Table S4. Irf6 Related Genes Involved in Different KEGG Pathways Analysed by DAVID Database

Table S4. Irf6 related genes involved in different KEGG pathways analysed by DAVID database

List Pop Pop Fold Term Count % P-Value Genes Bonferroni Benjamini FDR Total Hits Total Enrichment

TNF, TBK1, TOLLIP, TLR1, TLR2, NFKBIA, TLR3,

TLR4, NFKB1, TLR5, TLR7, TLR8, TLR9, MAP3K7, hsa04620:Toll-like receptor 2.96296 IRAK4, FOS, MYD88, TICAM1, IL1B, LBP, TRAF6, 40 6.84E-22 322 101 5085 6.254227907 6.84E-20 6.84E-20 7.60E-19 signaling pathway 3 CHUK, TRAF3, IRAK1, IL6, RELA, CD40, STAT1,

TAB1, TAB2, IFNAR1, IFNAR2, IKBKE, IRF5, IRF7,

RIPK1, IKBKG, IRF3, IKBKB, CD14

HLA-DQB1, HLA-DRB1, HLA-DRB3, TGFB3,

TNFSF12, HLA-DMB, HLA-DMA, IL10, TGFB1,

TGFB2, ITGB7, ICOS, HLA-DRB4, HLA-DRB5, hsa04672:Intestinal immune 2.14814 29 9.07E-22 HLA-DPB1, HLA-DOA, HLA-DOB, CD28, IL6, IL5, 322 49 5085 9.346241602 9.07E-20 4.54E-20 1.01E-18 network for IgA production 8 CD40, HLA-DQA2, HLA-DQA1, CD40LG,

MADCAM1, HLA-DPA1, MAP3K14, ICOSLG,

HLA-DRA, IL2

UBE2Z, UBE3B, UBE2G2, PML, UBA6, KEAP1,

CDC34, UBE3C, UBE2R2, CUL3, FBXW7, FBXW8,

CUL7, MGRN1, KLHL9, FBXO4, NEDD4L, RCHY1, hsa04120:Ubiquitin 3.25925 TRAF6, TRIP12, UBE2A, UBE4A, SOCS3, SOCS1, 44 5.65E-20 322 137 5085 5.071859274 5.65E-18 1.88E-18 6.27E-17 mediated proteolysis 9 CBL, FBXO2, UBE2J1, PARK2, UBE2J2, UBOX5,

UBE2Q1, UBE2B, UBE2N, TRIM37, UBE2O, CBLB,

UBA1, NEDD4, TRIM32, UBA3, DET1, KLHL13,

PIAS1, UBE2E2 hsa05332:Graft-versus-host 25 1.85185 7.11E-20 HLA-DQB1, TNF, HLA-DRB1, HLA-DRB3, 322 39 5085 10.12302914 7.11E-18 1.78E-18 7.89E-17 disease 2 HLA-DMB, HLA-DMA, IFNG, HLA-DRB4, IL1B,

HLA-DRB5, HLA-DPB1, FAS, HLA-DOA, HLA-DOB,

KLRD1, IL1A, CD28, IL6, HLA-DQA2, HLA-DQA1,

HLA-DPA1, KIR3DL1, KLRC1, IL2, KIR3DL2,

HLA-DRA

HLA-DQB1, TNF, IL5, HLA-DRB1, HLA-DRB3, CD40,

HLA-DMB, HLA-DQA2, HLA-DMA, IL10, hsa05330:Allograft 22 1.62963 7.58E-17 HLA-DQA1, CD40LG, IFNG, HLA-DRB4, HLA-DRB5, 322 36 5085 9.650621118 1.11E-14 2.22E-15 1.22E-13 rejection HLA-DPA1, HLA-DPB1, FAS, HLA-DOA, HLA-DOB,

CD28, IL2, HLA-DRA

MAVS, TRAF2, OTUD5, IFIH1, TNF, TBK1, NFKBIB,

DAK, NFKBIA, NLRX1, NFKB1, MAP3K7, RNF125, hsa04622:RIG-I-like 2.14814 29 2.86E-16 CYLD, ATG5, TRAF6, TBKBP1, CHUK, TRAF3, 322 71 5085 6.450223078 3.33E-14 5.55E-15 3.66E-13 receptor signaling pathway 8 RELA, TANK, DDX58, IKBKE, SIKE1, RIPK1, IRF7,

IKBKG, IRF3, IKBKB

E2F1, FGF8, PTGS2, FGF9, STAT5B, TGFB3, FGF10,

NFKB1, NFKB2, GLI2, PTEN, GLI3, TGFB1, TGFB2,

FOS, CDKN2A, RARA, FAS, MYC, CHUK, CSF2RA,

EGFR, RELA, RXRA, TP53, RB1, SMO, CRKL, EP300, hsa05200:Pathways in 4.66666 VEGFA, PIAS1, TRAF1, WNT5A, FGFR2, TRAF2, 63 4.72E-16 322 328 5085 3.033205196 4.44E-14 6.33E-15 4.88E-13 cancer 7 FGFR1, ERBB2, PML, KITLG, NFKBIA, CDH1, KIT,

ZBTB16, IGF1R, TRAF6, AXIN1, TRAF3, APC, BMP4,

IL6, BMP2, CBL, CREBBP, SMAD4, SMAD3, SMAD2,

STAT1, STAT3, CBLB, CDKN1A, CDKN1B, IKBKG,

IKBKB hsa05310:Asthma 19 1.40740 2.93E-15 HLA-DQB1, IL3, TNF, IL5, HLA-DRB1, HLA-DRB3, 322 29 5085 10.34643393 2.89E-13 3.61E-14 3.21E-12 7 CD40, HLA-DMB, HLA-DQA2, HLA-DMA, IL10,

HLA-DQA1, CD40LG, HLA-DRB4, HLA-DRB5,

HLA-DPA1, HLA-DPB1, HLA-DOA, HLA-DOB,

HLA-DRA

CSH1, CSF2, STAT5B, IL7R, IL10, IFNG, IL2RG,

IFNGR2, PRL, MYC, IFNGR1, CSF2RA, GHR, PTPN6, hsa04630:Jak-STAT 2.96296 IL3, IL6, IL2RA, IL5, IL7, SOCS3, SOCS1, CBL, 40 1.65E-14 322 155 5085 4.075335604 1.65E-12 1.84E-13 1.84E-11 signaling pathway 3 CREBBP, STAT1, CISH, STAT3, STAT2, IFNAR1,

GH2, IRF9, GH1, IFNAR2, CBLB, EP300, PRLR, JAK3,

IL5RA, PIAS1, IL3RA, IL2

IL18, TGFB3, TNFSF12, TGFB1, IL10, TGFB2,

TNFRSF11A, IL1RAP, IFNG, IL1B, FAS, PRL,

IFNGR2, IFNGR1, CSF2RA, IL1A, GHR, EGFR, CD40,

IFNAR1, IFNAR2, CCR6, TNFRSF10B, TNFRSF10D, hsa04060:Cytokine-cytokin 3.92592 53 2.04E-14 CD40LG, CCR2, VEGFA, NGFR, EDA, CSF2, IL1R2, 322 262 5085 3.194549808 2.04E-12 2.04E-13 2.27E-11 e receptor interaction 6 IL1R1, TNF, TNFRSF12A, KITLG, KIT, IL7R,

TNFRSF1A, TNFRSF1B, IL2RG, IL3, IL6, BMP2, IL5,

IL2RA, IL7, GH2, GH1, TNFSF11, PRLR, IL5RA,

IL3RA, IL2

CSF2, TNF, CD8A, NFKBIE, NFKBIB, CD247,

NFKBIA, NFKB1, IL10, PDCD1, MAP3K7, FOS, ICOS, hsa04660:T cell receptor 32 2.37037 2.09E-13 RASGRP1, IFNG, CHUK, CD28, NFATC1, BCL10, 322 108 5085 4.679089027 2.09E-11 1.90E-12 2.32E-10 signaling pathway PTPN6, IL5, RELA, CBL, CTLA4, MALT1, CARD11,

CBLB, CD40LG, IKBKG, MAP3K14, IKBKB, IL2 hsa04940:Type I diabetes 1.48148 HLA-DQB1, TNF, HLA-DRB1, HLA-DRB3, 20 1.12E-12 322 42 5085 7.519964508 1.12E-10 9.36E-12 1.25E-09 mellitus 1 HLA-DMB, HLA-DQA2, HLA-DMA, HLA-DQA1, IFNG, HLA-DRB4, HLA-DRB5, IL1B, HLA-DPA1,

HLA-DPB1, FAS, HLA-DOA, HLA-DOB, IL1A, CD28,

IL2, HLA-DRA

HLA-DQB1, HLA-DRB1, CD8A, HLA-DRB3, IFI30,

HLA-DMB, HLA-DMA, CANX, TAPBP, TAP2, TAP1, hsa04612:Antigen HLA-DRB4, HLA-DRB5, HLA-DPB1, HLA-DOA, 27 2 2.14E-12 322 83 5085 5.13713238 2.14E-10 1.64E-11 2.37E-09 processing and presentation KLRD1, HLA-DOB, CIITA, KIR2DS2, KIR2DS1,

CTSS, HLA-DQA2, HLA-DQA1, HLA-DPA1,

KIR3DL1, KLRC1, KIR3DL2, HLA-DRA

IL6, CARD9, TNF, NFKBIB, IL18, RELA, NFKBIA, hsa04621:NOD-like 1.70370 NFKB1, TAB1, TAB2, NLRP1, MAP3K7, NOD1, 23 6.74E-12 322 62 5085 5.858294931 6.74E-10 4.82E-11 7.48E-09 receptor signaling pathway 4 MEFV, IKBKG, PYCARD, PSTPIP1, RIPK2, IL1B,

TNFAIP3, TRAF6, IKBKB, CHUK

HLA-DQB1, IL5, HLA-DRB1, HLA-DRB3, CTLA4,

CD40, HLA-DMB, HLA-DMA, HLA-DQA2, IL10, hsa05320:Autoimmune 1.55555 21 7.29E-12 HLA-DQA1, CD40LG, HLA-DRB4, HLA-DRB5, 322 51 5085 6.502557545 7.29E-10 4.86E-11 8.09E-09 thyroid disease 6 HLA-DPA1, HLA-DPB1, FAS, HLA-DOA, HLA-DOB,

CD28, IL2, HLA-DRA

HLA-DQB1, PVR, HLA-DRB1, CD8A, HLA-DRB3,

CDH1, HLA-DMB, HLA-DMA, PDCD1, VCAM1,

PVRL1, ITGB7, ICOS, HLA-DRB4, HLA-DRB5, hsa04514:Cell adhesion 2.44444 33 1.32E-11 HLA-DPB1, HLA-DOA, HLA-DOB, CD28, ICAM3, 322 132 5085 3.947981366 1.32E-09 8.22E-11 1.46E-08 molecules (CAMs) 4 CTLA4, CD40, HLA-DQA2, PDCD1LG2, HLA-DQA1,

NCAM1, CD34, CD40LG, CD274, MADCAM1,

HLA-DPA1, CD226, ICOSLG, HLA-DRA hsa04640:Hematopoietic 26 1.92592 3.67E-11 CSF2, IL1R2, IL1R1, TNF, HLA-DRB1, CD8A, 322 86 5085 4.774303048 3.67E-09 2.16E-10 4.07E-08 cell lineage 6 HLA-DRB3, KITLG, KIT, IL7R, CD44, HLA-DRB4,

IL1B, HLA-DRB5, CSF2RA, IL1A, IL3, IL6, IL5,

IL2RA, IL7, CD19, CD34, IL5RA, CD14, IL3RA,

HLA-DRA

TRAF2, IL1R1, TNF, NFKBIA, NFKB1, IRAK4,

IRAK3, TNFRSF1A, MYD88, IL1RAP, IL1B, FAS, 1.92592 hsa04210:Apoptosis 26 4.86E-11 CHUK, IL1A, IRAK2, IL3, IRAK1, RELA, TP53, 322 87 5085 4.719426001 4.86E-09 2.70E-10 5.39E-08 6 TNFRSF10B, TNFRSF10D, RIPK1, IKBKG, MAP3K14,

IKBKB, IL3RA

MAVS, IL6, TBK1, IL18, RELA, NFKBIB, NFKBIA, hsa04623:Cytosolic 1.48148 20 3.30E-10 NFKB1, AIM2, DDX58, IKBKE, RIPK1, IRF7, IKBKG, 322 55 5085 5.742518351 3.30E-08 1.74E-09 3.67E-07 DNA-sensing pathway 1 PYCARD, IL1B, IRF3, IKBKB, CHUK, ADAR

E2F1, RELA, STAT5B, CBL, TP53, TGFB3, SMAD4, hsa05220:Chronic myeloid 1.70370 SMAD3, NFKBIA, NFKB1, RB1, TGFB1, TGFB2, 23 4.75E-10 322 75 5085 4.842857143 4.75E-08 2.38E-09 5.28E-07 leukemia 4 CBLB, CDKN1A, CRKL, CDKN2A, CDKN1B, GAB2,

IKBKG, IKBKB, MYC, CHUK

CSF2, TNF, CD247, KLRK1, RAET1E, PTK2B, IFNG,

FAS, FCGR3A, KLRD1, IFNGR2, IFNGR1, TYROBP, hsa04650:Natural killer cell 2.07407 28 3.58E-08 NFATC1, SYK, PTPN6, KIR2DS2, KIR2DS1, HCST, 322 133 5085 3.324615888 3.58E-06 1.70E-07 3.97E-05 mediated cytotoxicity 4 IFNAR1, IFNAR2, TNFRSF10B, ULBP3, TNFRSF10D,

ULBP2, KIR3DL1, KLRC1, KIR3DL2

E2F1, EGFR, ERBB2, RELA, TP53, TGFB3, SMAD4,

1.48148 SMAD3, NFKB1, SMAD2, RB1, STAT1, STAT3, hsa05212:Pancreatic cancer 20 5.14E-08 322 72 5085 4.386645963 5.14E-06 2.34E-07 5.71E-05 1 TGFB1, TGFB2, CDKN2A, VEGFA, IKBKG, IKBKB,

CHUK hsa04662:B cell receptor 20 1.48148 1.05E-07 BCL10, PTPN6, NFKBIE, NFKBIB, RELA, NFKBIA, 322 75 5085 4.211180124 1.05E-05 4.57E-07 1.17E-04 signaling pathway 1 MALT1, NFKB1, CARD11, FOS, CD19, FCGR2B,

CD81, IKBKG, INPP5D, IKBKB, CHUK, NFATC1,

SYK, BLNK

TRAF2, IRS2, TNF, SOCS3, NFKBIE, STK11, hsa04920:Adipocytokine 1.33333 NFKBIB, RXRA, RELA, NFKBIA, NFKB1, IRS1, 18 4.90E-07 322 67 5085 4.242606842 4.90E-05 2.04E-06 5.44E-04 signaling pathway 3 STAT3, TNFRSF1A, TNFRSF1B, IKBKG, IKBKB,

CHUK

NFKBIE, NFKBIB, CAMK2G, NFKBIA, NFKB1,

IRAK4, IRAK3, MAP3K3, CAMK2D, CAMK2B, hsa04722:Neurotrophin 1.85185 25 5.41E-07 SH2B1, TRAF6, CAMK2A, RAPGEF1, IRAK2, IRAK1, 322 124 5085 3.183855941 5.41E-05 2.16E-06 6.00E-04 signaling pathway 2 IRS2, RELA, TP53, IRS1, TP73, CRKL, RIPK2, NGFR,

IKBKB

HLA-DQB1, TNF, HLA-DRB1, HLA-DRB3, CD40,

HLA-DMB, HLA-DQA2, HLA-DMA, TRIM21, IL10, hsa05322:Systemic lupus 22 1.62963 5.81E-07 HLA-DQA1, FCGR2B, CD40LG, IFNG, HLA-DRB4, 322 99 5085 3.50931677 5.81E-05 2.24E-06 6.45E-04 erythematosus HLA-DRB5, HLA-DPA1, HLA-DPB1, FCGR3A,

HLA-DOA, HLA-DOB, CD28, HLA-DRA hsa05340:Primary 0.96296 CIITA, CD8A, CD40, IL7R, CD19, CD40LG, ICOS, 13 7.29E-07 322 35 5085 5.865572316 7.29E-05 2.70E-06 8.09E-04 immunodeficiency 3 TAP2, TAP1, IKBKG, IL2RG, JAK3, BLNK

E2F1, TRAF1, TRAF2, PTGS2, RXRA, RELA, TP53, hsa05222:Small cell lung 1.40740 0.00361 19 3.26E-06 NFKBIA, NFKB1, RB1, PTEN, CDKN1B, IKBKG, 322 84 5085 3.571983141 3.26E-04 1.16E-05 cancer 7 5 PIAS1, TRAF6, IKBKB, MYC, CHUK, TRAF3

HLA-DQB1, CAV1, HLA-DRB1, HLA-DRB3, CD40,

1.25925 HLA-DMB, HLA-DMA, HLA-DQA2, HLA-DQA1, 0.00643 hsa05416:Viral myocarditis 17 5.80E-06 322 71 5085 3.781165252 5.80E-04 2.00E-05 9 CD40LG, HLA-DRB4, HLA-DRB5, HLA-DPA1, 8

HLA-DPB1, HLA-DOA, HLA-DOB, HLA-DRA, CD28 E2F1, EGFR, FGFR2, FGFR1, ERBB2, RELA, 1.40740 0.00861 hsa05215:Prostate cancer 19 7.76E-06 CREBBP, TP53, NFKBIA, NFKB1, RB1, PTEN, IGF1R, 322 89 5085 3.371309931 7.76E-04 2.59E-05 7 4 CDKN1A, CDKN1B, EP300, IKBKG, IKBKB, CHUK

FGFR2, TRAF2, FGFR1, IL1R2, IL1R1, FGF8, TNF,

FGF9, TGFB3, FGF10, NFKB1, NFKB2, TGFB1, hsa04010:MAPK signaling 2.66666 TGFB2, MAP3K7, TNFRSF1A, FOS, MAP3K3, 0.00212705 0.02363 36 2.13E-05 322 267 5085 2.129248377 6.87E-05 pathway 7 RASGRP1, IL1B, FAS, TRAF6, MYC, CHUK, IL1A, 7 1

EGFR, RELA, RELB, TP53, TAB1, TAB2, CRKL,

IKBKG, MAP3K14, IKBKB, CD14

BMP4, BMP2, NOG, TNF, SMAD5, CREBBP, TGFB3, hsa04350:TGF-beta 1.25925 0.00844673 0.09410 17 8.48E-05 SMAD4, SMAD3, SMAD2, SMAD1, TGFB1, TGFB2, 322 87 5085 3.085778539 2.65E-04 signaling pathway 9 3 7 EP300, IFNG, MYC, PITX2 hsa05221:Acute myeloid 0.88888 RELA, IKBKG, STAT5B, PML, RARA, NFKB1, 0.08000725 0.00252376 0.92129 12 8.34E-04 322 58 5085 3.267294924 leukemia 9 ZBTB16, KIT, IKBKB, MYC, CHUK, STAT3 7 4 9

EGFR, FGFR1, PTPN6, ERBB2, CREBBP, SMAD4, hsa04520:Adherens 1.03703 0.08777167 0.00269826 14 9.18E-04 SMAD3, SMAD2, CDH1, MAP3K7, IGF1R, EP300, 322 77 5085 2.871259176 1.01446 junction 7 2 4 PVRL1, PTPN1

0.74074 E2F1, EGFR, CDKN1A, CDKN2A, ERBB2, VEGFA, 0.09435611 0.00282768 1.09401 hsa05219:Bladder cancer 10 9.91E-04 322 42 5085 3.759982254 1 TP53, CDH1, RB1, MYC 3 3 8

0.96296 0.00142165 EGFR, E2F1, FGFR1, FGF8, FGF9, TP53, FGF10, 0.13260995 1.56666 hsa05218:Melanoma 13 322 71 5085 2.891479311 0.00394405 3 4 CDH1, RB1, PTEN, IGF1R, CDKN1A, CDKN2A 1 4

0.88888 0.00169814 E2F1, EGFR, IGF1R, CDKN1A, CDKN2A, CAMK2G, 0.15630046 0.00458294 hsa05214:Glioma 12 322 63 5085 3.007985803 1.86875 9 5 CAMK2D, TP53, CAMK2B, RB1, CAMK2A, PTEN 5 9

E2F1, CREBBP, TP53, TGFB3, SMAD4, SMAD3, 1.33333 0.00200546 0.18188111 0.00526890 2.20352 hsa04110:Cell cycle 18 PRKDC, SMAD2, RB1, SFN, TGFB1, TGFB2, 322 125 5085 2.274037267 3 3 8 2 7 CDKN1C, CDKN1A, CDKN2A, EP300, CDKN1B, MYC

0.96296 0.00599951 EGFR, TP53, TGFB3, SMAD4, SMAD3, SMAD2, 0.45215232 0.01531126 6.46095 hsa05210:Colorectal cancer 13 322 84 5085 2.443988465 3 1 TGFB1, TGFB2, FOS, IGF1R, MYC, APC, AXIN1 3 4 2

EGFR, ERBB2, CAMK2G, STAT5B, CBL, CBLB, hsa04012:ErbB signaling 0.96296 0.00794822 0.54977042 0.01975225 8.47632 13 CDKN1A, CDKN1B, CRKL, CAMK2D, CAMK2B, 322 87 5085 2.359713001 pathway 3 1 5 8 7 CAMK2A, MYC hsa05213:Endometrial 0.66666 0.01517979 EGFR, ERBB2, ILK, TP53, CDH1, MYC, PTEN, 0.78338182 15.6147 9 322 52 5085 2.733217869 0.03662042 cancer 7 8 AXIN1, APC 1 6 hsa05217:Basal cell 0.66666 0.02085935 WNT5A, BMP4, SMO, BMP2, TP53, GLI2, GLI3, 0.87851908 0.04895170 20.8617 9 322 55 5085 2.584133258 carcinoma 7 1 AXIN1, APC 2 1 6

WNT5A, CAMK2G, CREBBP, TP53, SMAD4, SMAD3, hsa04310:Wnt signaling 1.25925 0.02764276 0.93938433 0.06311125 26.7386 17 SMAD2, MAP3K7, EP300, LRP6, CAMK2D, 322 151 5085 1.777898894 pathway 9 8 8 9 6 CAMK2B, CAMK2A, MYC, AXIN1, APC, NFATC1 hsa05120:Epithelial cell 0.66666 0.06278571 EGFR, NOD1, RELA, IKBKG, NFKBIA, NFKB1, 0.13702641 51.3110 signaling in Helicobacter 9 322 68 5085 2.090107782 0.99847282 7 2 IKBKB, MAP3K14, CHUK 6 7 pylori infection hsa04115:p53 signaling 0.66666 0.06278571 CDKN1A, CDKN2A, TNFRSF10B, TP53, RCHY1, 0.13702641 51.3110 9 322 68 5085 2.090107782 0.99847282 pathway 7 2 SFN, FAS, PTEN, TP73 6 7

0.44444 0.06644553 0.99896731 0.14169095 53.3802 hsa05020:Prion diseases 6 EGR1, NCAM1, IL6, NOTCH1, IL1B, IL1A 322 35 5085 2.707187223 4 4 9 3 7