthase 1 ALAS1 0,032 -2,55 ENSG00000110042 deltex homolog 4 (Drosophila) DTX4 0,021 -2,55 ENSG00000156535 CD109 molecule CD109 0,040 -2,51 ENSG00000134242 protein tyrosine phosphatase, non-receptor type 22 (lymphoid) PTPN22 0,036 -2,48 ENSG00000137265 interferon regulatory factor 4 IRF4 0,030 -2,47 ENSG00000170779 cell division cycle associated 4 CDCA4 0,033 -2,46 ENSG00000157224 claudin 12 CLDN12 0,015 -2,46 ENSG00000074660 scavenger receptor class F, member 1 SCARF1 0,009 -2,46 ENSG00000132661 NTF2-like export factor 1 NXT1 0,015 -2,46 ENSG00000117143 UDP-N-acteylglucosamine pyrophosphorylase 1 UAP1 0,034 -2,45 ENSG00000259758 N/A N/A 0,022 -2,44 ENSG00000139496 nucleoporin like 1 NUPL1 0,043 -2,44 ENSG00000161091 chromosome 19 open reading frame 28 C19orf28 0,020 -2,41 ENSG00000160883 hexokinase 3 (white cell) HK3 0,023 -2,40 ENSG00000242247 ADP-ribosylation factor GTPase activating protein 3 ARFGAP3 0,012 -2,39 ENSG00000136891 testis expressed 10 TEX10 0,027 -2,39 ENSG00000077238 interleukin 4 receptor IL4R 0,015 -2,38 ENSG00000104447 trichorhinophalangeal syndrome I TRPS1 0,049 -2,37 ENSG00000186111 phosphatidylinositol-4-phosphate 5-kinase, type I, gamma PIP5K1C 0,023 -2,36 ENSG00000151689 inositol polyphosphate-1-phosphatase INPP1 0,030 -2,36 ENSG00000173334 tribbles homolog 1 (Drosophila) TRIB1 0,046 -2,36 ENSG00000134830 G protein-coupled receptor 77 GPR77 0,030 -2,36 ENSG00000176597 UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 5 B3GNT5 0,030 -2,36 ENSG00000126003 pleiomorphic adenoma gene-like 2 PLAGL2 0,032 -2,35 ENSG00000177150 chromosome 18 open reading frame 19 C18orf19 0,018 -2,35 ENSG00000169504 chloride intracellular channel 4 CLIC4 0,015 -2,34 ENSG00000068383 inositol polyphosphate-5-phosphatase, 40kDa INPP5A 0,037 -2,33 ENSG00000100219 X-box binding protein 1 XBP1 0,031 -2,32 ENSG00000172530 BTG3 associated nuclear protein BANP 0,017 -2,31 ENSG00000251136 N/A RP11-37B2.1 0,026 -2,30 ENSG00000165030 nuclear factor, interleukin 3 regulated NFIL3 0,046 -2,29 ENSG00000172818 ovo-like 1(Drosophila) OVOL1 0,036 -2,29 ENSG00000155926 Src-like-adaptor SLA 0,047 -2,29 ENSG00000144837 phospholipase A1 member A PLA1A 0,028 -2,29 ENSG00000123983 acyl-CoA synthetase long-chain family member 3 ACSL3 0,027 -2,28 ENSG00000143393 phosphatidylinositol 4-kinase, catalytic, beta PI4KB 0,015 -2,27 ENSG00000102226 ubiquitin specific peptidase 11 USP11 0,018 -2,27 ENSG00000131370 SH3-domain binding protein 5 (BTK-associated) SH3BP5 0,030 -2,26 ENSG00000196396 protein tyrosine phosphatase, non-receptor type 1 PTPN1 0,033 -2,26 ENSG00000170776 A kinase (PRKA) anchor protein 13 AKAP13 0,023 -2,26 ENSG00000162723 SLAM family member 9 SLAMF9 0,021 -2,25 ENSG00000170425 adenosine A2b receptor ADORA2B 0,035 -2,23 ENSG00000106178 chemokine (C-C motif) ligand 24 CCL24 0,032 -2,22 ENSG00000136052 solute carrier family 41, member 2 SLC41A2 0,030 -2,22 ENSG00000103018 cytochrome b5 type B (outer mitochondrial membrane) CYB5B 0,041 -2,22 ENSG00000102225 cyclin-dependent kinase 16 CDK16 0,009 -2,21 ENSG00000173548 sorting nexin 33 SNX33 0,044 -2,20 ENSG00000122694 GLI pathogenesis-related 2 GLIPR2 0,040 -2,20 ENSG00000064225 ST3 beta-galactoside alpha-2,3-sialyltransferase 6 ST3GAL6 0,030 -2,19 ENSG00000183484 G protein-coupled receptor 132 GPR132 0,019 -2,19 ENSG00000138623 semaphorin 7A, GPI membrane anchor (John Milton Hagen blood group) SEMA7A 0,027 -2,18 ENSG00000107175 cAMP responsive element binding protein 3 CREB3 0,027 -2,18 ENSG00000117868 extended synaptotagmin-like protein 2 ESYT2 0,015 -2,18 ENSG00000102119 emerin EMD 0,039 -2,18 ENSG00000112941 PAP associated domain containing 7 PAPD7 0,032 -2,17 ENSG00000130052 StAR-related lipid transfer (START) domain containing 8 STARD8 0,019 -2,16 ENSG00000198805 purine nucleoside phosphorylase PNP 0,025 -2,16 ENSG00000151092 N-glycanase 1 NGLY1 0,035 -2,16 ENSG00000141540 tweety homolog 2 (Drosophila) TTYH2 0,020 -2,16 ENSG00000099194 stearoyl-CoA desaturase (delta-9-desaturase) SCD 0,049 -2,15 ENSG00000100483 methyltransferase like 21D METTL21D 0,044 -2,15 ENSG00000196781 transducin-like enhancer of split 1 (E(sp1) homolog, Drosophila) TLE1 0,030 -2,15 ENSG00000206560 ankyrin repeat domain 28 ANKRD28 0,021 -2,15 ENSG00000119977 tectonic family member 3 TCTN3 0,019 -2,15 ENSG00000197249 serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1 SERPINA1 0,018 -2,14 ENSG00000181191 praja ring finger 1 PJA1 0,017 -2,14 ENSG00000037897 methyltransferase like 1 METTL1 0,044 -2,13 ENSG00000167552 tubulin, alpha 1a TUBA1A 0,037 -2,13 ENSG00000154122 ankylosis, progressive homolog (mouse) ANKH 0,039 -2,12 ENSG00000104450 sperm associated antigen 1 SPAG1 0,048 -2,11 ENSG00000015475 BH3 interacting domain death agonist BID 0,039 -2,10 ENSG00000085117 CD82 molecule CD82 0,040 -2,10 ENSG00000102393 galactosidase, alpha GLA 0,025 -2,09 ENSG00000000938 Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog FGR 0,023 -2,09 ENSG00000130340 sorting nexin 9 SNX9 0,015 -2,09 ENSG00000008294 sperm associated antigen 9 SPAG9 0,026 -2,08 ENSG00000151748 salvador homolog 1 (Drosophila) SAV1 0,034 -2,08 ENSG00000115758 ornithine decarboxylase 1 ODC1 0,012 -2,08 ENSG00000101384 jagged 1 JAG1 0,038 -2,07 ENSG00000225968 na na 0,018 -2,07 ENSG00000162889 mitogen-activated protein kinase-activated protein kinase 2 MAPKAPK2 0,020 -2,07 ENSG00000164164 OTU domain containing 4 OTUD4 0,039 -2,06 ENSG00000119408 NIMA (never in mitosis gene a)-related kinase 6 NEK6 0,019 -2,06 ENSG00000198900 topoisomerase (DNA) I TOP1 0,026 -2,06 ENSG00000120539 microtubule associated serine/threonine kinase-like MASTL 0,038 -2,06 ENSG00000196843 AT rich interactive domain 5A (MRF1-like) ARID5A 0,025 -2,05 ENSG00000136295 tweety homolog 3 (Drosophila) TTYH3 0,049 -2,05 ENSG00000143384 myeloid cell leukemia sequence 1 (BCL2-related) MCL1 0,032 -2,04 ENSG00000104689 tumor necrosis factor receptor superfamily, member 10a TNFRSF10A 0,037 -2,04 ENSG00000115159 glycerol-3-phosphate dehydrogenase 2 (mitochondrial) GPD2 0,030 -2,03 ENSG00000127124 human immunodeficiency virus type I enhancer binding protein 3 HIVEP3 0,020 -2,03 ENSG00000167553 tubulin, alpha 1c TUBA1C 0,032 -2,02 ENSG00000168246 ubiquitin domain containing 2 UBTD2 0,021 -2,02 ENSG00000043462 lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa) LCP2 0,048 -2,02 ENSG00000197121 post-GPI attachment to proteins 1 PGAP1 0,036 -2,02 ENSG00000100139 MICAL-like 1 MICALL1 0,044 -2,01 ENSG00000166579 nudE nuclear distribution gene E homolog (A. nidulans)-like 1 NDEL1 0,040 -2,01 ENSG00000166938 DIS3 mitotic control homolog (S. cerevisiae)-like DIS3L 0,042 2,00 ENSG00000116062 mutS homolog 6 (E. coli) MSH6 0,022 2,00 ENSG00000084090 StAR-related lipid transfer (START) domain containing 7 STARD7 0,012 2,00 ENSG00000154889 metallophosphoesterase 1 MPPE1 0,018 2,01 ENSG00000170365 SMAD family member 1 SMAD1 0,023 2,01 ENSG00000168918 inositol polyphosphate-5-phosphatase, 145kDa INPP5D 0,017 2,01 ENSG00000145431 platelet derived growth factor C PDGFC 0,025 2,01 ENSG00000169925 bromodomain containing 3 BRD3 0,026 2,01 ENSG00000006007 glycerophosphodiester phosphodiesterase 1 GDE1 0,027 2,02 ENSG00000168061 SAC3 domain containing 1 SAC3D1 0,046 2,02 ENSG00000169926 na na 0,028 2,02 ENSG00000163535 shugoshin-like 2 (S. pombe) SGOL2 0,046 2,02 ENSG00000186298 protein phosphatase 1, catalytic subunit, gamma isozyme PPP1CC 0,013 2,02 ENSG00000121858 tumor necrosis factor (ligand) superfamily, member 10 TNFSF10 0,046 2,03 ENSG00000108055 structural maintenance of chromosomes 3 SMC3 0,010 2,03 ENSG00000115548 lysine (K)-specific demethylase 3A KDM3A 0,041 2,03 ENSG00000168476 receptor accessory protein 4 REEP4 0,039 2,03 ENSG00000014123 KIAA0776 KIAA0776 0,032 2,04 ENSG00000072121 zinc finger, FYVE domain containing 26 ZFYVE26 0,017 2,04 ENSG00000197442 mitogen-activated protein kinase kinase kinase 5 MAP3K5 0,033 2,04 ENSG00000112234 F-box and leucine-rich repeat protein 4 FBXL4 0,038 2,04 ENSG00000136193 secernin 1 SCRN1 0,021 2,04 ENSG00000166793 yippee-like 4 (Drosophila) YPEL4 0,047 2,05 ENSG00000147905 zinc finger, CCHC domain containing 7 ZCCHC7 0,018 2,05 ENSG00000152219 chromosome 11 open reading frame 46 C11orf46 0,028 2,06 ENSG00000084092 chromosome 4 open reading frame 14 C4orf14 0,018 2,07 ENSG00000124370 methylmalonyl CoA epimerase MCEE 0,035 2,07 ENSG00000144567 family with sequence similarity 134, member A FAM134A 0,022 2,07 ENSG00000259623 N/A N/A 0,039 2,07 ENSG00000157741 ubinuclein 2 UBN2 0,012 2,07 ENSG00000168297 PX domain containing serine/threonine kinase PXK 0,012 2,08 ENSG00000165025 spleen tyrosine kinase SYK 0,020 2,08 ENSG00000170836 protein phosphatase, Mg2+/Mn2+ dependent, 1D PPM1D 0,016 2,09 ENSG00000187796 caspase recruitment domain family, member 9 CARD9 0,014 2,09 ENSG00000162688 amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase AGL 0,019 2,09 ENSG00000148090 AU RNA binding protein/enoyl-CoA hydratase AUH 0,017 2,09 ENSG00000156136 deoxycytidine kinase DCK 0,026 2,09 ENSG00000121897 lipoic acid synthetase LIAS 0,032 2,10 ENSG00000079950 syntaxin 7 STX7 0,018 2,10 ENSG00000196214 zinc finger protein 766 ZNF766 0,036 2,10 ENSG00000189144 zinc finger protein 573 ZNF573 0,046 2,10 ENSG00000101596 structural maintenance of chromosomes flexible hinge domain containing 1 SMCHD1 0,017 2,10 ENSG00000121486 TRM1 tRNA methyltransferase 1-like TRMT1L 0,014 2,11 ENSG00000123609 N-myc (and STAT) interactor NMI 0,017 2,11 ENSG00000138794 caspase 6, apoptosis-related cysteine peptidase CASP6 0,043 2,12 ENSG00000168291 pyruvate dehydrogenase (lipoamide) beta PDHB 0,015 2,12 ENSG00000064012 caspase 8, apoptosis-related cysteine peptidase CASP8 0,034 2,12 ENSG00000113851 cereblon CRBN 0,021 2,13 ENSG00000068024 histone deacetylase 4 HDAC4 0,037 2,14 ENSG00000166783 KIAA0430 KIAA0430 0,014 2,14 ENSG00000260539 na na 0,018 2,14 ENSG00000082074 FYN binding protein FYB 0,026 2,15 ENSG00000169220 regulator of G-protein signaling 14 RGS14 0,023 2,15 ENSG00000163946 chromosome 3 open reading frame 63 C3orf63 0,019 2,15 ENSG00000173801 junction plakoglobin JUP 0,014 2,16 ENSG00000198829 succinate receptor 1 SUCNR1 0,025 2,17 ENSG00000172086 lysine-rich coiled-coil 1 KRCC1 0,012 2,17 ENSG00000132357 caspase recruitment domain family, member 6 CARD6 0,032 2,17 ENSG00000251442 N/A RP11-792D21.2 0,030 2,17 ENSG00000198824 zinc finger protein 828 ZNF828 0,017 2,17 ENSG00000180917 FtsJ methyltransferase domain containing 1 FTSJD1 0,028 2,17 ENSG00000151461 UPF2 regulator of nonsense transcripts homolog (yeast) UPF2 0,013 2,18 ENSG00000168792 abhydrolase domain containing 15 ABHD15 0,012 2,18 ENSG00000196372 ankyrin repeat and SOCS box containing 13 ASB13 0,032 2,18 ENSG00000110876 selectin P ligand SELPLG 0,024 2,18 ENSG00000112406 headcase homolog (Drosophila) HECA 0,012 2,19 ENSG00000171681 activating transcription factor 7 interacting protein ATF7IP 0,015 2,19 ENSG00000257093 protein LCHN AC004918.4 0,047 2,19 ENSG00000135828 ribonuclease L (2',5'-oligoisoadenylate synthetase-dependent) RNASEL 0,012 2,20 ENSG00000137414 family with sequence similarity 8, member A1 FAM8A1 0,025 2,20 ENSG00000114541 FERM domain containing 4B FRMD4B 0,026 2,21 ENSG00000096968 Janus kinase 2 JAK2 0,015 2,21 ENSG00000163104 SWI/SNF-related, matrix-associated actin-dependent regulator of chromatin, subfamily a, SMARCAD1containing DEAD/H0,049 box 1 2,22 ENSG00000169967 mitogen-activated protein kinase kinase kinase 2 MAP3K2 0,016 2,23 ENSG00000164414 solute carrier family 35 (CMP-sialic acid transporter), member A1 SLC35A1 0,019 2,23 ENSG00000112312 geminin, DNA replication inhibitor GMNN 0,025 2,24 ENSG00000121152 non-SMC condensin I complex, subunit H NCAPH 0,021 2,24 ENSG00000048392 ribonucleotide reductase M2 B (TP53 inducible) RRM2B 0,022 2,25 ENSG00000135999 enhancer of polycomb homolog 2 (Drosophila) EPC2 0,035 2,26 ENSG00000187147 ring finger protein 220 RNF220 0,049 2,27 ENSG00000139508 solute carrier family 46, member 3 SLC46A3 0,009 2,27 ENSG00000147854 ubiquitin-like with PHD and ring finger domains 2 UHRF2 0,032 2,27 ENSG00000112079 serine/threonine kinase 38 STK38 0,019 2,28 ENSG00000163154 tumor necrosis factor, alpha-induced protein 8-like 2 TNFAIP8L2 0,024 2,28 ENSG00000164331 ankyrin repeat, family A (RFXANK-like), 2 ANKRA2 0,031 2,28 ENSG00000144228 speckle-type POZ protein-like SPOPL 0,028 2,29 ENSG00000184992 BRI3 binding protein BRI3BP 0,026 2,29 ENSG00000116266 syntaxin binding protein 3 STXBP3 0,019 2,30 ENSG00000214013 glucosidase, alpha; neutral C GANC 0,036 2,31 ENSG00000144635 dynein, cytoplasmic 1, light intermediate chain 1 DYNC1LI1 0,018 2,31 ENSG00000175538 potassium voltage-gated channel, Isk-related family, member 3 KCNE3 0,042 2,31 ENSG00000117616 chromosome 1 open reading frame 63 C1orf63 0,028 2,32 ENSG00000163513 transforming growth factor, beta receptor II (70/80kDa) TGFBR2 0,015 2,32 ENSG00000121067 speckle-type POZ protein SPOP 0,010 2,32 ENSG00000138433 corepressor interacting with RBPJ, 1 CIR1 0,016 2,33 ENSG00000111875 ASF1 anti-silencing function 1 homolog A (S. cerevisiae) ASF1A 0,027 2,33 ENSG00000158092 NCK adaptor protein 1 NCK1 0,027 2,34 ENSG00000143337 torsin A interacting protein 1 TOR1AIP1 0,018 2,34 ENSG00000075188 nucleoporin 37kDa NUP37 0,034 2,35 ENSG00000152409 junction mediating and regulatory protein, p53 cofactor JMY 0,022 2,36 ENSG00000105516 D site of albumin promoter (albumin D-box) binding protein DBP 0,044 2,37 ENSG00000117643 mannosidase, alpha, class 1C, member 1 MAN1C1 0,023 2,37 ENSG00000075643 molybdenum cofactor sulfurase MOCOS 0,049 2,38 ENSG00000196323 zinc finger and BTB domain containing 44 ZBTB44 0,021 2,38 ENSG00000165983 phosphotriesterase related PTER 0,016 2,38 ENSG00000127720 chromosome 12 open reading frame 26 C12orf26 0,018 2,38 ENSG00000130816 DNA (cytosine-5-)-methyltransferase 1 DNMT1 0,049 2,38 ENSG00000164221 coiled-coil domain containing 112 CCDC112 0,025 2,39 ENSG00000126775 ATG14 autophagy related 14 homolog (S. cerevisiae) ATG14 0,023 2,39 ENSG00000181192 dehydrogenase E1 and transketolase domain containing 1 DHTKD1 0,012 2,40 ENSG00000187626 zinc finger with KRAB and SCAN domains 4 ZKSCAN4 0,047 2,40 ENSG00000008869 HEAT repeat containing 5B HEATR5B 0,015 2,41 ENSG00000205302 sorting nexin 2 SNX2 0,019 2,41 ENSG00000185862 ecotropic viral integration site 2B EVI2B 0,030 2,41 ENSG00000171940 zinc finger protein 217 ZNF217 0,023 2,43 ENSG00000147592 lactamase, beta 2 LACTB2 0,035 2,45 ENSG00000157107 FCH domain only 2 FCHO2 0,015 2,45 ENSG00000215256 Full-length cDNA clone CS0DF029YN24 of Fetal brain of Homo sapiens (human) AL136419.1 0,040 2,45 ENSG00000117226 guanylate binding protein 3 GBP3 0,023 2,46 ENSG00000186188 omega-3 fatty acid receptor 1 O3FAR1 0,041 2,47 ENSG00000136514 receptor (chemosensory) transporter protein 4 RTP4 0,043 2,47 ENSG00000158109 tumor protein p63 regulated 1-like TPRG1L 0,036 2,48 ENSG00000118482 PHD finger protein 3 PHF3 0,018 2,49 ENSG00000170293 CKLF-like MARVEL transmembrane domain containing 8 CMTM8 0,047 2,49 ENSG00000165516 kelch domain containing 2 KLHDC2 0,018 2,50 ENSG00000152359 POC5 centriolar protein homolog (Chlamydomonas) POC5 0,035 2,50 ENSG00000198771 RCSD domain containing 1 RCSD1 0,040 2,50 ENSG00000132405 TBC1 domain family, member 14 TBC1D14 0,043 2,52 ENSG00000174197 MAX gene associated MGA 0,016 2,54 ENSG00000169019 COMM domain containing 8 COMMD8 0,030 2,55 ENSG00000107738 chromosome 10 open reading frame 54 C10orf54 0,014 2,55 ENSG00000144909 oxysterol binding protein-like 11 OSBPL11 0,021 2,56 ENSG00000232941 N/A AC090186.1 0,026 2,56 ENSG00000177409 sterile alpha motif domain containing 9-like SAMD9L 0,043 2,56 ENSG00000133574 GTPase, IMAP family member 4 GIMAP4 0,039 2,57 ENSG00000055917 pumilio homolog 2 (Drosophila) PUM2 0,025 2,57 ENSG00000166439 ring finger protein 169 RNF169 0,025 2,58 ENSG00000162378 zyg-11 homolog B (C. elegans) ZYG11B 0,012 2,60 ENSG00000143457 golgi phosphoprotein 3-like GOLPH3L 0,019 2,60 ENSG00000080503 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, SMARCA2member 2 0,009 2,60 ENSG00000152457 DNA cross-link repair 1C DCLRE1C 0,019 2,61 ENSG00000165322 Rho GTPase activating protein 12 ARHGAP12 0,034 2,61 ENSG00000136044 adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 2APPL2 0,021 2,61 ENSG00000155508 CCR4-NOT transcription complex, subunit 8 CNOT8 0,024 2,62 ENSG00000148835 TAF5 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 100kDa TAF5 0,025 2,63 ENSG00000164649 cell division cycle associated 7-like CDCA7L 0,019 2,67 ENSG00000119950 MAX interactor 1 MXI1 0,014 2,67 ENSG00000178966 RMI1, RecQ mediated genome instability 1, homolog (S. cerevisiae) RMI1 0,016 2,68 ENSG00000239213 N/A RP11-85F14.5 0,034 2,69 ENSG00000124496 transcriptional regulating factor 1 TRERF1 0,009 2,69 ENSG00000095015 mitogen-activated protein kinase kinase kinase 1 MAP3K1 0,049 2,70 ENSG00000171631 pyrimidinergic receptor P2Y, G-protein coupled, 6 P2RY6 0,025 2,70 ENSG00000174946 G protein-coupled receptor 171 GPR171 0,026 2,70 ENSG00000023516 A kinase (PRKA) anchor protein 11 AKAP11 0,023 2,71 ENSG00000164117 F-box protein 8 FBXO8 0,012 2,71 ENSG00000100354 trinucleotide repeat containing 6B TNRC6B 0,024 2,72 ENSG00000204103 v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (avian) MAFB 0,023 2,72 ENSG00000180573 histone cluster 1, H2ac HIST1H2AC 0,048 2,73 ENSG00000213689 three prime repair exonuclease 1 TREX1 0,015 2,74 ENSG00000165533 tetratricopeptide repeat domain 8 TTC8 0,041 2,76 ENSG00000038274 methionine adenosyltransferase II, beta MAT2B 0,014 2,76 ENSG00000266753 na na 0,032 2,77 ENSG00000111231 GPN-loop GTPase 3 GPN3 0,018 2,77 ENSG00000198382 UV radiation resistance associated gene UVRAG 0,017 2,81 ENSG00000182511 feline sarcoma oncogene FES 0,030 2,83 ENSG00000181481 ring finger protein 135 RNF135 0,022 2,84 ENSG00000188906 leucine-rich repeat kinase 2 LRRK2 0,022 2,84 ENSG00000071073 mannosyl (alpha-1,3-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferase, isozyme A MGAT4A 0,028 2,84 ENSG00000160179 na na 0,010 2,87 ENSG00000104205 serum/glucocorticoid regulated kinase family, member 3 SGK3 0,029 2,87 ENSG00000115718 protein C (inactivator of coagulation factors Va and VIIIa) PROC 0,028 2,87 ENSG00000021574 spastin SPAST 0,028 2,88 ENSG00000145241 centromere protein C 1 CENPC1 0,028 2,88 ENSG00000136161 regulator of chromosome condensation (RCC1) and BTB (POZ) domain containing protein RCBTB22 0,026 2,89 ENSG00000107719 KIAA1274 KIAA1274 0,028 2,89 ENSG00000138463 disrupted in renal carcinoma 2 DIRC2 0,017 2,91 ENSG00000167528 zinc finger protein 641 ZNF641 0,019 2,92 ENSG00000174738 nuclear receptor subfamily 1, group D, member 2 NR1D2 0,027 2,94 ENSG00000174718 chromosome 12 open reading frame 35 C12orf35 0,019 2,94 ENSG00000167716 WD repeat domain 81 WDR81 0,027 2,95 ENSG00000106780 multiple EGF-like-domains 9 MEGF9 0,018 2,98 ENSG00000101236 ring finger protein 24 RNF24 0,023 2,99 ENSG00000125703 ATG4 autophagy related 4 homolog C (S. cerevisiae) ATG4C 0,024 3,00 ENSG00000138172 calcium homeostasis modulator 2 CALHM2 0,030 3,04 ENSG00000189227 chromosome 15 open reading frame 61 C15orf61 0,032 3,06 ENSG00000178977 non-protein coding RNA 324 NCRNA00324 0,046 3,14 ENSG00000117289 thioredoxin interacting protein TXNIP 0,027 3,14 ENSG00000146083 ring finger protein 44 RNF44 0,012 3,15 ENSG00000136826 Kruppel-like factor 4 (gut) KLF4 0,032 3,16 ENSG00000145569 family with sequence similarity 105, member A FAM105A 0,012 3,17 ENSG00000005175 RNA polymerase II associated protein 3 RPAP3 0,013 3,17 ENSG00000027697 interferon gamma receptor 1 IFNGR1 0,021 3,17 ENSG00000080546 sestrin 1 SESN1 0,012 3,18 ENSG00000170385 solute carrier family 30 (zinc transporter), member 1 SLC30A1 0,024 3,18 ENSG00000150593 programmed cell death 4 (neoplastic transformation inhibitor) PDCD4 0,022 3,22 ENSG00000261799 na na 0,017 3,24 ENSG00000001084 glutamate-cysteine ligase, catalytic subunit GCLC 0,009 3,24 ENSG00000148158 sorting nexin family member 30 SNX30 0,015 3,25 ENSG00000145246 ATPase, class V, type 10D ATP10D 0,016 3,30 ENSG00000155189 1-acylglycerol-3-phosphate O-acyltransferase 5 (lysophosphatidic acid acyltransferase, epsilon)AGPAT5 0,018 3,31 ENSG00000205413 sterile alpha motif domain containing 9 SAMD9 0,021 3,38 ENSG00000112773 family with sequence similarity 46, member A FAM46A 0,010 3,40 ENSG00000096717 sirtuin 1 SIRT1 0,033 3,40 ENSG00000164104 high mobility group box 2 HMGB2 0,033 3,43 ENSG00000170915 progestin and adipoQ receptor family member VIII PAQR8 0,018 3,44 ENSG00000178199 zinc finger CCCH-type containing 12D ZC3H12D 0,040 3,54 ENSG00000119922 interferon-induced protein with tetratricopeptide repeats 2 IFIT2 0,049 3,60 ENSG00000163565 interferon, gamma-inducible protein 16 IFI16 0,035 3,60 ENSG00000129518 E2F-associated phosphoprotein EAPP 0,013 3,60 ENSG00000175155 yippee-like 2 (Drosophila) YPEL2 0,033 3,62 ENSG00000185950 insulin receptor substrate 2 IRS2 0,030 3,63 ENSG00000118308 lymphoid-restricted membrane protein LRMP 0,044 3,67 ENSG00000007944 myosin regulatory light chain interacting protein MYLIP 0,038 3,75 ENSG00000196227 chromosome 20 open reading frame 177 C20orf177 0,047 3,82 ENSG00000047346 KIAA1370 KIAA1370 0,014 3,84 ENSG00000134326 cytidine monophosphate (UMP-CMP) kinase 2, mitochondrial CMPK2 0,027 4,08 ENSG00000132646 proliferating cell nuclear antigen PCNA 0,012 4,14 ENSG00000179144 GTPase, IMAP family member 7 GIMAP7 0,045 4,33 ENSG00000163563 myeloid cell nuclear differentiation antigen MNDA 0,022 4,35 ENSG00000198740 zinc finger protein 652 ZNF652 0,013 4,55 ENSG00000101916 toll-like receptor 8 TLR8 0,018 4,58 ENSG00000077063 cortactin binding protein 2 CTTNBP2 0,029 4,79 ENSG00000152804 hematopoietically expressed homeobox HHEX 0,028 4,82 ENSG00000114796 kelch-like 24 (Drosophila) KLHL24 0,013 4,84 ENSG00000095585 B-cell linker BLNK 0,023 4,85 ENSG00000145416 membrane-associated ring finger (C3HC4) 1 MARCH1 0,026 4,85 ENSG00000110852 C-type lectin domain family 2, member B CLEC2B 0,012 5,06 ENSG00000129534 MIS18 binding protein 1 MIS18BP1 0,024 5,50 ENSG00000164463 chromosome 5 open reading frame 41 C5orf41 0,015 5,55 ENSG00000121933 adenosine A3 receptor ADORA3 0,023 5,58 ENSG00000139679 lysophosphatidic acid receptor 6 LPAR6 0,043 5,83 ENSG00000174944 purinergic receptor P2Y, G-protein coupled, 14 P2RY14 0,030 7,02 ENSG00000106560 GTPase, IMAP family member 2 GIMAP2 0,023 7,41 ENSG00000180340 frizzled homolog 2 (Drosophila) FZD2 0,017 7,85 ENSG00000170448 nuclear transcription factor, X-box binding-like 1 NFXL1 0,019 8,36 ENSG00000150681 regulator of G-protein signaling 18 RGS18 0,018 10,45 ENSG00000169087 HSPB (heat shock 27kDa) associated protein 1 HSPBAP1 0,018 10,53 Supplementary Table 1C. Genes regulated by OSCAR-ColII signaling Overlap of ColII-regulated genes and OSCAR-regulated genes ColII vs iDC comparison ColII+anti-OSCAR vs ColII+isotype Overlapping genes gene title Gene Symbol q-value Fold change q-value Fold change ENSG00000115009 chemokine (C-C motif) ligand 20 CCL20 0,002 158,54 0,02 -102,55 ENSG00000073756 prostaglandin-endoperoxide synthase 2 (prostaglandinPTGS2 G/H synthase and0,003 cyclooxygenase)56,05 0,03 -35,61 ENSG00000115008 interleukin 1, alpha IL1A 0,010 43,04 0,03 -36,58 ENSG00000153234 nuclear receptor subfamily 4, group A, member 2 NR4A2 0,003 39,00 0,05 -20,68 ENSG00000164949 GTP binding protein overexpressed in skeletal muscleGEM 0,003 36,00 0,02 -26,49 ENSG00000234883 MIR155 host gene (non-protein coding) MIR155HG 0,005 32,15 0,01 -31,22 ENSG00000078401 endothelin 1 EDN1 0,011 26,45 0,02 -17,90 ENSG00000163734 chemokine (C-X-C motif) ligand 3 CXCL3 0,011 26,13 0,03 -19,65 ENSG00000081041 chemokine (C-X-C motif) ligand 2 CXCL2 0,010 24,83 0,04 -17,15 ENSG00000123689 G0/G1switch 2 G0S2 0,004 24,05 0,03 -18,43 ENSG00000232810 tumor necrosis factor TNF 0,003 23,13 0,02 -27,14 ENSG00000125538 interleukin 1, beta IL1B 0,007 23,07 0,05 -21,71 ENSG00000158050 dual specificity phosphatase 2 DUSP2 0,003 22,23 0,03 -15,65 ENSG00000163739 chemokine (C-X-C motif) ligand 1 (melanoma growthCXCL1 stimulating activity,0,011 alpha) 21,49 0,03 -16,79 ENSG00000120875 dual specificity phosphatase 4 DUSP4 0,004 20,84 0,02 -15,21 ENSG00000178726 thrombomodulin THBD 0,008 19,30 0,03 -18,39 ENSG00000101187 solute carrier organic anion transporter family, memberSLCO4A1 4A1 0,003 18,32 0,01 -13,48 ENSG00000041982 tenascin C TNC 0,008 17,85 0,02 -11,82 ENSG00000117525 coagulation factor III (thromboplastin, tissue factor)F3 0,003 17,12 0,05 -14,66 ENSG00000164181 ELOVL family member 7, elongation of long chain fattyELOVL7 acids (yeast) 0,004 15,63 0,01 -12,92 ENSG00000113070 heparin-binding EGF-like growth factor HBEGF 0,005 15,14 0,02 -14,78 ENSG00000108691 chemokine (C-C motif) ligand 2 CCL2 0,010 14,11 0,04 -15,36 ENSG00000153162 bone morphogenetic protein 6 BMP6 0,004 13,46 0,02 -11,47 ENSG00000013619 mastermind-like domain containing 1 MAMLD1 0,004 12,79 0,02 -12,11 ENSG00000140379 BCL2-related protein A1 BCL2A1 0,007 12,23 0,02 -13,16 ENSG00000232956 chromosome 7 open reading frame 40 C7orf40 0,005 11,74 0,02 -12,98 ENSG00000116717 growth arrest and DNA-damage-inducible, alpha GADD45A 0,005 11,17 0,05 -6,78 ENSG00000186827 tumor necrosis factor receptor superfamily, memberTNFRSF4 4 0,004 11,15 0,04 -8,52 ENSG00000180758 G protein-coupled receptor 157 GPR157 0,011 11,14 0,03 -7,58 ENSG00000149289 zinc finger CCCH-type containing 12C ZC3H12C 0,003 11,11 0,05 -8,75 ENSG00000056558 TNF receptor-associated factor 1 TRAF1 0,004 10,51 0,03 -8,55 ENSG00000099985 oncostatin M OSM 0,002 10,47 0,02 -15,19 ENSG00000157557 v-ets erythroblastosis virus E26 oncogene homolog ETS22 (avian) 0,006 10,15 0,02 -10,25 ENSG00000112394 solute carrier family 16, member 10 (aromatic aminoSLC16A10 acid transporter) 0,010 10,06 0,02 -9,29 ENSG00000144802 nuclear factor of kappa light polypeptide gene enhancerNFKBIZ in B-cells inhibitor,0,004 zeta 9,42 0,03 -9,58 ENSG00000108702 chemokine (C-C motif) ligand 1 CCL1 0,011 8,91 0,02 -9,11 ENSG00000170542 serpin peptidase inhibitor, clade B (ovalbumin), memberSERPINB9 9 0,008 8,63 0,02 -8,10 ENSG00000132510 lysine (K)-specific demethylase 6B KDM6B 0,002 8,55 0,03 -6,74 ENSG00000125735 tumor necrosis factor (ligand) superfamily, memberTNFSF14 14 0,002 8,54 0,02 -7,64 ENSG00000110047 EH-domain containing 1 EHD1 0,008 8,48 0,02 -7,68 ENSG00000173846 polo-like kinase 3 PLK3 0,003 8,37 0,02 -7,72 ENSG00000167604 nuclear factor of kappa light polypeptide gene enhancerNFKBID in B-cells inhibitor,0,004 delta 8,27 0,01 -7,52 ENSG00000116285 ERBB receptor feedback inhibitor 1 ERRFI1 0,007 8,04 0,02 -7,76 ENSG00000099860 growth arrest and DNA-damage-inducible, beta GADD45B 0,002 7,92 0,02 -7,41 ENSG00000118503 tumor necrosis factor, alpha-induced protein 3 TNFAIP3 0,006 7,87 0,03 -6,06 ENSG00000134070 interleukin-1 receptor-associated kinase 2 IRAK2 0,003 7,65 0,03 -5,21 ENSG00000135476 extra spindle pole bodies homolog 1 (S. cerevisiae) ESPL1 0,020 7,49 0,05 -6,61 ENSG00000114473 IQ motif containing G IQCG 0,006 7,31 0,02 -7,10 ENSG00000253522 microRNA 146a (MIR146A), microRNA CTC-231O11.1 0,010 7,19 0,01 -8,77 ENSG00000112096 superoxide dismutase 2, mitochondrial SOD2 0,004 7,13 0,02 -5,85 ENSG00000065809 family with sequence similarity 107, member B FAM107B 0,003 7,02 0,02 -5,10 ENSG00000103257 solute carrier family 7 (cationic amino acid transporter,SLC7A5 y+ system), member0,008 5 6,94 0,01 -7,30 ENSG00000152413 homer homolog 1 (Drosophila) HOMER1 0,006 6,93 0,03 -7,83 ENSG00000010810 FYN oncogene related to SRC, FGR, YES FYN 0,011 6,83 0,03 -5,15 ENSG00000185022 v-maf musculoaponeurotic fibrosarcoma oncogene MAFFhomolog F (avian) 0,008 6,81 0,04 -5,58 ENSG00000124145 syndecan 4 SDC4 0,003 6,60 0,03 -7,40 ENSG00000184371 colony stimulating factor 1 (macrophage) CSF1 0,003 6,33 0,01 -5,95 ENSG00000167772 angiopoietin-like 4 ANGPTL4 0,022 6,22 0,04 -6,32 ENSG00000034152 mitogen-activated protein kinase kinase 3 MAP2K3 0,002 6,17 0,02 -5,20 ENSG00000249992 transmembrane protein 158 (gene/pseudogene) TMEM158 0,013 6,04 0,03 -6,09 ENSG00000162645 guanylate binding protein 2, interferon-inducible GBP2 0,003 6,02 0,02 -4,83 ENSG00000186665 chromosome 17 open reading frame 58 C17orf58 0,005 5,96 0,02 -5,68 ENSG00000154640 BTG family, member 3 BTG3 0,006 5,94 0,03 -5,39 ENSG00000179294 chromosome 17 open reading frame 96 C17orf96 0,008 5,59 0,04 -5,21 ENSG00000167695 family with sequence similarity 57, member A FAM57A 0,015 5,57 0,03 -5,12 ENSG00000112715 vascular endothelial growth factor A VEGFA 0,007 5,57 0,03 -4,44 ENSG00000131016 A kinase (PRKA) anchor protein 12 AKAP12 0,014 5,52 0,02 -5,62 ENSG00000136158 sprouty homolog 2 (Drosophila) SPRY2 0,007 5,51 0,03 -7,00 ENSG00000136689 interleukin 1 receptor antagonist IL1RN 0,005 5,48 0,02 -6,72 ENSG00000106366 serpin peptidase inhibitor, clade E (nexin, plasminogenSERPINE1 activator inhibitor0,009 type 1), member5,47 1 0,02 -3,67 ENSG00000165997 ADP-ribosylation factor-like 5B ARL5B 0,004 5,38 0,04 -4,40 ENSG00000121797 chemokine (C-C motif) receptor-like 2 CCRL2 0,004 5,35 0,03 -5,03 ENSG00000162924 v-rel reticuloendotheliosis viral oncogene homolog (avian)REL 0,011 5,14 0,03 -4,96 ENSG00000090339 intercellular adhesion molecule 1 ICAM1 0,010 5,13 0,02 -6,71 ENSG00000138670 RasGEF domain family, member 1B RASGEF1B 0,003 5,13 0,03 -3,48 ENSG00000186891 tumor necrosis factor receptor superfamily, memberTNFRSF18 18 0,002 4,95 0,02 -4,82 ENSG00000108179 peptidylprolyl isomerase F PPIF 0,006 4,91 0,03 -5,31 ENSG00000139289 pleckstrin homology-like domain, family A, memberPHLDA1 1 0,013 4,90 0,02 -6,55 ENSG00000117090 signaling lymphocytic activation molecule family memberSLAMF1 1 0,022 4,88 0,03 -5,35 ENSG00000139318 dual specificity phosphatase 6 DUSP6 0,007 4,85 0,03 -6,01 ENSG00000159200 regulator of calcineurin 1 RCAN1 0,004 4,83 0,04 -3,81 ENSG00000145777 thymic stromal lymphopoietin TSLP 0,047 4,82 0,04 -4,91 ENSG00000163347 claudin 1 CLDN1 0,003 4,76 0,02 -5,39 ENSG00000214900 chromosome 14 open reading frame 182 C14orf182 0,009 4,75 0,01 -4,08 ENSG00000172175 mucosa associated lymphoid tissue lymphoma translocationMALT1 gene 1 0,003 4,72 0,02 -4,46 ENSG00000121594 CD80 molecule CD80 0,011 4,67 0,02 -7,62 ENSG00000144655 cysteine-serine-rich nuclear protein 1 CSRNP1 0,004 4,57 0,03 -4,08 ENSG00000109320 nuclear factor of kappa light polypeptide gene enhancerNFKB1 in B-cells 1 0,007 4,56 0,04 -4,28 ENSG00000198355 pim-3 oncogene PIM3 0,006 4,53 0,03 -5,05 ENSG00000175040 carbohydrate (N-acetylglucosamine-6-O) sulfotransferaseCHST2 2 0,025 4,51 0,05 -4,37 ENSG00000198369 sprouty-related, EVH1 domain containing 2 SPRED2 0,008 4,49 0,02 -4,67 ENSG00000138378 signal transducer and activator of transcription 4 STAT4 0,012 4,48 0,03 -4,98 ENSG00000011422 plasminogen activator, urokinase receptor PLAUR 0,005 4,47 0,03 -4,52 ENSG00000100985 matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase,MMP9 92kDa type IV0,014 collagenase) 4,46 0,03 -4,12 ENSG00000145990 glucose-fructose oxidoreductase domain containingGFOD1 1 0,013 4,44 0,03 -3,34 ENSG00000110042 deltex homolog 4 (Drosophila) DTX4 0,018 4,43 0,02 -2,55 ENSG00000137267 tubulin, beta 2A TUBB2A 0,011 4,42 0,02 -4,53 ENSG00000168685 interleukin 7 receptor IL7R 0,013 4,40 0,04 -6,52 ENSG00000143067 zinc finger protein 697 ZNF697 0,007 4,40 0,04 -4,23 ENSG00000148841 inositol 1,4,5-trisphosphate receptor interacting proteinITPRIP 0,003 4,39 0,03 -4,03 ENSG00000123358 nuclear receptor subfamily 4, group A, member 1 NR4A1 0,002 4,36 0,03 -3,45 ENSG00000150977 Rab interacting lysosomal protein-like 2 RILPL2 0,004 4,26 0,02 -3,66 ENSG00000154127 ubiquitin associated and SH3 domain containing B UBASH3B 0,007 4,23 0,02 -4,91 ENSG00000236700 N/A RP11-557H15.2 0,015 4,21 0,03 -3,76 ENSG00000166592 Ras-related associated with diabetes RRAD 0,007 4,19 0,01 -4,14 ENSG00000166881 transmembrane protein 194A TMEM194A 0,008 4,18 0,02 -5,60 ENSG00000153721 CNKSR family member 3 CNKSR3 0,016 4,16 0,02 -4,32 ENSG00000120129 dual specificity phosphatase 1 DUSP1 0,005 4,07 0,04 -4,12 ENSG00000163171 CDC42 effector protein (Rho GTPase binding) 3 CDC42EP3 0,003 4,07 0,04 -3,25 ENSG00000172071 eukaryotic translation initiation factor 2-alpha kinaseEIF2AK3 3 0,003 4,06 0,02 -3,64 ENSG00000186480 insulin induced gene 1 INSIG1 0,003 4,01 0,03 -3,36 ENSG00000260196 na na 0,005 3,99 0,02 -3,44 ENSG00000164211 StAR-related lipid transfer (START) domain containingSTARD4 4 0,016 3,99 0,03 -5,03 ENSG00000182224 cytochrome b5 domain containing 1 CYB5D1 0,008 3,96 0,03 -3,91 ENSG00000124731 triggering receptor expressed on myeloid cells 1 TREM1 0,010 3,91 0,05 -3,39 ENSG00000168906 methionine adenosyltransferase II, alpha MAT2A 0,015 3,90 0,03 -3,99 ENSG00000131873 chondroitin sulfate synthase 1 CHSY1 0,005 3,85 0,02 -3,50 ENSG00000060982 branched chain amino-acid transaminase 1, cytosolicBCAT1 0,006 3,85 0,02 -4,02 ENSG00000054523 kinesin family member 1B KIF1B 0,006 3,81 0,05 -3,26 ENSG00000125740 FBJ murine osteosarcoma viral oncogene homolog BFOSB 0,021 3,78 0,03 -3,18 ENSG00000131669 ninjurin 1 NINJ1 0,008 3,77 0,03 -3,73 ENSG00000007264 megakaryocyte-associated tyrosine kinase MATK 0,036 3,71 0,04 -4,41 ENSG00000197405 complement component 5a receptor 1 C5AR1 0,023 3,69 0,04 -3,33 ENSG00000133639 B-cell translocation gene 1, anti-proliferative BTG1 0,005 3,67 0,02 -2,81 ENSG00000168884 TNFAIP3 interacting protein 2 TNIP2 0,004 3,66 0,02 -3,71 ENSG00000139725 na na 0,007 3,66 0,02 -3,30 ENSG00000137449 cytoplasmic polyadenylation element binding proteinCPEB2 2 0,003 3,63 0,03 -4,05 ENSG00000118985 elongation factor, RNA polymerase II, 2 ELL2 0,007 3,62 0,02 -3,48 ENSG00000095794 cAMP responsive element modulator CREM 0,011 3,61 0,03 -3,66 ENSG00000135919 serpin peptidase inhibitor, clade E (nexin, plasminogenSERPINE2 activator inhibitor0,018 type 1), member3,58 2 0,05 -3,05 ENSG00000183696 uridine phosphorylase 1 UPP1 0,003 3,49 0,02 -4,79 ENSG00000102755 fms-related tyrosine kinase 1 (vascular endothelial growthFLT1 factor/vascular0,008 permeability 3,49factor receptor) 0,01 -4,57 ENSG00000125730 complement component 3 C3 0,028 3,47 0,03 -3,68 ENSG00000106952 tumor necrosis factor (ligand) superfamily, memberTNFSF8 8 0,021 3,46 0,02 -3,35 ENSG00000117036 ets variant 3 ETV3 0,007 3,45 0,04 -3,08 ENSG00000163874 zinc finger CCCH-type containing 12A ZC3H12A 0,005 3,44 0,02 -3,40 ENSG00000142178 salt-inducible kinase 1 SIK1 0,011 3,40 0,03 -2,59 ENSG00000188001 tumor protein p63 regulated 1 TPRG1 0,011 3,40 0,03 -4,20 ENSG00000138166 dual specificity phosphatase 5 DUSP5 0,004 3,36 0,02 -6,13 ENSG00000164935 transmembrane 7 superfamily member 4 TM7SF4 0,019 3,31 0,01 -3,35 ENSG00000104312 receptor-interacting serine-threonine kinase 2 RIPK2 0,002 3,29 0,02 -3,33 ENSG00000176845 meteorin, glial cell differentiation regulator-like METRNL 0,006 3,25 0,03 -3,19 ENSG00000077984 cystatin F (leukocystatin) CST7 0,013 3,20 0,02 -3,12 ENSG00000134242 protein tyrosine phosphatase, non-receptor type 22PTPN22 (lymphoid) 0,007 3,19 0,04 -2,48 ENSG00000134830 G protein-coupled receptor 77 GPR77 0,008 3,19 0,03 -2,36 ENSG00000223749 N/A AC004383.4 0,007 3,19 0,02 -3,00 ENSG00000156711 mitogen-activated protein kinase 13 MAPK13 0,010 3,18 0,01 -3,44 ENSG00000107968 mitogen-activated protein kinase kinase kinase 8 MAP3K8 0,005 3,17 0,02 -3,13 ENSG00000100906 nuclear factor of kappa light polypeptide gene enhancerNFKBIA in B-cells inhibitor,0,008 alpha 3,17 0,05 -2,92 ENSG00000163399 ATPase, Na+/K+ transporting, alpha 1 polypeptide ATP1A1 0,003 3,16 0,02 -3,02 ENSG00000101017 CD40 molecule, TNF receptor superfamily member 5CD40 0,008 3,15 0,03 -4,55 ENSG00000224818 N/A RP11-134G8.8 0,008 3,14 0,03 -3,47 ENSG00000087074 protein phosphatase 1, regulatory (inhibitor) subunitPPP1R15A 15A 0,004 3,12 0,02 -2,96 ENSG00000179241 low density lipoprotein receptor class A domain containingLDLRAD3 3 0,003 3,11 0,01 -2,95 ENSG00000172818 ovo-like 1(Drosophila) OVOL1 0,015 3,10 0,04 -2,29 ENSG00000102760 chromosome 13 open reading frame 15 C13orf15 0,008 3,09 0,02 -2,73 ENSG00000006062 mitogen-activated protein kinase kinase kinase 14 MAP3K14 0,003 3,09 0,02 -3,14 ENSG00000173517 Pseudopodium-enriched atypical kinase 1 AC087465.1 0,005 3,08 0,03 -2,70 ENSG00000165312 OTU domain containing 1 OTUD1 0,007 3,04 0,05 -2,60 ENSG00000151247 eukaryotic translation initiation factor 4E EIF4E 0,008 3,02 0,02 -2,89 ENSG00000137094 DnaJ (Hsp40) homolog, subfamily B, member 5 DNAJB5 0,014 3,01 0,03 -2,71 ENSG00000146676 purine-rich element binding protein B PURB 0,004 3,00 0,03 -2,96 ENSG00000115956 pleckstrin PLEK 0,008 2,98 0,05 -2,74 ENSG00000104783 potassium intermediate/small conductance calcium-activatedKCNN4 channel, subfamily0,011 N, member2,98 4 0,02 -2,88 ENSG00000123908 eukaryotic translation initiation factor 2C, 2 EIF2C2 0,007 2,97 0,01 -3,27 ENSG00000184557 suppressor of cytokine signaling 3 SOCS3 0,009 2,96 0,02 -3,97 ENSG00000113811 Selenoprotein K RP11-884K10.5 0,006 2,96 0,03 -2,76 ENSG00000173166 Ras association (RalGDS/AF-6) and pleckstrin homologyRAPH1 domains 1 0,004 2,95 0,03 -2,90 ENSG00000136891 testis expressed 10 TEX10 0,011 2,94 0,03 -2,39 ENSG00000133657 ATPase type 13A3 ATP13A3 0,007 2,93 0,03 -2,90 ENSG00000140406 mesoderm development candidate 1 MESDC1 0,030 2,91 0,05 -4,40 ENSG00000137193 pim-1 oncogene PIM1 0,008 2,90 0,04 -4,89 ENSG00000003402 CASP8 and FADD-like apoptosis regulator CFLAR 0,005 2,89 0,03 -3,05 ENSG00000136653 Ras association (RalGDS/AF-6) domain family memberRASSF5 5 0,003 2,88 0,03 -2,95 ENSG00000138119 myoferlin MYOF 0,004 2,87 0,04 -2,76 ENSG00000175352 nuclear receptor interacting protein 3 NRIP3 0,006 2,84 0,02 -2,75 ENSG00000008083 jumonji, AT rich interactive domain 2 JARID2 0,018 2,83 0,02 -3,36 ENSG00000095951 human immunodeficiency virus type I enhancer bindingHIVEP1 protein 1 0,008 2,81 0,03 -2,56 ENSG00000213859 potassium channel tetramerisation domain containingKCTD11 11 0,013 2,79 0,03 -2,68 ENSG00000175445 lipoprotein lipase LPL 0,008 2,77 0,03 -3,00 ENSG00000100221 Josephin domain containing 1 JOSD1 0,004 2,76 0,02 -2,68 ENSG00000120539 microtubule associated serine/threonine kinase-likeMASTL 0,007 2,74 0,04 -2,06 ENSG00000121769 fatty acid binding protein 3, muscle and heart (mammary-derivedFABP3 growth0,003 inhibitor) 2,73 0,02 -2,78 ENSG00000168994 chromosome 6 open reading frame 145 C6orf145 0,004 2,72 0,03 -2,71 ENSG00000196083 interleukin 1 receptor accessory protein IL1RAP 0,008 2,72 0,02 -4,15 ENSG00000115738 inhibitor of DNA binding 2, dominant negative helix-loop-helixID2 protein 0,013 2,71 0,04 -2,91 ENSG00000183484 G protein-coupled receptor 132 GPR132 0,015 2,71 0,02 -2,19 ENSG00000196396 protein tyrosine phosphatase, non-receptor type 1 PTPN1 0,010 2,69 0,03 -2,26 ENSG00000160883 hexokinase 3 (white cell) HK3 0,007 2,69 0,02 -2,40 ENSG00000151689 inositol polyphosphate-1-phosphatase INPP1 0,008 2,68 0,03 -2,36 ENSG00000124225 prostate transmembrane protein, androgen inducedPMEPA1 1 0,008 2,67 0,02 -2,93 ENSG00000260231 na na 0,016 2,67 0,03 -2,73 ENSG00000101665 SMAD family member 7 SMAD7 0,007 2,67 0,01 -3,26 ENSG00000139722 vacuolar protein sorting 37 homolog B (S. cerevisiae)VPS37B 0,007 2,66 0,02 -2,61 ENSG00000114013 CD86 molecule CD86 0,005 2,65 0,02 -2,66 ENSG00000161091 chromosome 19 open reading frame 28 C19orf28 0,004 2,65 0,02 -2,41 ENSG00000156535 CD109 molecule CD109 0,013 2,64 0,04 -2,51 ENSG00000102226 ubiquitin specific peptidase 11 USP11 0,005 2,63 0,02 -2,27 ENSG00000181649 pleckstrin homology-like domain, family A, memberPHLDA2 2 0,006 2,60 0,03 -2,84 ENSG00000131370 SH3-domain binding protein 5 (BTK-associated) SH3BP5 0,009 2,56 0,03 -2,26 ENSG00000006327 tumor necrosis factor receptor superfamily, memberTNFRSF12A 12A 0,011 2,56 0,03 -2,68 ENSG00000196449 yrdC domain containing (E. coli) YRDC 0,007 2,54 0,03 -2,74 ENSG00000008405 cryptochrome 1 (photolyase-like) CRY1 0,012 2,53 0,02 -2,56 ENSG00000126003 pleiomorphic adenoma gene-like 2 PLAGL2 0,013 2,50 0,03 -2,35 ENSG00000165195 phosphatidylinositol glycan anchor biosynthesis, classPIGA A 0,014 2,50 0,04 -2,90 ENSG00000137462 toll-like receptor 2 TLR2 0,022 2,50 0,05 -2,58 ENSG00000259758 N/A N/A 0,007 2,49 0,02 -2,44 ENSG00000141540 tweety homolog 2 (Drosophila) TTYH2 0,006 2,49 0,02 -2,16 ENSG00000151092 N-glycanase 1 NGLY1 0,007 2,48 0,03 -2,16 ENSG00000170779 cell division cycle associated 4 CDCA4 0,013 2,47 0,03 -2,46 ENSG00000103855 CD276 molecule CD276 0,017 2,47 0,02 -2,74 ENSG00000138623 semaphorin 7A, GPI membrane anchor (John MiltonSEMA7A Hagen blood group)0,003 2,47 0,03 -2,18 ENSG00000144136 solute carrier family 20 (phosphate transporter), memberSLC20A1 1 0,008 2,42 0,02 -2,61 ENSG00000181788 seven in absentia homolog 2 (Drosophila) SIAH2 0,009 2,41 0,03 -2,57 ENSG00000102908 nuclear factor of activated T-cells 5, tonicity-responsiveNFAT5 0,011 2,40 0,03 -2,59 ENSG00000242247 ADP-ribosylation factor GTPase activating protein 3ARFGAP3 0,004 2,40 0,01 -2,39 ENSG00000197147 leucine rich repeat containing 8 family, member B LRRC8B 0,019 2,39 0,03 -2,82 ENSG00000197249 serpin peptidase inhibitor, clade A (alpha-1 antiproteinase,SERPINA1 antitrypsin), 0,004member 1 2,37 0,02 -2,14 ENSG00000143384 myeloid cell leukemia sequence 1 (BCL2-related) MCL1 0,003 2,37 0,03 -2,04 ENSG00000102962 chemokine (C-C motif) ligand 22 CCL22 0,011 2,36 0,03 -2,61 ENSG00000074660 scavenger receptor class F, member 1 SCARF1 0,004 2,36 0,01 -2,46 ENSG00000155366 ras homolog gene family, member C RHOC 0,006 2,32 0,02 -2,72 ENSG00000147650 low density lipoprotein receptor-related protein 12 LRP12 0,006 2,32 0,02 -2,82 ENSG00000015475 BH3 interacting domain death agonist BID 0,007 2,32 0,04 -2,10 ENSG00000107175 cAMP responsive element binding protein 3 CREB3 0,004 2,32 0,03 -2,18 ENSG00000117143 UDP-N-acteylglucosamine pyrophosphorylase 1 UAP1 0,012 2,31 0,03 -2,45 ENSG00000140968 interferon regulatory factor 8 IRF8 0,005 2,30 0,02 -2,85 ENSG00000104450 sperm associated antigen 1 SPAG1 0,016 2,27 0,05 -2,11 ENSG00000127124 human immunodeficiency virus type I enhancer bindingHIVEP3 protein 3 0,005 2,27 0,02 -2,03 ENSG00000173548 sorting nexin 33 SNX33 0,015 2,27 0,04 -2,20 ENSG00000197461 platelet-derived growth factor alpha polypeptide PDGFA 0,018 2,26 0,02 -2,67 ENSG00000132661 NTF2-like export factor 1 NXT1 0,011 2,25 0,01 -2,46 ENSG00000023330 aminolevulinate, delta-, synthase 1 ALAS1 0,018 2,25 0,03 -2,55 ENSG00000077238 interleukin 4 receptor IL4R 0,007 2,24 0,01 -2,38 ENSG00000172530 BTG3 associated nuclear protein BANP 0,007 2,24 0,02 -2,31 ENSG00000155926 Src-like-adaptor SLA 0,043 2,23 0,05 -2,29 ENSG00000117868 extended synaptotagmin-like protein 2 ESYT2 0,004 2,23 0,01 -2,18 ENSG00000130340 sorting nexin 9 SNX9 0,003 2,23 0,01 -2,09 ENSG00000157224 claudin 12 CLDN12 0,015 2,22 0,01 -2,46 ENSG00000170425 adenosine A2b receptor ADORA2B 0,010 2,21 0,04 -2,23 ENSG00000064225 ST3 beta-galactoside alpha-2,3-sialyltransferase 6 ST3GAL6 0,003 2,21 0,03 -2,19 ENSG00000177150 chromosome 18 open reading frame 19 C18orf19 0,003 2,21 0,02 -2,35 ENSG00000186594 chromosome 17 open reading frame 91 C17orf91 0,017 2,21 0,03 -2,70 ENSG00000101384 jagged 1 JAG1 0,004 2,20 0,04 -2,07 ENSG00000169504 chloride intracellular channel 4 CLIC4 0,003 2,20 0,01 -2,34 ENSG00000104447 trichorhinophalangeal syndrome I TRPS1 0,005 2,19 0,05 -2,37 ENSG00000115758 ornithine decarboxylase 1 ODC1 0,004 2,19 0,01 -2,08 ENSG00000225968 na na 0,044 2,18 0,02 -2,07 ENSG00000100139 MICAL-like 1 MICALL1 0,026 2,17 0,04 -2,01 ENSG00000037897 methyltransferase like 1 METTL1 0,017 2,16 0,04 -2,13 ENSG00000196843 AT rich interactive domain 5A (MRF1-like) ARID5A 0,005 2,15 0,02 -2,05 ENSG00000251136 N/A RP11-37B2.1 0,023 2,14 0,03 -2,30 ENSG00000112941 PAP associated domain containing 7 PAPD7 0,007 2,14 0,03 -2,17 ENSG00000170776 A kinase (PRKA) anchor protein 13 AKAP13 0,012 2,14 0,02 -2,26 ENSG00000162723 SLAM family member 9 SLAMF9 0,018 2,14 0,02 -2,25 ENSG00000102119 emerin EMD 0,003 2,13 0,04 -2,18 ENSG00000132170 peroxisome proliferator-activated receptor gamma PPARG 0,021 2,13 0,05 -2,74 ENSG00000162889 mitogen-activated protein kinase-activated protein MAPKAPK2kinase 2 0,004 2,12 0,02 -2,07 ENSG00000143393 phosphatidylinositol 4-kinase, catalytic, beta PI4KB 0,002 2,11 0,02 -2,27 ENSG00000139496 nucleoporin like 1 NUPL1 0,008 2,10 0,04 -2,44 ENSG00000196781 transducin-like enhancer of split 1 (E(sp1) homolog, TLE1Drosophila) 0,038 2,10 0,03 -2,15 ENSG00000206560 ankyrin repeat domain 28 ANKRD28 0,015 2,07 0,02 -2,15 ENSG00000180611 Mab-21 domain containing 2 MB21D2 0,018 2,07 0,03 -2,66 ENSG00000154122 ankylosis, progressive homolog (mouse) ANKH 0,021 2,06 0,04 -2,12 ENSG00000118971 cyclin D2 CCND2 0,041 2,06 0,02 -3,03 ENSG00000085117 CD82 molecule CD82 0,011 2,05 0,04 -2,10 ENSG00000173334 tribbles homolog 1 (Drosophila) TRIB1 0,019 2,03 0,05 -2,36 ENSG00000008294 sperm associated antigen 9 SPAG9 0,011 2,02 0,03 -2,08 ENSG00000120217 CD274 molecule CD274 0,024 2,00 0,02 -2,96 ENSG00000136052 solute carrier family 41, member 2 SLC41A2 0,009 2,00 0,03 -2,22 ENSG00000173801 junction plakoglobin JUP 0,024 0,50 0,01 2,16 ENSG00000064012 caspase 8, apoptosis-related cysteine peptidase CASP8 0,027 0,50 0,03 2,12 ENSG00000198824 zinc finger protein 828 ZNF828 0,009 0,50 0,02 2,17 ENSG00000152359 POC5 centriolar protein homolog (Chlamydomonas)POC5 0,036 0,50 0,04 2,50 ENSG00000108055 structural maintenance of chromosomes 3 SMC3 0,021 0,50 0,01 2,03 ENSG00000084090 StAR-related lipid transfer (START) domain containingSTARD7 7 0,009 0,50 0,01 2,00 ENSG00000168291 pyruvate dehydrogenase (lipoamide) beta PDHB 0,007 0,50 0,01 2,12 ENSG00000170915 progestin and adipoQ receptor family member VIII PAQR8 0,012 0,49 0,02 3,44 ENSG00000115548 lysine (K)-specific demethylase 3A KDM3A 0,006 0,49 0,04 2,03 ENSG00000187796 caspase recruitment domain family, member 9 CARD9 0,006 0,49 0,01 2,09 ENSG00000181192 dehydrogenase E1 and transketolase domain containingDHTKD1 1 0,004 0,49 0,01 2,40 ENSG00000163535 shugoshin-like 2 (S. pombe) SGOL2 0,012 0,49 0,05 2,02 ENSG00000121486 TRM1 tRNA methyltransferase 1-like TRMT1L 0,008 0,48 0,01 2,11 ENSG00000144228 speckle-type POZ protein-like SPOPL 0,006 0,48 0,03 2,29 ENSG00000170836 protein phosphatase, Mg2+/Mn2+ dependent, 1D PPM1D 0,012 0,48 0,02 2,09 ENSG00000168918 inositol polyphosphate-5-phosphatase, 145kDa INPP5D 0,024 0,48 0,02 2,01 ENSG00000014123 KIAA0776 KIAA0776 0,011 0,48 0,03 2,04 ENSG00000107738 chromosome 10 open reading frame 54 C10orf54 0,014 0,48 0,01 2,55 ENSG00000006007 glycerophosphodiester phosphodiesterase 1 GDE1 0,011 0,48 0,03 2,02 ENSG00000084092 chromosome 4 open reading frame 14 C4orf14 0,009 0,48 0,02 2,07 ENSG00000136193 secernin 1 SCRN1 0,022 0,48 0,02 2,04 ENSG00000075188 nucleoporin 37kDa NUP37 0,014 0,47 0,03 2,35 ENSG00000169967 mitogen-activated protein kinase kinase kinase 2 MAP3K2 0,010 0,47 0,02 2,23 ENSG00000121858 tumor necrosis factor (ligand) superfamily, memberTNFSF10 10 0,040 0,47 0,05 2,03 ENSG00000121152 non-SMC condensin I complex, subunit H NCAPH 0,017 0,47 0,02 2,24 ENSG00000251442 N/A RP11-792D21.2 0,018 0,47 0,03 2,17 ENSG00000121897 lipoic acid synthetase LIAS 0,029 0,47 0,03 2,10 ENSG00000048392 ribonucleotide reductase M2 B (TP53 inducible) RRM2B 0,005 0,47 0,02 2,25 ENSG00000008869 HEAT repeat containing 5B HEATR5B 0,006 0,47 0,01 2,41 ENSG00000260539 na na 0,018 0,47 0,02 2,14 ENSG00000170293 CKLF-like MARVEL transmembrane domain containingCMTM8 8 0,012 0,46 0,05 2,49 ENSG00000158109 tumor protein p63 regulated 1-like TPRG1L 0,020 0,46 0,04 2,48 ENSG00000168297 PX domain containing serine/threonine kinase PXK 0,010 0,46 0,01 2,08 ENSG00000163946 chromosome 3 open reading frame 63 C3orf63 0,011 0,46 0,02 2,15 ENSG00000112312 geminin, DNA replication inhibitor GMNN 0,016 0,46 0,02 2,24 ENSG00000144567 family with sequence similarity 134, member A FAM134A 0,009 0,46 0,02 2,07 ENSG00000147854 ubiquitin-like with PHD and ring finger domains 2 UHRF2 0,035 0,46 0,03 2,27 ENSG00000257093 protein LCHN AC004918.4 0,027 0,46 0,05 2,19 ENSG00000123609 N-myc (and STAT) interactor NMI 0,009 0,45 0,02 2,11 ENSG00000166938 DIS3 mitotic control homolog (S. cerevisiae)-like DIS3L 0,013 0,45 0,04 2,00 ENSG00000115718 protein C (inactivator of coagulation factors Va and PROCVIIIa) 0,031 0,45 0,03 2,87 ENSG00000164221 coiled-coil domain containing 112 CCDC112 0,018 0,45 0,02 2,39 ENSG00000187147 ring finger protein 220 RNF220 0,016 0,45 0,05 2,27 ENSG00000133574 GTPase, IMAP family member 4 GIMAP4 0,048 0,45 0,04 2,57 ENSG00000135828 ribonuclease L (2',5'-oligoisoadenylate synthetase-dependent)RNASEL 0,013 0,45 0,01 2,20 ENSG00000185862 ecotropic viral integration site 2B EVI2B 0,016 0,45 0,03 2,41 ENSG00000151461 UPF2 regulator of nonsense transcripts homolog (yeast)UPF2 0,012 0,45 0,01 2,18 ENSG00000144635 dynein, cytoplasmic 1, light intermediate chain 1 DYNC1LI1 0,007 0,45 0,02 2,31 ENSG00000112079 serine/threonine kinase 38 STK38 0,005 0,45 0,02 2,28 ENSG00000148835 TAF5 RNA polymerase II, TATA box binding protein (TBP)-associatedTAF5 factor,0,010 100kDa 0,45 0,03 2,63 ENSG00000121067 speckle-type POZ protein SPOP 0,009 0,44 0,01 2,32 ENSG00000114541 FERM domain containing 4B FRMD4B 0,008 0,44 0,03 2,21 ENSG00000171940 zinc finger protein 217 ZNF217 0,018 0,44 0,02 2,43 ENSG00000082074 FYN binding protein FYB 0,015 0,44 0,03 2,15 ENSG00000164331 ankyrin repeat, family A (RFXANK-like), 2 ANKRA2 0,014 0,44 0,03 2,28 ENSG00000163513 transforming growth factor, beta receptor II (70/80kDa)TGFBR2 0,005 0,44 0,01 2,32 ENSG00000165983 phosphotriesterase related PTER 0,007 0,44 0,02 2,38 ENSG00000165025 spleen tyrosine kinase SYK 0,010 0,44 0,02 2,08 ENSG00000143337 torsin A interacting protein 1 TOR1AIP1 0,010 0,44 0,02 2,34 ENSG00000156136 deoxycytidine kinase DCK 0,009 0,44 0,03 2,09 ENSG00000148090 AU RNA binding protein/enoyl-CoA hydratase AUH 0,005 0,43 0,02 2,09 ENSG00000174197 MAX gene associated MGA 0,009 0,43 0,02 2,54 ENSG00000113851 cereblon CRBN 0,005 0,43 0,02 2,13 ENSG00000169926 na na 0,006 0,43 0,03 2,02 ENSG00000157107 FCH domain only 2 FCHO2 0,004 0,43 0,01 2,45 ENSG00000126775 ATG14 autophagy related 14 homolog (S. cerevisiae)ATG14 0,006 0,43 0,02 2,39 ENSG00000068024 histone deacetylase 4 HDAC4 0,030 0,43 0,04 2,14 ENSG00000172086 lysine-rich coiled-coil 1 KRCC1 0,005 0,43 0,01 2,17 ENSG00000117226 guanylate binding protein 3 GBP3 0,007 0,43 0,02 2,46 ENSG00000164414 solute carrier family 35 (CMP-sialic acid transporter),SLC35A1 member A1 0,010 0,42 0,02 2,23 ENSG00000152457 DNA cross-link repair 1C DCLRE1C 0,007 0,42 0,02 2,61 ENSG00000170365 SMAD family member 1 SMAD1 0,007 0,42 0,02 2,01 ENSG00000165516 kelch domain containing 2 KLHDC2 0,014 0,42 0,02 2,50 ENSG00000169019 COMM domain containing 8 COMMD8 0,008 0,42 0,03 2,55 ENSG00000079950 syntaxin 7 STX7 0,008 0,42 0,02 2,10 ENSG00000136044 adaptor protein, phosphotyrosine interaction, PH domainAPPL2 and leucine zipper0,017 containing 0,422 0,02 2,61 ENSG00000165533 tetratricopeptide repeat domain 8 TTC8 0,027 0,42 0,04 2,76 ENSG00000023516 A kinase (PRKA) anchor protein 11 AKAP11 0,009 0,42 0,02 2,71 ENSG00000137414 family with sequence similarity 8, member A1 FAM8A1 0,008 0,42 0,03 2,20 ENSG00000138794 caspase 6, apoptosis-related cysteine peptidase CASP6 0,014 0,42 0,04 2,12 ENSG00000180917 FtsJ methyltransferase domain containing 1 FTSJD1 0,028 0,41 0,03 2,17 ENSG00000112234 F-box and leucine-rich repeat protein 4 FBXL4 0,002 0,41 0,04 2,04 ENSG00000239213 N/A RP11-85F14.5 0,013 0,41 0,03 2,69 ENSG00000169220 regulator of G-protein signaling 14 RGS14 0,011 0,41 0,02 2,15 ENSG00000171681 activating transcription factor 7 interacting protein ATF7IP 0,010 0,41 0,01 2,19 ENSG00000174946 G protein-coupled receptor 171 GPR171 0,032 0,41 0,03 2,70 ENSG00000005175 RNA polymerase II associated protein 3 RPAP3 0,009 0,41 0,01 3,17 ENSG00000110876 selectin P ligand SELPLG 0,008 0,41 0,02 2,18 ENSG00000213689 three prime repair exonuclease 1 TREX1 0,008 0,41 0,01 2,74 ENSG00000132357 caspase recruitment domain family, member 6 CARD6 0,019 0,40 0,03 2,17 ENSG00000162378 zyg-11 homolog B (C. elegans) ZYG11B 0,005 0,40 0,01 2,60 ENSG00000143457 golgi phosphoprotein 3-like GOLPH3L 0,015 0,40 0,02 2,60 ENSG00000215256 Full-length cDNA clone CS0DF029YN24 of Fetal brainAL136419.1 of Homo sapiens (human)0,006 0,40 0,04 2,45 ENSG00000125703 ATG4 autophagy related 4 homolog C (S. cerevisiae)ATG4C 0,018 0,40 0,02 3,00 ENSG00000127720 chromosome 12 open reading frame 26 C12orf26 0,007 0,40 0,02 2,38 ENSG00000145569 family with sequence similarity 105, member A FAM105A 0,007 0,40 0,01 3,17 ENSG00000170385 solute carrier family 30 (zinc transporter), member 1SLC30A1 0,018 0,40 0,02 3,18 ENSG00000180573 histone cluster 1, H2ac HIST1H2AC 0,026 0,40 0,05 2,73 ENSG00000096968 Janus kinase 2 JAK2 0,003 0,40 0,01 2,21 ENSG00000198382 UV radiation resistance associated gene UVRAG 0,006 0,40 0,02 2,81 ENSG00000164649 cell division cycle associated 7-like CDCA7L 0,013 0,40 0,02 2,67 ENSG00000096717 sirtuin 1 SIRT1 0,013 0,39 0,03 3,40 ENSG00000146083 ring finger protein 44 RNF44 0,007 0,39 0,01 3,15 ENSG00000174718 chromosome 12 open reading frame 35 C12orf35 0,018 0,39 0,02 2,94 ENSG00000184992 BRI3 binding protein BRI3BP 0,015 0,39 0,03 2,29 ENSG00000117616 chromosome 1 open reading frame 63 C1orf63 0,012 0,39 0,03 2,32 ENSG00000107719 KIAA1274 KIAA1274 0,047 0,39 0,03 2,89 ENSG00000080546 sestrin 1 SESN1 0,014 0,39 0,01 3,18 ENSG00000174738 nuclear receptor subfamily 1, group D, member 2 NR1D2 0,022 0,39 0,03 2,94 ENSG00000196323 zinc finger and BTB domain containing 44 ZBTB44 0,007 0,39 0,02 2,38 ENSG00000055917 pumilio homolog 2 (Drosophila) PUM2 0,007 0,39 0,02 2,57 ENSG00000145246 ATPase, class V, type 10D ATP10D 0,013 0,38 0,02 3,30 ENSG00000164117 F-box protein 8 FBXO8 0,009 0,38 0,01 2,71 ENSG00000038274 methionine adenosyltransferase II, beta MAT2B 0,005 0,38 0,01 2,76 ENSG00000072121 zinc finger, FYVE domain containing 26 ZFYVE26 0,006 0,38 0,02 2,04 ENSG00000160179 na na 0,003 0,38 0,01 2,87 ENSG00000001084 glutamate-cysteine ligase, catalytic subunit GCLC 0,008 0,38 0,01 3,24 ENSG00000189144 zinc finger protein 573 ZNF573 0,011 0,38 0,05 2,10 ENSG00000266753 na na 0,006 0,38 0,03 2,77 ENSG00000118482 PHD finger protein 3 PHF3 0,005 0,38 0,02 2,49 ENSG00000119950 MAX interactor 1 MXI1 0,003 0,38 0,01 2,67 ENSG00000106780 multiple EGF-like-domains 9 MEGF9 0,007 0,38 0,02 2,98 ENSG00000181481 ring finger protein 135 RNF135 0,015 0,38 0,02 2,84 ENSG00000138433 corepressor interacting with RBPJ, 1 CIR1 0,010 0,38 0,02 2,33 ENSG00000185950 insulin receptor substrate 2 IRS2 0,015 0,38 0,03 3,63 ENSG00000112773 family with sequence similarity 46, member A FAM46A 0,003 0,38 0,01 3,40 ENSG00000261799 na na 0,024 0,38 0,02 3,24 ENSG00000155508 CCR4-NOT transcription complex, subunit 8 CNOT8 0,004 0,38 0,02 2,62 ENSG00000188906 leucine-rich repeat kinase 2 LRRK2 0,033 0,38 0,02 2,84 ENSG00000163154 tumor necrosis factor, alpha-induced protein 8-like 2TNFAIP8L2 0,006 0,37 0,02 2,28 ENSG00000124496 transcriptional regulating factor 1 TRERF1 0,007 0,37 0,01 2,69 ENSG00000080503 SWI/SNF related, matrix associated, actin dependentSMARCA2 regulator of chromatin,0,003 subfamily 0,37a, member 2 0,01 2,60 ENSG00000111231 GPN-loop GTPase 3 GPN3 0,016 0,37 0,02 2,77 ENSG00000178966 RMI1, RecQ mediated genome instability 1, homologRMI1 (S. cerevisiae) 0,004 0,37 0,02 2,68 ENSG00000100354 trinucleotide repeat containing 6B TNRC6B 0,007 0,37 0,02 2,72 ENSG00000021574 spastin SPAST 0,007 0,37 0,03 2,88 ENSG00000158092 NCK adaptor protein 1 NCK1 0,010 0,37 0,03 2,34 ENSG00000205302 sorting nexin 2 SNX2 0,002 0,37 0,02 2,41 ENSG00000144909 oxysterol binding protein-like 11 OSBPL11 0,013 0,37 0,02 2,56 ENSG00000007944 myosin regulatory light chain interacting protein MYLIP 0,015 0,37 0,04 3,75 ENSG00000150593 programmed cell death 4 (neoplastic transformationPDCD4 inhibitor) 0,008 0,36 0,02 3,22 ENSG00000232941 N/A AC090186.1 0,008 0,36 0,03 2,56 ENSG00000187626 zinc finger with KRAB and SCAN domains 4 ZKSCAN4 0,011 0,36 0,05 2,40 ENSG00000145241 centromere protein C 1 CENPC1 0,023 0,36 0,03 2,88 ENSG00000135999 enhancer of polycomb homolog 2 (Drosophila) EPC2 0,008 0,36 0,03 2,26 ENSG00000132405 TBC1 domain family, member 14 TBC1D14 0,030 0,36 0,04 2,52 ENSG00000204103 v-maf musculoaponeurotic fibrosarcoma oncogene MAFBhomolog B (avian) 0,008 0,36 0,02 2,72 ENSG00000168061 SAC3 domain containing 1 SAC3D1 0,009 0,35 0,05 2,02 ENSG00000186188 omega-3 fatty acid receptor 1 O3FAR1 0,007 0,34 0,04 2,47 ENSG00000167716 WD repeat domain 81 WDR81 0,022 0,34 0,03 2,95 ENSG00000117289 thioredoxin interacting protein TXNIP 0,025 0,34 0,03 3,14 ENSG00000197442 mitogen-activated protein kinase kinase kinase 5 MAP3K5 0,006 0,34 0,03 2,04 ENSG00000167528 zinc finger protein 641 ZNF641 0,007 0,33 0,02 2,92 ENSG00000047346 KIAA1370 KIAA1370 0,006 0,33 0,01 3,84 ENSG00000177409 sterile alpha motif domain containing 9-like SAMD9L 0,018 0,33 0,04 2,56 ENSG00000134326 cytidine monophosphate (UMP-CMP) kinase 2, mitochondrialCMPK2 0,023 0,32 0,03 4,08 ENSG00000138463 disrupted in renal carcinoma 2 DIRC2 0,007 0,32 0,02 2,91 ENSG00000205413 sterile alpha motif domain containing 9 SAMD9 0,014 0,32 0,02 3,38 ENSG00000198829 succinate receptor 1 SUCNR1 0,007 0,32 0,02 2,17 ENSG00000027697 interferon gamma receptor 1 IFNGR1 0,013 0,32 0,02 3,17 ENSG00000101916 toll-like receptor 8 TLR8 0,012 0,31 0,02 4,58 ENSG00000198740 zinc finger protein 652 ZNF652 0,006 0,31 0,01 4,55 ENSG00000104205 serum/glucocorticoid regulated kinase family, memberSGK3 3 0,009 0,30 0,03 2,87 ENSG00000075643 molybdenum cofactor sulfurase MOCOS 0,006 0,30 0,05 2,38 ENSG00000182511 feline sarcoma oncogene FES 0,003 0,29 0,03 2,83 ENSG00000117643 mannosidase, alpha, class 1C, member 1 MAN1C1 0,003 0,29 0,02 2,37 ENSG00000196227 chromosome 20 open reading frame 177 C20orf177 0,008 0,29 0,05 3,82 ENSG00000175155 yippee-like 2 (Drosophila) YPEL2 0,007 0,29 0,03 3,62 ENSG00000136161 regulator of chromosome condensation (RCC1) and RCBTB2BTB (POZ) domain containing0,008 protein0,29 2 0,03 2,89 ENSG00000130816 DNA (cytosine-5-)-methyltransferase 1 DNMT1 0,005 0,29 0,05 2,38 ENSG00000138172 calcium homeostasis modulator 2 CALHM2 0,009 0,28 0,03 3,04 ENSG00000178199 zinc finger CCCH-type containing 12D ZC3H12D 0,004 0,28 0,04 3,54 ENSG00000095015 mitogen-activated protein kinase kinase kinase 1 MAP3K1 0,003 0,28 0,05 2,70 ENSG00000071073 mannosyl (alpha-1,3-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferase,MGAT4A 0,004 isozyme A0,28 0,03 2,84 ENSG00000189227 chromosome 15 open reading frame 61 C15orf61 0,017 0,27 0,03 3,06 ENSG00000129518 E2F-associated phosphoprotein EAPP 0,006 0,27 0,01 3,60 ENSG00000178977 non-protein coding RNA 324 NCRNA00324 0,011 0,26 0,05 3,14 ENSG00000148158 sorting nexin family member 30 SNX30 0,013 0,26 0,01 3,25 ENSG00000163563 myeloid cell nuclear differentiation antigen MNDA 0,017 0,25 0,02 4,35 ENSG00000164104 high mobility group box 2 HMGB2 0,003 0,25 0,03 3,43 ENSG00000114796 kelch-like 24 (Drosophila) KLHL24 0,007 0,24 0,01 4,84 ENSG00000077063 cortactin binding protein 2 CTTNBP2 0,011 0,23 0,03 4,79 ENSG00000101236 ring finger protein 24 RNF24 0,006 0,23 0,02 2,99 ENSG00000132646 proliferating cell nuclear antigen PCNA 0,023 0,22 0,01 4,14 ENSG00000152804 hematopoietically expressed homeobox HHEX 0,010 0,22 0,03 4,82 ENSG00000095585 B-cell linker BLNK 0,023 0,22 0,02 4,85 ENSG00000171631 pyrimidinergic receptor P2Y, G-protein coupled, 6 P2RY6 0,008 0,21 0,02 2,70 ENSG00000145416 membrane-associated ring finger (C3HC4) 1 MARCH1 0,011 0,21 0,03 4,85 ENSG00000110852 C-type lectin domain family 2, member B CLEC2B 0,003 0,20 0,01 5,06 ENSG00000164463 chromosome 5 open reading frame 41 C5orf41 0,005 0,20 0,01 5,55 ENSG00000118308 lymphoid-restricted membrane protein LRMP 0,014 0,20 0,04 3,67 ENSG00000121933 adenosine A3 receptor ADORA3 0,010 0,20 0,02 5,58 ENSG00000129534 MIS18 binding protein 1 MIS18BP1 0,010 0,19 0,02 5,50 ENSG00000163565 interferon, gamma-inducible protein 16 IFI16 0,007 0,18 0,03 3,60 ENSG00000136826 Kruppel-like factor 4 (gut) KLF4 0,004 0,17 0,03 3,16 ENSG00000170448 nuclear transcription factor, X-box binding-like 1 NFXL1 0,013 0,15 0,02 8,36 ENSG00000174944 purinergic receptor P2Y, G-protein coupled, 14 P2RY14 0,003 0,15 0,03 7,02 ENSG00000106560 GTPase, IMAP family member 2 GIMAP2 0,007 0,14 0,02 7,41 ENSG00000139679 lysophosphatidic acid receptor 6 LPAR6 0,014 0,14 0,04 5,83 ENSG00000180340 frizzled homolog 2 (Drosophila) FZD2 0,009 0,11 0,02 7,85 ENSG00000169087 HSPB (heat shock 27kDa) associated protein 1 HSPBAP1 0,012 0,10 0,02 10,53 ENSG00000150681 regulator of G-protein signaling 18 RGS18 0,007 0,10 0,02 10,45