CBA
HoliRD REPORT:
Retinitis Pigmentosa
Marina Esteban Medina
María Peña-Chilet
Carlos Loucera
Joaquín Dopazo
Clinical Bioinformatics Area - FPS
Sevilla, January 13, 2020
Collaborators:
Dra.Carmen Ayuso ’s group - U704 CIBERER
Research group at Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid .
Dra.Regina Rodrigo ’s group - U755 CIBERER
Research group at IIS La Fe - Instituto de Investigación Sanitaria La Fe, Valencia.
Dra.Gemma Marfany ’s group - U718 CIBERER
Research group at Instituto de Biomedicina de la Universidad de Barcelona (IBUB), Barcelona. CBA
Objectives and methodology:
The Holistic Rare Disease project (HoliRD) aims to build Diseases Maps for as many Rare Diseases as possible and to model them to systematize research in drug repurposing. In order to achieve this purpose several databases such as ORPHANET, OMIM, HPO, PubMed, KEGG, STRING, as well as the literature is used to collect all the up-to-date knowledge of the diseases under study and defining a Disease Map that contains the functional relationships among the known disease genes, as well as the functional consequences of their activity. Then, a mechanistic model that accounts for the activity of such map is used. The HiPathia algorithm, which has successfully proven to predict cell activities related to cancer hallmarks (Hidalgo et al., Oncotarget 2017; 8:5160-5178; Hidalgo et al., Biol Direct. 2018;13:16) as well as the effect of protein inhibitions on cell survival (Cubuk et al., Cancer Res. 2018; 78:6059-6072) is used to simulate the activity of the disease map.
Finally, machine learning algorithms are used to find other proteins, already target of drugs with another indication, which display a potential causal effect on the activity of the previously defined disease map. The drugs that target these proteins are potential candidates for repurposing.
Schematic representation of the method used.
Examples of the use of this approach can be found in Esteban-Medina et al., BMC Bioinformatics. 2019, 20(1):370. CBA
Report
This report describes the results of the different steps of the HoliRD approach applied to Retinitis Pigmentosa.
Identification of genes highly related to the rare disease (RD) under study in Orphanet/OMIM.
A total of 94 genes annotated as Retinitis Pigmentosa (RP) were found in the OMIM/ORPHANET database.
RP highly related genes
Disease ID Entrez ID Gene symbol Disease ID Entrez ID Gene Symbol
OMIM:615565 4751 NEK2 OMIM:613862 10461 MERTK
OMIM:613341 9227 LRAT OMIM:617763 23404 EXOSC2
OMIM:615233 5949 RBP3 OMIM:615922 9128 PRPF4
OMIM:613731 6010 RHO OMIM:312600 6102 RP2
OMIM:613767 1258 CNGB1 OMIM:613581 50939 IMPG2
OMIM:617781 9742 IFT140 OMIM:609033 28982 FLVCR1
OMIM:613809 7399 USH2A OMIM:613582 5148 PDE6G
OMIM:617023 60509 AGBL5 OMIM:300029 6103 RPGR
OMIM:613794 6121 RPE65 OMIM:613464 123016 TTC8
OMIM:616544 138050 HGSNAT OMIM:604232 55812 SPATA7
OMIM:180100 6101 RP1 OMIM:180105 3614 IMPDH1
OMIM:615725 57709 SLC7A14 OMIM:600132 7287 TULP1
OMIM:613801 5158 PDE6B OMIM:609923 10210 TOPORS
OMIM:612674 26090 ABHD12 OMIM:613758 6295 SAG
OMIM:617871 112752 IFT43 OMIM:250410 10283 CWC27 CBA
OMIM:608380 375298 CERKL OMIM:268000 23746 AIPL1
OMIM:600059 10594 PRPF8 OMIM:268000 1259 CNGA1
OMIM:276900 10083 USH1C OMIM:268000 157657 C8ORF37
OMIM:276900 4647 MYO7A OMIM:268000 1406 CRX
OMIM:180104 6100 RP9 OMIM:268000 6094 ROM1
OMIM:617460 3098 HK1 OMIM:613810 5145 PDE6A
OMIM:614180 7401 CLRN1 OMIM:613660 92211 CDHR1
OMIM:617304 92840 REEP6 OMIM:612572 3420 IDH3B
OMIM:617433 23370 ARHGEF18 OMIM:606068 84140 FAM161A
OMIM:300424 8481 OFD1 OMIM:608133 5961 PRPH2
OMIM:602772 346007 EYS OMIM:613617 130557 ZNF513
OMIM:614181 4117 MAK OMIM:607921 25794 FSCN2
OMIM:618345 196 AHR OMIM:607236 80025 PANK2
OMIM:600105 23418 CRB1 OMIM:616959 51095 TRNT1
OMIM:610282 64218 SEMA4A OMIM:610599 768206 PRCD
OMIM:618220 9785 DHX38 OMIM:613428 388939 PCARE
OMIM:616469 79797 ZNF408 ORPHA:791 6017 RLBP1
OMIM:613861 79947 DHDDS ORPHA:791 8842 PROM1
OMIM:618195 49855 SCAPER ORPHA:791 7439 BEST1
OMIM:601718 24 ABCA4 ORPHA:791 54806 AHI1
ORPHA:436274 2677 GGCX ORPHA:791 8100 IFT88
OMIM:600138 26121 PRPF31 ORPHA:791 4901 NRL
OMIM:613575 84100 ARL6 ORPHA:791 55975 KLHL7
OMIM:615780 55857 KIZ ORPHA:791 9129 PRPF3
OMIM:613983 24148 PRPF6 ORPHA:791 57670 KIAA1549
OMIM:613827 2979 GUCA1B ORPHA:791 583 BBS2 CBA
OMIM:611131 10002 NR2E3 ORPHA:791 145226 RDH12
OMIM:615434 23568 ARL2BP ORPHA:791 3419 IDH3A
OMIM:610359 23020 SNRNP200 ORPHA:791 7275 TUB
OMIM:617123 55624 POMGNT1 ORPHA:791 762 CA4
OMIM:613769 5995 RGR OMIM:551500 4508 ATP6
OMIM:616394 26160 IFT172 OMIM:613862 10461 MERTK
OMIM:618173 403 ARL3 OMIM:617763 23404 EXOSC2
Identification of highly related HPO to the RD under study:
A total of 22 HPO codes associated to RP with specificity >=7 were selected.
RP highly related HPOs
HPO ID HPO term Specificity level
HP:0000035 Abnormal testis morphology 9
HP:0000135 Hypogonadism 8
HP:0000405 Conductive hearing impairment 10
Sensorineural hearing HP:0000407 10 impairment
HP:0000431 Wide nasal bridge 8
HP:0000463 Anteverted nares 11
HP:0000518 Cataract 7
HP:0000563 Keratoconus 11
HP:0000602 Ophthalmoplegia 7
HP:0000613 Photophobia 9
HP:0000618 Blindness 8 CBA
HP:0000639 Nystagmus 7
HP:0000648 Optic atrophy 9
HP:0000842 Hyperinsulinemia 10
HP:0000987 Atypical scarring of skin 9
HP:0001249 Intellectual disability 7
HP:0001347 Hyperreflexia 7
HP:0005978 Type II diabetes mellitus 9
HP:0007675 Progressive night blindness 7
Abnormality of retinal HP:0007703 8 pigmentation
Abnormal retinal vascular HP:0008046 11 morphology
HP:0008736 Hypoplasia of penis 12
Identification of genes that shared at least HPO-RD codes
Genes with >= 8 RP-HPO codes
Gene Symbol Entrez Gene Symbol Entrez Gene Symbol Entrez Gene Symbol Entrez
ABCA4 24 TRNS1 4574 KDM6A 7403 SUFU 51684
ACTB 60 TRNW 4578 BEST1 7439 NDUFB11 54539
AHR 196 NDP 4693 CLIP2 7461 AHI1 54806
ARL3 403 NDUFS1 4719 WFS1 7466 MKS1 54903
RERE 473 NDUFS2 4720 XRCC4 7518 FANCL 55120
ATP6V1A 523 NDUFS3 4722 RNF113A 7737 SETD5 55209
ATRX 546 NDUFV1 4723 ALMS1 7840 SLC29A3 55315
BBS2 583 NDUFS4 4724 IFT88 8100 FOXRED1 55572 CBA
BCS1L 617 NDUFS8 4728 SMC1A 8243 POMGNT1 55624
BMP4 652 NDUFV2 4729 OFD1 8481 CHD7 55636
BRAF 673 NEK2 4751 PEX3 8504 PEX26 55670
CA4 762 NPHP1 4867 KCNAB2 8514 SPATA7 55812
CDH11 1009 NRAS 4893 CASK 8573 KIZ 55857
ERCC8 1161 NRL 4901 TP63 8626 HDAC8 55869
CNGB1 1258 OPA1 4976 PEX11B 8799 KLHL7 55975
CNGA1 1259 PDE6A 5145 PROM1 8842 RPGRIP1 57096
CRX 1406 PDE6G 5148 BAZ1B 9031 TBC1D24 57465
DHCR7 1717 PDE6B 5158 SMC3 9126 CC2D2A 57545
ELN 2006 PDHA1 5160 PRPF4 9128 KIAA1549 57670
ERCC1 2067 PEX1 5189 PRPF3 9129 SLC7A14 57709
ERCC2 2068 PEX6 5190 LARGE1 9215 AGBL5 60509
ERCC3 2071 PEX10 5192 LRAT 9227 PIEZO2 63895
ERCC4 2072 PEX12 5193 PEX16 9409 PRDM16 63976
ERCC5 2073 PEX13 5194 GTF2IRD1 9569 SEMA4A 64218
ERCC6 2074 PEX14 5195 SEMA3E 9723 NMNAT1 64802
FBN1 2200 POLG 5428 IFT140 9742 NDUFAF5 79133
FGFR1 2260 PEX19 5824 DHX38 9785 FKRP 79147
FLNB 2317 PEX2 5828 NR2E3 10002 TMEM231 79583
GABRD 2563 PEX5 5830 TOPORS 10210 ZNF408 79797
GJA1 2697 RAD21 5885 MERTK 10461 DHDDS 79947
GJB2 2706 RBP3 5949 POMT1 10585 CEP290 80184
GNAS 2778 PRPH2 5961 PRPF8 10594 ARL6 84100
GP1BB 2812 RFC2 5982 PNPLA6 10908 FAM161A 84140
GTF2I 2969 RGR 5995 POLR3A 11128 POMK 84197 CBA
GUCA1B 2979 RHO 6010 RAB3GAP1 22930 TMEM67 91147
GUCY2D 3000 RLBP1 6017 RAB18 22931 NDUFAF2 91942
IDH3B 3420 ROM1 6094 SNRNP200 23020 CDHR1 92211
IMPDH1 3614 RP9 6100 ARHGEF18 23370 REEP6 92840
KIF11 3832 RP1 6101 CRB1 23418 TTC8 123016
KRAS 3845 RP2 6102 ARL2BP 23568 TBC1D20 128637
LIMK1 3984 RPGR 6103 AIPL1 23746 ZNF513 130557
LMNA 4000 RPE65 6121 PRPF6 24148 MPLKIP 136647
LRP5 4041 SAG 6295 RAB3GAP2 25782 HGSNAT 138050
MAK 4117 SDHA 6389 FSCN2 25794 RDH12 145226
KMT2A 4297 SDHB 6390 NIPBL 25836 C8orf37 157657
ATP6 4508 SDHD 6392 PRPF31 26121 ARX 170302
COX1 4512 SKI 6497 IFT172 26160 EYS 346007
COX3 4514 SMARCB1 6598 TBL2 26608 NDUFS7 374291
ND1 4535 SOX10 6663 GMPPB 29925 KIF7 374654
ND4 4538 TFAP2A 7020 POMT2 29954 CERKL 375298
ND5 4540 TUB 7275 SCAPER 49855 PCARE 388939
ND6 4541 TULP1 7287 IMPG2 50939 GDF6 392255
TRNK 4566 USH2A 7399 WDPCP 51057 PRCD 768206
TRNL1 4567 CLRN1 7401 TMEM216 51259 CBA
Genes with >= 10 RP-HPO codes
Gene Symbol Entrez Gene Symbol Entrez Gene Symbol Entrez
ABCA4 24 RGR 5995 RAB18 22931
AHR 196 RHO 6010 SNRNP200 23020
ARL3 403 RLBP1 6017 ARHGEF18 23370
RERE 473 ROM1 6094 CRB1 23418
ATRX 546 RP9 6100 ARL2BP 23568
BBS2 583 RP1 6101 PRPF6 24148
CA4 762 RP2 6102 FSCN2 25794
ERCC8 1161 RPGR 6103 PRPF31 26121
CNGB1 1258 RPE65 6121 IFT172 26160
CNGA1 1259 SAG 6295 TBL2 26608
CRX 1406 SDHA 6389 GMPPB 29925
ELN 2006 SDHD 6392 SCAPER 49855
ERCC2 2068 SKI 6497 IMPG2 50939
ERCC3 2071 TUB 7275 SUFU 51684
ERCC5 2073 TULP1 7287 AHI1 54806
ERCC6 2074 USH2A 7399 POMGNT1 55624
FBN1 2200 CLRN1 7401 SPATA7 55812
GABRD 2563 BEST1 7439 KIZ 55857
GJA1 2697 CLIP2 7461 KLHL7 55975
GTF2I 2969 WFS1 7466 KIAA1549 57670
GUCA1B 2979 XRCC4 7518 SLC7A14 57709
IDH3B 3420 ALMS1 7840 AGBL5 60509
IMPDH1 3614 IFT88 8100 PRDM16 63976
KRAS 3845 OFD1 8481 SEMA4A 64218 CBA
LIMK1 3984 KCNAB2 8514 ZNF408 79797
MAK 4117 PEX11B 8799 DHDDS 79947
ND1 4535 PROM1 8842 CEP290 80184
NEK2 4751 BAZ1B 9031 ARL6 84100
NRL 4901 PRPF4 9128 FAM161A 84140
PDE6A 5145 PRPF3 9129 CDHR1 92211
PDE6G 5148 LRAT 9227 REEP6 92840
PDE6B 5158 GTF2IRD1 9569 TTC8 123016
PEX1 5189 IFT140 9742 ZNF513 130557
PEX6 5190 DHX38 9785 HGSNAT 138050
PEX10 5192 NR2E3 10002 RDH12 145226
PEX12 5193 TOPORS 10210 C8orf37 157657
PEX2 5828 MERTK 10461 EYS 346007
PEX5 5830 PRPF8 10594 CERKL 375298
RBP3 5949 PNPLA6 10908 PCARE 388939
PRPH2 5961 POLR3A 11128 PRCD 768206
RFC2 5982 RAB3GAP1 22930
Genes with >= 22 (all) RP-HPO codes
Gene Symbol Entrez Gene Symbol Entrez Gene Symbol Entrez Gene Symbol Entrez
ABCA4 24 RHO 6010 IFT140 9742 KLHL7 55975
AHR 196 RLBP1 6017 DHX38 9785 KIAA1549 57670
ARL3 403 ROM1 6094 NR2E3 10002 SLC7A14 57709
BBS2 583 RP9 6100 TOPORS 10210 AGBL5 60509
CA4 762 RP1 6101 MERTK 10461 SEMA4A 64218
CNGB1 1258 RP2 6102 PRPF8 10594 ZNF408 79797 CBA
CNGA1 1259 RPGR 6103 SNRNP200 23020 DHDDS 79947
CRX 1406 RPE65 6121 ARHGEF18 23370 ARL6 84100
GUCA1B 2979 SAG 6295 CRB1 23418 FAM161A 84140
IDH3B 3420 TUB 7275 ARL2BP 23568 CDHR1 92211
IMPDH1 3614 TULP1 7287 PRPF6 24148 REEP6 92840
MAK 4117 USH2A 7399 FSCN2 25794 TTC8 123016
NEK2 4751 CLRN1 7401 PRPF31 26121 ZNF513 130557
NRL 4901 BEST1 7439 IFT172 26160 HGSNAT 138050
PDE6A 5145 IFT88 8100 SCAPER 49855 RDH12 145226
PDE6G 5148 OFD1 8481 IMPG2 50939 C8orf37 157657
PDE6B 5158 PROM1 8842 AHI1 54806 EYS 346007
RBP3 5949 PRPF4 9128 POMGNT1 55624 CERKL 375298
PRPH2 5961 PRPF3 9129 SPATA7 55812 PCARE 388939
RGR 5995 LRAT 9227 KIZ 55857 PRCD 768206
In order to maintain the specificity and not over expand the Disease Map of action only genes with >=10 RP-HPO codes were selected.
**Take into account that not all genes can be found in HiPathia pathways, even though it seems like genes sharing 22 (all) RP-HPO codes are enough to expand the RD Map, only 3 of those genes could be found in HiPathia pathways. We have selected those genes that expand the affected HiPathia circuits enough within a certain threshold for the model. ** CBA
Location of the selected disease related genes in KEGG pathways to define the Disease Map of action.
After locating the RD associated genes within KEGG pathways, a total of 226 circuits belonging to 40 KEGG pathways were found as part of the disease map.
KEGG-pathway KEGG-pathway KEGG pathway KEGG pathway code code
Signaling pathways regulating MAPK signaling pathway hsa04010 hsa04550 pluripotency of stem cells
Natural killer cell mediated ErbB signaling pathway hsa04012 hsa04650 cytotoxicity
T cell receptor signaling Ras signaling pathway hsa04014 hsa04660 pathway
B cell receptor signaling Rap1 signaling pathway hsa04015 hsa04662 pathway
cGMP-PKG signaling Fc epsilon RI signaling hsa04022 hsa04664 pathway pathway
Fc gamma R-mediated cAMP signaling pathway hsa04024 hsa04666 phagocytosis
Chemokine signaling Neurotrophin signaling hsa04062 hsa04722 pathway pathway
HIF-1 signaling pathway hsa04066 Cholinergic synapse hsa04725
FoxO signaling pathway hsa04068 Serotonergic synapse hsa04726
Sphingolipid signaling hsa04071 GABAergic synapse hsa04727 pathway
Phospholipase D Regulation of actin hsa04072 hsa04810 signaling pathway cytoskeleton
mTOR signaling pathway hsa04150 Insulin signaling pathway hsa04910
PI3K-Akt signaling hsa04151 GnRH signaling pathway hsa04912 pathway
Progesterone-mediated Apoptosis hsa04210 hsa04914 oocyte maturation CBA
Longevity regulating hsa04211 Estrogen signaling pathway hsa04915 pathway - mammal
Hedgehog signaling hsa04340 Melanogenesis hsa04916 pathway
Axon guidance hsa04360 Prolactin signaling pathway hsa04917
Thyroid hormone signaling VEGF signaling pathway hsa04370 hsa04919 pathway
Tight junction hsa04530 Oxytocin signaling pathway hsa04921
Aldosterone-regulated Gap junction hsa04540 hsa04960 sodium reabsorption
HiPathia is a signal propagation algorithm that considers pathways as collections of circuits defined as sub-pathways or sequences of proteins connecting signal receptor proteins to effector proteins. HiPathia uses expression values genes as proxies of the level of activation of the corresponding protein in the circuit. Taking into account the inferred protein activity and the interactions between the proteins (activation or inhibition) defined in the pathway, the level of activity of a circuit is estimated using a signal propagation algorithm. Ultimately, effector proteins are annotated with a cellular function.
In order to enable a better visualization of the RD Map the HiPathia viewer has been used. The circuits that define the RD Map are marked in RED (please ignore the color legend). The pathways that contain these circuits are highlighted in the right window with a red arrow. The only purpose of this report is to represent the components (genes and interaction) and functions of the circuits that compose the RD Map.
Click to access the RD Map Report
HiPathia uses KEGG pathway for the graphical representation of the circuits. The original pathways can also be visualized in the KEGG repository
https://www.genome.jp/kegg/pathway.html
Select prefix: hsa (Organism) Enter keywords: e.g. FoxOsignalingpathway (any HiPathia pathway) CBA
Prediction of relevance of gene targets from approved drugs extracted from DRUGBANK database (release 5.1.4)
The HoliRD approach takes the mechanistic model of the disease map as the proxy for the molecular basis of the disease outcome. Then, a Multi-Output Random Forest (MORF) regressor, a machine learning algorithm that predicts the circuit activities across the whole disease map, is trained on GTEx gene expression data to find proteins (which are targets for drugs with indications for other diseases) that correctly predict the behavior of the disease map. The drugs targeting the best predictor proteins are candidate for drug repurposing. The relevance score accounts for the accuracy of the prediction contributed by each individual protein. Relevance are absolute values and do not account for the direction of the prediction, that is, if the interaction is an activation or an inhibition.
From a total of 683 targets for approved drugs in the DRUGBANK database (release 5.1.4) the machine learning algorithm selected the 69 most relevant ones.
Entrez Gene symbol Relevance score Entrez Gene symbol Relevance score
41 ASIC1 0.0502591907 2261 FGFR3 0.0039322169
5159 PDGFRB 0.0296326131 4988 OPRM1 0.0038783469
3746 KCNC1 0.0255998206 2335 FN1 0.003839329
11255 HRH3 0.0255148651 6093 ROCK1 0.0034962522
6616 SNAP25 0.0254040526 1441 CSF3R 0.0032551445
2554 GABRA1 0.0251678509 775 CACNA1C 0.0030846682
2742 GLRA2 0.0228657846 6785 ELOVL4 0.0029546928
2563 GABRD 0.0227706901 7068 THRB 0.0029518009
2690 GHR 0.0191701293 3932 LCK 0.0028615588
695 BTK 0.0187155993 338442 HCAR2 0.0028394562
2564 GABRE 0.0182653818 240 ALOX5 0.0027861036
6850 SYK 0.0177121467 2185 PTK2B 0.0027507044
3554 IL1R1 0.0176343903 3945 LDHB 0.0025626085
5327 PLAT 0.0174339453 2247 FGF2 0.0024616473
7097 TLR2 0.0140290294 5894 RAF1 0.0023827902
51175 TUBE1 0.0128894296 10268 RAMP3 0.0023187153 CBA
4214 MAP3K1 0.0100046419 1141 CHRNB2 0.0022857683
6323 SCN1A 0.009438047 786 CACNG1 0.0022558341
5916 RARG 0.008913528 2512 FTL 0.0022552933
1956 EGFR 0.0077361305 6337 SCNN1A 0.0022297033
6718 AKR1D1 0.0067171074 55800 SCN3B 0.0022038451
2593 GAMT 0.0061007533 2568 GABRP 0.0021825875
6324 SCN1B 0.005847443 3614 IMPDH1 0.0021408884
6261 RYR1 0.005710848 116447 TOP1MT 0.0020938788
9475 ROCK2 0.0056217445 3561 IL2RG 0.0020741642
1158 CKM 0.0055433278 6715 SRD5A1 0.0019470211
774 CACNA1B 0.0051321754 3695 ITGB7 0.0018052442
57053 CHRNA10 0.0050653785 6529 SLC6A1 0.0017996186
4921 DDR2 0.0048701953 3718 JAK3 0.0017521897
2161 F12 0.0048430195 291 SLC25A4 0.0017109017
761 CA3 0.0048038891 87 ACTN1 0.0017001003
645 BLVRB 0.0046617892 55 ACPP 0.0016261955
4134 MAP4 0.0046535284 4306 NR3C2 0.0015618201
3683 ITGAL 0.0043098378 301 ANXA1 0.0015237013
64127 NOD2 0.0043031915 CBA
Relevance plot depicting the 69 most relevant gene targets.
Drugs from DRUGBANK db (release 5.1.4) that target top AT.
And the list of drugs that target the 69 most relevant genes follows:
You can click on the hyperlink of the Drug ID to see more detailed information about the drug in DrugBank DB.
Associated Relevance Drug ID Drug Name Drug Effect Target condition score
Actinic Keratosis DB00586 Diclofenac inhibitor ASIC1 0,05026 (AK)
DB00102 Becaplermin PDGFRB 0,02963
Advanced Renal Cell DB00398 Sorafenib antagonist PDGFRB 0,02963 Carcinoma
Advanced Renal Cell DB01268 Sunitinib inhibitor PDGFRB 0,02963 Carcinoma
Advanced Renal Cell DB06589 Pazopanib inhibitor PDGFRB 0,02963 Carcinoma
Leukemia Acute antagonist,inh DB06595 Midostaurin PDGFRB Myeloid Leukemia 0,02963 ibitor (AML) CBA
Metastatic DB08896 Regorafenib inhibitor PDGFRB Gastrointestinal 0,02963 Stromal Tumor
DB06637 Dalfampridine antagonist KCNC1 0,0256
DB05381 Histamine agonist HRH3 0,02551
DB06698 Betahistine antagonist HRH3 0,02551
antagonist,inv Excessive Daytime DB11642 Pitolisant HRH3 0,02551 erse agonist Sleepiness
Botulinum toxin DB00083 inhibitor SNAP25 Blepharospasm 0,0254 type A
positive DB00186 Lorazepam allosteric GABRA1 Agitation 0,02517 modulator
positive DB00228 Enflurane allosteric GABRA1 0,02517 modulator
DB00231 Temazepam potentiator GABRA1 0,02517
positive DB00231 Temazepam allosteric GABRA1 0,02517 modulator
positive DB00237 Butabarbital allosteric GABRA1 0,02517 modulator
Headache, DB00241 Butalbital potentiator GABRA1 0,02517 Tension-Type
positive Headache, DB00241 Butalbital allosteric GABRA1 0,02517 Tension-Type modulator
DB00273 Topiramate agonist GABRA1 Alcohol Dependence 0,02517
positive DB00273 Topiramate allosteric GABRA1 Alcohol Dependence 0,02517 modulator
DB00292 Etomidate agonist GABRA1 0,02517 CBA
positive DB00292 Etomidate allosteric GABRA1 0,02517 modulator
DB00306 Talbutal potentiator GABRA1 0,02517
positive DB00306 Talbutal allosteric GABRA1 0,02517 modulator
DB00312 Pentobarbital potentiator GABRA1 Insomnia 0,02517
positive DB00312 Pentobarbital allosteric GABRA1 Insomnia 0,02517 modulator
positive DB00349 Clobazam allosteric GABRA1 0,02517 modulator
DB00371 Meprobamate agonist GABRA1 0,02517
positive DB00371 Meprobamate allosteric GABRA1 0,02517 modulator
DB00402 Eszopiclone potentiator GABRA1 0,02517
positive DB00402 Eszopiclone allosteric GABRA1 0,02517 modulator
positive DB00404 Alprazolam allosteric GABRA1 Anxiety 0,02517 modulator
DB00418 Secobarbital potentiator GABRA1 0,02517
DB00425 Zolpidem agonist GABRA1 0,02517
DB00474 Methohexital antagonist GABRA1 0,02517
positive Alcohol Withdrawal DB00475 Chlordiazepoxide allosteric GABRA1 0,02517 Syndrome(AWS) modulator
DB00599 Thiopental potentiator GABRA1 0,02517
DB00628 Clorazepic acid positive GABRA1 Acute Alcohol 0,02517 CBA
allosteric Withdrawal modulator
positive DB00659 Acamprosate GABRA1 0,02517 modulator
DB00683 Midazolam potentiator GABRA1 Seizures, Epileptic 0,02517
DB00690 Flurazepam potentiator GABRA1 0,02517
DB00753 Isoflurane agonist GABRA1 0,02517
positive DB00753 Isoflurane allosteric GABRA1 0,02517 modulator
Grand mal DB00794 Primidone potentiator GABRA1 Generalized 0,02517 tonic-clonic seizure
positive Grand mal DB00794 Primidone allosteric GABRA1 Generalized 0,02517 modulator tonic-clonic seizure
positive DB00818 Propofol allosteric GABRA1 0,02517 modulator
Alcohol Withdrawal DB00829 Diazepam potentiator GABRA1 0,02517 Syndrome(AWS)
positive Alcohol Withdrawal DB00829 Diazepam allosteric GABRA1 0,02517 Syndrome(AWS) modulator
Alcohol Withdrawal DB00842 Oxazepam potentiator GABRA1 0,02517 Syndrome(AWS)
positive Alcohol Withdrawal DB00842 Oxazepam allosteric GABRA1 0,02517 Syndrome(AWS) modulator
Methylphenobar DB00849 potentiator GABRA1 0,02517 bital
DB00897 Triazolam potentiator GABRA1 0,02517
DB00897 Triazolam positive GABRA1 0,02517 allosteric CBA
modulator
DB00898 Ethanol agonist GABRA1 Bacterial Infections 0,02517
DB00962 Zaleplon potentiator GABRA1 0,02517
DB01028 Methoxyflurane agonist GABRA1 Severe Pain 0,02517
positive DB01028 Methoxyflurane allosteric GABRA1 Severe Pain 0,02517 modulator
positive DB01068 Clonazepam allosteric GABRA1 Akinetic seizures 0,02517 modulator
DB01154 Thiamylal agonist GABRA1 0,02517
positive DB01159 Halothane allosteric GABRA1 0,02517 modulator
Alcohol Withdrawal DB01174 Phenobarbital potentiator GABRA1 0,02517 Syndrome(AWS)
positive DB01189 Desflurane allosteric GABRA1 0,02517 modulator
DB01198 Zopiclone potentiator GABRA1 0,02517
DB01205 Flumazenil antagonist GABRA1 Anesthesia reversal 0,02517
positive DB01205 Flumazenil allosteric GABRA1 Anesthesia reversal 0,02517 modulator
DB01215 Estazolam potentiator GABRA1 0,02517
positive DB01215 Estazolam allosteric GABRA1 0,02517 modulator
DB01236 Sevoflurane agonist GABRA1 0,02517
positive DB01236 Sevoflurane allosteric GABRA1 0,02517 modulator CBA
Quinidine DB01346 potentiator GABRA1 0,02517 barbiturate
DB01351 Amobarbital potentiator GABRA1 0,02517
DB01353 Butobarbital potentiator GABRA1 0,02517
DB01437 Glutethimide agonist GABRA1 0,02517
positive DB01437 Glutethimide allosteric GABRA1 0,02517 modulator
DB01558 Bromazepam potentiator GABRA1 Acute Anxiety 0,02517
DB01559 Clotiazepam potentiator GABRA1 0,02517
DB01587 Ketazolam potentiator GABRA1 0,02517
DB01588 Prazepam potentiator GABRA1 0,02517
positive DB01588 Prazepam allosteric GABRA1 0,02517 modulator
DB01589 Quazepam potentiator GABRA1 0,02517
positive DB01589 Quazepam allosteric GABRA1 0,02517 modulator
DB01595 Nitrazepam potentiator GABRA1 Insomnia 0,02517
DB01956 Taurine agonist GABRA1 0,02517
agonist,positi DB09118 Stiripentol ve allosteric GABRA1 0,02517 modulator
positive DB11859 Brexanolone allosteric GABRA1 0,02517 modulator
positive DB13872 Lormetazepam allosteric GABRA1 0,02517 modulator
DB00898 Ethanol agonist GLRA2 Bacterial Infections 0,02287 CBA
DB01956 Taurine agonist GLRA2 0,02287
DB00231 Temazepam potentiator GABRD 0,02277
DB00690 Flurazepam potentiator GABRD 0,02277
Alcohol Withdrawal DB00829 Diazepam potentiator GABRD 0,02277 Syndrome(AWS)
Alcohol Withdrawal DB00842 Oxazepam potentiator GABRD 0,02277 Syndrome(AWS)
DB00897 Triazolam potentiator GABRD 0,02277
DB01215 Estazolam potentiator GABRD 0,02277
DB01558 Bromazepam potentiator GABRD Acute Anxiety 0,02277
DB01559 Clotiazepam potentiator GABRD 0,02277
DB01587 Ketazolam potentiator GABRD 0,02277
DB01588 Prazepam potentiator GABRD 0,02277
DB01589 Quazepam potentiator GABRD 0,02277
DB01595 Nitrazepam potentiator GABRD Insomnia 0,02277
Adult Onset Growth DB00052 Somatotropin binder GHR 0,01917 Hormone Deficiency
DB00082 Pegvisomant antagonist GHR 0,01917
Chronic Lymphocytic DB09053 Ibrutinib inhibitor BTK 0,01872 Leukaemia (CLL)
DB11703 Acalabrutinib inhibitor BTK 0,01872
DB00231 Temazepam potentiator GABRE 0,01827
DB00690 Flurazepam potentiator GABRE 0,01827
Alcohol Withdrawal DB00829 Diazepam potentiator GABRE 0,01827 Syndrome(AWS)
Alcohol Withdrawal DB00842 Oxazepam potentiator GABRE 0,01827 Syndrome(AWS)
DB00897 Triazolam potentiator GABRE 0,01827 CBA
DB01215 Estazolam potentiator GABRE 0,01827
DB01558 Bromazepam potentiator GABRE Acute Anxiety 0,01827
DB01559 Clotiazepam potentiator GABRE 0,01827
DB01587 Ketazolam potentiator GABRE 0,01827
DB01588 Prazepam potentiator GABRE 0,01827
DB01589 Quazepam potentiator GABRE 0,01827
DB01595 Nitrazepam potentiator GABRE Insomnia 0,01827
DB12010 Fostamatinib inhibitor SYK 0,01771
Juvenile Idiopathic DB00026 Anakinra antagonist IL1R1 0,01763 Arthritis (JIA)
Aminocaproic DB00513 antagonist PLAT Bleeding 0,01743 Acid
Human DB06404 C1-esterase inhibitor PLAT 0,01743 inhibitor
DB09228 Conestat alfa inhibitor PLAT 0,01743
Tuberculin DB11601 Purified Protein ligand TLR2 0,01403 Derivative
Advanced Soft DB00570 Vinblastine adduct TUBE1 0,01289 Tissue Sarcoma
Metastatic DB11967 Binimetinib inhibitor MAP3K1 0,01 Melanoma
Complex Partial DB00252 Phenytoin inhibitor SCN1A 0,00944 Seizures
DB00273 Topiramate inhibitor SCN1A Alcohol Dependence 0,00944
DB00909 Zonisamide inhibitor SCN1A 0,00944
DB01121 Phenacemide inhibitor SCN1A 0,00944
DB01438 Phenazopyridine inhibitor SCN1A 0,00944
DB04930 Permethrin inhibitor SCN1A Norwegian scabies 0,00944 CBA
DB05541 Brivaracetam inhibitor SCN1A 0,00944
Dichlorobenzyl DB13269 antagonist SCN1A Mouth infection 0,00944 alcohol
DB00210 Adapalene agonist RARG Acne Vulgaris 0,00891
Keratinization DB00459 Acitretin agonist RARG 0,00891 disorders
Chronic Eczema of DB00523 Alitretinoin agonist RARG 0,00891 the hand
DB00755 Tretinoin agonist RARG Acne Vulgaris 0,00891
Psoriasis Vulgaris DB00799 Tazarotene agonist RARG 0,00891 (Plaque Psoriasis)
Metastatic DB00002 Cetuximab antagonist EGFR 0,00774 Colorectal Cancers
DB00317 Gefitinib antagonist EGFR 0,00774
Locally Advanced DB00530 Erlotinib antagonist EGFR Non-Small Cell Lung 0,00774 Cancer
Metastatic Breast DB01259 Lapatinib antagonist EGFR 0,00774 Cancer (MBC)
DB01269 Panitumumab suppressor EGFR 0,00774
Metastatic DB08916 Afatinib inhibitor EGFR Non-Small Cell Lung 0,00774 Cancer
DB09330 Osimertinib inhibitor EGFR 0,00774
DB09559 Necitumumab antagonist EGFR 0,00774
Foreskin DB10772 keratinocyte agonist EGFR 0,00774 (neonatal)
DB11828 Neratinib inhibitor EGFR 0,00774
DB11963 Dacomitinib inhibitor EGFR 0,00774
DB12267 Brigatinib inhibitor EGFR 0,00774 CBA
DB00548 Azelaic acid inhibitor AKR1D1 Acne Vulgaris 0,00672
DB00148 Creatine product of GAMT 0,0061
DB00909 Zonisamide inhibitor SCN1B 0,00585
Malignant DB01219 Dantrolene antagonist RYR1 0,00571 Hyperthermia
DB09085 Tetracaine modulator RYR1 0,00571
DB13931 Netarsudil inhibitor ROCK2 0,00562
DB00148 Creatine ligand CKM 0,00554
Partial-Onset DB00996 Gabapentin inhibitor CACNA1B 0,00513 Seizures
DB01202 Levetiracetam inhibitor CACNA1B Epilepsies 0,00513
DB00202 Succinylcholine agonist CHRNA10 0,00507
DB00333 Methadone antagonist CHRNA10 Opioid Addiction 0,00507
DB01090 Pentolinium antagonist CHRNA10 0,00507
DB01116 Trimethaphan antagonist CHRNA10 0,00507
Metastatic DB08896 Regorafenib inhibitor DDR2 Gastrointestinal 0,00487 Stromal Tumor
Human DB06404 C1-esterase inhibitor F12 0,00484 inhibitor
DB09228 Conestat alfa inhibitor F12 0,00484
Angle-Closure DB00819 Acetazolamide inhibitor CA3 0,0048 Glaucoma
DB00140 Riboflavin product of BLVRB Ariboflavinosis 0,00466
Advanced Cervical DB01229 Paclitaxel #N/A MAP4 0,00465 Cancer
DB01248 Docetaxel #N/A MAP4 Esophageal Cancers 0,00465
DB00095 Efalizumab antibody ITGAL 0,00431 CBA
Antithymocyte Acute cellular DB00098 immunoglobulin #N/A ITGAL 0,00431 rejection (rabbit)
DB11611 Lifitegrast antagonist ITGAL 0,00431
High-grade, DB13615 Mifamurtide ligand NOD2 nonmetastatic 0,0043 Osteosarcoma
Advanced Renal Cell DB09078 Lenvatinib inhibitor FGFR3 0,00393 Carcinoma
Decreased DB09079 Nintedanib inhibitor FGFR3 0,00393 Pulmonary Function
Locally Advanced, Susceptible FGFR3 or FGFR2 genetic alterations, Condition has progressed during or following at least one line of prior DB12147 Erdafitinib inhibitor FGFR3 platinum- containing 0,00393 chemotherapy including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy urothelial carcinoma
DB00193 Tramadol agonist OPRM1 Pain, Acute 0,00388
DB00295 Morphine agonist OPRM1 Pain, Chronic 0,00388
DB00318 Codeine agonist OPRM1 Coughing 0,00388
DB00327 Hydromorphone agonist OPRM1 Pain 0,00388
DB00333 Methadone agonist OPRM1 Opioid Addiction 0,00388
DB00497 Oxycodone agonist OPRM1 Severe Pain 0,00388
DB00504 Levallorphan partial agonist OPRM1 0,00388 CBA
partial DB00611 Butorphanol OPRM1 Pain 0,00388 antagonist
DB00652 Pentazocine antagonist OPRM1 Mild pain 0,00388
DB00704 Naltrexone antagonist OPRM1 Alcohol Dependence 0,00388
DB00708 Sufentanil agonist OPRM1 Pain, Acute 0,00388
DB00802 Alfentanil agonist OPRM1 0,00388
Cancer Related Pain DB00813 Fentanyl agonist OPRM1 0,00388 (Breakthrough Pain)
Chronic Functional DB00836 Loperamide agonist OPRM1 0,00388 Diarrhea
DB00844 Nalbuphine antagonist OPRM1 Severe Pain 0,00388
DB00854 Levorphanol agonist OPRM1 Severe Pain 0,00388
DB00899 Remifentanil agonist OPRM1 0,00388
DB00913 Anileridine agonist OPRM1 0,00388
DB00921 Buprenorphine partial agonist OPRM1 Opioid Dependence 0,00388
Cough caused by DB00956 Hydrocodone agonist OPRM1 0,00388 Allergic Rhinitis
DB01081 Diphenoxylate agonist OPRM1 0,00388
DB01183 Naloxone antagonist OPRM1 Opioid Dependence 0,00388
DB01192 Oxymorphone agonist OPRM1 Anxiety 0,00388
DB01209 Dezocine agonist OPRM1 0,00388
Levacetylmethad DB01227 agonist OPRM1 0,00388 ol
DB01452 Diamorphine agonist OPRM1 0,00388
Diabetic Peripheral DB06204 Tapentadol agonist OPRM1 Neuropathic Pain 0,00388 (DPN)
DB06274 Alvimopan antagonist OPRM1 0,00388
DB06800 Methylnaltrexon antagonist OPRM1 0,00388 CBA
e
DB09049 Naloxegol antagonist OPRM1 0,00388
Irritable Bowel DB09089 Trimebutine agonist OPRM1 0,00388 Syndrome (IBS)
DB09209 Pholcodine antagonist OPRM1 0,00388
DB09272 Eluxadoline agonist OPRM1 0,00388
DB11130 Opium agonist OPRM1 0,00388
DB11691 Naldemedine antagonist OPRM1 0,00388
DB08888 Ocriplasmin cleavage FN1 0,00384
DB13931 Netarsudil inhibitor ROCK1 0,0035
Chemotherapy DB00019 Pegfilgrastim agonist CSF3R Induced 0,00326 Neutropenia
Hematopoietic Subsyndrome of DB00099 Filgrastim stimulator CSF3R 0,00326 Acute Radiation Syndrome
DB13144 Lenograstim agonist CSF3R 0,00326
DB13200 Lipegfilgrastim agonist CSF3R Neutropenia, Febrile 0,00326
DB00270 Isradipine inhibitor CACNA1C 0,00308
Atrial Fibrillation DB00308 Ibutilide activator CACNA1C 0,00308 (AF)
DB00343 Diltiazem blocker CACNA1C Anal Fissures 0,00308
DB00381 Amlodipine inhibitor CACNA1C Anginal Pain 0,00308
DB00393 Nimodipine inhibitor CACNA1C 0,00308
DB00401 Nisoldipine inhibitor CACNA1C 0,00308
DB00568 Cinnarizine inhibitor CACNA1C 0,00308
Chronic Stable DB00622 Nicardipine inhibitor CACNA1C 0,00308 Angina Pectoris CBA
Atrial Fibrillation DB00661 Verapamil inhibitor CACNA1C 0,00308 (AF)
DB00825 Levomenthol antagonist CACNA1C Coughing 0,00308
DB01023 Felodipine inhibitor CACNA1C 0,00308
DB01054 Nitrendipine inhibitor CACNA1C 0,00308
Chronic Stable DB01115 Nifedipine inhibitor CACNA1C 0,00308 Angina Pectoris
DB01373 Calcium ligand CACNA1C 0,00308
DB06712 Nilvadipine inhibitor CACNA1C 0,00308
Irritable Bowel DB09089 Trimebutine inhibitor CACNA1C 0,00308 Syndrome (IBS)
DB09236 Lacidipine antagonist CACNA1C 0,00308
DB09238 Manidipine blocker CACNA1C 0,00308
DB12278 Propiverine antagonist CACNA1C Micturition urgency 0,00308
Autonomy of DB00279 Liothyronine agonist THRB 0,00295 thyroid gland
DB00451 Levothyroxine agonist THRB Hypothyroidism 0,00295
DB00509 Dextrothyroxine agonist THRB 0,00295
DB01583 Liotrix agonist THRB 0,00295
Omega-3-carboxy DB09568 potentiator ELOVL4 0,00295 lic acids
Acute Lymphoblastic DB01254 Dasatinib multitarget LCK 0,00286 Leukaemias (ALL)
DB00627 Niacin agonist HCAR2 Atherosclerosis 0,00284
DB00179 Masoprocol inhibitor ALOX5 0,00279
DB00244 Mesalazine inhibitor ALOX5 Crohn' 0,00279
Actinic Keratosis DB00586 Diclofenac potentiator ALOX5 0,00279 (AK)
DB00711 Diethylcarbamazi inhibitor ALOX5 0,00279 CBA
ne
DB00795 Sulfasalazine inhibitor ALOX5 Crohn' 0,00279
Meclofenamic Acute Gouty DB00939 inhibitor ALOX5 0,00279 acid Arthritis
Mild Ulcerative DB01014 Balsalazide inhibitor ALOX5 0,00279 Colitis
Moderate, active DB11817 Baricitinib inhibitor PTK2B 0,00275 Rheumatoid arthritis
DB09118 Stiripentol inhibitor LDHB 0,00256
agonist,induc DB00364 Sucralfate FGF2 Gastric Ulcer (GU) 0,00246 er
Pentosan DB00686 antagonist FGF2 0,00246 Polysulfate
other/unkno DB00877 Sirolimus FGF2 Chordomas 0,00246 wn
Advanced Renal Cell DB00398 Sorafenib inhibitor RAF1 0,00238 Carcinoma
Metastatic DB08896 Regorafenib inhibitor RAF1 Gastrointestinal 0,00238 Stromal Tumor
antagonist,inh Metastatic DB08912 Dabrafenib RAF1 0,00238 ibitor Melanoma
Type 1 DB01278 Pramlintide agonist RAMP3 Insulin-Dependent 0,00232 Diabetes Mellitus
DB00184 Nicotine agonist CHRNB2 Dental Cavity 0,00229
DB00343 Diltiazem blocker CACNG1 Anal Fissures 0,00226
DB00381 Amlodipine blocker CACNG1 Anginal Pain 0,00226
DB00528 Lercanidipine inhibitor CACNG1 0,00226
DB00893 Iron Dextran other FTL 0,00226
DB01054 Nitrendipine inhibitor CACNG1 0,00226 CBA
Sodium ferric DB09517 gluconate binding FTL Anemias 0,00226 complex
Ferric DB13995 pyrophosphate binder FTL 0,00226 citrate
DB00384 Triamterene inhibitor SCNN1A Edema 0,00223
DB00594 Amiloride inhibitor SCNN1A Ascites 0,00223
DB00909 Zonisamide inhibitor SCN3B 0,0022
DB00231 Temazepam potentiator GABRP 0,00218
DB00690 Flurazepam potentiator GABRP 0,00218
Alcohol Withdrawal DB00829 Diazepam potentiator GABRP 0,00218 Syndrome(AWS)
Alcohol Withdrawal DB00842 Oxazepam potentiator GABRP 0,00218 Syndrome(AWS)
DB00897 Triazolam potentiator GABRP 0,00218
DB01215 Estazolam potentiator GABRP 0,00218
DB01558 Bromazepam potentiator GABRP Acute Anxiety 0,00218
DB01559 Clotiazepam potentiator GABRP 0,00218
DB01588 Prazepam potentiator GABRP 0,00218
DB01589 Quazepam potentiator GABRP 0,00218
DB01595 Nitrazepam potentiator GABRP Insomnia 0,00218
Mycophenolate Heart Transplant DB00688 inhibitor IMPDH1 0,00214 mofetil Rejection
Chronic Hepatitis C DB00811 Ribavirin inhibitor IMPDH1 0,00214 Virus (HCV) Infection
Mycophenolic DB01024 inhibitor IMPDH1 0,00214 acid
DB00762 Irinotecan inhibitor TOP1MT Esophageal Cancers 0,00209
DB00041 Aldesleukin agonist IL2RG High Risk 0,00207 CBA
Neuroblastoma
DB00367 Levonorgestrel inhibitor SRD5A1 Endometrial Cancers 0,00195
Benign Prostatic DB01126 Dutasteride inhibitor SRD5A1 0,00195 Hyperplasia (BPH)
Abnormal Uterine DB09389 Norgestrel inhibitor SRD5A1 0,00195 Bleeding
DB09033 Vedolizumab antibody ITGB7 Severe Crohn' 0,00181
DB00906 Tiagabine inhibitor SLC6A1 0,0018
Moderate DB08895 Tofacitinib inhibitor JAK3 0,00175 Rheumatoid arthritis
Moderate, active DB11817 Baricitinib inhibitor JAK3 0,00175 Rheumatoid arthritis
Hypercalcemia of DB00720 Clodronic acid inhibitor SLC25A4 0,00171 Malignancy
incorporation into and DB06773 Human calcitonin ACTN1 0,0017 destabilizatio n
Asymptomatic, metastatic DB06688 Sipuleucel-T other ACPP 0,00163 hormone-refractory Prostate cancer
antagonist,ag Abnormal Uterine DB00396 Progesterone NR3C2 0,00156 onist Bleeding
DB00421 Spironolactone antagonist NR3C2 Acne 0,00156
Primary DB00687 Fludrocortisone agonist NR3C2 adrenocortical 0,00156 insufficiency
High Blood Pressure DB00700 Eplerenone antagonist NR3C2 0,00156 (Hypertension)
DB01395 Drospirenone antagonist NR3C2 Acne Vulgaris 0,00156
Fluocinolone Atopic Dermatitis DB00591 inducer ANXA1 0,00152 acetonide (AD) CBA
Acute Gouty DB00741 Hydrocortisone agonist ANXA1 0,00152 Arthritis
Hydrocortisone Adrenal cortical DB14539 ANXA1 0,00152 acetate hypofunctions
Hydrocortisone Atopic Dermatitis DB14540 ANXA1 0,00152 butyrate (AD)
Hydrocortisone DB14541 ANXA1 0,00152 cypionate
Hydrocortisone DB14542 ANXA1 0,00152 phosphate
Hydrocortisone DB14543 ANXA1 Itching 0,00152 probutate
Hydrocortisone DB14544 ANXA1 0,00152 valerate
Location of top AT in HiPathia circuits and selection of those circuits shared with the Disease Map. A total of 193 /226 circuits from RD Map containing top AT are shown.
Disease Map circuits with top AT
HiPathia pathway: HiPathia pathway: HiPathia pathway: HiPathia pathway: Effector gene Effector gene Effector gene Effector gene
MAPK signaling cAMP signaling FoxO signaling T cell receptor pathway: ATF4* pathway: GRIA1 pathway: FBXO32 signaling pathway: FOS
MAPK signaling cAMP signaling Sphingolipid signaling B cell receptor pathway: FOS pathway: CFTR pathway: MAPK1 signaling pathway: FOS
Phospholipase D MAPK signaling cAMP signaling Fc epsilon RI signaling signaling pathway: pathway: MAPT pathway: SLC9A1 pathway: PLA2G4B MAPK1
Phospholipase D MAPK signaling cAMP signaling Fc gamma R-mediated signaling pathway: pathway: STMN1 pathway: ATP2B1 phagocytosis: CFL1 C06124 CBA
Phospholipase D MAPK signaling cAMP signaling Neurotrophin signaling signaling pathway: pathway: PLA2G4B pathway: CACNA1C pathway: ATF4 MTOR
MAPK signaling cAMP signaling mTOR signaling Neurotrophin signaling pathway: MYC pathway: PDE3A pathway: EIF4E pathway: NFKB1
ErbB signaling cAMP signaling mTOR signaling Neurotrophin signaling pathway: MYC pathway: LIPE pathway: EIF4B pathway: FOXO3
ErbB signaling cAMP signaling mTOR signaling Neurotrophin signaling pathway: ELK1 pathway: TNNI3 pathway: RPS6 pathway: BAD
cAMP signaling Ras signaling pathway: PI3K-Akt signaling Neurotrophin signaling pathway: ATP1B4 PLA2G4B pathway: GYS1 pathway: GSK3B FXYD1
Ras signaling pathway: cAMP signaling PI3K-Akt signaling Serotonergic synapse: ELK1 pathway: AKT3 pathway: MYC CASP3
Ras signaling pathway: cAMP signaling PI3K-Akt signaling GABAergic synapse: ETS1 pathway: RHOA* pathway: CCND1 GABRA1 GPHN
Regulation of actin Ras signaling pathway: cAMP signaling PI3K-Akt signaling cytoskeleton: ACTB BCL2L1 pathway: C00165 pathway: CDKN1B ARPC5
Regulation of actin Ras signaling pathway: cAMP signaling PI3K-Akt signaling cytoskeleton: CFL1 NFKB1 pathway: C01245 pathway: RBL2 ACTB
Regulation of actin Ras signaling pathway: cAMP signaling PI3K-Akt signaling cytoskeleton: MYL12B FASLG pathway: PAK1 pathway: PCK1 MYH9 ACTB
Ras signaling pathway: cAMP signaling PI3K-Akt signaling Regulation of actin PAK4 pathway: AFDN pathway: G6PC cytoskeleton: PXN
Ras signaling pathway: cAMP signaling PI3K-Akt signaling Regulation of actin RHOA pathway: C00416 pathway: FASLG cytoskeleton: IQGAP2
Regulation of actin Ras signaling pathway: cAMP signaling PI3K-Akt signaling cytoskeleton: PFN3 MAPK8 pathway: MAPK8 pathway: BCL2L11 ACTB
Ras signaling pathway: cAMP signaling PI3K-Akt signaling Regulation of actin RAC1* pathway: HCN4 pathway: BCL2L1 cytoskeleton: VCL*
Ras signaling pathway: Chemokine signaling PI3K-Akt signaling Regulation of actin CBA
REL pathway: MAPK1 pathway: BCL2* cytoskeleton: ACTN4
Ras signaling pathway: HIF-1 signaling PI3K-Akt signaling Regulation of actin PLD1 pathway: HK1 pathway: TP53 cytoskeleton: MSN
Ras signaling pathway: FoxO signaling PI3K-Akt signaling Insulin signaling PRKCA pathway: CCNB3 pathway: BCL2L1* pathway: EIF4E
Ras signaling pathway: FoxO signaling PI3K-Akt signaling Insulin signaling C01245 pathway: CCND1 pathway: MYB pathway: ELK1
Ras signaling pathway: FoxO signaling PI3K-Akt signaling GnRH signaling ABL1 pathway: CCNG2 pathway: CCND1 CDK2 pathway: ELK1
Progesterone-mediate Ras signaling pathway: FoxO signaling PI3K-Akt signaling d oocyte maturation: RAB5A pathway: CDKN2B pathway: MAPK1 ARAF
Ras signaling pathway: FoxO signaling PI3K-Akt signaling Estrogen signaling RAP1A pathway: CDKN2D pathway: BCL2 pathway: CREB3***
Ras signaling pathway: FoxO signaling PI3K-Akt signaling Estrogen signaling RAC1** pathway: CDKN1A pathway: MCL1 pathway: CREB3
Ras signaling pathway: FoxO signaling PI3K-Akt signaling Estrogen signaling KSR2 pathway: CDKN1B pathway: RXRA pathway: ESR1 C00951
Ras signaling pathway: FoxO signaling PI3K-Akt signaling Estrogen signaling STK4 STK4 pathway: RBL2 pathway: BCL2** pathway: ESR1 FOS
Estrogen signaling Ras signaling pathway: FoxO signaling PI3K-Akt signaling pathway: ESR1 MLLT4 pathway: PLK4 pathway: EIF4E C00951*
Ras signaling pathway: FoxO signaling PI3K-Akt signaling Melanogenesis: TYR* RAF1* pathway: GADD45G pathway: EIF4B
Rap1 signaling FoxO signaling PI3K-Akt signaling Melanogenesis: TYRP1 pathway: MAPK1 pathway: FASLG pathway: RPS6
Rap1 signaling FoxO signaling PI3K-Akt signaling Melanogenesis: DCT pathway: PLCE1 pathway: BCL2L11 pathway: NOS3
cAMP signaling FoxO signaling PI3K-Akt signaling Prolactin signaling pathway: BDNF pathway: TNFSF10 pathway: CASP9 pathway: CCND1
cAMP signaling FoxO signaling PI3K-Akt signaling Prolactin signaling pathway: FOS pathway: BCL6 pathway: PRKCA pathway: CCND1* CBA
Thyroid hormone cAMP signaling FoxO signaling PI3K-Akt signaling signaling pathway: pathway: JUN pathway: BNIP3 pathway: PKN3 ATP1B4
cAMP signaling PI3K-Akt signaling Thyroid hormone FoxO signaling pathway: CREB3 pathway: signaling pathway: pathway: ATG12 CREBBP C8orf44-SGK3 STAT1
Thyroid hormone cAMP signaling FoxO signaling Apoptosis: BCL2* signaling pathway: pathway: MYL9 pathway: GABARAP TP53
Thyroid hormone cAMP signaling FoxO signaling Axon guidance: RAF1 signaling pathway: pathway: GLI1 pathway: CAT ESR1
Thyroid hormone cAMP signaling FoxO signaling VEGF signaling signaling pathway: pathway: PTCH1 pathway: SOD2 pathway: PLA2G4B THRB
cAMP signaling FoxO signaling Gap junction: GJA1 Oxytocin signaling pathway: HHIP pathway: GADD45G* GJA1 pathway: C00219
cAMP signaling FoxO signaling Gap junction: GJA1 Oxytocin signaling pathway: ACOX1 pathway: ATM GJA1* pathway: PTGS2
cAMP signaling FoxO signaling Gap junction: GJA1 Oxytocin signaling pathway: F2R pathway: PCK1 TJP1 pathway: MEF2C
cAMP signaling FoxO signaling Gap junction: GJA1 Oxytocin signaling pathway: AMH pathway: G6PC GJA1** pathway: JUN
Signaling pathways cAMP signaling FoxO signaling Oxytocin signaling regulating pluripotency pathway: ORAI1 pathway: BCL6* pathway: CCND1 of stem cells: MAPK1*
Natural killer cell cAMP signaling FoxO signaling Oxytocin signaling mediated cytotoxicity: pathway: BAD pathway: IL7R pathway: FOS TNF
cAMP signaling Natural killer cell FoxO signaling Oxytocin signaling pathway: NFKBIA mediated cytotoxicity: pathway: KLF2 pathway: ELK1 NFKB1 CSF2
Natural killer cell Aldosterone-regulated cAMP signaling FoxO signaling mediated cytotoxicity: sodium reabsorption: pathway: PLN pathway: S1PR1 FAS SCNN1A CBA
Natural killer cell Aldosterone-regulated cAMP signaling FoxO signaling mediated cytotoxicity: sodium reabsorption: pathway: RYR2 pathway: RAG1 TNFRSF10D KCNJ1
cAMP signaling pathway: GRIN3A
Matrix correlation of the expression of top AT with the activity of the circuits that compose the RD Map.
In order to understand the nature of the interaction (activation or inhibition) between the most relevant targets and the circuits of the disease map a correlation plot was derived. The plot represents the correlation between the expression level of the most relevant targets and the activity levels of the circuits in the disease map inferred by HiPathia across the GTEx data set. Additionally, the top of the figure represents the effect (pharmacological action) of the drugs.
Hint: a drug with an inhibitory effect in a given target will potentially produce an inhibitory effect in circuits positively correlated (and, it is likely that activation in circuits negatively correlated with the target.)
Click to access and download the Correlation Matrix