rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p q 1 HSA04510_FOCAL_ADHESION Genes involved in focal adhesion ACTB, ACTG1, ACTN1, ACTN2, ACTN3, ACTN4, AKT1, AKT2, AKT3, ARHGAP5, BAD, BCAR1, BCL2, BIRC2, BIRC3, BIRC4, BRAF, CAPN2, CAV1, CAV2, CAV3, CCND1, CCND2, CCND3, CDC42, CHAD, COL11A1, COL11A2, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A2, COL4A4, COL4A6, COL5A1, COL5A2, COL5A3, COL6A1, COL6A2, COL6A3, COL6A6, COMP, CRK, CRKL, CTNNB1, DIAPH1, DOCK1, EGF, EGFR, ELK1, ERBB2, FARP2, FIGF, FLNA, FLNB, FLNC, FLT1, FN1, FYN, GRB2, GRLF1, GSK3B, HGF, HRAS, IBSP, IGF1, IGF1R, ILK, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAV, ITGB1, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, JUN, KDR, LAMA1, LAMA2, LAMA3, LAMA4, LAMA5, LAMB1, LAMB2, LAMB3, LAMB4, LAMC1, LAMC2, LAMC3, LOC653852, MAP2K1, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MET, MLCK, MRCL3, MRLC2, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLK, MYLK2, MYLPF, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PARVA, PARVB, PARVG, PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, PDGFRB, PDPK1, PGF, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIP5K1C, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PRKCA, PRKCB1, PRKCG, PTEN, PTK2, PXN, RAC1, RAC2, RAC3, RAF1, RAP1A, RAP1B, RAPGEF1, RELN, RHOA, ROCK1, ROCK2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SPP1, SRC, THBS1, THBS2, THBS3, THBS4, TLN1, TLN2, TNC, TNN, TNR, TNXB, VASP, VAV1, VAV2, VAV3, VCL, VEGFA, VEGFB, VEGFC, VTN, VWF, ZYX 185 ACTB(2), ACTG1(1), ACTN2(4), ACTN3(1), ACTN4(4), AKT1(12), AKT2(1), AKT3(2), ARHGAP5(3), BAD(1), BRAF(2), CAPN2(2), CAV1(1), CCND1(1), CCND3(5), COL11A1(2), COL11A2(1), COL1A1(6), COL1A2(3), COL2A1(3), COL3A1(1), COL4A1(4), COL4A2(2), COL4A4(1), COL4A6(3), COL5A1(2), COL5A2(4), COL5A3(4), COL6A3(5), COL6A6(4), COMP(3), CRKL(1), EGF(2), EGFR(4), ELK1(2), ERBB2(4), FARP2(3), FIGF(1), FLNA(4), FLNB(7), FLNC(8), FLT1(2), FN1(3), GRB2(1), GRLF1(4), HGF(3), IGF1(1), IGF1R(1), ILK(2), ITGA1(3), ITGA10(1), ITGA11(4), ITGA2(2), ITGA2B(2), ITGA4(1), ITGA6(3), ITGA7(5), ITGA8(2), ITGAV(3), ITGB1(2), ITGB3(2), ITGB4(4), ITGB5(2), ITGB8(1), JUN(1), KDR(2), LAMA1(6), LAMA2(7), LAMA3(6), LAMA4(4), LAMB1(3), LAMB2(3), LAMB3(4), LAMB4(6), LAMC1(2), LAMC2(1), LAMC3(1), MAP2K1(1), MAPK1(1), MAPK10(1), MAPK3(1), MAPK8(2), MET(4), MYL7(1), MYLK(5), PAK1(2), PAK2(1), PAK3(1), PAK7(1), PARVA(1), PDGFB(1), PDGFRA(3), PDGFRB(2), PIK3CA(168), PIK3CB(3), PIK3CG(2), PIK3R1(14), PIK3R3(1), PIP5K1C(3), PPP1R12A(1), PRKCG(1), PTEN(15), PTK2(1), PXN(1), RAF1(1), RAPGEF1(3), RELN(10), RHOA(2), ROCK1(1), ROCK2(2), SHC1(1), SHC3(1), SHC4(2), SOS1(3), SOS2(1), SPP1(1), THBS1(3), THBS3(1), THBS4(1), TLN1(7), TLN2(4), TNC(3), TNN(3), TNR(1), TNXB(3), VAV1(1), VAV3(1), VCL(3), VWF(6) 263403231 529 325 378 116 112 131 163 29 86 8 <1.00e-15 <5.98e-15 2 HSA04210_APOPTOSIS Genes involved in apoptosis AIFM1, AKT1, AKT2, AKT3, APAF1, ATM, BAD, BAX, BCL2, BCL2L1, BID, BIRC2, BIRC3, BIRC4, CAPN1, CAPN2, CASP10, CASP3, CASP6, CASP7, CASP8, CASP9, CFLAR, CHP, CHUK, CSF2RB, CYCS, DFFA, DFFB, ENDOG, FADD, FAS, FASLG, IKBKB, IKBKG, IL1A, IL1B, IL1R1, IL1RAP, IL3, IL3RA, IRAK1, IRAK2, IRAK3, IRAK4, MAP3K14, MYD88, NFKB1, NFKB2, NFKBIA, NGFB, NTRK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RELA, RIPK1, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFRSF1A, TNFSF10, TP53, TRADD, TRAF2 79 AKT1(12), AKT2(1), AKT3(2), APAF1(1), ATM(9), BAD(1), BID(4), CAPN1(3), CAPN2(2), CASP6(1), CASP8(2), CSF2RB(2), DFFB(2), FAS(1), FASLG(1), IKBKB(2), IL1A(1), IL1R1(1), IL1RAP(2), IL3RA(1), IRAK1(1), IRAK2(2), IRAK3(1), IRAK4(2), NFKB1(1), NFKB2(4), NTRK1(1), PIK3CA(168), PIK3CB(3), PIK3CG(2), PIK3R1(14), PIK3R3(1), PPP3CA(3), PPP3CB(2), PRKACA(1), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), RELA(1), RIPK1(3), TNFRSF10D(1), TNFRSF1A(1), TP53(142) 59436624 408 310 210 20 82 90 118 15 100 3 <1.00e-15 <5.98e-15 3 HSA04010_MAPK_SIGNALING_PATHWAY Genes involved in MAPK signaling pathway ACVR1B, ACVR1C, AKT1, AKT2, AKT3, ARRB1, ARRB2, ATF2, ATF4, BDNF, BRAF, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1F, CACNA1G, CACNA1H, CACNA1I, CACNA1S, CACNA2D1, CACNA2D2, CACNA2D3, CACNA2D4, CACNB1, CACNB2, CACNB3, CACNB4, CACNG1, CACNG2, CACNG3, CACNG4, CACNG5, CACNG6, CACNG7, CACNG8, CASP3, CD14, CDC25B, CDC42, CHP, CHUK, CRK, CRKL, DAXX, DDIT3, DUSP1, DUSP10, DUSP14, DUSP16, DUSP2, DUSP3, DUSP4, DUSP5, DUSP6, DUSP7, DUSP8, DUSP9, ECSIT, EGF, EGFR, ELK1, ELK4, EVI1, FAS, FASLG, FGF1, FGF10, FGF11, FGF12, FGF13, FGF14, FGF16, FGF17, FGF18, FGF19, FGF2, FGF20, FGF21, FGF22, FGF23, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGFR1, FGFR2, FGFR3, FGFR4, FLNA, FLNB, FLNC, FOS, GADD45A, GADD45B, GADD45G, GNA12, GNG12, GRB2, HRAS, IKBKB, IKBKG, IL1A, IL1B, IL1R1, IL1R2, JUN, JUND, KRAS, LOC653852, MAP2K1, MAP2K1IP1, MAP2K2, MAP2K3, MAP2K4, MAP2K5, MAP2K6, MAP2K7, MAP3K1, MAP3K10, MAP3K12, MAP3K13, MAP3K14, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K6, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAP3K8, MAP4K1, MAP4K2, MAP4K3, MAP4K4, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK7, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, MAPKAPK2, MAPKAPK3, MAPKAPK5, MAPT, MAX, MEF2C, MKNK1, MKNK2, MOS, MRAS, MYC, NF1, NFATC2, NFATC4, NFKB1, NFKB2, NGFB, NLK, NR4A1, NRAS, NTF3, NTF5, NTRK1, NTRK2, PAK1, PAK2, PDGFA, PDGFB, PDGFRA, PDGFRB, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PPM1A, PPM1B, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PPP5C, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, PTPN5, PTPN7, PTPRR, RAC1, RAC2, RAC3, RAF1, RAP1A, RAP1B, RAPGEF2, RASA1, RASA2, RASGRF1, RASGRF2, RASGRP1, RASGRP2, RASGRP3, RASGRP4, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA4, RPS6KA5, RPS6KA6, RRAS, RRAS2, SOS1, SOS2, SRF, STK3, STK4, STMN1, TAOK1, TAOK2, TAOK3, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TNF, TNFRSF1A, TP53, TRAF2, TRAF6, ZAK 231 ACVR1B(4), ACVR1C(1), AKT1(12), AKT2(1), AKT3(2), ARRB1(1), ATF4(1), BDNF(1), BRAF(2), CACNA1A(5), CACNA1B(1), CACNA1C(4), CACNA1D(4), CACNA1E(8), CACNA1F(6), CACNA1G(5), CACNA1I(2), CACNA1S(1), CACNA2D1(4), CACNA2D2(2), CACNA2D3(5), CACNA2D4(1), CACNB1(1), CACNB2(2), CACNG2(1), CACNG3(2), CACNG4(1), CACNG6(1), CD14(1), CDC25B(3), CRKL(1), DUSP10(1), DUSP16(3), DUSP6(1), DUSP7(1), DUSP9(1), EGF(2), EGFR(4), ELK1(2), FAS(1), FASLG(1), FGF11(1), FGF13(2), FGF18(2), FGF23(1), FGF3(1), FGF5(1), FGF6(1), FGF7(2), FGFR2(2), FGFR4(3), FLNA(4), FLNB(7), FLNC(8), GRB2(1), IKBKB(2), IL1A(1), IL1R1(1), IL1R2(3), JUN(1), KRAS(1), MAP2K1(1), MAP2K3(1), MAP2K4(18), MAP2K5(1), MAP3K1(53), MAP3K10(4), MAP3K12(2), MAP3K13(3), MAP3K4(3), MAP3K5(1), MAP3K6(1), MAP3K8(2), MAP4K1(1), MAP4K4(1), MAPK1(1), MAPK10(1), MAPK14(1), MAPK3(1), MAPK8(2), MAPK8IP1(1), MAPKAPK3(1), MAPT(1), MAX(1), MEF2C(2), MOS(2), MYC(1), NF1(13), NFATC4(3), NFKB1(1), NFKB2(4), NLK(1), NR4A1(1), NTRK1(1), NTRK2(1), PAK1(2), PAK2(1), PDGFB(1), PDGFRA(3), PDGFRB(2), PLA2G2D(1), PLA2G2F(1), PLA2G3(3), PLA2G4A(6), PLA2G6(2), PPP3CA(3), PPP3CB(2), PRKACA(1), PRKCG(1), PTPN5(2), PTPN7(1), PTPRR(1), RAF1(1), RAPGEF2(1), RASA1(2), RASA2(1), RASGRF1(3), RASGRP2(2), RASGRP4(1), RPS6KA1(1), RPS6KA2(2), RPS6KA3(2), RPS6KA4(1), RPS6KA6(3), SOS1(3), SOS2(1), SRF(1), STK3(1), STK4(1), TAOK1(2), TAOK2(1), TGFB3(1), TGFBR1(2), TNFRSF1A(1), TP53(142), TRAF6(1), ZAK(1) 202419750 491 304 428 74 74 134 70 28 152 33 <1.00e-15 <5.98e-15 4 HSA04810_REGULATION_OF_ACTIN_CYTOSKELETON Genes involved in regulation of actin cytoskeleton ABI2, ACTN1, ACTN2, ACTN3, ACTN4, APC, APC2, ARAF, ARHGEF1, ARHGEF12, ARHGEF4, ARHGEF6, ARHGEF7, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, ARPC5, ARPC5L, BAIAP2, BCAR1, BDKRB1, BDKRB2, BRAF, C3orf10, CD14, CDC42, CFL1, CFL2, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, CRK, CRKL, CSK, CYFIP1, CYFIP2, DIAPH1, DIAPH2, DIAPH3, DOCK1, EGF, EGFR, EZR, F2, F2R, FGD1, FGD3, FGF1, FGF10, FGF11, FGF12, FGF13, FGF14, FGF16, FGF17, FGF18, FGF19, FGF2, FGF20, FGF21, FGF22, FGF23, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGFR1, FGFR2, FGFR3, FGFR4, FN1, GIT1, GNA12, GNA13, GNG12, GRLF1, GSN, HRAS, INS, IQGAP1, IQGAP2, IQGAP3, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAD, ITGAE, ITGAL, ITGAM, ITGAV, ITGAX, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, KRAS, LIMK1, LIMK2, LOC200025, LOC645126, LOC653888, MAP2K1, MAP2K2, MAPK1, MAPK3, MLCK, MOS, MRAS, MRCL3, MRLC2, MSN, MYH10, MYH14, MYH9, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLK, MYLK2, MYLPF, NCKAP1, NCKAP1L, NRAS, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDGFA, PDGFB, PDGFRA, PDGFRB, PFN1, PFN2, PFN3, PFN4, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIP4K2A, PIP4K2B, PIP4K2C, PIP5K1A, PIP5K1B, PIP5K1C, PIP5K3, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PPP1R12B, PTK2, PXN, RAC1, RAC2, RAC3, RAF1, RDX, RHOA, ROCK1, ROCK2, RRAS, RRAS2, SCIN, SLC9A1, SOS1, SOS2, SSH1, SSH2, SSH3, TIAM1, TIAM2, TMSB4X, TMSB4Y, TMSL3, VAV1, VAV2, VAV3, VCL, WAS, WASF1, WASF2, WASL 193 ACTN2(4), ACTN3(1), ACTN4(4), APC(3), ARAF(1), ARHGEF1(5), ARHGEF12(2), ARHGEF4(2), ARHGEF6(1), ARHGEF7(2), ARPC1A(1), ARPC1B(1), ARPC2(2), BAIAP2(1), BDKRB1(2), BRAF(2), C3orf10(1), CD14(1), CHRM1(2), CHRM2(2), CHRM3(1), CHRM5(2), CRKL(1), CYFIP2(2), DIAPH3(1), EGF(2), EGFR(4), EZR(2), F2(2), F2R(2), FGD3(2), FGF11(1), FGF13(2), FGF18(2), FGF23(1), FGF3(1), FGF5(1), FGF6(1), FGF7(2), FGFR2(2), FGFR4(3), FN1(3), GIT1(1), GRLF1(4), GSN(1), IQGAP1(1), IQGAP2(2), IQGAP3(3), ITGA1(3), ITGA10(1), ITGA11(4), ITGA2(2), ITGA2B(2), ITGA4(1), ITGA6(3), ITGA7(5), ITGA8(2), ITGAD(1), ITGAL(1), ITGAM(1), ITGAV(3), ITGAX(2), ITGB1(2), ITGB2(3), ITGB3(2), ITGB4(4), ITGB5(2), ITGB8(1), KRAS(1), LIMK1(3), LIMK2(1), MAP2K1(1), MAPK1(1), MAPK3(1), MOS(2), MSN(1), MYH10(4), MYH14(5), MYH9(5), MYL7(1), MYLK(5), NCKAP1(3), NCKAP1L(3), PAK1(2), PAK2(1), PAK3(1), PAK7(1), PDGFB(1), PDGFRA(3), PDGFRB(2), PIK3CA(168), PIK3CB(3), PIK3CG(2), PIK3R1(14), PIK3R3(1), PIP4K2A(1), PIP4K2C(5), PIP5K1A(1), PIP5K1C(3), PPP1R12A(1), PTK2(1), PXN(1), RAF1(1), RDX(1), RHOA(2), ROCK1(1), ROCK2(2), SCIN(2), SOS1(3), SOS2(1), SSH1(1), SSH2(1), SSH3(2), TIAM1(1), TIAM2(4), VAV1(1), VAV3(1), VCL(3), WAS(1), WASF1(1), WASL(1) 197302092 416 288 275 90 103 88 140 24 61 0 <1.00e-15 <5.98e-15 5 ARFPATHWAY Cyclin-dependent kinase inhibitor 2A is a tumor suppressor that induces G1 arrest and can activate the p53 pathway, leading to G2/M arrest. ABL1, CDKN2A, E2F1, MDM2, MYC, PIK3CA, PIK3R1, POLR1A, POLR1B, POLR1C, POLR1D, RAC1, RB1, TBX2, TP53, TWIST1 15 ABL1(2), E2F1(2), MDM2(1), MYC(1), PIK3CA(168), PIK3R1(14), POLR1A(1), POLR1B(2), POLR1C(2), POLR1D(1), RB1(9), TP53(142) 14867268 345 285 157 11 72 53 112 11 97 0 <1.00e-15 <5.98e-15 6 HSA04910_INSULIN_SIGNALING_PATHWAY Genes involved in insulin signaling pathway ACACA, ACACB, AKT1, AKT2, AKT3, ARAF, BAD, BRAF, CALM1, CALM2, CALM3, CALML3, CALML6, CBL, CBLB, CBLC, CRK, CRKL, EIF4EBP1, ELK1, EXOC7, FASN, FBP1, FBP2, FLOT1, FLOT2, FOXO1, FRAP1, G6PC, G6PC2, GCK, GRB2, GSK3B, GYS1, GYS2, HRAS, IKBKB, INPP5D, INS, INSR, IRS1, IRS2, IRS4, KIAA1303, KRAS, LIPE, MAP2K1, MAP2K2, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MKNK1, MKNK2, NRAS, PCK1, PCK2, PDE3A, PDE3B, PDPK1, PFKL, PFKM, PFKP, PHKA1, PHKA2, PHKB, PHKG1, PHKG2, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PKLR, PKM2, PPARGC1A, PPP1CA, PPP1CB, PPP1CC, PPP1R3A, PPP1R3B, PPP1R3C, PPP1R3D, PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKACA, PRKACB, PRKACG, PRKAG1, PRKAG2, PRKAG3, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCI, PRKCZ, PRKX, PRKY, PTPN1, PTPRF, PYGB, PYGL, PYGM, RAF1, RAPGEF1, RHEB, RHOQ, RPS6, RPS6KB1, RPS6KB2, SH2B2, SHC1, SHC2, SHC3, SHC4, SKIP, SLC2A4, SOCS1, SOCS2, SOCS3, SOCS4, SORBS1, SOS1, SOS2, SREBF1, TRIP10, TSC1, TSC2 123 ACACA(1), ACACB(8), AKT1(12), AKT2(1), AKT3(2), ARAF(1), BAD(1), BRAF(2), CBLB(7), CBLC(3), CRKL(1), ELK1(2), G6PC2(1), GCK(2), GRB2(1), GYS1(5), GYS2(1), IKBKB(2), INPP5D(2), INSR(2), IRS1(1), IRS4(1), KRAS(1), LIPE(2), MAP2K1(1), MAPK1(1), MAPK10(1), MAPK3(1), MAPK8(2), PCK1(1), PCK2(1), PDE3A(6), PDE3B(1), PFKM(3), PFKP(2), PHKA2(4), PHKB(2), PHKG2(1), PIK3CA(168), PIK3CB(3), PIK3CG(2), PIK3R1(14), PIK3R3(1), PPARGC1A(1), PPP1R3A(6), PPP1R3B(1), PRKAA2(2), PRKAB1(1), PRKACA(1), PRKAG2(1), PRKAG3(2), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), PRKCI(1), PRKCZ(1), PTPRF(3), PYGB(3), PYGL(1), PYGM(2), RAF1(1), RAPGEF1(3), RPS6(1), RPS6KB2(3), SHC1(1), SHC3(1), SHC4(2), SLC2A4(1), SOCS4(1), SORBS1(4), SOS1(3), SOS2(1), TRIP10(3), TSC1(2), TSC2(2) 107951961 335 261 185 44 86 81 112 14 42 0 <1.00e-15 <5.98e-15 7 HSA04070_PHOSPHATIDYLINOSITOL_SIGNALING_SYSTEM Genes involved in phosphatidylinositol signaling system CALM1, CALM2, CALM3, CALML3, CALML6, CARKL, CDIPT, CDS1, CDS2, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKI, DGKQ, DGKZ, FN3K, IMPA1, IMPA2, INPP1, INPP4A, INPP4B, INPP5A, INPP5B, INPP5D, INPP5E, INPPL1, ITGB1BP3, ITPK1, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, OCRL, PI4KA, PI4KB, PIB5PA, PIK3C2A, PIK3C2B, PIK3C2G, PIK3C3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIP4K2A, PIP4K2B, PIP4K2C, PIP5K1A, PIP5K1B, PIP5K1C, PIP5K3, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCD3, PLCD4, PLCE1, PLCG1, PLCG2, PLCZ1, PRKCA, PRKCB1, PRKCG, PTEN, PTPMT1, SKIP, SYNJ1, SYNJ2 70 CDS1(2), DGKA(3), DGKD(1), DGKE(1), DGKG(4), DGKH(1), DGKI(5), IMPA1(1), INPP4A(2), INPP4B(3), INPP5B(4), INPP5D(2), INPPL1(1), ITGB1BP3(1), ITPK1(1), ITPKB(7), ITPR1(7), ITPR3(4), OCRL(3), PI4KA(3), PI4KB(1), PIK3C2A(2), PIK3C2B(2), PIK3C2G(1), PIK3C3(2), PIK3CA(168), PIK3CB(3), PIK3CG(2), PIK3R1(14), PIK3R3(1), PIP4K2A(1), PIP4K2C(5), PIP5K1A(1), PIP5K1C(3), PLCB1(3), PLCB2(2), PLCB3(1), PLCB4(6), PLCD1(1), PLCD3(2), PLCE1(5), PLCG1(4), PLCG2(2), PLCZ1(1), PRKCG(1), PTEN(15), SYNJ2(1) 89527581 306 254 165 39 77 50 113 14 50 2 <1.00e-15 <5.98e-15 8 HSA04630_JAK_STAT_SIGNALING_PATHWAY Genes involved in Jak-STAT signaling pathway AKT1, AKT2, AKT3, BCL2L1, CBL, CBLB, CBLC, CCND1, CCND2, CCND3, CISH, CLCF1, CNTF, CNTFR, CREBBP, CRLF2, CSF2, CSF2RA, CSF2RB, CSF3, CSF3R, CTF1, EP300, EPO, EPOR, GH1, GH2, GHR, GRB2, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IFNE1, IFNG, IFNGR1, IFNGR2, IFNK, IFNW1, IL10, IL10RA, IL10RB, IL11, IL11RA, IL12A, IL12B, IL12RB1, IL12RB2, IL13, IL13RA1, IL13RA2, IL15, IL15RA, IL19, IL2, IL20, IL20RA, IL21, IL21R, IL22, IL22RA1, IL22RA2, IL23A, IL23R, IL24, IL26, IL28A, IL28B, IL28RA, IL29, IL2RA, IL2RB, IL2RG, IL3, IL3RA, IL4, IL4R, IL5, IL5RA, IL6, IL6R, IL6ST, IL7, IL7R, IL9, IL9R, IRF9, JAK1, JAK2, JAK3, LEP, LEPR, LIF, LIFR, MPL, MYC, OSM, OSMR, PIAS1, PIAS2, PIAS3, PIAS4, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIM1, PRL, PRLR, PTPN11, PTPN6, SOCS1, SOCS2, SOCS3, SOCS4, SOCS5, SOCS7, SOS1, SOS2, SPRED1, SPRED2, SPRY1, SPRY2, SPRY3, SPRY4, STAM, STAM2, STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6, TPO, TSLP, TYK2 148 AKT1(12), AKT2(1), AKT3(2), CBLB(7), CBLC(3), CCND1(1), CCND3(5), CNTFR(1), CREBBP(2), CSF2RA(1), CSF2RB(2), CSF3R(2), EP300(3), EPOR(1), GH2(1), GHR(2), GRB2(1), IFNA10(1), IFNA14(1), IFNA2(2), IFNA4(1), IFNAR2(1), IFNB1(1), IFNK(1), IL10RA(1), IL10RB(3), IL11RA(1), IL12A(1), IL12B(1), IL12RB1(2), IL13RA1(1), IL13RA2(2), IL15(1), IL2(1), IL21(1), IL21R(1), IL22(1), IL22RA1(1), IL22RA2(1), IL23R(3), IL28B(3), IL28RA(1), IL2RG(1), IL3RA(1), IL5RA(1), IL6(2), IL6R(1), IL6ST(3), IRF9(2), JAK1(1), JAK2(2), JAK3(1), LEPR(3), LIF(3), LIFR(4), MYC(1), OSMR(3), PIAS2(1), PIAS4(2), PIK3CA(168), PIK3CB(3), PIK3CG(2), PIK3R1(14), PIK3R3(1), PRLR(1), SOCS4(1), SOCS5(1), SOS1(3), SOS2(1), SPRED1(2), SPRED2(1), STAM(1), STAM2(1), STAT1(1), STAT2(1), STAT3(1), STAT4(5), STAT5B(4), TPO(6), TSLP(1), TYK2(3) 106057302 335 251 183 40 87 64 116 18 47 3 <1.00e-15 <5.98e-15 9 HSA04012_ERBB_SIGNALING_PATHWAY Genes involved in ErbB signaling pathway ABL1, ABL2, AKT1, AKT2, AKT3, ARAF, AREG, BAD, BRAF, BTC, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CBL, CBLB, CBLC, CDKN1A, CDKN1B, CRK, CRKL, EGF, EGFR, EIF4EBP1, ELK1, ERBB2, ERBB3, ERBB4, EREG, FRAP1, GAB1, GRB2, GSK3B, HBEGF, HRAS, JUN, KRAS, MAP2K1, MAP2K2, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MYC, NCK1, NCK2, NRAS, NRG1, NRG2, NRG3, NRG4, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PLCG2, PRKCA, PRKCB1, PRKCG, PTK2, RAF1, RPS6KB1, RPS6KB2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SRC, STAT5A, STAT5B, TGFA 82 ABL1(2), ABL2(2), AKT1(12), AKT2(1), AKT3(2), ARAF(1), BAD(1), BRAF(2), BTC(1), CAMK2A(1), CAMK2D(3), CBLB(7), CBLC(3), CDKN1B(5), CRKL(1), EGF(2), EGFR(4), ELK1(2), ERBB2(4), ERBB3(8), ERBB4(4), GAB1(1), GRB2(1), JUN(1), KRAS(1), MAP2K1(1), MAP2K4(18), MAPK1(1), MAPK10(1), MAPK3(1), MAPK8(2), MYC(1), NRG3(1), PAK1(2), PAK2(1), PAK3(1), PAK7(1), PIK3CA(168), PIK3CB(3), PIK3CG(2), PIK3R1(14), PIK3R3(1), PLCG1(4), PLCG2(2), PRKCG(1), PTK2(1), RAF1(1), RPS6KB2(3), SHC1(1), SHC3(1), SHC4(2), SOS1(3), SOS2(1), STAT5B(4), TGFA(1) 72661719 316 246 164 29 72 58 116 19 51 0 <1.00e-15 <5.98e-15 10 ST_INTEGRIN_SIGNALING_PATHWAY Integrins are transmembrane receptors that mediate cell growth, survival, and migration by binding to ligands in the extracellular matrix. ABL1, ACK1, ACTN1, ACTR2, ACTR3, AKT1, AKT2, AKT3, ANGPTL2, ARHGEF6, ARHGEF7, BCAR1, BRAF, CAV1, CDC42, CDKN2A, CRK, CSE1L, DDEF1, DOCK1, EPHB2, FYN, GRAF, GRB2, GRB7, GRF2, GRLF1, ILK, ITGA1, ITGA10, ITGA11, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGB3BP, MAP2K4, MAP2K7, MAP3K11, MAPK1, MAPK10, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, MRAS, MYLK, MYLK2, P4HB, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PIK3CA, PIK3CB, PKLR, PLCG1, PLCG2, PTEN, PTK2, RAF1, RALA, RHO, ROCK1, ROCK2, SHC1, SOS1, SOS2, SRC, TERF2IP, TLN1, TLN2, VASP, WAS, ZYX 74 ABL1(2), AKT1(12), AKT2(1), AKT3(2), ARHGEF6(1), ARHGEF7(2), BRAF(2), CAV1(1), CSE1L(2), EPHB2(1), GRB2(1), GRB7(3), GRLF1(4), ILK(2), ITGA1(3), ITGA10(1), ITGA11(4), ITGA2(2), ITGA4(1), ITGA6(3), ITGA7(5), ITGA8(2), ITGB3BP(1), MAP2K4(18), MAP3K11(1), MAPK1(1), MAPK10(1), MAPK8(2), MAPK8IP1(1), MYLK(5), PAK1(2), PAK2(1), PAK3(1), PAK7(1), PIK3CA(168), PIK3CB(3), PLCG1(4), PLCG2(2), PTEN(15), PTK2(1), RAF1(1), RHO(2), ROCK1(1), ROCK2(2), SHC1(1), SOS1(3), SOS2(1), TERF2IP(2), TLN1(7), TLN2(4), WAS(1) 87730266 310 241 160 37 74 59 111 10 54 2 <1.00e-15 <5.98e-15 11 HSA04620_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY Genes involved in Toll-like receptor signaling pathway AKT1, AKT2, AKT3, CASP8, CCL3, CCL4, CCL5, CD14, CD40, CD80, CD86, CHUK, CXCL10, CXCL11, CXCL9, FADD, FOS, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IKBKB, IKBKE, IKBKG, IL12A, IL12B, IL1B, IL6, IL8, IRAK1, IRAK4, IRF3, IRF5, IRF7, JUN, LBP, LY96, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAP3K8, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK8, MAPK9, MYD88, NFKB1, NFKB2, NFKBIA, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, RAC1, RELA, RIPK1, SPP1, STAT1, TBK1, TICAM1, TICAM2, TIRAP, TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TNF, TOLLIP, TRAF3, TRAF6 93 AKT1(12), AKT2(1), AKT3(2), CASP8(2), CD14(1), CD40(1), CD86(1), IFNA10(1), IFNA14(1), IFNA2(2), IFNA4(1), IFNAR2(1), IFNB1(1), IKBKB(2), IKBKE(1), IL12A(1), IL12B(1), IL6(2), IRAK1(1), IRAK4(2), IRF3(1), JUN(1), LBP(1), MAP2K1(1), MAP2K3(1), MAP2K4(18), MAP3K8(2), MAPK1(1), MAPK10(1), MAPK14(1), MAPK3(1), MAPK8(2), NFKB1(1), NFKB2(4), PIK3CA(168), PIK3CB(3), PIK3CG(2), PIK3R1(14), PIK3R3(1), RELA(1), RIPK1(3), SPP1(1), STAT1(1), TICAM1(2), TIRAP(2), TLR1(1), TLR2(1), TLR3(1), TLR4(7), TLR5(1), TLR7(3), TLR8(2), TRAF6(1) 63743082 288 235 136 22 71 54 104 7 49 3 <1.00e-15 <5.98e-15 12 PHOSPHATIDYLINOSITOL_SIGNALING_SYSTEM ACVR1, ACVR1B, ACVRL1, AKT1, AURKB, BMPR1A, BMPR2, BUB1, CDC2L5, CDIPT, CDKL1, CDKL2, CDS1, CDS2, CLK1, CLK2, CLK4, COL4A3BP, CSNK2A1, CSNK2A1, CSNK2A1P, CSNK2A2, CSNK2B, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKQ, DGKZ, IMPA1, INPP1, INPP4A, INPP4B, INPP5A, INPPL1, ITPKA, ITPKB, MAP3K10, MOS, NEK1, NEK3, OCRL, PAK4, PCTK1, PCTK2, PIK3C2A, PIK3C2B, PIK3C2G, PIK3CA, PIK3CB, PIK3CG, PIK4CA, PIK4CA, LOC220686, PIM2, PIP5K2B, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCG1, PLCG2, PLK3, PRKACA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCQ, PRKCZ, PRKD1, PRKG1, RAF1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA4, RPS6KB1, STK11, TGFBR1, VRK1 79 ACVR1(1), ACVR1B(4), AKT1(12), BMPR2(2), CDKL1(2), CDKL2(1), CDS1(2), CLK1(1), CLK4(1), COL4A3BP(1), CSNK2A1(1), CSNK2A2(1), DGKA(3), DGKD(1), DGKE(1), DGKG(4), DGKH(1), IMPA1(1), INPP4A(2), INPP4B(3), INPPL1(1), ITPKB(7), MAP3K10(4), MOS(2), NEK1(1), NEK3(2), OCRL(3), PIK3C2A(2), PIK3C2B(2), PIK3C2G(1), PIK3CA(168), PIK3CB(3), PIK3CG(2), PIM2(1), PLCB1(3), PLCB2(2), PLCB3(1), PLCB4(6), PLCD1(1), PLCG1(4), PLCG2(2), PRKACA(1), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), PRKCG(1), PRKCH(1), PRKCQ(2), PRKCZ(1), PRKD1(1), PRKG1(1), RAF1(1), RPS6KA1(1), RPS6KA2(2), RPS6KA3(2), RPS6KA4(1), TGFBR1(2) 82032093 283 234 132 33 74 56 112 13 28 0 <1.00e-15 <5.98e-15 13 HSA04650_NATURAL_KILLER_CELL_MEDIATED_CYTOTOXICITY Genes involved in natural killer cell mediated cytotoxicity ARAF, BID, BRAF, CASP3, CD244, CD247, CD48, CHP, CSF2, FAS, FASLG, FCER1G, FCGR3A, FCGR3B, FYN, GRB2, GZMB, HCST, HLA-A, HLA-B, HLA-C, HLA-E, HLA-G, HRAS, ICAM1, ICAM2, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IFNG, IFNGR1, IFNGR2, ITGAL, ITGB2, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DS1, KIR2DS2, KIR3DL1, KIR3DL2, KLRC1, KLRC2, KLRC3, KLRD1, KLRK1, KRAS, LAT, LCK, LCP2, LOC652578, MAP2K1, MAP2K2, MAPK1, MAPK3, MICA, MICB, NCR1, NCR2, NCR3, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NRAS, PAK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PLCG2, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRF1, PRKCA, PRKCB1, PRKCG, PTK2B, PTPN11, PTPN6, RAC1, RAC2, RAC3, RAF1, SH2D1A, SH2D1B, SH3BP2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SYK, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFSF10, TYROBP, ULBP1, ULBP2, ULBP3, VAV1, VAV2, VAV3, ZAP70 122 ARAF(1), BID(4), BRAF(2), CD244(1), FAS(1), FASLG(1), GRB2(1), HLA-A(4), HLA-C(3), HLA-E(2), HLA-G(2), IFNA10(1), IFNA14(1), IFNA2(2), IFNA4(1), IFNAR2(1), IFNB1(1), ITGAL(1), ITGB2(3), KIR2DL3(1), KIR2DL4(1), KIR3DL2(4), KLRC1(3), KLRC2(1), KLRC3(1), KLRK1(2), KRAS(1), LAT(1), LCP2(1), MAP2K1(1), MAPK1(1), MAPK3(1), NCR2(1), NFAT5(1), NFATC3(3), NFATC4(3), PAK1(2), PIK3CA(168), PIK3CB(3), PIK3CG(2), PIK3R1(14), PIK3R3(1), PLCG1(4), PLCG2(2), PPP3CA(3), PPP3CB(2), PRF1(2), PRKCG(1), PTK2B(3), RAF1(1), SH3BP2(1), SHC1(1), SHC3(1), SHC4(2), SOS1(3), SOS2(1), TNFRSF10D(1), ULBP3(2), VAV1(1), VAV3(1), ZAP70(1) 80572947 283 228 142 36 72 51 116 7 37 0 <1.00e-15 <5.98e-15 14 HSA04670_LEUKOCYTE_TRANSENDOTHELIAL_MIGRATION Genes involved in Leukocyte transendothelial migration ACTN1, ACTN2, ACTN3, ACTN4, ARHGAP5, BCAR1, CD99, CDC42, CDH5, CLDN1, CLDN10, CLDN11, CLDN14, CLDN15, CLDN16, CLDN17, CLDN18, CLDN19, CLDN2, CLDN20, CLDN22, CLDN23, CLDN3, CLDN4, CLDN5, CLDN6, CLDN7, CLDN8, CLDN9, CTNNA1, CTNNA2, CTNNA3, CTNNB1, CTNND1, CXCL12, CXCR4, CYBA, CYBB, ESAM, EZR, F11R, GNAI1, GNAI2, GNAI3, GRLF1, ICAM1, ITGA4, ITGAL, ITGAM, ITGB1, ITGB2, ITK, JAM2, JAM3, MAPK11, MAPK12, MAPK13, MAPK14, MLLT4, MMP2, MMP9, MRCL3, MRLC2, MSN, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLPF, NCF1, NCF2, NCF4, NOX1, NOX3, OCLN, PECAM1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PLCG2, PRKCA, PRKCB1, PRKCG, PTK2, PTK2B, PTPN11, PXN, RAC1, RAC2, RAP1A, RAP1B, RAPGEF3, RAPGEF4, RASSF5, RHOA, RHOH, ROCK1, ROCK2, SIPA1, THY1, TXK, VASP, VAV1, VAV2, VAV3, VCAM1, VCL 103 ACTN2(4), ACTN3(1), ACTN4(4), ARHGAP5(3), CD99(2), CLDN11(1), CLDN15(1), CLDN17(1), CLDN19(1), CLDN6(1), CTNNA1(1), CTNNA2(2), CTNNA3(2), CTNND1(1), CYBB(1), ESAM(2), EZR(2), F11R(1), GNAI1(1), GNAI2(1), GRLF1(4), ITGA4(1), ITGAL(1), ITGAM(1), ITGB1(2), ITGB2(3), ITK(3), MAPK14(1), MLLT4(7), MMP9(1), MSN(1), MYL7(1), NCF2(2), NOX1(1), NOX3(1), PIK3CA(168), PIK3CB(3), PIK3CG(2), PIK3R1(14), PIK3R3(1), PLCG1(4), PLCG2(2), PRKCG(1), PTK2(1), PTK2B(3), PXN(1), RAPGEF3(2), RAPGEF4(2), RASSF5(1), RHOA(2), ROCK1(1), ROCK2(2), SIPA1(1), TXK(1), VAV1(1), VAV3(1), VCAM1(2), VCL(3) 88595208 282 228 142 42 77 46 107 7 45 0 <1.00e-15 <5.98e-15 15 HSA04664_FC_EPSILON_RI_SIGNALING_PATHWAY Genes involved in Fc epsilon RI signaling pathway AKT1, AKT2, AKT3, BTK, CSF2, FCER1A, FCER1G, FYN, GAB2, GRB2, HRAS, IL13, IL3, IL4, IL5, INPP5D, KRAS, LAT, LCP2, LYN, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK8, MAPK9, MS4A2, NRAS, PDK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCG1, PLCG2, PRKCA, PRKCB1, PRKCD, PRKCE, RAC1, RAC2, RAC3, RAF1, SOS1, SOS2, SYK, TNF, VAV1, VAV2, VAV3 69 AKT1(12), AKT2(1), AKT3(2), BTK(2), FCER1A(2), GAB2(1), GRB2(1), INPP5D(2), KRAS(1), LAT(1), LCP2(1), LYN(3), MAP2K1(1), MAP2K3(1), MAP2K4(18), MAPK1(1), MAPK10(1), MAPK14(1), MAPK3(1), MAPK8(2), PDK1(1), PIK3CA(168), PIK3CB(3), PIK3CG(2), PIK3R1(14), PIK3R3(1), PLA2G2D(1), PLA2G2F(1), PLA2G3(3), PLA2G4A(6), PLA2G6(2), PLCG1(4), PLCG2(2), RAF1(1), SOS1(3), SOS2(1), VAV1(1), VAV3(1) 49987665 270 227 117 16 68 56 102 7 37 0 <1.00e-15 <5.98e-15 16 FCER1PATHWAY In mast cells, Fc epsilon receptor 1 activates BTK, PKC, and the MAP kinase pathway to promote degranulation and arachnidonic acid release. BTK, CALM1, CALM2, CALM3, ELK1, FCER1A, FCER1G, FOS, GRB2, HRAS, JUN, LYN, MAP2K1, MAP2K4, MAP2K7, MAP3K1, MAPK1, MAPK3, MAPK8, NFATC1, NFATC2, NFATC3, NFATC4, PAK2, PIK3CA, PIK3R1, PLA2G4A, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCB1, RAF1, SHC1, SOS1, SYK, SYT1, VAV1 36 BTK(2), ELK1(2), FCER1A(2), GRB2(1), JUN(1), LYN(3), MAP2K1(1), MAP2K4(18), MAP3K1(53), MAPK1(1), MAPK3(1), MAPK8(2), NFATC3(3), NFATC4(3), PAK2(1), PIK3CA(168), PIK3R1(14), PLA2G4A(6), PLCG1(4), PPP3CA(3), PPP3CB(2), RAF1(1), SHC1(1), SOS1(3), VAV1(1) 30805320 297 226 154 8 66 36 107 3 57 28 <1.00e-15 <5.98e-15 17 HSA00562_INOSITOL_PHOSPHATE_METABOLISM Genes involved in inositol phosphate metabolism CARKL, FN3K, IMPA1, IMPA2, INPP1, INPP4A, INPP4B, INPP5A, INPP5B, INPP5E, INPPL1, IPMK, ISYNA1, ITGB1BP3, ITPK1, ITPKA, ITPKB, MINPP1, MIOX, OCRL, PI4KA, PI4KB, PIB5PA, PIK3C3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIP4K2A, PIP4K2B, PIP4K2C, PIP5K1A, PIP5K1B, PIP5K1C, PIP5K3, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCD3, PLCD4, PLCE1, PLCG1, PLCG2, PLCZ1, PTEN, PTPMT1, SKIP, SYNJ1, SYNJ2 44 IMPA1(1), INPP4A(2), INPP4B(3), INPP5B(4), INPPL1(1), IPMK(1), ITGB1BP3(1), ITPK1(1), ITPKB(7), MINPP1(1), OCRL(3), PI4KA(3), PI4KB(1), PIK3C3(2), PIK3CA(168), PIK3CB(3), PIK3CG(2), PIP4K2A(1), PIP4K2C(5), PIP5K1A(1), PIP5K1C(3), PLCB1(3), PLCB2(2), PLCB3(1), PLCB4(6), PLCD1(1), PLCD3(2), PLCE1(5), PLCG1(4), PLCG2(2), PLCZ1(1), PTEN(15), SYNJ2(1) 51750504 257 222 118 23 69 39 105 8 34 2 <1.00e-15 <5.98e-15 18 TCRPATHWAY T cell receptors bind to foreign peptides presented by MHC molecules and induce T cell activation. CALM1, CALM2, CALM3, CD3D, CD3E, CD3G, CD3Z, ELK1, FOS, FYN, GRB2, HRAS, JUN, LAT, LCK, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKBIA, PIK3CA, PIK3R1, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCA, PRKCB1, PTPN7, RAC1, RAF1, RASA1, RELA, SHC1, SOS1, SYT1, TRA@, TRB@, VAV1, ZAP70 42 CD3E(1), CD3G(1), ELK1(2), GRB2(1), JUN(1), LAT(1), MAP2K1(1), MAP2K4(18), MAP3K1(53), MAPK3(1), MAPK8(2), NFATC3(3), NFATC4(3), NFKB1(1), PIK3CA(168), PIK3R1(14), PLCG1(4), PPP3CA(3), PPP3CB(2), PTPN7(1), RAF1(1), RASA1(2), RELA(1), SHC1(1), SOS1(3), VAV1(1), ZAP70(1) 34815183 291 222 149 11 64 32 106 2 59 28 <1.00e-15 <5.98e-15 19 GLEEVECPATHWAY The drug Gleevec specifically targets the abnormal bcr-abl protein, an apoptosis inhibitor present in chronic myeloid leukemia. AKT1, BCL2, BCR, CRKL, FOS, GRB2, HRAS, JAK2, JUN, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, MYC, PIK3CA, PIK3R1, RAF1, SOS1, STAT1, STAT5A, STAT5B 22 AKT1(12), BCR(1), CRKL(1), GRB2(1), JAK2(2), JUN(1), MAP2K1(1), MAP2K4(18), MAP3K1(53), MAPK3(1), MAPK8(2), MYC(1), PIK3CA(168), PIK3R1(14), RAF1(1), SOS1(3), STAT1(1), STAT5B(4) 20230821 285 220 133 8 60 39 97 3 58 28 <1.00e-15 <5.98e-15 20 SIG_CHEMOTAXIS Genes related to chemotaxis ACTR2, ACTR3, AKT1, AKT2, AKT3, ANGPTL2, ARHGAP1, ARHGAP4, ARHGEF11, BTK, CDC42, CFL1, CFL2, GDI1, GDI2, INPPL1, ITPR1, ITPR2, ITPR3, LIMK1, MYLK, MYLK2, P101-PI3K, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDK1, PIK3CA, PIK3CD, PIK3CG, PIK3R1, PITX2, PPP1R13B, PTEN, RACGAP1, RHO, ROCK1, ROCK2, RPS4X, SAG, WASF1, WASL 44 AKT1(12), AKT2(1), AKT3(2), ARHGEF11(1), BTK(2), GDI1(3), INPPL1(1), ITPR1(7), ITPR3(4), LIMK1(3), MYLK(5), PAK1(2), PAK2(1), PAK3(1), PAK7(1), PDK1(1), PIK3CA(168), PIK3CG(2), PIK3R1(14), PITX2(1), PTEN(15), RHO(2), ROCK1(1), ROCK2(2), RPS4X(1), WASF1(1), WASL(1) 52170300 255 220 105 25 64 41 103 7 38 2 <1.00e-15 <5.98e-15 21 CELL_CYCLE_KEGG ABL1, ASK, ATM, BUB1, BUB1B, BUB3, CCNA1, CCNA2, CCNB1, CCNB2, CCNB3, CCND2, CCND3, CCNE1, CCNE2, CCNH, CDAN1, CDC14A, CDC14B, CDC14B, CDC14C, CDC2, CDC20, CDC25A, CDC25B, CDC25C, CDC45L, CDC6, CDC7, CDH1, CDK2, CDK4, CDKN1A, CDKN2A, CHEK1, CHEK2, DTX4, E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, EP300, ESPL1, FLJ14001, GADD45A, GSK3B, HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7A, HDAC8, MAD1L1, MAD2L1, MAD2L2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, MPEG1, MPL, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, PLK1, PRKDC, PTPRA, PTTG1, PTTG2, PTTG3, RB1, RBL1, SKP2, SMAD4, SMC1L1, TBC1D8, TFDP1, TGFB1, TP53, WEE1 82 ABL1(2), ATM(9), CCNA2(2), CCNB1(2), CCNB3(3), CCND3(5), CDC25B(3), CDC7(1), CDH1(31), CDK2(1), CHEK2(2), DTX4(1), E2F1(2), E2F3(1), E2F4(2), EP300(3), ESPL1(6), HDAC1(2), HDAC2(2), HDAC3(1), HDAC6(2), HDAC8(2), MAD2L2(1), MCM2(1), MCM3(1), MCM4(2), MCM6(2), MCM7(2), MDM2(1), ORC2L(1), ORC3L(1), PLK1(1), PRKDC(7), PTPRA(1), RB1(9), RBL1(1), SMAD4(1), TBC1D8(1), TP53(142) 82755075 260 219 209 22 28 57 31 14 127 3 <1.00e-15 <5.98e-15 22 HSA04660_T_CELL_RECEPTOR_SIGNALING_PATHWAY Genes involved in T cell receptor signaling pathway AKT1, AKT2, AKT3, BCL10, CARD11, CBL, CBLB, CBLC, CD247, CD28, CD3D, CD3E, CD3G, CD4, CD40LG, CD8A, CD8B, CDC42, CDK4, CHP, CHUK, CSF2, CTLA4, FOS, FYN, GRAP2, GRB2, HRAS, ICOS, IFNG, IKBKB, IKBKG, IL10, IL2, IL4, IL5, ITK, JUN, KRAS, LAT, LCK, LCP2, MALT1, MAP3K14, MAP3K8, NCK1, NCK2, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NRAS, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDCD1, PDK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKCQ, PTPN6, PTPRC, RASGRP1, RHOA, SOS1, SOS2, TEC, TNF, VAV1, VAV2, VAV3, ZAP70 91 AKT1(12), AKT2(1), AKT3(2), CARD11(2), CBLB(7), CBLC(3), CD3E(1), CD3G(1), CD4(1), CD40LG(1), CD8A(1), GRB2(1), IKBKB(2), IL2(1), ITK(3), JUN(1), KRAS(1), LAT(1), LCP2(1), MALT1(1), MAP3K8(2), NFAT5(1), NFATC3(3), NFATC4(3), NFKB1(1), NFKB2(4), PAK1(2), PAK2(1), PAK3(1), PAK7(1), PDK1(1), PIK3CA(168), PIK3CB(3), PIK3CG(2), PIK3R1(14), PIK3R3(1), PLCG1(4), PPP3CA(3), PPP3CB(2), PRKCQ(2), PTPRC(1), RHOA(2), SOS1(3), SOS2(1), TEC(1), VAV1(1), VAV3(1), ZAP70(1) 72247500 274 219 124 29 69 54 111 9 28 3 <1.00e-15 <5.98e-15 23 EGFPATHWAY The epidermal growth factor (EGF) peptide stimulates the EGF receptor to promote cell proliferation via the MAP kinase and Ras pathways. CSNK2A1, EGF, EGFR, ELK1, FOS, GRB2, HRAS, JAK1, JUN, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, RAF1, RASA1, SHC1, SOS1, SRF, STAT1, STAT3, STAT5A 26 CSNK2A1(1), EGF(2), EGFR(4), ELK1(2), GRB2(1), JAK1(1), JUN(1), MAP2K1(1), MAP2K4(18), MAP3K1(53), MAPK3(1), MAPK8(2), PIK3CA(168), PIK3R1(14), PLCG1(4), RAF1(1), RASA1(2), SHC1(1), SOS1(3), SRF(1), STAT1(1), STAT3(1) 27825174 283 218 141 7 63 29 98 7 58 28 <1.00e-15 <5.98e-15 24 PDGFPATHWAY Platelet-derived growth factor (PDGF) receptor is phosphorylated on ligand binding and promotes cell proliferation. CSNK2A1, ELK1, FOS, GRB2, HRAS, JAK1, JUN, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, PDGFA, PDGFRA, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, RAF1, RASA1, SHC1, SOS1, SRF, STAT1, STAT3, STAT5A 25 CSNK2A1(1), ELK1(2), GRB2(1), JAK1(1), JUN(1), MAP2K1(1), MAP2K4(18), MAP3K1(53), MAPK3(1), MAPK8(2), PDGFRA(3), PIK3CA(168), PIK3R1(14), PLCG1(4), RAF1(1), RASA1(2), SHC1(1), SOS1(3), SRF(1), STAT1(1), STAT3(1) 25663326 280 215 138 7 64 28 99 3 58 28 <1.00e-15 <5.98e-15 25 SIG_INSULIN_RECEPTOR_PATHWAY_IN_CARDIAC_MYOCYTES Genes related to the insulin receptor pathway AKT1, AKT2, AKT3, BRD4, CAP1, CBL, CDC42, CDKN2A, F2RL2, FLOT1, FLOT2, FOXO1A, GRB2, GSK3A, GSK3B, IGFBP1, INPPL1, IRS1, IRS2, IRS4, LNPEP, MAPK1, MAPK3, PARD3, PARD6A, PDK1, PIK3CA, PIK3CD, PIK3R1, PPYR1, PSCD3, PTEN, PTPN1, RAF1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SERPINB6, SFN, SHC1, SLC2A4, SORBS1, SOS1, SOS2, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ 48 AKT1(12), AKT2(1), AKT3(2), CAP1(2), F2RL2(1), GRB2(1), GSK3A(1), INPPL1(1), IRS1(1), IRS4(1), MAPK1(1), MAPK3(1), PARD3(3), PDK1(1), PIK3CA(168), PIK3R1(14), PTEN(15), RAF1(1), RPS6KA1(1), RPS6KA2(2), RPS6KA3(2), SHC1(1), SLC2A4(1), SORBS1(4), SOS1(3), SOS2(1), YWHAB(1) 42707145 243 215 93 18 61 41 102 4 33 2 <1.00e-15 <5.98e-15 26 SIG_PIP3_SIGNALING_IN_CARDIAC_MYOCTES Genes related to PIP3 signaling in cardiac myocytes AKT1, AKT2, AKT3, BAD, BCL2L1, CDC42, CDK2, CDKN1B, CDKN2A, CREB1, CREB3, CREB5, EBP, ERBB4, F2RL2, FOXO3A, FRAP1, GAB1, GADD45A, GRB2, GSK3A, GSK3B, IFI27, IGF1, IGFBP1, INPPL1, IRS1, IRS2, IRS4, MET, MYC, NOLC1, P101-PI3K, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PARD3, PARD6A, PDK1, PIK3CA, PIK3CD, PPP1R13B, PREX1, PSCD3, PTEN, PTK2, PTPN1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SFN, SHC1, SLC2A4, SOS1, SOS2, TSC1, TSC2, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ 62 AKT1(12), AKT2(1), AKT3(2), BAD(1), CDK2(1), CDKN1B(5), CREB3(1), EBP(1), ERBB4(4), F2RL2(1), GAB1(1), GRB2(1), GSK3A(1), IGF1(1), INPPL1(1), IRS1(1), IRS4(1), MET(4), MYC(1), PAK1(2), PAK2(1), PAK3(1), PAK7(1), PARD3(3), PDK1(1), PIK3CA(168), PREX1(5), PTEN(15), PTK2(1), RPS6KA1(1), RPS6KA2(2), RPS6KA3(2), SHC1(1), SLC2A4(1), SOS1(3), SOS2(1), TSC1(2), TSC2(2), YWHAB(1) 54199314 255 215 105 17 64 49 102 5 30 5 <1.00e-15 <5.98e-15 27 HSA04370_VEGF_SIGNALING_PATHWAY Genes involved in VEGF signaling pathway AKT1, AKT2, AKT3, BAD, CASP9, CDC42, CHP, HRAS, KDR, KRAS, MAP2K1, MAP2K2, MAPK1, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPKAPK2, MAPKAPK3, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NOS3, NRAS, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCG1, PLCG2, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKCA, PRKCB1, PRKCG, PTGS2, PTK2, PXN, RAC1, RAC2, RAC3, RAF1, SH2D2A, SHC2, SPHK1, SPHK2, SRC, VEGFA 64 AKT1(12), AKT2(1), AKT3(2), BAD(1), KDR(2), KRAS(1), MAP2K1(1), MAPK1(1), MAPK14(1), MAPK3(1), MAPKAPK3(1), NFAT5(1), NFATC3(3), NFATC4(3), NOS3(2), PIK3CA(168), PIK3CB(3), PIK3CG(2), PIK3R1(14), PIK3R3(1), PLA2G2D(1), PLA2G2F(1), PLA2G3(3), PLA2G4A(6), PLA2G6(2), PLCG1(4), PLCG2(2), PPP3CA(3), PPP3CB(2), PRKCG(1), PTGS2(1), PTK2(1), PXN(1), RAF1(1), SH2D2A(2), SPHK2(2) 48350562 254 214 102 20 64 51 106 8 25 0 <1.00e-15 <5.98e-15 28 ST_ADRENERGIC Adrenergic receptors respond to epinephrine and norepinephrine signaling. AKT1, APC, AR, ASAH1, BF, BRAF, CAMP, CCL13, CCL15, CCL16, DAG1, EGFR, GAS, GNA11, GNA15, GNAI1, GNAQ, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, KCNJ3, KCNJ5, KCNJ9, MAPK1, MAPK10, MAPK14, PHKA2, PIK3CA, PIK3CD, PIK3R1, PITX2, PTX1, PTX3, RAF1, SRC 33 AKT1(12), APC(3), AR(3), BRAF(2), CCL13(1), EGFR(4), GNAI1(1), GNAQ(1), ITPKB(7), ITPR1(7), ITPR3(4), KCNJ3(1), MAPK1(1), MAPK10(1), MAPK14(1), PHKA2(4), PIK3CA(168), PIK3R1(14), PITX2(1), PTX3(1), RAF1(1) 39066885 238 214 88 19 63 43 96 9 27 0 <1.00e-15 <5.98e-15 29 PPARAPATHWAY Peroxisome proliferators regulate gene expression via PPAR/RXR heterodimers which bind to peroxisome-proliferator response elements (PPREs). ACOX1, APOA1, APOA2, CD36, CITED2, CPT1B, CREBBP, DUSP1, DUT, EHHADH, EP300, FABP1, FAT, FRA8B, HSD17B4, HSPA1A, HSPCA, INS, JUN, LPL, MAPK1, MAPK3, ME1, MRPL11, MYC, NCOA1, NCOR1, NCOR2, NFKBIA, NOS2A, NR0B2, NR1H3, NR2F1, NRIP1, PDGFA, PIK3CA, PIK3R1, PPARA, PPARBP, PPARGC1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, PTGS2, RB1, RELA, RXRA, SP1, SRA1, STAT5A, STAT5B, TNF 46 ACOX1(2), CD36(1), CITED2(1), CREBBP(2), EHHADH(2), EP300(3), FABP1(1), HSD17B4(3), JUN(1), LPL(1), MAPK1(1), MAPK3(1), MYC(1), NCOA1(1), NCOR1(16), NCOR2(3), NR0B2(2), PIK3CA(168), PIK3R1(14), PPARA(1), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), PTGS2(1), RB1(9), RELA(1), SP1(1), STAT5B(4) 43690218 244 213 103 16 61 30 99 6 46 2 <1.00e-15 <5.98e-15 30 ST_JNK_MAPK_PATHWAY JNKs are MAP kinases regulated by several levels of kinases (MAPKK, MAPKKK) and phosphorylate transcription factors and regulatory proteins. AKT1, ATF2, CDC42, DLD, DUSP10, DUSP4, DUSP8, GAB1, GADD45A, GCK, IL1R1, JUN, MAP2K4, MAP2K5, MAP2K7, MAP3K1, MAP3K10, MAP3K11, MAP3K12, MAP3K13, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAP3K9, MAPK10, MAPK7, MAPK8, MAPK9, MYEF2, NFATC3, NR2C2, PAPPA, SHC1, TP53, TRAF6, ZAK 36 AKT1(12), DLD(1), DUSP10(1), GAB1(1), GCK(2), IL1R1(1), JUN(1), MAP2K4(18), MAP2K5(1), MAP3K1(53), MAP3K10(4), MAP3K11(1), MAP3K12(2), MAP3K13(3), MAP3K4(3), MAP3K5(1), MAP3K9(1), MAPK10(1), MAPK8(2), MYEF2(1), NFATC3(3), PAPPA(4), SHC1(1), TP53(142), TRAF6(1), ZAK(1) 36173943 262 213 202 11 28 57 29 7 113 28 <1.00e-15 <5.98e-15 31 SIG_BCR_SIGNALING_PATHWAY Members of the BCR signaling pathway AKT1, AKT2, AKT3, BAD, BCL2, BCR, BLNK, BTK, CD19, CD22, CD81, CR2, CSK, DAG1, FLOT1, FLOT2, GRB2, GSK3A, GSK3B, INPP5D, ITPR1, ITPR2, ITPR3, LYN, MAP4K1, MAPK1, MAPK3, NFATC1, NFATC2, NR0B2, PDK1, PIK3CA, PIK3CD, PIK3R1, PLCG2, PPP1R13B, PPP3CA, PPP3CB, PPP3CC, PTPRC, RAF1, SHC1, SOS1, SOS2, SYK, VAV1 45 AKT1(12), AKT2(1), AKT3(2), BAD(1), BCR(1), BLNK(1), BTK(2), CD19(1), CD22(1), CR2(2), GRB2(1), GSK3A(1), INPP5D(2), ITPR1(7), ITPR3(4), LYN(3), MAP4K1(1), MAPK1(1), MAPK3(1), NR0B2(2), PDK1(1), PIK3CA(168), PIK3R1(14), PLCG2(2), PPP3CA(3), PPP3CB(2), PTPRC(1), RAF1(1), SHC1(1), SOS1(3), SOS2(1), VAV1(1) 53513850 245 212 95 19 62 52 104 4 23 0 <1.00e-15 <5.98e-15 32 HCMVPATHWAY Cytomegalovirus activates MAP kinase pathways in the host cell, inducing transcription of viral genes. AKT1, CREB1, MAP2K1, MAP2K2, MAP2K3, MAP2K6, MAP3K1, MAPK1, MAPK14, MAPK3, NFKB1, PIK3CA, PIK3R1, RB1, RELA, SP1 15 AKT1(12), MAP2K1(1), MAP2K3(1), MAP3K1(53), MAPK1(1), MAPK14(1), MAPK3(1), NFKB1(1), PIK3CA(168), PIK3R1(14), RB1(9), RELA(1), SP1(1) 14376492 264 211 113 8 56 37 93 2 48 28 <1.00e-15 <5.98e-15 33 HSA04662_B_CELL_RECEPTOR_SIGNALING_PATHWAY Genes involved in B cell receptor signaling pathway AKT1, AKT2, AKT3, BCL10, BLNK, BTK, CARD11, CD19, CD22, CD72, CD79A, CD79B, CD81, CHP, CHUK, CR2, FCGR2B, FOS, GSK3B, HRAS, IFITM1, IKBKB, IKBKG, INPP5D, JUN, KRAS, LILRB3, LYN, MALT1, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NRAS, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG2, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKCB1, PTPN6, RAC1, RAC2, RAC3, RASGRP3, SYK, VAV1, VAV2, VAV3 60 AKT1(12), AKT2(1), AKT3(2), BLNK(1), BTK(2), CARD11(2), CD19(1), CD22(1), CD79A(1), CR2(2), IFITM1(1), IKBKB(2), INPP5D(2), JUN(1), KRAS(1), LYN(3), MALT1(1), NFAT5(1), NFATC3(3), NFATC4(3), NFKB1(1), NFKB2(4), PIK3CA(168), PIK3CB(3), PIK3CG(2), PIK3R1(14), PIK3R3(1), PLCG2(2), PPP3CA(3), PPP3CB(2), VAV1(1), VAV3(1) 52241787 245 211 95 23 61 49 102 5 25 3 <1.00e-15 <5.98e-15 34 ST_B_CELL_ANTIGEN_RECEPTOR B cell receptors bind antigens and promote B cell activation. AKT1, AKT2, AKT3, BAD, BCR, BLNK, BTK, CD19, CSK, DAG1, EPHB2, GRB2, ITPKA, ITPKB, LYN, MAP2K1, MAP2K2, MAPK1, NFAT5, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PAG, PI3, PIK3CA, PIK3CD, PIK3R1, PLCG2, PPP1R13B, RAF1, SERPINA4, SHC1, SOS1, SOS2, SYK, VAV1 37 AKT1(12), AKT2(1), AKT3(2), BAD(1), BCR(1), BLNK(1), BTK(2), CD19(1), EPHB2(1), GRB2(1), ITPKB(7), LYN(3), MAP2K1(1), MAPK1(1), NFAT5(1), NFKB1(1), NFKB2(4), PI3(1), PIK3CA(168), PIK3R1(14), PLCG2(2), RAF1(1), SERPINA4(3), SHC1(1), SOS1(3), SOS2(1), VAV1(1) 36893883 236 210 86 10 60 48 96 5 24 3 <1.00e-15 <5.98e-15 35 ST_FAS_SIGNALING_PATHWAY The Fas receptor induces apoptosis and NF-kB activation when bound to Fas ligand. ADPRT, ALG2, BAK1, BAX, BFAR, BIRC4, BTK, CAD, CASP10, CASP3, CASP8, CASP8AP2, CD7, CDK2AP1, CSNK1A1, DAXX, DEDD, DEDD2, DFFA, DIABLO, EGFR, EPHB2, FADD, FAF1, FAIM2, FREQ, HRB, HSPB1, IL1A, IL8, MAP2K4, MAP2K7, MAP3K1, MAP3K5, MAPK1, MAPK10, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, MCP, MET, NFAT5, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, NR0B2, PFN1, PFN2, PTPN13, RALBP1, RIPK1, ROCK1, SMPD1, TNFRSF6, TNFRSF6B, TP53, TPX2, TRAF2, TUFM, VIL2 54 ALG2(1), BAK1(1), BFAR(1), BTK(2), CAD(7), CASP8(2), EGFR(4), EPHB2(1), IL1A(1), MAP2K4(18), MAP3K1(53), MAP3K5(1), MAPK1(1), MAPK10(1), MAPK8(2), MAPK8IP1(1), MET(4), NFAT5(1), NFKB1(1), NFKB2(4), NR0B2(2), PTPN13(4), RIPK1(3), ROCK1(1), TP53(142), TUFM(2) 51259728 261 210 211 15 29 50 25 12 111 34 <1.00e-15 <5.98e-15 36 APOPTOSIS APAF1, BAD, BAK1, BCL2L7P1, BAX, BCL2, BCL2L1, BCL2L11, BID, BIRC2, BIRC3, BIRC4, BIRC5, BNIP3L, CASP1, CASP10, CASP1, COPl, CASP2, CASP3, CASP4, CASP6, CASP7, CASP8, CASP9, CHUK, CYCS, DFFA, DFFB, FADD, FAS, FASLG, GZMB, HELLS, HRK, IKBKB, IKBKG, IRF1, IRF2, IRF3, IRF4, IRF5, IRF6, IRF7, JUN, LTA, MAP2K4, MAP3K1, MAPK10, MDM2, MYC, NFKB1, NFKBIA, NFKBIB, NFKBIE, PRF1, RELA, RIPK1, TNF, TNFRSF10B, TNFRSF1A, TNFRSF1B, TNFRSF21, TNFRSF25, TNFRSF25, PLEKHG5, TNFSF10, TP53, TP73, TRADD, TRAF1, TRAF2, TRAF3 63 APAF1(1), BAD(1), BAK1(1), BCL2L11(1), BID(4), CASP1(1), CASP2(2), CASP6(1), CASP8(2), DFFB(2), FAS(1), FASLG(1), IKBKB(2), IRF3(1), IRF6(2), JUN(1), MAP2K4(18), MAP3K1(53), MAPK10(1), MDM2(1), MYC(1), NFKB1(1), PLEKHG5(3), PRF1(2), RELA(1), RIPK1(3), TNFRSF1A(1), TNFRSF21(2), TP53(142) 40308528 253 209 203 13 27 51 26 9 112 28 <1.00e-15 <5.98e-15 37 SIG_PIP3_SIGNALING_IN_B_LYMPHOCYTES Genes related to PIP3 signaling in B lymphocytes AKT1, AKT2, AKT3, BCR, BTK, CD19, CDKN2A, DAPP1, FLOT1, FLOT2, FOXO3A, GAB1, ITPR1, ITPR2, ITPR3, LYN, NR0B2, P101-PI3K, PDK1, PHF11, PIK3CA, PITX2, PLCG2, PPP1R13B, PREX1, PSCD3, PTEN, PTPRC, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SAG, SYK, TEC, VAV1 33 AKT1(12), AKT2(1), AKT3(2), BCR(1), BTK(2), CD19(1), GAB1(1), ITPR1(7), ITPR3(4), LYN(3), NR0B2(2), PDK1(1), PIK3CA(168), PITX2(1), PLCG2(2), PREX1(5), PTEN(15), PTPRC(1), RPS6KA1(1), RPS6KA2(2), RPS6KA3(2), TEC(1), VAV1(1) 41165358 236 208 87 13 61 44 100 4 25 2 <1.00e-15 <5.98e-15 38 ST_DICTYOSTELIUM_DISCOIDEUM_CAMP_CHEMOTAXIS_PATHWAY The fungus Dictyostelium discoideum is a model system for cytoskeletal organization during chemotaxis. ACTR2, ACTR3, AKT1, ANGPTL2, BF, DAG1, DGKA, ETFA, GCA, ITGA9, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, MAP2K1, MAPK1, MAPK3, NR1I3, PAK1, PDE3A, PDE3B, PI3, PIK3C2G, PIK3CA, PIK3CD, PIK3R1, PLDN, PSME1, RIPK3, RPS4X, SGCB, VASP 31 AKT1(12), DGKA(3), ITPKB(7), ITPR1(7), ITPR3(4), MAP2K1(1), MAPK1(1), MAPK3(1), PAK1(2), PDE3A(6), PDE3B(1), PI3(1), PIK3C2G(1), PIK3CA(168), PIK3R1(14), RIPK3(1), RPS4X(1) 36446709 231 208 81 18 61 41 96 9 24 0 <1.00e-15 <5.98e-15 39 NFATPATHWAY Cardiac hypertrophy is induced by NF-ATc4 and GATA4, which are stimulated through calcineurin activated by CaMK. ACTA1, AGT, AKT1, CALM1, CALM2, CALM3, CALR, CAMK1, CAMK1G, CAMK4, CREBBP, CSNK1A1, CTF1, DTR, EDN1, ELSPBP1, F2, FGF2, FKBP1A, GATA4, GSK3B, HAND1, HAND2, HRAS, IGF1, LIF, MAP2K1, MAPK1, MAPK14, MAPK3, MAPK8, MEF2C, MYH2, NFATC1, NFATC2, NFATC3, NFATC4, NKX2-5, NPPA, PIK3CA, PIK3R1, PPP3CA, PPP3CB, PPP3CC, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RAF1, RPS6KB1, SYT1 50 AGT(3), AKT1(12), CALR(1), CAMK1(1), CAMK1G(1), CREBBP(2), EDN1(2), F2(2), IGF1(1), LIF(3), MAP2K1(1), MAPK1(1), MAPK14(1), MAPK3(1), MAPK8(2), MEF2C(2), MYH2(1), NFATC3(3), NFATC4(3), NPPA(1), PIK3CA(168), PIK3R1(14), PPP3CA(3), PPP3CB(2), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), RAF1(1) 36006126 235 207 85 17 61 43 102 7 22 0 <1.00e-15 <5.98e-15 40 RAC1PATHWAY Rac-1 is a Rho family G protein that stimulates formation of actin-dependent structures such as filopodia and lamellopodia. ARFIP2, CDK5, CDK5R1, CFL1, CHN1, LIMK1, MAP3K1, MYL2, MYLK, NCF2, PAK1, PDGFRA, PIK3CA, PIK3R1, PLD1, PPP1R12B, RAC1, RALBP1, RPS6KB1, TRIO, VAV1, WASF1 22 CDK5(1), CHN1(1), LIMK1(3), MAP3K1(53), MYLK(5), NCF2(2), PAK1(2), PDGFRA(3), PIK3CA(168), PIK3R1(14), PLD1(1), TRIO(2), VAV1(1), WASF1(1) 26292006 257 206 116 17 62 28 95 5 39 28 <1.00e-15 <5.98e-15 41 ST_DIFFERENTIATION_PATHWAY_IN_PC12_CELLS Rat-derived PC12 cells respond to nerve growth factor (NGF) and PACAP to differentiate into neuronal cells. AKT1, ASAH1, ATF1, BRAF, CAMP, CREB1, CREB3, CREB5, CREBBP, CRKL, DAG1, EGR1, EGR2, EGR3, EGR4, ELK1, FRS2, GAS, GNAQ, GRF2, JUN, MAP1B, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK3, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, NTRK1, OPN1LW, PACAP, PIK3C2G, PIK3CA, PIK3CD, PIK3R1, PTPN11, RPS6KA3, SH2B, SHC1, SRC, TERF2IP, TH, TUBA3 37 AKT1(12), BRAF(2), CREB3(1), CREBBP(2), CRKL(1), EGR1(1), EGR2(1), EGR3(3), ELK1(2), GNAQ(1), JUN(1), MAP2K4(18), MAPK1(1), MAPK10(1), MAPK3(1), MAPK8(2), MAPK8IP1(1), NTRK1(1), OPN1LW(1), PIK3C2G(1), PIK3CA(168), PIK3R1(14), RPS6KA3(2), SHC1(1), TERF2IP(2) 34096257 241 206 90 11 64 37 99 4 37 0 <1.00e-15 <5.98e-15 42 HSA04150_MTOR_SIGNALING_PATHWAY Genes involved in mTOR signaling pathway AKT1, AKT2, AKT3, BRAF, CAB39, DDIT4, EIF4B, EIF4EBP1, FIGF, FRAP1, GBL, HIF1A, IGF1, INS, KIAA1303, LYK5, MAPK1, MAPK3, PDPK1, PGF, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PRKAA1, PRKAA2, RHEB, RICTOR, RPS6, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA6, RPS6KB1, RPS6KB2, STK11, TSC1, TSC2, ULK1, ULK2, ULK3, VEGFA, VEGFB, VEGFC 41 AKT1(12), AKT2(1), AKT3(2), BRAF(2), EIF4B(1), FIGF(1), IGF1(1), MAPK1(1), MAPK3(1), PIK3CA(168), PIK3CB(3), PIK3CG(2), PIK3R1(14), PIK3R3(1), PRKAA2(2), RICTOR(3), RPS6(1), RPS6KA1(1), RPS6KA2(2), RPS6KA3(2), RPS6KA6(3), RPS6KB2(3), TSC1(2), TSC2(2) 34767018 231 205 81 17 62 43 98 6 22 0 <1.00e-15 <5.98e-15 43 METPATHWAY The hepatocyte growth factor receptor c-Met stimulates proliferation and alters cell motility and adhesion on binding the ligand HGF. ACTA1, CRK, CRKL, DOCK1, ELK1, FOS, GAB1, GRB2, GRF2, HGF, HRAS, ITGA1, ITGB1, JUN, MAP2K1, MAP2K2, MAP4K1, MAPK1, MAPK3, MAPK8, MET, PAK1, PIK3CA, PIK3R1, PTEN, PTK2, PTK2B, PTPN11, PXN, RAF1, RAP1A, RAP1B, RASA1, SOS1, SRC, STAT3 34 CRKL(1), ELK1(2), GAB1(1), GRB2(1), HGF(3), ITGA1(3), ITGB1(2), JUN(1), MAP2K1(1), MAP4K1(1), MAPK1(1), MAPK3(1), MAPK8(2), MET(4), PAK1(2), PIK3CA(168), PIK3R1(14), PTEN(15), PTK2(1), PTK2B(3), PXN(1), RAF1(1), RASA1(2), SOS1(3), STAT3(1) 32792760 235 205 95 9 59 33 103 4 31 5 <1.00e-15 <5.98e-15 44 HSA04110_CELL_CYCLE Genes involved in cell cycle ABL1, ANAPC1, ANAPC10, ANAPC11, ANAPC2, ANAPC4, ANAPC5, ANAPC7, ATM, ATR, BUB1, BUB1B, BUB3, CCNA1, CCNA2, CCNB1, CCNB2, CCNB3, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCNH, CDC14A, CDC14B, CDC16, CDC2, CDC20, CDC23, CDC25A, CDC25B, CDC25C, CDC26, CDC27, CDC45L, CDC6, CDC7, CDK2, CDK4, CDK6, CDK7, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CHEK1, CHEK2, CREBBP, CUL1, DBF4, E2F1, E2F2, E2F3, EP300, ESPL1, FZR1, GADD45A, GADD45B, GADD45G, GSK3B, hCG_1982709, HDAC1, HDAC2, LOC440917, LOC728919, MAD1L1, MAD2L1, MAD2L2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, PKMYT1, PLK1, PRKDC, PTTG1, PTTG2, RB1, RBL1, RBL2, RBX1, SFN, SKP1, SKP2, SMAD2, SMAD3, SMAD4, SMC1A, SMC1B, TFDP1, TGFB1, TGFB2, TGFB3, TP53, WEE1, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ 104 ABL1(2), ANAPC1(1), ANAPC5(4), ANAPC7(1), ATM(9), ATR(2), CCNA2(2), CCNB1(2), CCNB3(3), CCND1(1), CCND3(5), CDC23(1), CDC25B(3), CDC27(1), CDC7(1), CDK2(1), CDK6(1), CDK7(1), CDKN1B(5), CHEK2(2), CREBBP(2), CUL1(1), E2F1(2), E2F3(1), EP300(3), ESPL1(6), HDAC1(2), HDAC2(2), MAD2L2(1), MCM2(1), MCM3(1), MCM4(2), MCM6(2), MCM7(2), MDM2(1), ORC2L(1), ORC3L(1), PLK1(1), PRKDC(7), RB1(9), RBL1(1), RBL2(1), SMAD2(3), SMAD3(2), SMAD4(1), SMC1A(2), SMC1B(2), TGFB3(1), TP53(142), YWHAB(1) 100298796 252 204 202 21 30 61 36 16 106 3 <1.00e-15 <5.98e-15 45 EIF4PATHWAY The eIF-4F complex recognizes 5' mRNA caps, recruits RNA helicases, and maintains mRNA-ribosome bridging. AKT1, EIF4A1, EIF4A2, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FRAP1, GHR, IRS1, MAPK1, MAPK14, MAPK3, MKNK1, PABPC1, PDK2, PDPK1, PIK3CA, PIK3R1, PRKCA, PRKCB1, PTEN, RPS6KB1 22 AKT1(12), EIF4A2(3), EIF4G2(1), EIF4G3(2), GHR(2), IRS1(1), MAPK1(1), MAPK14(1), MAPK3(1), PABPC1(3), PDK2(1), PIK3CA(168), PIK3R1(14), PTEN(15) 21027825 225 203 75 12 56 37 95 4 31 2 <1.00e-15 <5.98e-15 46 HSA04310_WNT_SIGNALING_PATHWAY Genes involved in Wnt signaling pathway APC, APC2, AXIN1, AXIN2, BTRC, CACYBP, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CCND1, CCND2, CCND3, CER1, CHD8, CHP, CREBBP, CSNK1A1, CSNK1A1L, CSNK1E, CSNK2A1, CSNK2A2, CSNK2B, CTBP1, CTBP2, CTNNB1, CTNNBIP1, CUL1, CXXC4, DAAM1, DAAM2, DKK1, DKK2, DKK4, DVL1, DVL2, DVL3, EP300, FBXW11, FOSL1, FRAT1, FRAT2, FZD1, FZD10, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD9, GSK3B, JUN, LEF1, LOC652788, LRP5, LRP6, MAP3K7, MAPK10, MAPK8, MAPK9, MMP7, MYC, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NKD1, NKD2, NLK, PLCB1, PLCB2, PLCB3, PLCB4, PORCN, PPARD, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRICKLE1, PRICKLE2, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, PSEN1, RAC1, RAC2, RAC3, RBX1, RHOA, ROCK1, ROCK2, RUVBL1, SENP2, SFRP1, SFRP2, SFRP4, SFRP5, SIAH1, SKP1, SMAD2, SMAD3, SMAD4, SOX17, TBL1X, TBL1XR1, TBL1Y, TCF7, TCF7L1, TCF7L2, TP53, VANGL1, VANGL2, WIF1, WNT1, WNT10A, WNT10B, WNT11, WNT16, WNT2, WNT2B, WNT3, WNT3A, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A, WNT8B, WNT9A, WNT9B 135 APC(3), AXIN1(1), CAMK2A(1), CAMK2D(3), CCND1(1), CCND3(5), CER1(1), CHD8(2), CREBBP(2), CSNK1A1L(2), CSNK1E(1), CSNK2A1(1), CSNK2A2(1), CUL1(1), DAAM1(1), DAAM2(1), DKK4(1), DVL3(1), EP300(3), FZD1(1), FZD3(2), FZD6(2), FZD9(1), JUN(1), LRP6(2), MAPK10(1), MAPK8(2), MYC(1), NFAT5(1), NFATC3(3), NFATC4(3), NKD1(1), NLK(1), PLCB1(3), PLCB2(2), PLCB3(1), PLCB4(6), PPP2CB(2), PPP3CA(3), PPP3CB(2), PRICKLE1(2), PRICKLE2(2), PRKACA(1), PRKCG(1), RHOA(2), ROCK1(1), ROCK2(2), SFRP1(2), SFRP4(1), SIAH1(2), SMAD2(3), SMAD3(2), SMAD4(1), TBL1X(3), TBL1XR1(6), TCF7(3), TCF7L2(1), TP53(142), VANGL2(1), WIF1(1), WNT10B(1), WNT11(2), WNT2B(1), WNT3A(1), WNT5B(1), WNT6(1), WNT7A(5), WNT8B(1), WNT9A(1) 111465471 266 203 216 42 41 67 45 16 92 5 <1.00e-15 <5.98e-15 47 APOPTOSIS_GENMAPP APAF1, BAK1, BCL2L7P1, BAX, BCL2, BCL2L1, BID, BIRC2, BIRC3, BIRC4, CASP2, CASP3, CASP6, CASP7, CASP8, CASP9, CYCS, FADD, FAS, FASLG, GZMB, IKBKG, JUN, MAP2K4, MAP3K1, MAP3K14, MAPK10, MCL1, MDM2, MYC, NFKB1, NFKBIA, PARP1, PRF1, RELA, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TNFSF10, TP53, TRADD, TRAF1, TRAF2 40 APAF1(1), BAK1(1), BID(4), CASP2(2), CASP6(1), CASP8(2), FAS(1), FASLG(1), JUN(1), MAP2K4(18), MAP3K1(53), MAPK10(1), MDM2(1), MYC(1), NFKB1(1), PARP1(1), PRF1(2), RELA(1), RIPK1(3), TNFRSF1A(1), TP53(142) 27048450 239 201 189 10 23 45 23 9 111 28 <1.00e-15 <5.98e-15 48 PTENPATHWAY PTEN suppresses AKT-induced cell proliferation and antagonizes the action of PI3K. AKT1, BCAR1, CDKN1B, FOXO3A, GRB2, ILK, ITGB1, MAPK1, MAPK3, PDK2, PDPK1, PIK3CA, PIK3R1, PTEN, PTK2, SHC1, SOS1, TNFSF6 15 AKT1(12), CDKN1B(5), GRB2(1), ILK(2), ITGB1(2), MAPK1(1), MAPK3(1), PDK2(1), PIK3CA(168), PIK3R1(14), PTEN(15), PTK2(1), SHC1(1), SOS1(3) 13484679 227 201 76 8 56 36 96 3 34 2 <1.00e-15 <5.98e-15 49 MTORPATHWAY Mammalian target of rapamycin (mTOR) senses mitogenic factors and nutrients, including ATP, and induces cell proliferation. AKT1, EIF3S10, EIF4A1, EIF4A2, EIF4B, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FKBP1A, FRAP1, MKNK1, PDK2, PDPK1, PIK3CA, PIK3R1, PPP2CA, PTEN, RPS6, RPS6KB1, TSC1, TSC2 21 AKT1(12), EIF4A2(3), EIF4B(1), EIF4G2(1), EIF4G3(2), PDK2(1), PIK3CA(168), PIK3R1(14), PTEN(15), RPS6(1), TSC1(2), TSC2(2) 19119477 222 199 72 10 57 35 95 4 29 2 <1.00e-15 <5.98e-15 50 ST_PHOSPHOINOSITIDE_3_KINASE_PATHWAY The phosphoinositide-3 kinase pathway produces the lipid second messenger PIP3 and regulates cell growth, survival, and movement. A1BG, AKT1, AKT2, AKT3, BAD, BTK, CDKN2A, CSL4, DAF, DAPP1, FOXO1A, GRB2, GSK3A, GSK3B, IARS, IGFBP1, INPP5D, P14, PDK1, PIK3CA, PPP1R13B, PSCD3, PTEN, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SFN, SHC1, SOS1, SOS2, TEC, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ 33 AKT1(12), AKT2(1), AKT3(2), BAD(1), BTK(2), GRB2(1), GSK3A(1), IARS(5), INPP5D(2), PDK1(1), PIK3CA(168), PTEN(15), RPS6KA1(1), RPS6KA2(2), RPS6KA3(2), SHC1(1), SOS1(3), SOS2(1), TEC(1), YWHAB(1) 26700648 223 199 74 10 59 38 99 3 22 2 <1.00e-15 <5.98e-15 51 IGF1MTORPATHWAY Growth factor IGF-1 activates AKT, Gsk3-beta, and mTOR to promote muscle hypertrophy. AKT1, EIF2B5, EIF2S1, EIF2S2, EIF2S3, EIF4E, EIF4EBP1, FRAP1, GSK3B, IGF1, IGF1R, INPPL1, PDK2, PDPK1, PIK3CA, PIK3R1, PPP2CA, PTEN, RPS6, RPS6KB1 19 AKT1(12), EIF2B5(1), EIF2S1(1), EIF2S2(1), IGF1(1), IGF1R(1), INPPL1(1), PDK2(1), PIK3CA(168), PIK3R1(14), PTEN(15), RPS6(1) 14779557 217 197 67 13 59 31 95 2 28 2 <1.00e-15 <5.98e-15 52 RACCYCDPATHWAY Ras, Rac, and Rho coordinate to induce cyclin D1 expression and activate cdk2 to promote the G1/S transition. AKT1, ARHA, CCND1, CCNE1, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, E2F1, HRAS, MAPK1, MAPK3, NFKB1, NFKBIA, PAK1, PIK3CA, PIK3R1, RAC1, RAF1, RB1, RELA, TFDP1 22 AKT1(12), CCND1(1), CDK2(1), CDK6(1), CDKN1B(5), E2F1(2), MAPK1(1), MAPK3(1), NFKB1(1), PAK1(2), PIK3CA(168), PIK3R1(14), RAF1(1), RB1(9), RELA(1) 14877408 220 197 69 6 58 34 93 3 32 0 <1.00e-15 <5.98e-15 53 CREBPATHWAY CREB is a transcription factor that binds to cAMP-responsive elements (CREs) to activate transcription in response to extracellular signaling. ADCY1, AKT1, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CREB1, GNAS, GRB2, HRAS, MAPK1, MAPK14, MAPK3, PIK3CA, PIK3R1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, RAC1, RPS6KA1, RPS6KA5, SOS1 26 ADCY1(3), AKT1(12), CAMK2A(1), CAMK2D(3), GNAS(4), GRB2(1), MAPK1(1), MAPK14(1), MAPK3(1), PIK3CA(168), PIK3R1(14), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), RPS6KA1(1), SOS1(3) 20339319 216 196 66 13 60 38 95 3 20 0 <1.00e-15 <5.98e-15 54 GSK3PATHWAY Bacterial lipopolysaccharide activates AKT to promote the survival and activation of macrophages and inhibits Gsk3-beta to promote beta-catenin accumulation in the nucleus. AKT1, APC, AXIN1, CCND1, CD14, CTNNB1, DVL1, FZD1, GJA1, GNAI1, GSK3B, IRAK1, LBP, LEF1, LY96, MYD88, NFKB1, PDPK1, PIK3CA, PIK3R1, PPP2CA, PRKR, RELA, TIRAP, TLR4, TOLLIP, WNT1 24 AKT1(12), APC(3), AXIN1(1), CCND1(1), CD14(1), FZD1(1), GJA1(2), GNAI1(1), IRAK1(1), LBP(1), NFKB1(1), PIK3CA(168), PIK3R1(14), RELA(1), TIRAP(2), TLR4(7) 20994363 217 196 66 14 59 36 98 3 21 0 <1.00e-15 <5.98e-15 55 HDACPATHWAY Myocyte enhancer factor MEF2 activates transcription of genes required for muscle cell differentiation and is inhibited by histone deacetylases. AKT1, AVP, CABIN1, CALM1, CALM2, CALM3, CAMK1, CAMK1G, HDAC5, IGF1, IGF1R, INS, INSR, MAP2K6, MAPK14, MAPK7, MEF2A, MEF2B, MEF2C, MEF2D, MYOD1, NFATC1, NFATC2, PIK3CA, PIK3R1, PPP3CA, PPP3CB, PPP3CC, SYT1, YWHAH 28 AKT1(12), CABIN1(5), CAMK1(1), CAMK1G(1), IGF1(1), IGF1R(1), INSR(2), MAPK14(1), MEF2A(1), MEF2C(2), PIK3CA(168), PIK3R1(14), PPP3CA(3), PPP3CB(2) 23987184 214 194 64 14 58 36 96 3 21 0 <1.00e-15 <5.98e-15 56 IL2RBPATHWAY The beta subunit of the IL-2 receptor is required for IL-2 and IL-15 signal recognition and activates JAK kinase on ligand binding. AKT1, BAD, BCL2, BCL2L1, CBL, CFLAR, CRKL, E2F1, FOS, GRB2, HRAS, IL2RA, IL2RB, IL2RG, IRS1, JAK1, JAK3, MAPK1, MAPK3, MYC, NMI, PIK3CA, PIK3R1, PPIA, PTPN6, RAF1, RPS6KB1, SHC1, SOCS1, SOCS3, SOS1, STAT5A, STAT5B, SYK, TNFRSF6, TNFSF6, ZNFN1A3 33 AKT1(12), BAD(1), CRKL(1), E2F1(2), GRB2(1), IL2RG(1), IRS1(1), JAK1(1), JAK3(1), MAPK1(1), MAPK3(1), MYC(1), PIK3CA(168), PIK3R1(14), RAF1(1), SHC1(1), SOS1(3), STAT5B(4) 26422305 215 194 65 13 57 38 95 4 21 0 <1.00e-15 <5.98e-15 57 EDG1PATHWAY The lipid S1P is an EDG1 ligand promoting chemotaxis via Rac1 and cell survival and proliferation via ERK activation. ADCY1, AKT1, ARHA, ASAH1, EDG1, GNAI1, GNB1, GNGT1, ITGAV, ITGB3, MAPK1, MAPK3, PDGFA, PDGFRA, PIK3CA, PIK3R1, PLCB1, PRKCA, PRKCB1, PTK2, RAC1, SKIP, SMPD1, SMPD2, SPHK1, SRC 21 ADCY1(3), AKT1(12), GNAI1(1), GNB1(1), ITGAV(3), ITGB3(2), MAPK1(1), MAPK3(1), PDGFRA(3), PIK3CA(168), PIK3R1(14), PLCB1(3), PTK2(1), SMPD2(2) 19871358 215 193 65 9 62 38 95 2 18 0 <1.00e-15 <5.98e-15 58 SIG_IL4RECEPTOR_IN_B_LYPHOCYTES Genes related to IL4 rceptor signaling in B lymphocytes AKT1, AKT2, AKT3, BAD, BCL2, GRB2, GSK3A, GSK3B, IL4R, IRS1, IRS2, JAK1, JAK3, MAP4K1, MAPK1, MAPK3, PDK1, PIK3CA, PIK3CD, PIK3R1, PPP1R13B, RAF1, SHC1, SOCS1, SOS1, SOS2, STAT6 25 AKT1(12), AKT2(1), AKT3(2), BAD(1), GRB2(1), GSK3A(1), IRS1(1), JAK1(1), JAK3(1), MAP4K1(1), MAPK1(1), MAPK3(1), PDK1(1), PIK3CA(168), PIK3R1(14), RAF1(1), SHC1(1), SOS1(3), SOS2(1) 25926966 213 193 63 10 56 38 94 3 22 0 <1.00e-15 <5.98e-15 59 BADPATHWAY When phosphorylated, BAD is inhibited by sequestration; when non-phosphorylated, it promotes apoptosis by inactivating pro-survival BCL-XL and BCL-2. ADCY1, AKT1, BAD, BAX, BCL2, BCL2L1, CSF2RB, IGF1, IGF1R, IL3, IL3RA, KIT, KITLG, PIK3CA, PIK3R1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, YWHAH 22 ADCY1(3), AKT1(12), BAD(1), CSF2RB(2), IGF1(1), IGF1R(1), IL3RA(1), KIT(3), KITLG(2), PIK3CA(168), PIK3R1(14), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1) 15549183 211 192 61 9 63 33 94 3 18 0 <1.00e-15 <5.98e-15 60 SA_PTEN_PATHWAY PTEN is a tumor suppressor that dephosphorylates the lipid messenger phosphatidylinositol triphosphate. AKT1, AKT2, AKT3, BPNT1, GRB2, ILK, MAPK1, MAPK3, PDK1, PIK3CA, PIK3CD, PIP3-E, PTEN, PTK2B, RBL2, SHC1, SOS1 16 AKT1(12), AKT2(1), AKT3(2), GRB2(1), ILK(2), MAPK1(1), MAPK3(1), PDK1(1), PIK3CA(168), PTEN(15), PTK2B(3), RBL2(1), SHC1(1), SOS1(3) 14801358 212 192 63 5 56 35 96 1 22 2 <1.00e-15 <5.98e-15 61 ECMPATHWAY Extracellular matrix induces integrin-mediated FAK phosphorylation in epithelial cells, leading to PI3 and MAP kinase activation and actin reorganization. ARHA, ARHGAP5, DIAPH1, FYN, GSN, HRAS, ITGA1, ITGB1, MAP2K1, MAPK1, MAPK3, MYL2, MYLK, PFN1, PIK3CA, PIK3R1, PTK2, PXN, RAF1, ROCK1, SHC1, SRC, TLN1 22 ARHGAP5(3), GSN(1), ITGA1(3), ITGB1(2), MAP2K1(1), MAPK1(1), MAPK3(1), MYLK(5), PIK3CA(168), PIK3R1(14), PTK2(1), PXN(1), RAF1(1), ROCK1(1), SHC1(1), TLN1(7) 28257645 211 191 71 12 56 31 97 5 22 0 <1.00e-15 <5.98e-15 62 ERK5PATHWAY Signaling between a tissue and its innervating axon stimulates retrograde transport via Trk receptors, which activate Erk5, which induces transcription of anti-apoptotic factors. AKT1, CREB1, GRB2, HRAS, MAPK1, MAPK3, MAPK7, MEF2A, MEF2B, MEF2C, MEF2D, NTRK1, PIK3CA, PIK3R1, PLCG1, RPS6KA1, SHC1 17 AKT1(12), GRB2(1), MAPK1(1), MAPK3(1), MEF2A(1), MEF2C(2), NTRK1(1), PIK3CA(168), PIK3R1(14), PLCG1(4), RPS6KA1(1), SHC1(1) 13869999 207 190 57 7 58 35 91 2 21 0 <1.00e-15 <5.98e-15 63 IGF1RPATHWAY Insulin-like growth factor receptor IGF-1R promotes cell growth and inhibits apoptosis on binding of ligands IGF-1 and 2 via Ras activation and the AKT pathway. AKT1, BAD, GRB2, HRAS, IGF1R, IRS1, MAP2K1, MAPK1, MAPK3, PIK3CA, PIK3R1, RAF1, SHC1, SOS1, YWHAH 15 AKT1(12), BAD(1), GRB2(1), IGF1R(1), IRS1(1), MAP2K1(1), MAPK1(1), MAPK3(1), PIK3CA(168), PIK3R1(14), RAF1(1), SHC1(1), SOS1(3) 14032239 206 190 56 8 57 35 93 2 19 0 <1.00e-15 <5.98e-15 64 INOSITOL_PHOSPHATE_METABOLISM IMPA1, INPP1, INPP4A, INPP4B, INPP5A, INPPL1, ITPKA, ITPKB, MIOX, OCRL, PIK3C2A, PIK3C2B, PIK3C2G, PIK3CA, PIK3CB, PIK3CG, PIK4CA, PIK4CA, LOC220686, PIP5K2B, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCG1, PLCG2 22 IMPA1(1), INPP4A(2), INPP4B(3), INPPL1(1), ITPKB(7), OCRL(3), PIK3C2A(2), PIK3C2B(2), PIK3C2G(1), PIK3CA(168), PIK3CB(3), PIK3CG(2), PLCB1(3), PLCB2(2), PLCB3(1), PLCB4(6), PLCD1(1), PLCG1(4), PLCG2(2) 33169968 214 190 75 13 63 32 97 5 17 0 <1.00e-15 <5.98e-15 65 TRKAPATHWAY Nerve growth factor (NGF) promotes neuronal survival and proliferation by binding its receptor TrkA, which activates PI3K/AKT, Ras, and the MAP kinase pathway. AKT1, DPM2, GRB2, HRAS, KLK2, NGFB, NTRK1, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, SHC1, SOS1 12 AKT1(12), GRB2(1), KLK2(2), NTRK1(1), PIK3CA(168), PIK3R1(14), PLCG1(4), SHC1(1), SOS1(3) 11610807 206 190 56 6 57 34 93 2 20 0 <1.00e-15 <5.98e-15 66 PLCPATHWAY Phospholipase C hydrolyzes the membrane lipid PIP2 to DAG, which activates protein kinase C, and IP3, which causes calcium influx. AKT1, PIK3CA, PIK3R1, PLCB1, PLCG1, PRKCA, PRKCB1, VAV1 7 AKT1(12), PIK3CA(168), PIK3R1(14), PLCB1(3), PLCG1(4), VAV1(1) 9661899 202 189 52 6 58 33 90 2 19 0 <1.00e-15 <5.98e-15 67 RASPATHWAY Ras activation stimulates many signaling cascades, including PI3K/AKT activation to inhibit apoptosis. AKT1, ARHA, BAD, BCL2L1, CASP9, CDC42, CHUK, ELK1, H2AFX, HRAS, MAP2K1, MAPK3, MLLT7, NFKB1, PIK3CA, PIK3R1, RAC1, RAF1, RALA, RALBP1, RALGDS, RELA, RHOA 21 AKT1(12), BAD(1), ELK1(2), MAP2K1(1), MAPK3(1), NFKB1(1), PIK3CA(168), PIK3R1(14), RAF1(1), RELA(1), RHOA(2) 13809159 204 189 54 9 57 34 93 2 18 0 <1.00e-15 <5.98e-15 68 SIG_CD40PATHWAYMAP Genes related to CD40 signaling DUSP1, GORASP1, IKBKG, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, MAPKAPK5, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PIK3CA, PIK3CD, PIK3R1, SYT1, TNFRSF5, TRAF2, TRAF3, TRAF5, TRAF6 27 MAP2K4(18), MAPK1(1), MAPK10(1), MAPK14(1), MAPK3(1), MAPK8(2), MAPK8IP1(1), NFKB1(1), NFKB2(4), PIK3CA(168), PIK3R1(14), TRAF6(1) 20489898 213 189 72 8 60 26 91 2 31 3 <1.00e-15 <5.98e-15 69 ST_INTERLEUKIN_4_PATHWAY Like IL-13, IL-4 is produced by Th2 cells on activation of the T cell antigen receptor, and by mast and basophil cells on activation of the IgE receptor. AKT1, AKT2, AKT3, CISH, GRB2, IARS, IL13RA1, IL2RG, IL4, IL4R, INPP5D, JAK1, JAK2, JAK3, NR0B2, PI3, PIK3CA, PPP1R13B, RPS6KB1, SERPINA4, SHC1, SOS1, SOS2, SRC, STAT6, TYK2 26 AKT1(12), AKT2(1), AKT3(2), GRB2(1), IARS(5), IL13RA1(1), IL2RG(1), INPP5D(2), JAK1(1), JAK2(2), JAK3(1), NR0B2(2), PI3(1), PIK3CA(168), SERPINA4(3), SHC1(1), SOS1(3), SOS2(1), TYK2(3) 27222351 211 189 61 11 56 39 98 2 16 0 <1.00e-15 <5.98e-15 70 GHPATHWAY Growth hormone receptors dimerize on ligand binding and activate the JAK2 protein kinase. GH1, GHR, GRB2, HRAS, INS, INSR, IRS1, JAK2, MAP2K1, MAPK1, MAPK3, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, PTPN6, RAF1, RPS6KA1, SHC1, SLC2A4, SOCS1, SOS1, SRF, STAT5A, STAT5B, TCF1 23 GHR(2), GRB2(1), INSR(2), IRS1(1), JAK2(2), MAP2K1(1), MAPK1(1), MAPK3(1), PIK3CA(168), PIK3R1(14), PLCG1(4), RAF1(1), RPS6KA1(1), SHC1(1), SLC2A4(1), SOS1(3), SRF(1), STAT5B(4) 24131679 209 188 69 9 56 30 95 4 24 0 <1.00e-15 <5.98e-15 71 PAR1PATHWAY Activated extracellular thrombin cleaves and activates the G-protein coupled receptors PAR1 and PAR4, which activate platelets. ADCY1, ARHA, ARHGEF1, F2, F2R, F2RL3, GNA12, GNA13, GNAI1, GNAQ, GNB1, GNGT1, MAP3K7, PIK3CA, PIK3R1, PLCB1, PPP1R12B, PRKCA, PRKCB1, PTK2B, ROCK1 18 ADCY1(3), ARHGEF1(5), F2(2), F2R(2), GNAI1(1), GNAQ(1), GNB1(1), PIK3CA(168), PIK3R1(14), PLCB1(3), PTK2B(3), ROCK1(1) 18676359 204 188 64 7 64 25 92 4 19 0 <1.00e-15 <5.98e-15 72 ACHPATHWAY Nicotinic acetylcholine receptors are ligand-gated ion channels that primarily mediate neuromuscular signaling and may inhibit neuronal apoptosis via the AKT pathway. AKT1, BAD, CHRNB1, CHRNG, FOXO3A, MUSK, PIK3CA, PIK3R1, PTK2, PTK2B, RAPSN, SRC, TERT, TNFSF6, YWHAH 13 AKT1(12), BAD(1), CHRNB1(2), CHRNG(1), MUSK(3), PIK3CA(168), PIK3R1(14), PTK2(1), PTK2B(3) 11523096 205 187 54 7 61 32 93 2 17 0 <1.00e-15 <5.98e-15 73 GCRPATHWAY Corticosteroids activate the glucocorticoid receptor (GR), which inhibits NF-kB and activates Annexin-1, thus inhibiting the inflammatory response. ADRB2, AKT1, ANXA1, CALM1, CALM2, CALM3, CRN, GNAS, GNB1, GNGT1, HSPCA, NFKB1, NOS3, NPPA, NR3C1, PIK3CA, PIK3R1, RELA, SYT1 17 AKT1(12), GNAS(4), GNB1(1), NFKB1(1), NOS3(2), NPPA(1), PIK3CA(168), PIK3R1(14), RELA(1) 12477270 204 186 54 6 56 33 93 3 19 0 <1.00e-15 <5.98e-15 74 LONGEVITYPATHWAY Caloric restriction in animals often increases lifespan, which may occur via decreased IGF receptor expression and consequent expression of stress-resistance proteins. AKT1, CAT, FOXO3A, GH1, GHR, HRAS, IGF1, IGF1R, PIK3CA, PIK3R1, SHC1, SOD1, SOD2, SOD3 12 AKT1(12), GHR(2), IGF1(1), IGF1R(1), PIK3CA(168), PIK3R1(14), SHC1(1), SOD1(1) 9677109 200 186 50 7 56 31 94 2 17 0 <1.00e-15 <5.98e-15 75 NKCELLSPATHWAY Natural killer (NK) lymphocytes are inhibited by MHC and activated by surface glycoproteins on tumor or virus-infected cells, which undergo perforin-mediated lysis. B2M, HLA-A, IL18, ITGB1, KLRC1, KLRC2, KLRC3, KLRC4, KLRD1, LAT, MAP2K1, MAPK3, PAK1, PIK3CA, PIK3R1, PTK2B, PTPN6, RAC1, SYK, VAV1 20 B2M(2), HLA-A(4), ITGB1(2), KLRC1(3), KLRC2(1), KLRC3(1), LAT(1), MAP2K1(1), MAPK3(1), PAK1(2), PIK3CA(168), PIK3R1(14), PTK2B(3), VAV1(1) 13901940 204 186 63 8 60 25 93 4 22 0 <1.00e-15 <5.98e-15 76 TPOPATHWAY Thrombopoietin binds to its receptor and activates cell growth through the Erk and JNK MAP kinase pathways, protein kinase C, and JAK/STAT activation. CSNK2A1, FOS, GRB2, HRAS, JAK2, JUN, MAP2K1, MAPK3, MPL, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, RAF1, RASA1, SHC1, SOS1, STAT1, STAT3, STAT5A, STAT5B, THPO 22 CSNK2A1(1), GRB2(1), JAK2(2), JUN(1), MAP2K1(1), MAPK3(1), PIK3CA(168), PIK3R1(14), PLCG1(4), RAF1(1), RASA1(2), SHC1(1), SOS1(3), STAT1(1), STAT3(1), STAT5B(4) 22285692 206 186 66 6 57 27 93 3 26 0 <1.00e-15 <5.98e-15 77 AKTPATHWAY Second messenger PIP3 promotes cell survival by activating the anti-apoptotic kinase AKT. AKT1, BAD, CASP9, CHUK, FOXO1A, FOXO3A, GH1, GHR, HSPCA, MLLT7, NFKB1, NFKBIA, PDPK1, PIK3CA, PIK3R1, PPP2CA, RELA, TNFSF6, YWHAH 14 AKT1(12), BAD(1), GHR(2), NFKB1(1), PIK3CA(168), PIK3R1(14), RELA(1) 10681983 199 185 49 6 56 32 91 2 18 0 <1.00e-15 <5.98e-15 78 HSA04115_P53_SIGNALING_PATHWAY Genes involved in p53 signaling pathway APAF1, ATM, ATR, BAI1, BAX, BBC3, BID, CASP3, CASP8, CASP9, CCNB1, CCNB2, CCNB3, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCNG1, CCNG2, CD82, CDC2, CDK2, CDK4, CDK6, CDKN1A, CDKN2A, CHEK1, CHEK2, CYCS, DDB2, EI24, FAS, GADD45A, GADD45B, GADD45G, GTSE1, IGF1, IGFBP3, LRDD, MDM2, MDM4, P53AIP1, PERP, PMAIP1, PPM1D, PTEN, RCHY1, RFWD2, RPRM, RRM2, RRM2B, SCOTIN, SERPINB5, SERPINE1, SESN1, SESN2, SESN3, SFN, SIAH1, STEAP3, THBS1, TNFRSF10B, TP53, TP53I3, TP73, TSC2, ZMAT3 60 APAF1(1), ATM(9), ATR(2), BAI1(6), BID(4), CASP8(2), CCNB1(2), CCNB3(3), CCND1(1), CCND3(5), CCNG2(2), CDK2(1), CDK6(1), CHEK2(2), DDB2(1), FAS(1), GTSE1(4), IGF1(1), IGFBP3(1), MDM2(1), PERP(2), PTEN(15), RRM2(1), SERPINE1(1), SESN2(2), SIAH1(2), STEAP3(1), THBS1(3), TP53(142), TP53I3(1), TSC2(2) 43983264 222 185 174 10 20 56 28 14 97 7 <1.00e-15 <5.98e-15 79 VEGFPATHWAY Vascular endothelial growth factor (VEGF) is upregulated by hypoxic conditions and promotes normal blood vessel formation and angiogenesis related to tumor growth or cardiac disease. ARNT, EIF1, EIF1A, EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5, EIF2S1, EIF2S2, EIF2S3, ELAVL1, FLT1, FLT4, HIF1A, HRAS, KDR, NOS3, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, PTK2, PXN, SHC1, VEGF, VHL 25 ARNT(2), EIF2B5(1), EIF2S1(1), EIF2S2(1), ELAVL1(2), FLT1(2), FLT4(1), KDR(2), NOS3(2), PIK3CA(168), PIK3R1(14), PLCG1(4), PTK2(1), PXN(1), SHC1(1) 23495394 203 185 63 15 59 25 94 5 20 0 <1.00e-15 <5.98e-15 80 NGFPATHWAY Nerve growth factor (NGF) stimulates neural survival and proliferation via the TrkA and p75 receptors, which induce DAG and IP3 production and activate Ras. CSNK2A1, DPM2, ELK1, FOS, GRB2, HRAS, JUN, KLK2, MAP2K1, MAPK3, MAPK8, NGFB, NGFR, PIK3CA, PIK3R1, PLCG1, RAF1, SHC1, SOS1 18 CSNK2A1(1), ELK1(2), GRB2(1), JUN(1), KLK2(2), MAP2K1(1), MAPK3(1), MAPK8(2), NGFR(1), PIK3CA(168), PIK3R1(14), PLCG1(4), RAF1(1), SHC1(1), SOS1(3) 14050491 203 184 63 5 57 27 94 2 23 0 <1.00e-15 <5.98e-15 81 CXCR4PATHWAY CXCR4 is a G-protein coupled receptor that responds to the ligand SDF-1 by activating Ras and PI3 kinase to promote lymphocyte chemotaxis. BCAR1, CRK, CXCL12, CXCR4, GNAI1, GNAQ, GNB1, GNGT1, HRAS, MAP2K1, MAPK1, MAPK3, NFKB1, PIK3C2G, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, PTK2, PTK2B, PXN, RAF1, RELA 22 GNAI1(1), GNAQ(1), GNB1(1), MAP2K1(1), MAPK1(1), MAPK3(1), NFKB1(1), PIK3C2G(1), PIK3CA(168), PIK3R1(14), PLCG1(4), PTK2(1), PTK2B(3), PXN(1), RAF1(1), RELA(1) 19769958 201 183 61 6 59 26 94 2 20 0 <1.00e-15 <5.98e-15 82 IGF1PATHWAY Growth factor IGF-1 stimulates growth and inhibits apoptosis by activating the MAP kinase pathway in a variety of cell types. CSNK2A1, ELK1, FOS, GRB2, HRAS, IGF1, IGF1R, IRS1, JUN, MAP2K1, MAPK3, MAPK8, PIK3CA, PIK3R1, PTPN11, RAF1, RASA1, SHC1, SOS1, SRF 20 CSNK2A1(1), ELK1(2), GRB2(1), IGF1(1), IGF1R(1), IRS1(1), JUN(1), MAP2K1(1), MAPK3(1), MAPK8(2), PIK3CA(168), PIK3R1(14), RAF1(1), RASA1(2), SHC1(1), SOS1(3), SRF(1) 18177978 202 183 62 7 57 25 96 2 22 0 <1.00e-15 <5.98e-15 83 INSULINPATHWAY Insulin regulates glucose levels via Ras-mediated transcriptional activation. CSNK2A1, ELK1, FOS, GRB2, HRAS, INS, INSR, IRS1, JUN, MAP2K1, MAPK3, MAPK8, PIK3CA, PIK3R1, PTPN11, RAF1, RASA1, SHC1, SLC2A4, SOS1, SRF 20 CSNK2A1(1), ELK1(2), GRB2(1), INSR(2), IRS1(1), JUN(1), MAP2K1(1), MAPK3(1), MAPK8(2), PIK3CA(168), PIK3R1(14), RAF1(1), RASA1(2), SHC1(1), SLC2A4(1), SOS1(3), SRF(1) 18530850 203 183 63 8 56 26 96 3 22 0 <1.00e-15 <5.98e-15 84 G1_TO_S_CELL_CYCLE_REACTOME ATM, CCNA1, CCNB1, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCNG2, CCNH, CDC25A, CDC45L, CDK2, CDK4, CDK7, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CREB3, CREB3L1, CREB3L3, CREB3L4, CREBL1, CREBL1, TNXB, E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, FLJ14001, GADD45A, GBA2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, MNAT1, MYC, MYT1, NACA, NACA, FKSG17, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, POLA2, POLE, POLE2, PRIM1, PRIM2A, RB1, RBL1, RPA1, RPA2, RPA3, TFDP1, TFDP2, TP53, WEE1 63 ATM(9), CCNB1(2), CCND1(1), CCND3(5), CCNG2(2), CDK2(1), CDK7(1), CDKN1B(5), CREB3(1), CREB3L1(2), CREB3L3(1), E2F1(2), E2F3(1), E2F4(2), MCM2(1), MCM3(1), MCM4(2), MCM6(2), MCM7(2), MDM2(1), MNAT1(1), MYC(1), NACA(3), ORC2L(1), ORC3L(1), POLE2(1), RB1(9), RBL1(1), RPA1(1), TFDP2(1), TNXB(3), TP53(142) 56141124 209 180 160 12 26 48 26 10 96 3 <1.00e-15 <5.98e-15 85 IL7PATHWAY IL-7 is required for B and T cell development and proliferation and may contribute to activation of VDJ recombination. BCL2, CREBBP, EP300, FYN, IL2RG, IL7, IL7R, JAK1, JAK3, LCK, NMI, PIK3CA, PIK3R1, PTK2B, STAT5A, STAT5B 16 CREBBP(2), EP300(3), IL2RG(1), JAK1(1), JAK3(1), PIK3CA(168), PIK3R1(14), PTK2B(3), STAT5B(4) 20444775 197 178 56 9 58 22 90 5 22 0 <1.00e-15 <5.98e-15 86 SA_TRKA_RECEPTOR The TrkA receptor binds nerve growth factor to activate MAP kinase pathways and promote cell growth. AKT1, AKT2, AKT3, ARHA, CDKN1A, ELK1, GRB2, HRAS, MAP2K1, MAP2K2, NGFB, NGFR, NTRK1, PIK3CA, PIK3CD, SHC1, SOS1 14 AKT1(12), AKT2(1), AKT3(2), ELK1(2), GRB2(1), MAP2K1(1), NGFR(1), NTRK1(1), PIK3CA(168), SHC1(1), SOS1(3) 11119524 193 178 44 6 55 33 92 1 12 0 <1.00e-15 <5.98e-15 87 CTLA4PATHWAY T cell activation requires interaction with an antigen-MHC-I complex on an antigen-presenting cell (APC), as well as CD28 interaction with the APC's CD80 or 86. CD28, CD3D, CD3E, CD3G, CD3Z, CD80, CD86, CTLA4, GRB2, HLA-DRA, HLA-DRB1, ICOS, ICOSL, IL2, ITK, LCK, PIK3CA, PIK3R1, PTPN11, TRA@, TRB@ 17 CD3E(1), CD3G(1), CD86(1), GRB2(1), HLA-DRB1(2), IL2(1), ITK(3), PIK3CA(168), PIK3R1(14) 9665448 192 177 52 10 55 24 92 4 17 0 <1.00e-15 <5.98e-15 88 CDC42RACPATHWAY PI3 kinase stimulates cell migration by activating cdc42, which activates ARP2/3, which in turn promotes formation of new actin fibers. ACTR2, ACTR3, ARHA, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, CDC42, PAK1, PDGFRA, PIK3CA, PIK3R1, RAC1, WASL 14 ARPC1A(1), ARPC1B(1), ARPC2(2), PAK1(2), PDGFRA(3), PIK3CA(168), PIK3R1(14), WASL(1) 10121241 192 176 52 10 60 19 92 3 18 0 <1.00e-15 <5.98e-15 89 ATRBRCAPATHWAY BRCA1 and 2 block cell cycle progression in response to DNA damage and promote double-stranded break repair; mutations induce breast cancer susceptibility. ATM, ATR, BRCA1, BRCA2, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, HUS1, MRE11A, NBS1, RAD1, RAD17, RAD50, RAD51, RAD9A, TP53, TREX1 21 ATM(9), ATR(2), BRCA1(8), BRCA2(10), CHEK2(2), FANCA(2), FANCD2(3), FANCF(1), FANCG(1), RAD17(2), RAD50(1), RAD9A(2), TP53(142) 33361107 185 169 137 7 18 43 24 11 89 0 <1.00e-15 <5.98e-15 90 CHEMICALPATHWAY DNA damage promotes Bid cleavage, which stimulates mitochondrial cytochrome c release and consequent caspase activation, resulting in apoptosis. ADPRT, AKT1, APAF1, ATM, BAD, BAX, BCL2, BCL2L1, BID, CASP3, CASP6, CASP7, CASP9, CYCS, EIF2S1, PRKCA, PRKCB1, PTK2, PXN, STAT1, TLN1, TP53 20 AKT1(12), APAF1(1), ATM(9), BAD(1), BID(4), CASP6(1), EIF2S1(1), PTK2(1), PXN(1), STAT1(1), TLN1(7), TP53(142) 20568990 181 167 123 6 17 53 22 9 80 0 <1.00e-15 <5.98e-15 91 G2PATHWAY Activated Cdc2-cyclin B kinase regulates the G2/M transition; DNA damage stimulates the DNA-PK/ATM/ATR kinases, which inactivate Cdc2. ATM, ATR, BRCA1, CCNB1, CDC2, CDC25A, CDC25B, CDC25C, CDC34, CDKN1A, CDKN2D, CHEK1, CHEK2, EP300, GADD45A, MDM2, MYT1, PLK, PRKDC, RPS6KA1, TP53, WEE1, YWHAH, YWHAQ 21 ATM(9), ATR(2), BRCA1(8), CCNB1(2), CDC25B(3), CHEK2(2), EP300(3), MDM2(1), PRKDC(7), RPS6KA1(1), TP53(142) 32064708 180 164 131 9 19 46 23 11 81 0 <1.00e-15 <5.98e-15 92 TELPATHWAY Telomerase is a ribonucleotide protein that adds telomeric repeats to the 3' ends of chromosomes. AKT1, BCL2, EGFR, G22P1, HSPCA, IGF1R, KRAS2, MYC, POLR2A, PPP2CA, PRKCA, RB1, TEP1, TERF1, TERT, TNKS, TP53, XRCC5 15 AKT1(12), EGFR(4), IGF1R(1), MYC(1), POLR2A(2), RB1(9), TEP1(7), TP53(142) 20513220 178 164 120 8 16 50 22 12 78 0 <1.00e-15 <5.98e-15 93 G1PATHWAY CDK4/6-cyclin D and CDK2-cyclin E phosphorylate Rb, which allows the transcription of genes needed for the G1/S cell cycle transition. ABL1, ATM, ATR, CCNA1, CCND1, CCNE1, CDC2, CDC25A, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, DHFR, E2F1, GSK3B, HDAC1, MADH3, MADH4, RB1, SKP2, TFDP1, TGFB1, TGFB2, TGFB3, TP53 24 ABL1(2), ATM(9), ATR(2), CCND1(1), CDK2(1), CDK6(1), CDKN1B(5), E2F1(2), HDAC1(2), RB1(9), TGFB3(1), TP53(142) 22265919 177 163 128 7 17 41 21 9 89 0 <1.00e-15 <5.98e-15 94 P53HYPOXIAPATHWAY Hypoxia induces p53 accumulation and consequent apoptosis with p53-mediated cell cycle arrest, which is present under conditions of DNA damage. ABCB1, AKT1, ATM, BAX, CDKN1A, CPB2, CSNK1A1, CSNK1D, FHL2, GADD45A, HIC1, HIF1A, HSPA1A, HSPCA, IGFBP3, MAPK8, MDM2, NFKBIB, NQO1, TP53 17 ABCB1(3), AKT1(12), ATM(9), CPB2(1), IGFBP3(1), MAPK8(2), MDM2(1), NQO1(1), TP53(142) 14946867 172 161 114 12 15 51 23 9 74 0 <1.00e-15 <5.98e-15 95 ATMPATHWAY The tumor-suppressing protein kinase ATM responds to radiation-induced DNA damage by blocking cell-cycle progression and activating DNA repair. ABL1, ATM, BRCA1, CDKN1A, CHEK1, CHEK2, GADD45A, JUN, MAPK8, MDM2, MRE11A, NBS1, NFKB1, NFKBIA, RAD50, RAD51, RBBP8, RELA, TP53, TP73 18 ABL1(2), ATM(9), BRCA1(8), CHEK2(2), JUN(1), MAPK8(2), MDM2(1), NFKB1(1), RAD50(1), RELA(1), TP53(142) 21702135 170 158 122 6 16 41 20 11 82 0 <1.00e-15 <5.98e-15 96 P53PATHWAY p53 induces cell cycle arrest or apoptosis under conditions of DNA damage. APAF1, ATM, BAX, BCL2, CCND1, CCNE1, CDK2, CDK4, CDKN1A, E2F1, GADD45A, MDM2, PCNA, RB1, TIMP3, TP53 16 APAF1(1), ATM(9), CCND1(1), CDK2(1), E2F1(2), MDM2(1), RB1(9), TP53(142) 13341705 166 157 118 4 17 38 21 8 82 0 <1.00e-15 <5.98e-15 97 RBPATHWAY The ATM protein kinase recognizes DNA damage and blocks cell cycle progression by phosphorylating chk1 and p53, which normally inhibits Rb to allow G1/S transitions. ATM, CDC2, CDC25A, CDC25B, CDC25C, CDK2, CDK4, CHEK1, MYT1, RB1, TP53, WEE1, YWHAH 12 ATM(9), CDC25B(3), CDK2(1), RB1(9), TP53(142) 13226616 164 155 116 6 15 38 19 10 82 0 <1.00e-15 <5.98e-15 98 PMLPATHWAY Ring-shaped PML nuclear bodies regulate transcription and are required co-activators in p53- and DAXX-mediated apoptosis. CREBBP, DAXX, HRAS, PAX3, PML, PRAM-1, RARA, RB1, SIRT1, SP100, TNF, TNFRSF1A, TNFRSF1B, TNFRSF6, TNFSF6, TP53, UBL1 13 CREBBP(2), PAX3(2), RARA(1), RB1(9), SP100(4), TNFRSF1A(1), TP53(142) 13647933 161 153 113 7 16 36 22 8 79 0 <1.00e-15 <5.98e-15 99 TIDPATHWAY On ligand binding, interferon gamma receptors stimulate JAK2 kinase to phosphorylate STAT transcription factors, which promote expression of interferon responsive genes. DNAJA3, HSPA1A, IFNG, IFNGR1, IFNGR2, IKBKB, JAK2, LIN7A, NFKB1, NFKBIA, RB1, RELA, TIP-1, TNF, TNFRSF1A, TNFRSF1B, TP53, USH1C, WT1 17 DNAJA3(1), IKBKB(2), JAK2(2), NFKB1(1), RB1(9), RELA(1), TNFRSF1A(1), TP53(142), USH1C(1), WT1(1) 13158678 161 151 113 6 17 37 19 7 81 0 <1.00e-15 <5.98e-15 100 SA_G1_AND_S_PHASES Cdk2, 4, and 6 bind cyclin D in G1, while cdk2/cyclin E promotes the G1/S transition. ARF1, ARF3, CCND1, CDK2, CDK4, CDKN1A, CDKN1B, CDKN2A, CFL1, E2F1, E2F2, MDM2, NXT1, PRB1, TP53 15 ARF1(1), CCND1(1), CDK2(1), CDKN1B(5), E2F1(2), MDM2(1), TP53(142) 5855343 153 149 104 3 18 33 20 7 75 0 <1.00e-15 <5.98e-15 101 PLK3PATHWAY Active Plk3 phosphorylates CDC25c, blocking the G2/M transition, and phosphorylates p53 to induce apoptosis. ATM, ATR, CDC25C, CHEK1, CHEK2, CNK, TP53, YWHAH 7 ATM(9), ATR(2), CHEK2(2), TP53(142) 12199941 155 148 107 5 15 39 19 9 73 0 <1.00e-15 <5.98e-15 102 TERTPATHWAY hTERC, the RNA subunit of telomerase, and hTERT, the catalytic protein subunit, are required for telomerase activity and are overexpressed in many cancers. HDAC1, MAX, MYC, SP1, SP3, TP53, WT1, ZNF42 7 HDAC1(2), MAX(1), MYC(1), SP1(1), SP3(3), TP53(142), WT1(1) 5161260 151 144 103 5 16 35 20 8 72 0 <1.00e-15 <5.98e-15 103 RNAPATHWAY dsRNA-activated protein kinase phosphorylates elF2a, which generally inhibits translation, and activates NF-kB to provoke inflammation. CHUK, DNAJC3, EIF2S1, EIF2S2, MAP3K14, NFKB1, NFKBIA, PRKR, RELA, TP53 9 DNAJC3(2), EIF2S1(1), EIF2S2(1), NFKB1(1), RELA(1), TP53(142) 7230834 148 141 100 3 16 35 20 7 70 0 <1.00e-15 <5.98e-15 104 HSA04520_ADHERENS_JUNCTION Genes involved in adherens junction ACP1, ACTB, ACTG1, ACTN1, ACTN2, ACTN3, ACTN4, ACVR1B, ACVR1C, BAIAP2, CDC42, CDH1, CREBBP, CSNK2A1, CSNK2A2, CSNK2B, CTNNA1, CTNNA2, CTNNA3, CTNNB1, CTNND1, EGFR, EP300, ERBB2, FARP2, FER, FGFR1, FYN, IGF1R, INSR, IQGAP1, LEF1, LMO7, MAP3K7, MAPK1, MAPK3, MET, MLLT4, NLK, PARD3, PTPN1, PTPN6, PTPRB, PTPRF, PTPRJ, PTPRM, PVRL1, PVRL2, PVRL3, PVRL4, RAC1, RAC2, RAC3, RHOA, SMAD2, SMAD3, SMAD4, SNAI1, SNAI2, SORBS1, SRC, SSX2IP, TCF7, TCF7L1, TCF7L2, TGFBR1, TGFBR2, TJP1, VCL, WAS, WASF1, WASF2, WASF3, WASL, YES1 74 ACTB(2), ACTG1(1), ACTN2(4), ACTN3(1), ACTN4(4), ACVR1B(4), ACVR1C(1), BAIAP2(1), CDH1(31), CREBBP(2), CSNK2A1(1), CSNK2A2(1), CTNNA1(1), CTNNA2(2), CTNNA3(2), CTNND1(1), EGFR(4), EP300(3), ERBB2(4), FARP2(3), IGF1R(1), INSR(2), IQGAP1(1), MAPK1(1), MAPK3(1), MET(4), MLLT4(7), NLK(1), PARD3(3), PTPRB(2), PTPRF(3), PTPRJ(1), PTPRM(2), PVRL1(1), PVRL2(3), PVRL3(1), RHOA(2), SMAD2(3), SMAD3(2), SMAD4(1), SNAI1(1), SNAI2(1), SORBS1(4), SSX2IP(1), TCF7(3), TCF7L2(1), TGFBR1(2), TJP1(4), VCL(3), WAS(1), WASF1(1), WASF3(1), WASL(1), YES1(1) 87978696 140 120 137 35 25 31 17 7 57 3 6.22e-15 3.68e-14 105 ST_GA13_PATHWAY G-alpha-13 influences the actin cytoskeleton and activates protein kinase D, PI3K, and Pyk2. AKT1, AKT2, AKT3, ARHGEF11, BCL2, BF, CDC42, DLG4, GNA13, IKBKG, LPA, MAP2K4, MAP3K1, MAP3K5, MAPK8, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PDK1, PHKA2, PI3, PIK3CB, PLD1, PLD2, PLD3, PRKCM, PTK2, RDX, ROCK1, ROCK2, SERPINA4, SRF, TBXA2R 33 AKT1(12), AKT2(1), AKT3(2), ARHGEF11(1), LPA(5), MAP2K4(18), MAP3K1(53), MAP3K5(1), MAPK8(2), NFKB1(1), NFKB2(4), PDK1(1), PHKA2(4), PI3(1), PIK3CB(3), PLD1(1), PLD3(1), PTK2(1), RDX(1), ROCK1(1), ROCK2(2), SERPINA4(3), SRF(1) 35629425 120 91 108 9 12 25 9 1 42 31 7.55e-15 4.43e-14 106 FASPATHWAY Binding of the Fas ligand to the Fas receptor induces caspase activation and consequent apoptosis in the Fas-expressing cell. ADPRT, ARHGDIB, CASP10, CASP3, CASP6, CASP7, CASP8, CFLAR, DAXX, DFFA, DFFB, FADD, FAF1, JUN, LMNA, LMNB1, LMNB2, MAP2K4, MAP3K1, MAP3K7, MAPK8, PAK1, PAK2, PRKDC, PTPN13, RB1, RIPK2, SPTAN1, TNFRSF6, TNFSF6 26 ARHGDIB(1), CASP6(1), CASP8(2), DFFB(2), JUN(1), LMNB1(1), MAP2K4(18), MAP3K1(53), MAPK8(2), PAK1(2), PAK2(1), PRKDC(7), PTPN13(4), RB1(9), SPTAN1(2) 31114590 106 84 104 4 11 8 9 3 47 28 8.88e-15 5.16e-14 107 NFKBPATHWAY Inactive nuclear factor kB (NF-kB) is inhibited by the IkB family in the cytoplasm; active NF-kB is localized in the nucleus and regulates transcription of a variety of genes. CHUK, FADD, IKBKB, IKBKG, IL1A, IL1R1, IRAK1, MAP3K1, MAP3K14, MAP3K7, MAP3K7IP1, MYD88, NFKB1, NFKBIA, RELA, RIPK1, TLR4, TNF, TNFAIP3, TNFRSF1A, TNFRSF1B, TRADD, TRAF6 20 IKBKB(2), IL1A(1), IL1R1(1), IRAK1(1), MAP3K1(53), NFKB1(1), RELA(1), RIPK1(3), TLR4(7), TNFAIP3(1), TNFRSF1A(1), TRAF6(1) 17466150 73 53 71 7 4 10 5 0 26 28 1.13e-14 6.52e-14 108 PYK2PATHWAY Pyk2 and Rac1 stimulate the JNK cascade and activate MKK3, which activates p38. BCAR1, CALM1, CALM2, CALM3, CRKL, GNAQ, GRB2, HRAS, JUN, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP3K1, MAPK1, MAPK14, MAPK3, MAPK8, PAK1, PLCG1, PRKCA, PRKCB1, PTK2B, RAC1, RAF1, SHC1, SOS1, SRC, SYT1 26 CRKL(1), GNAQ(1), GRB2(1), JUN(1), MAP2K1(1), MAP2K3(1), MAP2K4(18), MAP3K1(53), MAPK1(1), MAPK14(1), MAPK3(1), MAPK8(2), PAK1(2), PLCG1(4), PTK2B(3), RAF1(1), SHC1(1), SOS1(3) 19511895 96 75 94 4 9 11 8 1 39 28 1.14e-14 6.52e-14 109 HSA04912_GNRH_SIGNALING_PATHWAY Genes involved in GnRH signaling pathway ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ATF4, CACNA1C, CACNA1D, CACNA1F, CACNA1S, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CDC42, CGA, EGFR, ELK1, FSHB, GNA11, GNAQ, GNAS, GNRH1, GNRH2, GNRHR, GRB2, HBEGF, HRAS, ITPR1, ITPR2, ITPR3, JUN, KRAS, LHB, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAP3K1, MAP3K2, MAP3K3, MAP3K4, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK7, MAPK8, MAPK9, MMP14, MMP2, NRAS, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCB1, PLCB2, PLCB3, PLCB4, PLD1, PLD2, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCD, PRKX, PRKY, PTK2B, RAF1, SOS1, SOS2, SRC 91 ADCY1(3), ADCY3(2), ADCY4(1), ADCY5(3), ADCY7(1), ADCY8(2), ADCY9(5), ATF4(1), CACNA1C(4), CACNA1D(4), CACNA1F(6), CACNA1S(1), CAMK2A(1), CAMK2D(3), EGFR(4), ELK1(2), GNAQ(1), GNAS(4), GNRH2(1), GRB2(1), ITPR1(7), ITPR3(4), JUN(1), KRAS(1), LHB(1), MAP2K1(1), MAP2K3(1), MAP2K4(18), MAP3K1(53), MAP3K4(3), MAPK1(1), MAPK10(1), MAPK14(1), MAPK3(1), MAPK8(2), MMP14(3), PLA2G2D(1), PLA2G2F(1), PLA2G3(3), PLA2G4A(6), PLA2G6(2), PLCB1(3), PLCB2(2), PLCB3(1), PLCB4(6), PLD1(1), PRKACA(1), PTK2B(3), RAF1(1), SOS1(3), SOS2(1) 92365767 184 139 179 37 26 43 26 9 52 28 1.35e-14 7.65e-14 110 STRESSPATHWAY Tumor necrosis factor receptor TNFR1 promotes apoptosis and activates the pro-inflammatory NF-kB, while TNFR2 activates stress-activated protein kinases (SAPKs). ATF1, CASP2, CHUK, CRADD, IKBKB, IKBKG, JUN, LTA, MAP2K3, MAP2K4, MAP2K6, MAP3K1, MAP3K14, MAP4K2, MAPK14, MAPK8, NFKB1, NFKBIA, RELA, RIPK1, TANK, TNF, TNFRSF1A, TRADD, TRAF2 23 CASP2(2), IKBKB(2), JUN(1), MAP2K3(1), MAP2K4(18), MAP3K1(53), MAPK14(1), MAPK8(2), NFKB1(1), RELA(1), RIPK1(3), TANK(1), TNFRSF1A(1) 17076774 87 67 85 4 5 11 4 1 38 28 1.39e-14 7.77e-14 111 EGFR_SMRTEPATHWAY EGF receptor activation inhibits SMRT, a transcriptional co-repressor that interacts with transcription factor complexes and gene silencers. EGF, EGFR, MAP2K1, MAP3K1, MAPK14, NCOR2, RARA, RXRA, THRA, THRB, ZNF145 10 EGF(2), EGFR(4), MAP2K1(1), MAP3K1(53), MAPK14(1), NCOR2(3), RARA(1), THRB(1) 11236134 66 48 65 5 4 4 2 4 24 28 1.48e-14 8.19e-14 112 KERATINOCYTEPATHWAY Keratinocyte differentiation, which models the differentiation of epidermal cells, requires the four main MAP kinase pathways. BCL2, CEBPA, CHUK, DAXX, EGF, EGFR, ETS1, ETS2, FOS, HOXA7, HRAS, IKBKB, JUN, MAP2K1, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAP3K1, MAP3K14, MAP3K5, MAPK1, MAPK13, MAPK14, MAPK3, MAPK8, NFKB1, NFKBIA, PPP2CA, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCQ, RAF1, RELA, RIPK1, SP1, TNF, TNFRSF1A, TNFRSF1B, TNFRSF6, TNFSF6, TRAF2 41 EGF(2), EGFR(4), ETS1(2), ETS2(3), HOXA7(1), IKBKB(2), JUN(1), MAP2K1(1), MAP2K3(1), MAP2K4(18), MAP3K1(53), MAP3K5(1), MAPK1(1), MAPK14(1), MAPK3(1), MAPK8(2), NFKB1(1), PRKCG(1), PRKCH(1), PRKCQ(2), RAF1(1), RELA(1), RIPK1(3), SP1(1), TNFRSF1A(1) 35395191 106 85 104 15 10 15 10 5 38 28 1.53e-14 8.39e-14 113 TGFBPATHWAY The TGF-beta receptor responds to ligand binding by activating the SMAD family of transcriptional regulations, commonly blocking cell growth. APC, CDH1, CREBBP, EP300, MADH2, MADH3, MADH4, MADH7, MADHIP, MAP2K1, MAP3K7, MAP3K7IP1, MAPK3, SKIL, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2 13 APC(3), CDH1(31), CREBBP(2), EP300(3), MAP2K1(1), MAPK3(1), SKIL(1), TGFB3(1), TGFBR1(2) 18997797 45 44 42 5 1 9 4 1 30 0 1.54e-14 8.39e-14 114 41BBPATHWAY TNF-type receptor 4-1BB is bound by TRAF1 to activate the MAP kinase pathway in activated T cells. ATF2, CHUK, IFNG, IKBKB, IL2, IL4, JUN, MAP3K1, MAP3K5, MAP4K5, MAPK14, MAPK8, NFKB1, NFKBIA, RELA, TNFRSF9, TNFSF9, TRAF2 17 IKBKB(2), IL2(1), JUN(1), MAP3K1(53), MAP3K5(1), MAPK14(1), MAPK8(2), NFKB1(1), RELA(1) 14513889 63 46 62 4 2 6 2 0 25 28 1.55e-14 8.39e-14 115 VIPPATHWAY Apoptosis of activated T cells is inhibited by vasoactive intestinal peptide (VIP) and its relative PACAP. CALM1, CALM2, CALM3, CHUK, EGR2, EGR3, GNAQ, MAP3K1, MYC, NFATC1, NFATC2, NFKB1, NFKBIA, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RELA, SYT1, VIP, VIPR2 27 EGR2(1), EGR3(3), GNAQ(1), MAP3K1(53), MYC(1), NFKB1(1), PLCG1(4), PPP3CA(3), PPP3CB(2), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), RELA(1), VIP(1) 19685289 74 56 73 7 6 7 4 1 28 28 1.57e-14 8.39e-14 116 TNFR2PATHWAY Tumor necrosis factor beta, produced by activated lymphocytes, binds to its receptor TNFR2 to induce activation in immune cells and apoptosis in many other cells. CHUK, DUSP1, IKBKAP, IKBKB, IKBKG, LTA, MAP3K1, MAP3K14, NFKB1, NFKBIA, RELA, RIPK1, TANK, TNFAIP3, TNFRSF1B, TRAF1, TRAF2, TRAF3 17 IKBKAP(3), IKBKB(2), MAP3K1(53), NFKB1(1), RELA(1), RIPK1(3), TANK(1), TNFAIP3(1) 16616418 65 47 64 6 2 8 3 0 24 28 1.59e-14 8.43e-14 117 BCRPATHWAY B cell antigen receptors (BCRs) activate tyrosine kinases and transiently increase tyrosine phosphorylation on binding to antigen. BLNK, BTK, CALM1, CALM2, CALM3, CD79A, CD79B, ELK1, FOS, GRB2, HRAS, JUN, LYN, MAP2K1, MAP3K1, MAPK14, MAPK3, MAPK8, NFATC1, NFATC2, NFATC3, NFATC4, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCA, PRKCB1, RAC1, RAF1, SHC1, SOS1, SYK, SYT1, VAV1 34 BLNK(1), BTK(2), CD79A(1), ELK1(2), GRB2(1), JUN(1), LYN(3), MAP2K1(1), MAP3K1(53), MAPK14(1), MAPK3(1), MAPK8(2), NFATC3(3), NFATC4(3), PLCG1(4), PPP3CA(3), PPP3CB(2), RAF1(1), SHC1(1), SOS1(3), VAV1(1) 27743547 90 70 89 6 4 16 13 0 29 28 1.64e-14 8.65e-14 118 TNFR1PATHWAY Tumor necrosis factor alpha binds to its receptor TNFR1 and induces caspase-dependent apoptosis. ADPRT, ARHGDIB, BAG4, CASP2, CASP3, CASP8, CRADD, DFFA, DFFB, FADD, JUN, LMNA, LMNB1, LMNB2, MADD, MAP2K4, MAP3K1, MAP3K7, MAPK8, PAK1, PAK2, PRKDC, RB1, RIPK1, SPTAN1, TNF, TNFRSF1A, TRADD, TRAF2 26 ARHGDIB(1), BAG4(1), CASP2(2), CASP8(2), DFFB(2), JUN(1), LMNB1(1), MADD(7), MAP2K4(18), MAP3K1(53), MAPK8(2), PAK1(2), PAK2(1), PRKDC(7), RB1(9), RIPK1(3), SPTAN1(2), TNFRSF1A(1) 28758561 115 89 113 6 11 15 9 3 49 28 1.71e-14 8.93e-14 119 HSA04514_CELL_ADHESION_MOLECULES Genes involved in cell adhesion molecules (CAMs) ALCAM, CADM1, CADM3, CD2, CD22, CD226, CD274, CD276, CD28, CD34, CD4, CD40, CD40LG, CD58, CD6, CD80, CD86, CD8A, CD8B, CD99, CDH1, CDH15, CDH2, CDH3, CDH4, CDH5, CLDN1, CLDN10, CLDN11, CLDN14, CLDN15, CLDN16, CLDN17, CLDN18, CLDN19, CLDN2, CLDN20, CLDN22, CLDN23, CLDN3, CLDN4, CLDN5, CLDN6, CLDN7, CLDN8, CLDN9, CNTN1, CNTN2, CNTNAP1, CNTNAP2, CTLA4, ESAM, F11R, GLG1, HLA-A, HLA-A29.1, HLA-B, HLA-C, HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-E, HLA-F, HLA-G, ICAM1, ICAM2, ICAM3, ICOS, ICOSLG, ITGA4, ITGA6, ITGA8, ITGA9, ITGAL, ITGAM, ITGAV, ITGB1, ITGB2, ITGB7, ITGB8, JAM2, JAM3, L1CAM, MADCAM1, MAG, MPZ, MPZL1, NCAM1, NCAM2, NEGR1, NEO1, NFASC, NLGN1, NLGN2, NLGN3, NRCAM, NRXN1, NRXN2, NRXN3, OCLN, PDCD1, PDCD1LG2, PECAM1, PTPRC, PTPRF, PTPRM, PVR, PVRL1, PVRL2, PVRL3, SDC1, SDC2, SDC3, SDC4, SELE, SELL, SELP, SELPLG, SIGLEC1, SPN, VCAM1, VCAN 124 ALCAM(1), CADM1(1), CD2(2), CD22(1), CD226(2), CD274(1), CD276(1), CD34(1), CD4(1), CD40(1), CD40LG(1), CD86(1), CD8A(1), CD99(2), CDH1(31), CDH2(1), CDH4(2), CLDN11(1), CLDN15(1), CLDN17(1), CLDN19(1), CLDN6(1), CNTN1(4), CNTN2(4), CNTNAP1(3), CNTNAP2(3), ESAM(2), F11R(1), GLG1(2), HLA-A(4), HLA-C(3), HLA-DMA(1), HLA-DMB(2), HLA-DQB1(1), HLA-DRB1(2), HLA-DRB5(1), HLA-E(2), HLA-F(2), HLA-G(2), ICOSLG(1), ITGA4(1), ITGA6(3), ITGA8(2), ITGAL(1), ITGAM(1), ITGAV(3), ITGB1(2), ITGB2(3), ITGB8(1), L1CAM(1), MAG(1), MPZL1(1), NCAM1(4), NCAM2(2), NEO1(3), NFASC(4), NLGN1(1), NLGN3(3), NRCAM(1), NRXN1(1), NRXN2(3), NRXN3(5), PTPRC(1), PTPRF(3), PTPRM(2), PVRL1(1), PVRL2(3), PVRL3(1), SDC4(1), SELE(1), SELL(4), SELP(3), SELPLG(1), SIGLEC1(1), SPN(2), VCAM1(2), VCAN(7) 106226133 176 132 172 44 36 38 35 11 56 0 1.73e-14 8.97e-14 120 CD40PATHWAY The CD40 receptor is a TNF-type receptor that regulates immunoglobulin expression in B cells and moderates T cell activation via T-cell expression of its ligand. CHUK, DUSP1, IKBKAP, IKBKB, IKBKG, MAP3K1, MAP3K14, NFKB1, NFKBIA, RELA, TNFAIP3, TNFRSF5, TNFSF5, TRAF3, TRAF6 12 IKBKAP(3), IKBKB(2), MAP3K1(53), NFKB1(1), RELA(1), TNFAIP3(1), TRAF6(1) 13432965 62 44 61 5 2 7 2 0 23 28 1.80e-14 9.23e-14 121 CERAMIDEPATHWAY Ceramide is a lipid signaling molecule that can activate proliferative or apoptotic pathways, depending on signaling context, localization, and cell type. BAD, BAX, BCL2, CASP8, CYCS, FADD, MAP2K1, MAP2K4, MAP3K1, MAPK1, MAPK3, MAPK8, NFKB1, NSMAF, PDCD8, RAF1, RELA, RIPK1, SMPD1, TNFRSF1A, TRADD, TRAF2 20 BAD(1), CASP8(2), MAP2K1(1), MAP2K4(18), MAP3K1(53), MAPK1(1), MAPK3(1), MAPK8(2), NFKB1(1), NSMAF(2), RAF1(1), RELA(1), RIPK1(3), TNFRSF1A(1) 14909349 88 69 85 4 6 9 7 0 38 28 1.83e-14 9.33e-14 122 HIVNEFPATHWAY HIV-infected CD4 helper T cells may express Fas ligand, which binds to the Fas receptors of uninfected cells and induces apoptosis. ACTG1, ADPRT, APAF1, ARHGDIB, BAG4, BCL2, BID, BIRC2, BIRC3, BIRC4, CASP2, CASP3, CASP6, CASP7, CASP8, CASP9, CDC2L1, CDC2L2, CFLAR, CHUK, CRADD, CYCS, DAXX, DFFA, DFFB, FADD, GSN, LMNA, LMNB1, LMNB2, MAP2K7, MAP3K1, MAP3K14, MAP3K5, MAPK8, MDM2, NFKB1, NFKBIA, NUMA1, PAK2, PRKCD, PRKDC, PSEN1, PSEN2, PTK2, RASA1, RB1, RELA, RIPK1, SPTAN1, TNF, TNFRSF1A, TNFRSF1B, TNFRSF6, TNFSF6, TRADD, TRAF1, TRAF2 49 ACTG1(1), APAF1(1), ARHGDIB(1), BAG4(1), BID(4), CASP2(2), CASP6(1), CASP8(2), DFFB(2), GSN(1), LMNB1(1), MAP3K1(53), MAP3K5(1), MAPK8(2), MDM2(1), NFKB1(1), NUMA1(2), PAK2(1), PRKDC(7), PSEN2(2), PTK2(1), RASA1(2), RB1(9), RELA(1), RIPK1(3), SPTAN1(2), TNFRSF1A(1) 50633076 106 84 105 7 6 18 12 2 40 28 1.95e-14 9.79e-14 123 P38MAPKPATHWAY The Rho family GTPases activate the p38 MAPKs under environmental stress or in the presence of pro-inflammatory cytokines. ATF2, CDC42, CREB1, DAXX, DDIT3, ELK1, GRB2, HMGN1, HRAS, HSPB1, HSPB2, MAP2K4, MAP2K6, MAP3K1, MAP3K5, MAP3K7, MAP3K9, MAPK14, MAPKAPK2, MAPKAPK5, MAX, MEF2A, MEF2B, MEF2C, MEF2D, MKNK1, MYC, PDZGEF1, PLA2G4A, RAC1, RIPK1, RPS6KA5, SHC1, STAT1, TGFB1, TGFB2, TGFB3, TGFBR1, TRADD, TRAF2 37 ELK1(2), GRB2(1), MAP2K4(18), MAP3K1(53), MAP3K5(1), MAP3K9(1), MAPK14(1), MAX(1), MEF2A(1), MEF2C(2), MYC(1), PLA2G4A(6), RIPK1(3), SHC1(1), STAT1(1), TGFB3(1), TGFBR1(2) 26936403 96 74 93 8 9 10 8 2 39 28 1.95e-14 9.79e-14 124 AT1RPATHWAY Binding of angiotensin II to AT1-R activates Ca2+ signaling and the JNK pathway. AGT, AGTR1, ATF2, CALM1, CALM2, CALM3, EGFR, ELK1, GNAQ, GRB2, HRAS, JUN, MAP2K1, MAP2K2, MAP2K4, MAP3K1, MAPK1, MAPK3, MAPK8, MEF2A, MEF2B, MEF2C, MEF2D, PAK1, PRKCA, PRKCB1, PTK2, PTK2B, RAC1, RAF1, SHC1, SOS1, SRC, SYT1 32 AGT(3), EGFR(4), ELK1(2), GNAQ(1), GRB2(1), JUN(1), MAP2K1(1), MAP2K4(18), MAP3K1(53), MAPK1(1), MAPK3(1), MAPK8(2), MEF2A(1), MEF2C(2), PAK1(2), PTK2(1), PTK2B(3), RAF1(1), SHC1(1), SOS1(3) 24519534 102 80 100 5 9 13 9 4 39 28 2.05e-14 1.02e-13 125 IL1RPATHWAY The cytokine IL-1 stimulates its primary receptor, IL-1R1, which induces transcription of inflammation-related genes such as interferons. CHUK, IFNA1, IFNB1, IKBKB, IL1A, IL1B, IL1R1, IL1RAP, IL1RN, IL6, IRAK1, IRAK2, IRAK3, JUN, MAP2K3, MAP2K6, MAP3K1, MAP3K14, MAP3K7, MAP3K7IP1, MAPK14, MAPK8, MYD88, NFKB1, NFKBIA, RELA, SITPEC, TGFB1, TGFB2, TGFB3, TNF, TOLLIP, TRAF6 30 IFNB1(1), IKBKB(2), IL1A(1), IL1R1(1), IL1RAP(2), IL1RN(2), IL6(2), IRAK1(1), IRAK2(2), IRAK3(1), JUN(1), MAP2K3(1), MAP3K1(53), MAPK14(1), MAPK8(2), NFKB1(1), RELA(1), TGFB3(1), TRAF6(1) 21342165 77 57 76 6 5 12 4 1 27 28 2.24e-14 1.11e-13 126 FMLPPATHWAY The fMLP receptor is a G-protein coupled receptor in neutrophils that recognizes formylated bacterial peptides and activates NADPH oxidase. CALM1, CALM2, CALM3, CAMK1, CAMK1G, ELK1, FPR1, GNA15, GNB1, GNGT1, HRAS, MAP2K1, MAP2K2, MAP2K3, MAP2K6, MAP3K1, MAPK1, MAPK14, MAPK3, NCF1, NCF2, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKBIA, PAK1, PIK3C2G, PLCB1, PPP3CA, PPP3CB, PPP3CC, RAC1, RAF1, RELA, SYT1 36 CAMK1(1), CAMK1G(1), ELK1(2), FPR1(1), GNB1(1), MAP2K1(1), MAP2K3(1), MAP3K1(53), MAPK1(1), MAPK14(1), MAPK3(1), NCF2(2), NFATC3(3), NFATC4(3), NFKB1(1), PAK1(2), PIK3C2G(1), PLCB1(3), PPP3CA(3), PPP3CB(2), RAF1(1), RELA(1) 27524016 86 66 85 11 7 12 14 1 24 28 2.30e-14 1.12e-13 127 GATA3PATHWAY GATA-3 is a transcription factor that promotes differentiation of helper T cells into Th2 cells, which secrete cytokines IL4, IL5, and IL13. GATA3, IL13, IL4, IL5, JUNB, MAF, MAP2K3, MAPK14, NFATC1, NFATC2, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B 15 GATA3(55), MAP2K3(1), MAPK14(1), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1) 7453914 60 58 37 6 3 3 0 1 51 2 2.34e-14 1.13e-13 128 SA_B_CELL_RECEPTOR_COMPLEXES Antigen binding to B cell receptors activates protein tyrosine kinases, such as the Src family, which ultimate activate MAP kinases. ATF2, BCR, BLNK, ELK1, FOS, GRB2, HRAS, JUN, LYN, MAP2K1, MAP3K1, MAPK1, MAPK3, MAPK8IP3, PAPPA, RAC1, RPS6KA1, RPS6KA3, SHC1, SOS1, SYK, VAV1, VAV2, VAV3 23 BCR(1), BLNK(1), ELK1(2), GRB2(1), JUN(1), LYN(3), MAP2K1(1), MAP3K1(53), MAPK1(1), MAPK3(1), PAPPA(4), RPS6KA1(1), RPS6KA3(2), SHC1(1), SOS1(3), VAV1(1), VAV3(1) 21072441 78 60 77 4 5 14 7 0 24 28 2.35e-14 1.13e-13 129 CALCINEURIN_NF_AT_SIGNALING Mouse genes associated with signal transduction through calcium, calcineurin, and NF-AT. ACTB, BAD, BCL2, CABIN1, CALM1, CALM2, CALM3, CAMK2B, CAMK4, CD3E, CD3G, CD3Z, CD69, CDKN1A, CEBPB, CNR1, CREBBP, CSF2, CSNK2A1, CSNK2B, CTLA4, EGR2, EGR3, EP300, FCER1A, FCGR3A, FKBP1B, FLJ14639, FOS, FOSL1, GAPD, GATA3, GATA4, GRLF1, GSK3A, GSK3B, HRAS, ICOS, IFNA1, IFNB1, IFNG, IL10, IL13, IL1B, IL2, IL2RA, IL3, IL4, IL6, IL8, IL8RA, ITK, JUNB, KPNA5, KPNB3, MAP2K7, MAPK14, MAPK8, MAPK9, MEF2A, MEF2B, MEF2D, MYF5, NCK2, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NFKB2, NFKBIB, NFKBIE, NPPB, NUP214, OPRD1, P2RX7, PAK1, PIN1, PPIA, PPP3CB, PPP3CC, PPP3R1, PTPRC, RELA, RPL13A, SFN, SLA, SP1, SP3, TGFB1, TNF, TNFSF5, TNFSF6, TRAF2, TRPV6, VAV1, VAV2, VAV3, VEGF, XPO5 89 ACTB(2), BAD(1), CABIN1(5), CD3E(1), CD3G(1), CD69(1), CNR1(1), CREBBP(2), CSNK2A1(1), EGR2(1), EGR3(3), EP300(3), FCER1A(2), GATA3(55), GRLF1(4), GSK3A(1), IFNB1(1), IL2(1), IL6(2), ITK(3), KPNA5(1), MAPK14(1), MAPK8(2), MEF2A(1), NFAT5(1), NFATC3(3), NFATC4(3), NFKB2(4), NUP214(4), OPRD1(1), P2RX7(1), PAK1(2), PPP3CB(2), PTPRC(1), RELA(1), RPL13A(2), SP1(1), SP3(3), TRPV6(1), VAV1(1), VAV3(1), XPO5(1) 65388804 129 115 105 31 14 17 18 3 72 5 2.53e-14 1.21e-13 130 TOLLPATHWAY Toll-like receptors are activated by bacterial lipoproteins, lipopolysaccharides, and other surface molecules, and activate pro-inflammatory factors such as NF-kB. CD14, CHUK, ELK1, FOS, IKBKB, IKBKG, IRAK1, JUN, LY96, MAP2K3, MAP2K4, MAP2K6, MAP3K1, MAP3K14, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAPK14, MAPK8, MYD88, NFKB1, NFKBIA, PGLYRP, PPARA, PRKR, RELA, SITPEC, TIRAP, TLR10, TLR2, TLR3, TLR4, TLR6, TLR7, TLR9, TOLLIP, TRAF6 30 CD14(1), ELK1(2), IKBKB(2), IRAK1(1), JUN(1), MAP2K3(1), MAP2K4(18), MAP3K1(53), MAPK14(1), MAPK8(2), NFKB1(1), PPARA(1), RELA(1), TIRAP(2), TLR10(1), TLR2(1), TLR3(1), TLR4(7), TLR7(3), TRAF6(1) 26549562 101 78 98 6 9 13 7 0 44 28 2.65e-14 1.26e-13 131 MAPKPATHWAY The mitogen-activated protein (MAP) kinase pathway is a common signaling mechanism and has four main sub-pathways: Erk, JNK/SAPK, p53, and ERK5. ARAF1, ATF2, BRAF, CEBPA, CHUK, CREB1, DAXX, ELK1, FOS, GRB2, HRAS, IKBKB, JUN, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K5, MAP2K6, MAP2K7, MAP3K1, MAP3K10, MAP3K11, MAP3K12, MAP3K13, MAP3K14, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K6, MAP3K7, MAP3K8, MAP3K9, MAP4K1, MAP4K2, MAP4K3, MAP4K4, MAP4K5, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK4, MAPK6, MAPK7, MAPK8, MAPK9, MAPKAPK2, MAPKAPK3, MAPKAPK5, MAX, MEF2A, MEF2B, MEF2C, MEF2D, MKNK1, MKNK2, MYC, NFKB1, NFKBIA, PAK1, PAK2, PDZGEF1, RAC1, RAF1, RELA, RIPK1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA4, RPS6KA5, RPS6KB1, RPS6KB2, SHC1, SP1, STAT1, TGFB1, TGFB2, TGFB3, TGFBR1, TRADD, TRAF2 79 BRAF(2), ELK1(2), GRB2(1), IKBKB(2), JUN(1), MAP2K1(1), MAP2K3(1), MAP2K4(18), MAP2K5(1), MAP3K1(53), MAP3K10(4), MAP3K11(1), MAP3K12(2), MAP3K13(3), MAP3K4(3), MAP3K5(1), MAP3K6(1), MAP3K8(2), MAP3K9(1), MAP4K1(1), MAP4K4(1), MAPK1(1), MAPK10(1), MAPK14(1), MAPK3(1), MAPK4(2), MAPK6(1), MAPK8(2), MAPKAPK3(1), MAX(1), MEF2A(1), MEF2C(2), MYC(1), NFKB1(1), PAK1(2), PAK2(1), RAF1(1), RELA(1), RIPK1(3), RPS6KA1(1), RPS6KA2(2), RPS6KA3(2), RPS6KA4(1), RPS6KB2(3), SHC1(1), SP1(1), STAT1(1), TGFB3(1), TGFBR1(2) 67732665 141 114 139 13 17 26 14 4 52 28 2.74e-14 1.29e-13 132 HSA05130_PATHOGENIC_ESCHERICHIA_COLI_INFECTION_EHEC Genes involved in pathogenic Escherichia coli infection - EHEC ABL1, ACTB, ACTG1, ARHGEF2, ARPC5, ARPC5L, CD14, CDC42, CDH1, CLDN1, CTNNB1, CTTN, EZR, FYN, HCLS1, ITGB1, KRT18, LOC643224, LOC654264, LY96, NCK1, NCK2, NCL, OCLN, PRKCA, RHOA, ROCK1, ROCK2, TLR4, TLR5, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, TUBB8, WAS, WASL, YWHAQ, YWHAZ 51 ABL1(2), ACTB(2), ACTG1(1), ARHGEF2(1), CD14(1), CDH1(31), CTTN(1), EZR(2), HCLS1(1), ITGB1(2), KRT18(1), NCL(1), RHOA(2), ROCK1(1), ROCK2(2), TLR4(7), TLR5(1), TUBA1B(1), TUBA3C(1), TUBA3D(1), TUBAL3(1), TUBB(1), TUBB2B(1), TUBB2C(2), TUBB4(1), WAS(1), WASL(1) 39551577 70 63 67 13 6 13 10 3 38 0 5.68e-13 2.63e-12 133 HSA05131_PATHOGENIC_ESCHERICHIA_COLI_INFECTION_EPEC Genes involved in pathogenic Escherichia coli infection - EPEC ABL1, ACTB, ACTG1, ARHGEF2, ARPC5, ARPC5L, CD14, CDC42, CDH1, CLDN1, CTNNB1, CTTN, EZR, FYN, HCLS1, ITGB1, KRT18, LOC643224, LOC654264, LY96, NCK1, NCK2, NCL, OCLN, PRKCA, RHOA, ROCK1, ROCK2, TLR4, TLR5, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, TUBB8, WAS, WASL, YWHAQ, YWHAZ 51 ABL1(2), ACTB(2), ACTG1(1), ARHGEF2(1), CD14(1), CDH1(31), CTTN(1), EZR(2), HCLS1(1), ITGB1(2), KRT18(1), NCL(1), RHOA(2), ROCK1(1), ROCK2(2), TLR4(7), TLR5(1), TUBA1B(1), TUBA3C(1), TUBA3D(1), TUBAL3(1), TUBB(1), TUBB2B(1), TUBB2C(2), TUBB4(1), WAS(1), WASL(1) 39551577 70 63 67 13 6 13 10 3 38 0 5.68e-13 2.63e-12 134 HSA04530_TIGHT_JUNCTION Genes involved in tight junction ACTB, ACTG1, ACTN1, ACTN2, ACTN3, ACTN4, AKT1, AKT2, AKT3, AMOTL1, ASH1L, CASK, CDC42, CDK4, CGN, CLDN1, CLDN10, CLDN11, CLDN14, CLDN15, CLDN16, CLDN17, CLDN18, CLDN19, CLDN2, CLDN20, CLDN22, CLDN23, CLDN3, CLDN4, CLDN5, CLDN6, CLDN7, CLDN8, CLDN9, CRB3, CSDA, CSNK2A1, CSNK2A2, CSNK2B, CTNNA1, CTNNA2, CTNNA3, CTNNB1, CTTN, EPB41, EPB41L1, EPB41L2, EPB41L3, EXOC3, EXOC4, F11R, GNAI1, GNAI2, GNAI3, HCLS1, HRAS, IGSF5, INADL, JAM2, JAM3, KRAS, LLGL1, LLGL2, MAGI1, MAGI2, MAGI3, MLLT4, MPDZ, MPP5, MRAS, MRCL3, MRLC2, MYH1, MYH10, MYH11, MYH13, MYH14, MYH15, MYH2, MYH3, MYH4, MYH6, MYH7, MYH7B, MYH8, MYH9, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLPF, NRAS, OCLN, PARD3, PARD6A, PARD6B, PARD6G, PPM1J, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, PPP2R3A, PPP2R3B, PPP2R4, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCI, PRKCQ, PRKCZ, PTEN, RAB13, RAB3B, RHOA, RRAS, RRAS2, SPTAN1, SRC, SYMPK, TJAP1, TJP1, TJP2, TJP3, VAPA, YES1, ZAK 126 ACTB(2), ACTG1(1), ACTN2(4), ACTN3(1), ACTN4(4), AKT1(12), AKT2(1), AKT3(2), ASH1L(4), CASK(2), CLDN11(1), CLDN15(1), CLDN17(1), CLDN19(1), CLDN6(1), CRB3(1), CSNK2A1(1), CSNK2A2(1), CTNNA1(1), CTNNA2(2), CTNNA3(2), CTTN(1), EPB41(1), EPB41L1(4), EPB41L2(2), EPB41L3(3), EXOC3(1), EXOC4(1), F11R(1), GNAI1(1), GNAI2(1), HCLS1(1), IGSF5(3), INADL(5), KRAS(1), LLGL1(1), LLGL2(5), MAGI1(3), MAGI2(6), MAGI3(3), MLLT4(7), MPDZ(2), MYH1(4), MYH10(4), MYH11(5), MYH13(2), MYH14(5), MYH15(5), MYH2(1), MYH3(1), MYH4(4), MYH6(7), MYH7(6), MYH7B(5), MYH8(4), MYH9(5), MYL7(1), PARD3(3), PARD6B(1), PPP2CB(2), PPP2R3A(3), PPP2R4(2), PRKCG(1), PRKCH(1), PRKCI(1), PRKCQ(2), PRKCZ(1), PTEN(15), RHOA(2), SPTAN1(2), SYMPK(3), TJP1(4), TJP3(2), VAPA(1), YES1(1), ZAK(1) 140757903 206 161 195 69 35 60 46 14 47 4 3.63e-12 1.67e-11 135 HISTONE_METHYLTRANSFERASE Genes with HMT activity AOF2, KDM6A, ASH1L, ASH2L, C17orf79, CARM1, CTCFL, DOT1L, EED, EHMT1, EHMT2, EZH1, EZH2, FBXL10, FBXL11, FBXO11, HCFC1, HSF4, JMJD1A, JMJD1B, JMJD2A, JMJD2B, JMJD2C, JMJD2D, JMJD3, JMJD4, JMJD6, MEN1, MLL, MLL2, MLL3, MLL4, MLL5, NSD1, OGT, PAXIP1, PPP1CA, PPP1CB, PPP1CC, PRDM2, PRDM6, PRDM7, PRDM9, PRMT1, PRMT5, PRMT6, PRMT7, PRMT8, RBBP5, SATB1, SETD1A, SETD1B, SETD2, SETD7, SETD8, SETDB1, SETDB2, SETMAR, SMYD3, STK38, SUV39H1, SUV39H2, SUV420H1, SUV420H2, SUZ12, WHSC1, WHSC1L1 55 ASH1L(4), ASH2L(3), CARM1(1), CTCFL(1), DOT1L(3), EED(2), EZH1(1), HCFC1(5), KDM6A(5), MEN1(1), MLL(5), MLL2(6), MLL3(30), MLL4(4), MLL5(4), OGT(2), PRDM2(2), PRMT5(2), PRMT6(2), PRMT7(1), PRMT8(1), RBBP5(1), SATB1(2), SETD2(4), SETD7(1), SETDB1(7), SETMAR(2), SMYD3(3), SUV420H1(2), SUZ12(3), WHSC1(4), WHSC1L1(1) 86453133 115 102 114 17 19 24 19 8 43 2 1.45e-10 6.62e-10 136 OVARIAN_INFERTILITY_GENES ATM, BMPR1B, CCND2, CDK4, CDKN1B, CEBPB, DAZL, DMC1, EGR1, ESR2, FSHR, GJA4, INHA, LHCGR, MLH1, MSH5, NCOR1, NR5A1, NRIP1, PGR, PRLR, PTGER2, SMPD1, VDR, ZP2 23 ATM(9), BMPR1B(2), CDKN1B(5), DMC1(2), EGR1(1), ESR2(2), FSHR(3), GJA4(1), LHCGR(4), NCOR1(16), PGR(2), PRLR(1), ZP2(1) 25400700 49 45 48 9 2 10 5 5 25 2 1.95e-09 8.85e-09 137 ST_P38_MAPK_PATHWAY p38 is a MAP kinase regulated by cytokines and cellular stress. AKT1, ATF1, CDC42, CREB1, CREB3, CREB5, DUSP1, DUSP10, EEF2K, EIF4E, ELK1, GADD45A, HSPB1, IL1R1, MAP2K3, MAP2K4, MAP2K6, MAP3K10, MAP3K4, MAP3K5, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAPK1, MAPK11, MAPK12, MAPK13, MAPK14, MAPKAPK2, MAPKAPK5, MKNK1, MKNK2, MYEF2, NFKB1, NR2C2, SRF, TRAF6 32 AKT1(12), CREB3(1), DUSP10(1), EEF2K(2), ELK1(2), IL1R1(1), MAP2K3(1), MAP2K4(18), MAP3K10(4), MAP3K4(3), MAP3K5(1), MAPK1(1), MAPK14(1), MYEF2(1), NFKB1(1), SRF(1), TRAF6(1) 23536461 52 48 41 8 7 20 11 0 14 0 2.11e-08 9.50e-08 138 HSA01430_CELL_COMMUNICATION Genes involved in cell communication ACTB, ACTG1, CHAD, COL11A1, COL11A2, COL17A1, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A2, COL4A4, COL4A6, COL5A1, COL5A2, COL5A3, COL6A1, COL6A2, COL6A3, COL6A6, COMP, DES, DSC1, DSC2, DSC3, DSG1, DSG2, DSG3, DSG4, FN1, GJA1, GJA10, GJA3, GJA4, GJA5, GJA8, GJA9, GJB1, GJB2, GJB3, GJB4, GJB5, GJB6, GJB7, GJC1, GJC2, GJC3, GJD2, GJD3, GJD4, IBSP, INA, ITGA6, ITGB4, KRT1, KRT10, KRT12, KRT13, KRT14, KRT15, KRT16, KRT17, KRT18, KRT19, KRT2, KRT20, KRT23, KRT24, KRT25, KRT27, KRT28, KRT3, KRT31, KRT32, KRT33A, KRT33B, KRT34, KRT35, KRT36, KRT37, KRT38, KRT39, KRT4, KRT40, KRT5, KRT6A, KRT6B, KRT6C, KRT7, KRT71, KRT72, KRT73, KRT74, KRT75, KRT76, KRT77, KRT78, KRT79, KRT8, KRT81, KRT82, KRT83, KRT84, KRT85, KRT86, KRT9, LAMA1, LAMA2, LAMA3, LAMA4, LAMA5, LAMB1, LAMB2, LAMB3, LAMB4, LAMC1, LAMC2, LAMC3, LMNA, LMNB1, LMNB2, LOC728760, NES, PRPH, RELN, SPP1, THBS1, THBS2, THBS3, THBS4, TNC, TNN, TNR, TNXB, VIM, VTN, VWF 126 ACTB(2), ACTG1(1), COL11A1(2), COL11A2(1), COL17A1(3), COL1A1(6), COL1A2(3), COL2A1(3), COL3A1(1), COL4A1(4), COL4A2(2), COL4A4(1), COL4A6(3), COL5A1(2), COL5A2(4), COL5A3(4), COL6A3(5), COL6A6(4), COMP(3), DSC2(3), DSC3(1), DSG1(2), DSG4(2), FN1(3), GJA1(2), GJA10(1), GJA4(1), GJA9(1), GJB2(1), GJB3(2), GJB4(1), GJB5(1), GJC1(1), INA(1), ITGA6(3), ITGB4(4), KRT1(3), KRT14(1), KRT15(1), KRT17(4), KRT18(1), KRT19(2), KRT2(2), KRT25(2), KRT28(1), KRT3(1), KRT33A(1), KRT34(1), KRT35(1), KRT36(2), KRT37(1), KRT4(2), KRT6A(1), KRT6C(1), KRT71(1), KRT72(1), KRT81(1), KRT82(2), KRT83(1), KRT84(1), KRT85(1), KRT86(1), KRT9(2), LAMA1(6), LAMA2(7), LAMA3(6), LAMA4(4), LAMB1(3), LAMB2(3), LAMB3(4), LAMB4(6), LAMC1(2), LAMC2(1), LAMC3(1), LMNB1(1), NES(3), RELN(10), SPP1(1), THBS1(3), THBS3(1), THBS4(1), TNC(3), TNN(3), TNR(1), TNXB(3), VWF(6) 166605270 202 161 201 72 41 74 42 10 35 0 5.43e-08 2.42e-07 139 ST_GRANULE_CELL_SURVIVAL_PATHWAY The survival and differentiation of granule cells in the brain is controlled by pro-growth PACAP and pro-apoptotic ceramides. ADPRT, APC, ASAH1, CAMP, CASP3, CERK, CREB1, CREB3, CREB5, CXCL2, DAG1, EPHB2, FOS, GNAQ, IL8RB, ITPKA, ITPKB, JUN, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, PACAP 21 APC(3), CERK(1), CREB3(1), EPHB2(1), GNAQ(1), ITPKB(7), JUN(1), MAP2K4(18), MAPK1(1), MAPK10(1), MAPK8(2), MAPK8IP1(1) 17847414 38 36 37 4 7 6 4 3 18 0 1.76e-07 7.78e-07 140 HSA04320_DORSO_VENTRAL_AXIS_FORMATION Genes involved in dorso-ventral axis formation BRAF, CPEB1, EGFR, ERBB2, ERBB4, ETS1, ETS2, ETV6, ETV7, FMN2, GRB2, KRAS, MAP2K1, MAPK1, MAPK3, NOTCH1, NOTCH2, NOTCH3, NOTCH4, PIWIL1, PIWIL2, PIWIL3, PIWIL4, RAF1, SOS1, SOS2, SPIRE1, SPIRE2 26 BRAF(2), CPEB1(2), EGFR(4), ERBB2(4), ERBB4(4), ETS1(2), ETS2(3), ETV6(1), FMN2(7), GRB2(1), KRAS(1), MAP2K1(1), MAPK1(1), MAPK3(1), NOTCH2(4), NOTCH3(3), NOTCH4(6), PIWIL1(8), PIWIL2(4), PIWIL4(1), RAF1(1), SOS1(3), SOS2(1), SPIRE1(1) 34373079 66 57 65 13 10 22 15 7 12 0 7.15e-07 3.15e-06 141 P27PATHWAY p27 blocks the G1/S transition by inhibiting the checkpoint kinase cdk2/cyclin E and is inhibited by cdk2-mediated ubiquitination. CCNE1, CDK2, CDKN1B, CKS1B, CUL1, E2F1, NEDD8, RB1, RBX1, SKP1A, SKP2, TFDP1, UBE2M 12 CDK2(1), CDKN1B(5), CUL1(1), E2F1(2), RB1(9) 6357780 18 18 17 0 1 1 2 0 14 0 7.84e-07 3.42e-06 142 CELLCYCLEPATHWAY Cyclins interact with cyclin-dependent kinases to form active kinase complexes that regulate progression through the cell cycle. CCNA1, CCNB1, CCND1, CCND2, CCND3, CCNE1, CCNH, CDC2, CDC25A, CDK2, CDK4, CDK6, CDK7, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, CDKN2D, E2F1, RB1, RBL1, TFDP1 21 CCNB1(2), CCND1(1), CCND3(5), CDK2(1), CDK6(1), CDK7(1), CDKN1B(5), E2F1(2), RB1(9), RBL1(1) 11409021 28 25 27 3 4 2 2 2 15 3 1.03e-06 4.46e-06 143 HSA05120_EPITHELIAL_CELL_SIGNALING_IN_HELICOBACTER_PYLORI_INFECTION Genes involved in epithelial cell signaling in Helicobacter pylori infection ADAM10, ADAM17, ATP6AP1, ATP6V0A1, ATP6V0A2, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0D1, ATP6V0D2, ATP6V0E1, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1E2, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, CASP3, CCL5, CDC42, CHUK, CSK, CXCL1, EGFR, F11R, GIT1, HBEGF, IGSF5, IKBKB, IKBKG, IL8, IL8RA, IL8RB, JAM2, JAM3, JUN, LYN, MAP2K4, MAP3K14, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK8, MAPK9, MET, NFKB1, NFKB2, NFKBIA, NOD1, PAK1, PLCG1, PLCG2, PTPN11, PTPRZ1, RAC1, RELA, SRC, TCIRG1, TJP1 63 ADAM10(1), ATP6V0A2(1), ATP6V0A4(2), ATP6V0B(1), ATP6V0D2(1), ATP6V0E1(1), ATP6V1B2(1), ATP6V1C1(1), ATP6V1G2(1), ATP6V1H(1), EGFR(4), F11R(1), GIT1(1), IGSF5(3), IKBKB(2), JUN(1), LYN(3), MAP2K4(18), MAPK10(1), MAPK14(1), MAPK8(2), MET(4), NFKB1(1), NFKB2(4), NOD1(3), PAK1(2), PLCG1(4), PLCG2(2), PTPRZ1(4), RELA(1), TCIRG1(1), TJP1(4) 50633583 78 70 77 11 13 16 10 10 23 6 2.95e-06 0.000013 144 HSA04350_TGF_BETA_SIGNALING_PATHWAY Genes involved in TGF-beta signaling pathway ACVR1, ACVR1B, ACVR1C, ACVR2A, ACVR2B, ACVRL1, AMH, AMHR2, BMP2, BMP4, BMP5, BMP6, BMP7, BMP8A, BMP8B, BMPR1A, BMPR1B, BMPR2, CDKN2B, CHRD, COMP, CREBBP, CUL1, DCN, E2F4, E2F5, EP300, FST, GDF5, GDF6, GDF7, hCG_1982709, ID1, ID2, ID3, ID4, IFNG, INHBA, INHBB, INHBC, INHBE, LEFTY1, LEFTY2, LTBP1, MAPK1, MAPK3, MYC, NODAL, NOG, PITX2, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, RBL1, RBL2, RBX1, RHOA, ROCK1, ROCK2, RPS6KB1, RPS6KB2, SKP1, SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD6, SMAD7, SMAD9, SMURF1, SMURF2, SP1, TFDP1, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, THBS1, THBS2, THBS3, THBS4, TNF, ZFYVE16, ZFYVE9 84 ACVR1(1), ACVR1B(4), ACVR1C(1), ACVR2A(3), AMHR2(2), BMP2(2), BMP4(2), BMP5(1), BMP6(1), BMP8B(1), BMPR1B(2), BMPR2(2), CHRD(2), COMP(3), CREBBP(2), CUL1(1), E2F4(2), EP300(3), FST(1), GDF6(2), ID2(1), INHBA(1), INHBC(1), INHBE(1), LEFTY2(1), LTBP1(2), MAPK1(1), MAPK3(1), MYC(1), NODAL(1), PITX2(1), PPP2CB(2), RBL1(1), RBL2(1), RHOA(2), ROCK1(1), ROCK2(2), RPS6KB2(3), SMAD2(3), SMAD3(2), SMAD4(1), SMAD9(2), SMURF2(1), SP1(1), TGFB3(1), TGFBR1(2), THBS1(3), THBS3(1), THBS4(1), ZFYVE16(3), ZFYVE9(3) 70610904 86 77 84 29 13 23 18 7 25 0 2.99e-06 0.000013 145 PTDINSPATHWAY Phosphoinositide 3 kinase (PI3K) phosphorylate inositol rings of phosphoinositide lipids, influencing vesicle trafficking, cell proliferation, and migration. AKT1, AP2A1, AP2M1, ARF1, BAD, BTK, EEA1, GRASP, GSK3A, GSK3B, LYN, PDPK1, PFKL, PFKM, PFKP, PFKX, PLCG1, PRKCE, PRKCZ, RAB5A, RAC1, RPS6KB1, VAV2 21 AKT1(12), AP2A1(3), AP2M1(2), ARF1(1), BAD(1), BTK(2), EEA1(1), GSK3A(1), LYN(3), PFKM(3), PFKP(2), PLCG1(4), PRKCZ(1) 16983993 36 36 26 10 6 18 4 2 6 0 5.05e-06 0.000021 146 HSA04020_CALCIUM_SIGNALING_PATHWAY Genes involved in calcium signaling pathway ADCY1, ADCY2, ADCY3, ADCY4, ADCY7, ADCY8, ADCY9, ADORA2A, ADORA2B, ADRA1A, ADRA1B, ADRA1D, ADRB1, ADRB2, ADRB3, AGTR1, ATP2A1, ATP2A2, ATP2A3, ATP2B1, ATP2B2, ATP2B3, ATP2B4, AVPR1A, AVPR1B, BDKRB1, BDKRB2, BST1, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1F, CACNA1G, CACNA1H, CACNA1I, CACNA1S, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, CCKAR, CCKBR, CD38, CHP, CHRM1, CHRM2, CHRM3, CHRM5, CHRNA7, CYSLTR1, CYSLTR2, DRD1, EDNRA, EDNRB, EGFR, ERBB2, ERBB3, ERBB4, F2R, GNA11, GNA14, GNA15, GNAL, GNAQ, GNAS, GRIN1, GRIN2A, GRIN2C, GRIN2D, GRM1, GRM5, GRPR, HRH1, HRH2, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, LHCGR, LTB4R2, MLCK, MYLK, MYLK2, NOS1, NOS2A, NOS3, NTSR1, OXTR, P2RX1, P2RX2, P2RX3, P2RX4, P2RX5, P2RX7, P2RXL1, PDE1A, PDE1B, PDE1C, PDGFRA, PDGFRB, PHKA1, PHKA2, PHKB, PHKG1, PHKG2, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCD3, PLCD4, PLCE1, PLCG1, PLCG2, PLCZ1, PLN, PPID, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, PTAFR, PTGER1, PTGER3, PTGFR, PTK2B, RYR1, RYR2, RYR3, SLC25A4, SLC25A5, SLC25A6, SLC8A1, SLC8A2, SLC8A3, SPHK1, SPHK2, TACR1, TACR2, TACR3, TBXA2R, TNNC1, TNNC2, TRHR, TRPC1, VDAC1, VDAC2, VDAC3 163 ADCY1(3), ADCY3(2), ADCY4(1), ADCY7(1), ADCY8(2), ADCY9(5), ADRA1A(1), ADRA1B(1), ATP2A1(2), ATP2B1(4), ATP2B2(4), ATP2B3(4), ATP2B4(1), AVPR1B(1), BDKRB1(2), CACNA1A(5), CACNA1B(1), CACNA1C(4), CACNA1D(4), CACNA1E(8), CACNA1F(6), CACNA1G(5), CACNA1I(2), CACNA1S(1), CAMK2A(1), CAMK2D(3), CD38(2), CHRM1(2), CHRM2(2), CHRM3(1), CHRM5(2), CYSLTR1(1), CYSLTR2(1), EDNRB(1), EGFR(4), ERBB2(4), ERBB3(8), ERBB4(4), F2R(2), GNAQ(1), GNAS(4), GRIN1(1), GRIN2A(9), GRIN2C(4), GRIN2D(3), GRM1(2), GRM5(1), GRPR(1), HRH2(2), HTR2A(3), HTR2B(1), HTR2C(1), HTR5A(3), ITPKB(7), ITPR1(7), ITPR3(4), LHCGR(4), LTB4R2(1), MYLK(5), NOS1(3), NOS3(2), P2RX3(1), P2RX4(1), P2RX5(1), P2RX7(1), PDE1A(2), PDE1B(1), PDGFRA(3), PDGFRB(2), PHKA2(4), PHKB(2), PHKG2(1), PLCB1(3), PLCB2(2), PLCB3(1), PLCB4(6), PLCD1(1), PLCD3(2), PLCE1(5), PLCG1(4), PLCG2(2), PLCZ1(1), PPP3CA(3), PPP3CB(2), PRKACA(1), PRKCG(1), PTGER3(2), PTGFR(1), PTK2B(3), RYR1(5), RYR2(13), RYR3(11), SPHK2(2), TACR2(1), TNNC2(1), TRPC1(2), VDAC2(1) 195029211 272 180 271 108 77 80 57 22 32 4 0.000012 0.000052 147 TERCPATHWAY hTERC, the RNA subunit of telomerase, and hTERT, the catalytic protein subunit, are required for telomerase activity and are overexpressed in many cancers. NFYA, NFYB, NFYC, RB1, SP1, SP3 6 NFYB(1), RB1(9), SP1(1), SP3(3) 5061888 14 14 14 2 0 0 3 0 11 0 0.000051 0.00021 148 ST_G_ALPHA_I_PATHWAY Gi and Go proteins are members of the same family that transduce cellular signals through both their alpha and beta subunits. AKT1, AKT2, AKT3, ASAH1, BF, BRAF, DAG1, DRD2, EGFR, EPHB2, GRB2, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, KCNJ3, KCNJ5, KCNJ9, MAPK1, PI3, PIK3CB, PITX2, PLCB1, PLCB2, PLCB3, PLCB4, RAF1, RAP1GA1, RGS20, SHC1, SOS1, SOS2, SRC, STAT3, TERF2IP 33 AKT1(12), AKT2(1), AKT3(2), BRAF(2), DRD2(1), EGFR(4), EPHB2(1), GRB2(1), ITPKB(7), ITPR1(7), ITPR3(4), KCNJ3(1), MAPK1(1), PI3(1), PIK3CB(3), PITX2(1), PLCB1(3), PLCB2(2), PLCB3(1), PLCB4(6), RAF1(1), RGS20(1), SHC1(1), SOS1(3), SOS2(1), STAT3(1), TERF2IP(2) 43331262 71 65 61 12 11 30 10 8 12 0 0.000087 0.00036 149 HSA04512_ECM_RECEPTOR_INTERACTION Genes involved in ECM-receptor interaction AGRN, CD36, CD44, CD47, CHAD, COL11A1, COL11A2, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A2, COL4A4, COL4A6, COL5A1, COL5A2, COL5A3, COL6A1, COL6A2, COL6A3, COL6A6, DAG1, FN1, FNDC1, FNDC3A, FNDC4, FNDC5, GP1BA, GP1BB, GP5, GP6, GP9, HMMR, HSPG2, IBSP, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAV, ITGB1, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, LAMA1, LAMA2, LAMA3, LAMA4, LAMA5, LAMB1, LAMB2, LAMB3, LAMB4, LAMC1, LAMC2, LAMC3, RELN, SDC1, SDC2, SDC3, SDC4, SPP1, SV2A, SV2B, SV2C, THBS1, THBS2, THBS3, THBS4, TNC, TNN, TNR, TNXB, VTN, VWF 82 CD36(1), COL11A1(2), COL11A2(1), COL1A1(6), COL1A2(3), COL2A1(3), COL3A1(1), COL4A1(4), COL4A2(2), COL4A4(1), COL4A6(3), COL5A1(2), COL5A2(4), COL5A3(4), COL6A3(5), COL6A6(4), FN1(3), FNDC1(4), FNDC3A(1), GP1BA(3), GP6(1), HSPG2(5), ITGA1(3), ITGA10(1), ITGA11(4), ITGA2(2), ITGA2B(2), ITGA4(1), ITGA6(3), ITGA7(5), ITGA8(2), ITGAV(3), ITGB1(2), ITGB3(2), ITGB4(4), ITGB5(2), ITGB8(1), LAMA1(6), LAMA2(7), LAMA3(6), LAMA4(4), LAMB1(3), LAMB2(3), LAMB3(4), LAMB4(6), LAMC1(2), LAMC2(1), LAMC3(1), RELN(10), SDC4(1), SPP1(1), SV2A(1), SV2B(1), THBS1(3), THBS3(1), THBS4(1), TNC(3), TNN(3), TNR(1), TNXB(3), VWF(6) 157698294 178 142 177 70 34 61 44 8 31 0 0.00014 0.00058 150 RIBOSOMAL_PROTEINS ANK2, APG10L, RPS23, B3GALT4, CDR1, DGKI, FAU, IL6ST, KIAA1394, LOC133957, MRPL19, NET_5, PIGK, RPL10, RPL11, RPL12, RPL13, RPL13, LOC388344, RPL13A, RPL13A, LOC283340, LOC387930, RPL14, RPL14, RPL14L, RPL15, RPL15, LOC136321, LOC402694, RPL17, RPL17, dJ612B15.1, RPL18, RPL18A, LOC285053, LOC347544, LOC390354, RPL18A, LOC390354, RPL19, RPL21, RPL21, LOC387753, LOC388143, LOC388532, LOC388621, LOC389156, LOC390488, LOC402336, LOC440487, LOC440575, RPL21, LOC387753, LOC388143, LOC388532, LOC388621, LOC389156, LOC390488, LOC440487, LOC440575, RPL22, RPL23, RPL24, RPL24, SLC36A2, RPL26, LOC391126, LOC392501, LOC400055, LOC441073, LOC441533, RPL27, RPL27A, RPL27A, LOC389435, RPL28, RPL29, RPL29, LOC283412, LOC284064, LOC389655, LOC391738, LOC401911, RPL3, RPL30, RPL31, RPL32, RPL34, LOC342994, RPL35, RPL35A, RPL36, RPL37, RPL38, RPL39, RPL3L, RPL4, RPL41, RPL5, RPL5, LOC388907, RPL5, RNU66, LOC388907, RPL6, RPL7, RPL7, LOC389305, RPL7, LOC90193, LOC388401, LOC389305, LOC392550, LOC439954, RPL7A, RPL7A, LOC133748, LOC388474, RPL7A, RNU36B, LOC133748, LOC388474, RPL8, RPL9, RPLP0, RPLP0, RPLP0_like, RPLP1, RPLP2, RPS10, RPS10, LOC158104, LOC388885, LOC389127, LOC390842, LOC401817, RPS10, LOC388885, RPS11, RPS12, RPS13, RPS14, RPS15, RPS16, RPS16, LOC441876, RPS17, RPS17, LOC402057, RPS18, RPS19, RPS2, RPS2, LOC91561, LOC148430, LOC286444, LOC400963, LOC440589, RPS20, RPS21, RPS23, RPS24, RPS25, RPS26, RPS26L, LOC440440, RPS27, RPS27A, RPS27A, LOC388720, LOC389425, RPS28, RPS29, RPS3, RPS3A, RPS3A, LOC146053, LOC400652, LOC401016, LOC439992, RPS4X, RPS4Y1, RPS5, RPS6, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA6, RPS6KB1, RPS6KB2, RPS7, RPS8, RPS9, RPSA, LOC388524, LOC388654, SCDR10, TBC1D10C, TSPAN9, UBA52, UBB, UBC 90 ANK2(4), B3GALT4(2), DGKI(5), IL6ST(3), RPL13A(2), RPL17(1), RPL18(1), RPL18A(1), RPL19(1), RPL26(1), RPL29(1), RPL35(2), RPL36(1), RPL3L(1), RPL4(1), RPL41(1), RPL5(2), RPLP2(1), RPS10(1), RPS14(1), RPS2(1), RPS21(1), RPS27(1), RPS4X(1), RPS5(2), RPS6(1), RPS6KA1(1), RPS6KA2(2), RPS6KA3(2), RPS6KA6(3), RPS6KB2(3), TBC1D10C(2), UBC(6) 37966695 59 56 59 11 16 9 18 9 7 0 0.00025 0.0010 151 STILBENE_COUMARINE_AND_LIGNIN_BIOSYNTHESIS EPX, GBA3, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TPO, TYR 10 EPX(1), LPO(5), MPO(1), PRDX1(1), TPO(6), TYR(3) 6880497 17 17 17 2 2 7 4 0 4 0 0.00029 0.0012 152 ST_TUMOR_NECROSIS_FACTOR_PATHWAY Tumor necrosis factor is a pro-inflammatory cytokine that activates NF-kB and c-Jun. BAG4, BIRC2, BIRC3, CASP3, CASP8, CFLAR, FADD, HRB, IKBKG, JUN, MAP2K4, MAP3K3, MAP3K7, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, NR2C2, RALBP1, RIPK1, TNF, TNFAIP3, TNFRSF1A, TNFRSF1B, TRADD, TRAF2 26 BAG4(1), CASP8(2), JUN(1), MAP2K4(18), NFKB1(1), NFKB2(4), RIPK1(3), TNFAIP3(1), TNFRSF1A(1) 19054074 32 29 31 8 6 4 3 0 16 3 0.00037 0.0015 153 HSA04640_HEMATOPOIETIC_CELL_LINEAGE Genes involved in hematopoietic cell lineage ANPEP, CD14, CD19, CD1A, CD1B, CD1C, CD1D, CD1E, CD2, CD22, CD24, CD33, CD34, CD36, CD37, CD38, CD3D, CD3E, CD3G, CD4, CD44, CD5, CD55, CD59, CD7, CD8A, CD8B, CD9, CR1, CR2, CSF1, CSF1R, CSF2, CSF2RA, CSF3, CSF3R, DNTT, EPO, EPOR, FCER2, FCGR1A, FLT3, FLT3LG, GP1BA, GP1BB, GP5, GP9, GYPA, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, IL11, IL11RA, IL1A, IL1B, IL1R1, IL1R2, IL2RA, IL3, IL3RA, IL4, IL4R, IL5, IL5RA, IL6, IL6R, IL7, IL7R, IL9R, ITGA1, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGAM, ITGB3, KIT, KITLG, MME, MS4A1, TFRC, THPO, TNF, TPO 83 ANPEP(3), CD14(1), CD19(1), CD1B(2), CD1C(2), CD1D(2), CD1E(1), CD2(2), CD22(1), CD33(1), CD34(1), CD36(1), CD37(1), CD38(2), CD3E(1), CD3G(1), CD4(1), CD5(2), CD55(2), CD8A(1), CD9(1), CR1(6), CR2(2), CSF1(2), CSF2RA(1), CSF3R(2), DNTT(2), EPOR(1), FCGR1A(1), FLT3(2), FLT3LG(1), GP1BA(3), HLA-DRB1(2), HLA-DRB5(1), IL11RA(1), IL1A(1), IL1R1(1), IL1R2(3), IL3RA(1), IL5RA(1), IL6(2), IL6R(1), ITGA1(3), ITGA2(2), ITGA2B(2), ITGA4(1), ITGA6(3), ITGAM(1), ITGB3(2), KIT(3), KITLG(2), TFRC(1), TPO(6) 61738911 93 78 93 26 17 28 25 7 16 0 0.00042 0.0017 154 FBW7PATHWAY Cyclin E interacts with cell cycle checkpoint kinase cdk2 to allow transcription of genes required for S phase, including transcription of additional cyclin E. CCNE1, CDC34, CDK2, CUL1, E2F1, FBXW7, RB1, SKP1A, TFDP1 7 CDK2(1), CUL1(1), E2F1(2), FBXW7(1), RB1(9) 6048003 14 14 14 0 1 1 3 0 9 0 0.00042 0.0017 155 HSA00592_ALPHA_LINOLENIC_ACID_METABOLISM Genes involved in alpha-Linolenic acid metabolism ACOX1, ACOX3, FADS2, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6 15 ACOX1(2), ACOX3(1), FADS2(4), PLA2G2D(1), PLA2G2F(1), PLA2G3(3), PLA2G4A(6), PLA2G6(2) 7195851 20 19 18 1 3 5 6 5 1 0 0.00057 0.0023 156 NO1PATHWAY Shear stress in endothelial cells increases cytoplasmic calcium, which activates nitric oxide synthase III to release NO, which in turn regulates cardiac contractions. ACTA1, AKT1, BDK, BDKRB2, CALM1, CALM2, CALM3, CAV1, CHRM1, CHRNA1, FLT1, FLT4, HSPCA, KDR, NOS3, PDE2A, PDE3A, PDE3B, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKG1, PRKG2, RYR2, SLC7A1, SYT1, TNNI1, VEGF 28 AKT1(12), CAV1(1), CHRM1(2), CHRNA1(1), FLT1(2), FLT4(1), KDR(2), NOS3(2), PDE2A(3), PDE3A(6), PDE3B(1), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), PRKG1(1), PRKG2(4), RYR2(13) 28407717 54 50 44 24 12 23 11 5 3 0 0.00063 0.0025 157 HSA04060_CYTOKINE_CYTOKINE_RECEPTOR_INTERACTION Genes involved in cytokine-cytokine receptor interaction ACVR1, ACVR1B, ACVR2A, ACVR2B, AMH, AMHR2, BMP2, BMP7, BMPR1A, BMPR1B, BMPR2, CCL1, CCL11, CCL13, CCL14, CCL15, CCL16, CCL17, CCL18, CCL19, CCL2, CCL20, CCL21, CCL22, CCL23, CCL24, CCL25, CCL26, CCL27, CCL28, CCL3, CCL4, CCL5, CCL7, CCL8, CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CD27, CD40, CD40LG, CD70, CLCF1, CNTF, CNTFR, CRLF2, CSF1, CSF1R, CSF2, CSF2RA, CSF2RB, CSF3, CSF3R, CTF1, CX3CL1, CX3CR1, CXCL1, CXCL10, CXCL11, CXCL12, CXCL13, CXCL14, CXCL16, CXCL2, CXCL3, CXCL5, CXCL6, CXCL9, CXCR3, CXCR4, CXCR6, EDA, EDA2R, EDAR, EGF, EGFR, EPO, EPOR, FAS, FASLG, FLJ78302, FLT1, FLT3, FLT3LG, FLT4, GDF5, GH1, GH2, GHR, HGF, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IFNE1, IFNG, IFNGR1, IFNGR2, IFNK, IFNW1, IL10, IL10RA, IL10RB, IL11, IL11RA, IL12A, IL12B, IL12RB1, IL12RB2, IL13, IL13RA1, IL15, IL15RA, IL17A, IL17B, IL17RA, IL17RB, IL18, IL18R1, IL18RAP, IL19, IL1A, IL1B, IL1R1, IL1R2, IL1RAP, IL2, IL20, IL20RA, IL21, IL21R, IL22, IL22RA1, IL22RA2, IL23A, IL23R, IL24, IL25, IL26, IL28A, IL28B, IL28RA, IL29, IL2RA, IL2RB, IL2RG, IL3, IL3RA, IL4, IL4R, IL5, IL5RA, IL6, IL6R, IL6ST, IL7, IL7R, IL8, IL8RA, IL8RB, IL9, IL9R, INHBA, INHBB, INHBC, INHBE, KDR, KIT, KITLG, LEP, LEPR, LIF, LIFR, LOC728045, LTA, LTB, LTBR, MET, MPL, NGFR, OSM, OSMR, PDGFB, PDGFC, PDGFRA, PDGFRB, PF4, PF4V1, PLEKHO2, PPBP, PRL, PRLR, RELT, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFRSF11A, TNFRSF11B, TNFRSF12A, TNFRSF13B, TNFRSF13C, TNFRSF14, TNFRSF17, TNFRSF18, TNFRSF19, TNFRSF1A, TNFRSF1B, TNFRSF21, TNFRSF25, TNFRSF4, TNFRSF6B, TNFRSF8, TNFRSF9, TNFSF10, TNFSF11, TNFSF12, TNFSF13, TNFSF13B, TNFSF14, TNFSF15, TNFSF18, TNFSF4, TNFSF8, TNFSF9, TPO, TSLP, VEGFA, VEGFB, VEGFC, XCL1, XCL2, XCR1 242 ACVR1(1), ACVR1B(4), ACVR2A(3), AMHR2(2), BMP2(2), BMPR1B(2), BMPR2(2), CCL11(1), CCL13(1), CCL21(1), CCL23(1), CCL7(1), CCR2(4), CCR3(1), CCR7(2), CD40(1), CD40LG(1), CNTFR(1), CSF1(2), CSF2RA(1), CSF2RB(2), CSF3R(2), CX3CR1(2), EDA2R(1), EGF(2), EGFR(4), EPOR(1), FAS(1), FASLG(1), FLT1(2), FLT3(2), FLT3LG(1), FLT4(1), GH2(1), GHR(2), HGF(3), IFNA10(1), IFNA14(1), IFNA2(2), IFNA4(1), IFNAR2(1), IFNB1(1), IFNK(1), IL10RA(1), IL10RB(3), IL11RA(1), IL12A(1), IL12B(1), IL12RB1(2), IL13RA1(1), IL15(1), IL17B(2), IL17RA(2), IL17RB(3), IL18R1(1), IL18RAP(2), IL1A(1), IL1R1(1), IL1R2(3), IL1RAP(2), IL2(1), IL21(1), IL21R(1), IL22(1), IL22RA1(1), IL22RA2(1), IL23R(3), IL25(1), IL28B(3), IL28RA(1), IL2RG(1), IL3RA(1), IL5RA(1), IL6(2), IL6R(1), IL6ST(3), INHBA(1), INHBC(1), INHBE(1), KDR(2), KIT(3), KITLG(2), LEPR(3), LIF(3), LIFR(4), MET(4), NGFR(1), OSMR(3), PDGFB(1), PDGFRA(3), PDGFRB(2), PLEKHO2(1), PRLR(1), TGFB3(1), TGFBR1(2), TNFRSF10D(1), TNFRSF11A(2), TNFRSF11B(2), TNFRSF1A(1), TNFRSF21(2), TNFRSF8(1), TNFSF13B(1), TNFSF18(1), TNFSF4(1), TPO(6), TSLP(1), XCR1(1) 127619505 180 137 178 55 45 49 35 17 31 3 0.00077 0.0030 158 SKP2E2FPATHWAY E2F-1, a transcription factor that promotes the G1/S transition, is repressed by Rb and activated by cdk2/cyclin E. CCNA1, CCNE1, CDC34, CDK2, CUL1, E2F1, RB1, SKP1A, SKP2, TFDP1 8 CDK2(1), CUL1(1), E2F1(2), RB1(9) 6195033 13 13 13 0 1 1 2 0 9 0 0.0014 0.0054 159 HSA04920_ADIPOCYTOKINE_SIGNALING_PATHWAY Genes involved in adipocytokine signaling pathway ACACB, ACSL1, ACSL3, ACSL4, ACSL5, ACSL6, ADIPOQ, ADIPOR1, ADIPOR2, AGRP, AKT1, AKT2, AKT3, CAMKK1, CAMKK2, CD36, CHUK, CPT1A, CPT1B, CPT1C, CPT2, FRAP1, G6PC, G6PC2, IKBKB, IKBKG, IRS1, IRS2, IRS4, JAK1, JAK2, JAK3, LEP, LEPR, MAPK10, MAPK8, MAPK9, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NPY, PCK1, PCK2, POMC, PPARA, PPARGC1A, PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKAG1, PRKAG2, PRKAG3, PRKCQ, PTPN11, RELA, RXRA, RXRB, RXRG, SLC2A1, SLC2A4, SOCS3, STAT3, STK11, TNF, TNFRSF1A, TNFRSF1B, TRADD, TRAF2, TYK2 67 ACACB(8), ACSL3(1), ACSL4(1), ACSL5(1), ACSL6(2), AKT1(12), AKT2(1), AKT3(2), CAMKK1(3), CAMKK2(2), CD36(1), CPT1A(2), CPT1C(2), CPT2(1), G6PC2(1), IKBKB(2), IRS1(1), IRS4(1), JAK1(1), JAK2(2), JAK3(1), LEPR(3), MAPK10(1), MAPK8(2), NFKB1(1), NFKB2(4), NPY(1), PCK1(1), PCK2(1), PPARA(1), PPARGC1A(1), PRKAA2(2), PRKAB1(1), PRKAG2(1), PRKAG3(2), PRKCQ(2), RELA(1), SLC2A4(1), STAT3(1), TNFRSF1A(1), TYK2(3) 59561346 79 68 68 20 13 36 9 4 14 3 0.0018 0.0068 160 HSA04612_ANTIGEN_PROCESSING_AND_PRESENTATION Genes involved in antigen processing and presentation B2M, CALR, CANX, CD4, CD74, CD8A, CD8B, CIITA, CREB1, CTSB, CTSL1, CTSS, HLA-A, HLA-A29.1, HLA-B, HLA-C, HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-E, HLA-F, HLA-G, HSP90AA1, HSP90AB1, HSPA5, IFI30, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, KIR3DL1, KIR3DL2, KIR3DL3, KLRC1, KLRC2, KLRC3, KLRC4, KLRD1, LGMN, LTA, NFYA, NFYB, NFYC, PDIA3, PSME1, PSME2, RFX5, RFXANK, RFXAP, TAP1, TAP2, TAPBP 72 B2M(2), CALR(1), CD4(1), CD74(1), CD8A(1), CIITA(3), CTSB(1), CTSS(1), HLA-A(4), HLA-C(3), HLA-DMA(1), HLA-DMB(2), HLA-DQB1(1), HLA-DRB1(2), HLA-DRB5(1), HLA-E(2), HLA-F(2), HLA-G(2), HSP90AA1(2), HSP90AB1(2), IFNA10(1), IFNA14(1), IFNA2(2), IFNA4(1), KIR2DL3(1), KIR2DL4(1), KIR2DS4(1), KIR3DL2(4), KIR3DL3(1), KLRC1(3), KLRC2(1), KLRC3(1), NFYB(1), RFXANK(1), TAP1(1) 35103666 56 49 55 16 8 16 13 5 14 0 0.0018 0.0070 161 HSA00830_RETINOL_METABOLISM Genes involved in retinol metabolism ALDH1A1, ALDH1A2, BCMO1, RDH5 4 ALDH1A1(2), ALDH1A2(1), BCMO1(3), RDH5(2) 2893449 8 8 8 3 1 4 0 0 3 0 0.0019 0.0071 162 SA_REG_CASCADE_OF_CYCLIN_EXPR Expression of cyclins regulates progression through the cell cycle by activating cyclin-dependent kinases. CCNA1, CCNA2, CCND1, CCNE1, CCNE2, CDK2, CDK4, CDKN1B, CDKN2A, E2F1, E2F2, E2F4, PRB1 13 CCNA2(2), CCND1(1), CDK2(1), CDKN1B(5), E2F1(2), E2F4(2) 6082986 13 13 12 0 2 1 2 0 8 0 0.0019 0.0071 163 HSA04080_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION Genes involved in neuroactive ligand-receptor interaction ADCYAP1R1, ADORA1, ADORA2A, ADORA2B, ADORA3, ADRA1A, ADRA1B, ADRA2A, ADRA2B, ADRA2C, ADRB1, ADRB2, ADRB3, AGTR1, AGTR2, AGTRL1, AVPR1A, AVPR1B, AVPR2, BDKRB1, BDKRB2, BRS3, C3AR1, C5AR1, CALCR, CALCRL, CCKAR, CCKBR, CGA, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, CNR1, CNR2, CRHR1, CRHR2, CTSG, CYSLTR1, CYSLTR2, DRD1, DRD2, DRD3, DRD4, DRD5, EDG1, EDG2, EDG3, EDG4, EDG5, EDG6, EDG7, EDG8, EDNRA, EDNRB, F2, F2R, F2RL1, F2RL2, F2RL3, FPR1, FPRL1, FPRL2, FSHB, FSHR, GABBR1, GABBR2, GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GABRB1, GABRB2, GABRB3, GABRD, GABRE, GABRG1, GABRG2, GABRG3, GABRP, GABRQ, GABRR1, GABRR2, GALR1, GALR2, GALR3, GCGR, GH1, GH2, GHR, GHRHR, GHSR, GIPR, GLP1R, GLP2R, GLRA1, GLRA2, GLRA3, GLRB, GNRHR, GPR156, GPR23, GPR35, GPR50, GPR63, GPR83, GRIA1, GRIA2, GRIA3, GRIA4, GRID1, GRID2, GRIK1, GRIK2, GRIK3, GRIK4, GRIK5, GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, GRIN3A, GRIN3B, GRM1, GRM2, GRM3, GRM4, GRM5, GRM6, GRM7, GRM8, GRPR, GZMA, HCRTR1, HCRTR2, HRH1, HRH2, HRH3, HRH4, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, KISS1R, LEP, LEPR, LHB, LHCGR, LTB4R, LTB4R2, MAS1, MC1R, MC2R, MC3R, MC4R, MC5R, MCHR1, MCHR2, MLNR, MTNR1A, MTNR1B, NMBR, NMUR1, NMUR2, NPBWR1, NPBWR2, NPFFR1, NPFFR2, NPY1R, NPY2R, NPY5R, NR3C1, NTSR1, NTSR2, OPRD1, OPRK1, OPRL1, OPRM1, OXTR, P2RX1, P2RX2, P2RX3, P2RX4, P2RX5, P2RX7, P2RXL1, P2RY1, P2RY10, P2RY11, P2RY13, P2RY14, P2RY2, P2RY4, P2RY5, P2RY6, P2RY8, PARD3, PPYR1, PRL, PRLHR, PRLR, PRSS1, PRSS2, PRSS3, PTAFR, PTGDR, PTGER1, PTGER2, PTGER3, PTGER4, PTGFR, PTGIR, PTH2R, PTHR1, RXFP1, RXFP2, SCTR, SSTR1, SSTR2, SSTR3, SSTR4, SSTR5, TAAR1, TAAR2, TAAR5, TAAR6, TAAR8, TAAR9, TACR1, TACR2, TACR3, TBXA2R, THRA, THRB, TRHR, TRPV1, TSHB, TSHR, TSPO, UTS2R, VIPR1, VIPR2 220 ADCYAP1R1(3), ADORA1(1), ADORA3(1), ADRA1A(1), ADRA1B(1), ADRA2B(1), AVPR1B(1), BDKRB1(2), BRS3(1), CALCR(1), CALCRL(1), CHRM1(2), CHRM2(2), CHRM3(1), CHRM5(2), CNR1(1), CRHR1(3), CRHR2(1), CTSG(1), CYSLTR1(1), CYSLTR2(1), DRD2(1), DRD3(1), EDNRB(1), F2(2), F2R(2), F2RL2(1), FPR1(1), FSHR(3), GABBR2(1), GABRA1(2), GABRA3(3), GABRA6(3), GABRB2(1), GABRB3(1), GABRG1(2), GABRG2(2), GABRG3(1), GABRQ(3), GABRR1(1), GALR1(2), GALR2(1), GH2(1), GHR(2), GHRHR(1), GHSR(1), GIPR(1), GLRA2(1), GLRA3(1), GPR156(1), GPR50(2), GPR63(1), GPR83(3), GRIA1(6), GRIA2(1), GRIA3(2), GRIA4(1), GRID1(5), GRID2(2), GRIK1(5), GRIK2(5), GRIK3(3), GRIK4(1), GRIK5(2), GRIN1(1), GRIN2A(9), GRIN2B(4), GRIN2C(4), GRIN2D(3), GRIN3A(4), GRM1(2), GRM2(1), GRM3(3), GRM4(1), GRM5(1), GRM6(1), GRM8(1), GRPR(1), HCRTR1(1), HCRTR2(1), HRH2(2), HRH4(1), HTR1A(1), HTR1B(1), HTR1E(2), HTR1F(1), HTR2A(3), HTR2B(1), HTR2C(1), HTR5A(3), LEPR(3), LHB(1), LHCGR(4), LTB4R2(1), MAS1(2), MC2R(1), MC3R(2), MC4R(1), MCHR2(1), NMUR1(1), NMUR2(1), NPFFR2(1), NPY1R(3), NPY2R(1), NTSR2(1), OPRD1(1), OPRK1(2), OPRM1(5), P2RX3(1), P2RX4(1), P2RX5(1), P2RX7(1), P2RY1(1), P2RY10(1), P2RY11(1), P2RY13(2), P2RY2(1), P2RY4(2), PARD3(3), PRLR(1), PTGDR(1), PTGER3(2), PTGFR(1), PTH2R(1), RXFP1(3), SSTR2(1), SSTR3(1), TAAR1(1), TAAR2(1), TAAR5(3), TAAR6(1), TACR2(1), THRB(1), TSHR(3) 155343279 235 160 234 83 52 79 58 20 23 3 0.0019 0.0071 164 SIG_REGULATION_OF_THE_ACTIN_CYTOSKELETON_BY_RHO_GTPASES Genes related to regulation of the actin cytoskeleton ACTG1, ACTG2, ACTR2, ACTR3, AKT1, ANGPTL2, CDC42, CFL1, CFL2, FLNA, FLNC, FSCN1, FSCN2, FSCN3, GDI1, GDI2, LIMK1, MYH2, MYLK, MYLK2, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PFN1, PFN2, RHO, ROCK1, ROCK2, RPS4X, VASP, WASF1, WASL 34 ACTG1(1), ACTG2(2), AKT1(12), FLNA(4), FLNC(8), FSCN3(1), GDI1(3), LIMK1(3), MYH2(1), MYLK(5), PAK1(2), PAK2(1), PAK3(1), PAK7(1), RHO(2), ROCK1(1), ROCK2(2), RPS4X(1), WASF1(1), WASL(1) 33949227 53 53 43 16 8 25 9 4 7 0 0.0021 0.0078 165 HSA04916_MELANOGENESIS Genes involved in melanogenesis ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ASIP, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CREB1, CREB3, CREB3L1, CREB3L2, CREB3L3, CREB3L4, CREBBP, CTNNB1, DCT, DVL1, DVL2, DVL3, EDN1, EDNRB, EP300, FZD1, FZD10, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD9, GNAI1, GNAI2, GNAI3, GNAO1, GNAQ, GNAS, GSK3B, HRAS, KIT, KITLG, KRAS, LEF1, LOC652788, MAP2K1, MAP2K2, MAPK1, MAPK3, MC1R, MITF, NRAS, PLCB1, PLCB2, PLCB3, PLCB4, POMC, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, RAF1, TCF7, TCF7L1, TCF7L2, TYR, TYRP1, WNT1, WNT10A, WNT10B, WNT11, WNT16, WNT2, WNT2B, WNT3, WNT3A, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A, WNT8B, WNT9A, WNT9B 95 ADCY1(3), ADCY3(2), ADCY4(1), ADCY5(3), ADCY7(1), ADCY8(2), ADCY9(5), CAMK2A(1), CAMK2D(3), CREB3(1), CREB3L1(2), CREB3L2(2), CREB3L3(1), CREBBP(2), DCT(2), DVL3(1), EDN1(2), EDNRB(1), EP300(3), FZD1(1), FZD3(2), FZD6(2), FZD9(1), GNAI1(1), GNAI2(1), GNAO1(1), GNAQ(1), GNAS(4), KIT(3), KITLG(2), KRAS(1), MAP2K1(1), MAPK1(1), MAPK3(1), PLCB1(3), PLCB2(2), PLCB3(1), PLCB4(6), PRKACA(1), PRKCG(1), RAF1(1), TCF7(3), TCF7L2(1), TYR(3), TYRP1(2), WNT10B(1), WNT11(2), WNT2B(1), WNT3A(1), WNT5B(1), WNT6(1), WNT7A(5), WNT8B(1), WNT9A(1) 74182719 99 85 98 39 26 34 21 4 14 0 0.0030 0.011 166 HSA00940_PHENYLPROPANOID_BIOSYNTHESIS Genes involved in phenylpropanoid biosynthesis EPX, GBA, GBA3, LPO, MPO, PRDX6, TPO 7 EPX(1), LPO(5), MPO(1), TPO(6) 6052566 13 13 13 0 2 5 3 0 3 0 0.0048 0.018 167 HSA00350_TYROSINE_METABOLISM Genes involved in tyrosine metabolism ABP1, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, AOX1, ARD1A, CARM1, COMT, DBH, DCT, DDC, ECH1, ESCO1, ESCO2, FAH, GOT1, GOT2, GSTZ1, HEMK1, HGD, HPD, LCMT1, LCMT2, LYCAT, MAOA, MAOB, METTL2B, METTL6, MIF, MYST3, MYST4, NAT5, NAT6, PNMT, PNPLA3, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, SH3GLB1, TAT, TH, TPO, TYR, TYRP1, WBSCR22 52 ADH1A(1), ADH7(2), ADHFE1(1), ALDH3B1(2), ALDH3B2(2), AOC2(1), AOC3(2), AOX1(3), CARM1(1), DBH(4), DCT(2), DDC(1), ECH1(1), ESCO1(3), FAH(1), GOT2(1), GSTZ1(1), HPD(1), LCMT1(1), LCMT2(3), MAOA(2), METTL2B(2), MYST3(1), MYST4(5), PNPLA3(4), PRMT3(2), PRMT5(2), PRMT6(2), PRMT7(1), PRMT8(1), TPO(6), TYR(3), TYRP1(2) 42266055 67 58 67 16 10 22 16 4 12 3 0.0059 0.022 168 NOS1PATHWAY Glutamate stimulates NMDA-mediates calcium influx, which promotes nitric oxide synthesis from arginine by neuronal nitric oxide synthase, activating guanylate cyclase. CALM1, CALM2, CALM3, DLG4, GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, NOS1, PPP3CA, PPP3CB, PPP3CC, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, SYT1 21 GRIN1(1), GRIN2A(9), GRIN2B(4), GRIN2C(4), GRIN2D(3), NOS1(3), PPP3CA(3), PPP3CB(2), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1) 18157191 32 31 31 7 12 5 10 2 3 0 0.0062 0.023 169 TYROSINE_METABOLISM ABP1, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, AOX1, COMT, DBH, DCT, DDC, FAH, GOT1, GOT2, GSTZ1, HGD, HPD, MAOA, MAOB, PNMT, TAT, TH, TPO, TYR 29 ADH1A(1), ADH7(2), ADHFE1(1), ALDH3B1(2), ALDH3B2(2), AOC2(1), AOC3(2), AOX1(3), DBH(4), DCT(2), DDC(1), FAH(1), GOT2(1), GSTZ1(1), HPD(1), MAOA(2), TPO(6), TYR(3) 21981999 36 35 36 11 4 16 7 3 6 0 0.0064 0.023 170 HSA04720_LONG_TERM_POTENTIATION Genes involved in long-term potentiation ADCY1, ADCY8, ARAF, ATF4, BRAF, CACNA1C, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, CHP, CREBBP, EP300, GNAQ, GRIA1, GRIA2, GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, GRM1, GRM5, HRAS, ITPR1, ITPR2, ITPR3, KRAS, MAP2K1, MAP2K2, MAPK1, MAPK3, NRAS, PLCB1, PLCB2, PLCB3, PLCB4, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PPP1R1A, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, RAF1, RAP1A, RAP1B, RAPGEF3, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA6 66 ADCY1(3), ADCY8(2), ARAF(1), ATF4(1), BRAF(2), CACNA1C(4), CAMK2A(1), CAMK2D(3), CREBBP(2), EP300(3), GNAQ(1), GRIA1(6), GRIA2(1), GRIN1(1), GRIN2A(9), GRIN2B(4), GRIN2C(4), GRIN2D(3), GRM1(2), GRM5(1), ITPR1(7), ITPR3(4), KRAS(1), MAP2K1(1), MAPK1(1), MAPK3(1), PLCB1(3), PLCB2(2), PLCB3(1), PLCB4(6), PPP1R12A(1), PPP1R1A(1), PPP3CA(3), PPP3CB(2), PRKACA(1), PRKCG(1), RAF1(1), RAPGEF3(2), RPS6KA1(1), RPS6KA2(2), RPS6KA3(2), RPS6KA6(3) 73788780 101 84 99 29 29 24 25 7 16 0 0.0066 0.024 171 PROSTAGLANDIN_AND_LEUKOTRIENE_METABOLISM AKR1C3, ALOX12, ALOX15, ALOX5, CBR1, CBR3, CYP4F2, CYP4F3, CYP4F3, CYP4F2, EPX, GGT1, LPO, LTA4H, MPO, PGDS, PLA2G1B, PLA2G2A, PLA2G2E, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PRDX1, PRDX2, PRDX5, PRDX6, PTGDS, PTGES2, PTGIS, PTGS1, PTGS2, TBXAS1, TPO 31 AKR1C3(1), ALOX12(1), CBR3(1), CYP4F2(1), EPX(1), GGT1(1), LPO(5), MPO(1), PLA2G3(3), PLA2G4A(6), PLA2G6(2), PRDX1(1), PTGDS(1), PTGS2(1), TBXAS1(1), TPO(6) 19579833 33 31 31 1 5 11 9 3 5 0 0.0073 0.026 172 PHENYLALANINE_METABOLISM ABP1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, DDC, EPX, GOT1, GOT2, HPD, LPO, MAOA, MAOB, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TAT, TPO 22 ALDH3B1(2), ALDH3B2(2), AOC2(1), AOC3(2), DDC(1), EPX(1), GOT2(1), HPD(1), LPO(5), MAOA(2), MPO(1), PRDX1(1), TPO(6) 15990273 26 26 26 5 4 8 4 3 7 0 0.0077 0.028 173 CFTRPATHWAY The cAMP-regulated chloride channel CFTR (deficient in cystic fibrosis) is regulated by the surface-localized beta-adrenergic receptor. ADCY1, ADRB2, CFTR, GNAS, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, SLC9A3R1, VIL2 11 ADCY1(3), CFTR(6), GNAS(4), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), SLC9A3R1(2) 8846136 18 18 18 3 5 3 5 1 4 0 0.0081 0.029 174 IL12PATHWAY IL12 and Stat4 Dependent Signaling Pathway in Th1 Development CCR5, CD3D, CD3E, CD3G, CD3Z, CXCR3, ETV5, IFNG, IL12A, IL12B, IL12RB1, IL12RB2, IL18, IL18R1, JAK2, JUN, MAP2K6, MAPK14, MAPK8, STAT4, TRA@, TRB@, TYK2 19 CD3E(1), CD3G(1), ETV5(1), IL12A(1), IL12B(1), IL12RB1(2), IL18R1(1), JAK2(2), JUN(1), MAPK14(1), MAPK8(2), STAT4(5), TYK2(3) 13537407 22 21 21 7 3 3 7 1 8 0 0.0083 0.029 175 CTLPATHWAY Cytotoxic T lymphocytes induce apoptosis in infected cells presenting antigen-MHC-I complexes via the perforin and Fas/Fas ligand pathways. B2M, CD3D, CD3E, CD3G, CD3Z, GZMB, HLA-A, ICAM1, ITGAL, ITGB2, PRF1, TNFRSF6, TNFSF6, TRA@, TRB@ 10 B2M(2), CD3E(1), CD3G(1), HLA-A(4), ITGAL(1), ITGB2(3), PRF1(2) 6079437 14 14 13 5 2 6 2 0 4 0 0.0084 0.029 176 GANGLIOSIDE_BIOSYNTHESIS B3GALT4, GALGT, SIAT4A, SIAT4B, SIAT7B, SIAT7D, SIAT9, ST3GAL1, ST3GAL2, ST3GAL4, ST3GAL5, ST6GALNAC2, ST6GALNAC4, ST8SIA1 8 B3GALT4(2), ST3GAL1(1), ST3GAL4(1), ST3GAL5(2), ST6GALNAC2(1), ST6GALNAC4(1), ST8SIA1(1) 3884127 9 9 9 0 2 5 1 0 1 0 0.0084 0.029 177 HSA00770_PANTOTHENATE_AND_COA_BIOSYNTHESIS Genes involved in pantothenate and CoA biosynthesis BCAT1, BCAT2, COASY, DPYD, DPYS, ENPP1, ENPP3, ILVBL, PANK1, PANK2, PANK3, PANK4, PPCDC, PPCS, UPB1, VNN1 16 BCAT1(3), BCAT2(2), COASY(3), DPYD(1), DPYS(1), ENPP1(3), ENPP3(2), ILVBL(2), PANK2(1), PANK4(1), UPB1(3), VNN1(1) 12231882 23 23 23 5 5 5 5 4 4 0 0.0088 0.031 178 ST_GAQ_PATHWAY G-alpha-q activates phospholipase C, resulting in calcium influx and increasing protein kinase C activity. ADRBK1, AKT1, AKT2, AKT3, BF, DAG1, GNAQ, IKBKG, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PDK1, PHKA2, PIK3CB, PITX2, PLD1, PLD2, PLD3, VN1R1 25 ADRBK1(1), AKT1(12), AKT2(1), AKT3(2), GNAQ(1), ITPKB(7), ITPR1(7), ITPR3(4), NFKB1(1), NFKB2(4), PDK1(1), PHKA2(4), PIK3CB(3), PITX2(1), PLD1(1), PLD3(1) 32230497 51 44 41 12 7 22 5 5 9 3 0.010 0.036 179 GAMMA_HEXACHLOROCYCLOHEXANE_DEGRADATION ACP1, ACP2, ACP5, ACPP, ACPT, ALPI, ALPL, ALPP, ALPP, ALPPL2, ALPPL2, CYP19A1, CYP1A1, CYP1A2, CYP2A6, CYP2A6, CYP2A7, CYP2A7P1, CYP2A13, CYP2B6, CYP2C18, CYP2C19, CYP2C19, CYP2C9, CYP2C8, CYP2C9, CYP2D6, CYP2E1, CYP2F1, CYP2J2, CYP3A4, CYP3A5, CYP3A7, CYP4B1, CYP4F8, CYP51A1, PON1 31 ACP5(1), ACPP(1), ACPT(2), ALPI(2), ALPL(1), ALPP(2), ALPPL2(3), CYP2A13(4), CYP2A6(1), CYP2A7(1), CYP2B6(2), CYP2C18(2), CYP2C19(1), CYP2C8(1), CYP2C9(2), CYP2D6(2), CYP2F1(1), CYP3A4(3), CYP3A7(4), CYP4B1(2), CYP4F8(2), PON1(1) 21563217 41 36 40 8 7 12 11 4 7 0 0.011 0.036 180 STARCH_AND_SUCROSE_METABOLISM AGL, AMY1A, AMY1B, AMY1C, AMY2A, AMY2B, AMY2B, RNPC3, ENPP1, ENPP3, G6PC, GAA, GANAB, GBA3, GBE1, GCK, GPI, GUSB, GYS1, GYS2, HK1, HK2, HK3, MGAM, PGM1, PGM3, PYGB, PYGL, PYGM, SI, UCHL1, UCHL3, UGDH, UGT1A10, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A9, UGT2B15, UGT2B4, UXS1 41 AGL(3), AMY2A(1), ENPP1(3), ENPP3(2), GAA(2), GBE1(3), GCK(2), GPI(2), GUSB(1), GYS1(5), GYS2(1), HK1(1), HK3(2), MGAM(8), PGM1(1), PGM3(1), PYGB(3), PYGL(1), PYGM(2), RNPC3(1), SI(4), UCHL3(1), UGT1A10(1), UGT1A6(2), UGT2B15(2), UGT2B4(1), UXS1(2) 41250534 58 54 58 16 11 15 16 6 10 0 0.011 0.038 181 IL17PATHWAY Activated T cells secrete IL-17, which stimulates fibroblasts and other cells to secrete inflammatory and hematopoietic cytokines. CD2, CD34, CD3D, CD3E, CD3G, CD3Z, CD4, CD58, CD8A, CSF3, IL17, IL3, IL6, IL8, KITLG, TRA@, TRB@ 13 CD2(2), CD34(1), CD3E(1), CD3G(1), CD4(1), CD8A(1), IL6(2), KITLG(2) 4662879 11 11 11 2 1 4 3 0 3 0 0.012 0.041 182 IL4PATHWAY IL-4 promotes Th2 cell differentiation via a heterodimeric receptor that activates Stat6/JAK and MAP kinase pathways. AKT1, GRB2, IL2RG, IL4, IL4R, IRS1, JAK1, JAK3, RPS6KB1, SHC1, STAT6 11 AKT1(12), GRB2(1), IL2RG(1), IRS1(1), JAK1(1), JAK3(1), SHC1(1) 11087076 18 18 8 4 0 13 2 1 2 0 0.012 0.041 183 GSPATHWAY Activated G-protein coupled receptors stimulate cAMP production and thus activate protein kinase A, involved in a number of signal transduction pathways. ADCY1, GNAS, GNB1, GNGT1, PRKACA, PRKAR1A 6 ADCY1(3), GNAS(4), GNB1(1), PRKACA(1), PRKAR1A(1) 4388085 10 10 10 3 3 2 3 1 1 0 0.012 0.042 184 HSA00052_GALACTOSE_METABOLISM Genes involved in galactose metabolism AKR1B1, AKR1B10, B4GALT1, B4GALT2, G6PC, G6PC2, GAA, GALE, GALK1, GALK2, GALT, GANC, GCK, GLA, GLB1, HK1, HK2, HK3, HSD3B7, LALBA, LCT, MGAM, PFKL, PFKM, PFKP, PGM1, PGM3, RDH11, RDH12, RDH13, RDH14, UGP2 31 AKR1B1(2), B4GALT1(2), G6PC2(1), GAA(2), GALT(1), GANC(1), GCK(2), GLA(2), GLB1(1), HK1(1), HK3(2), LCT(3), MGAM(8), PFKM(3), PFKP(2), PGM1(1), PGM3(1), RDH11(2), RDH12(1), RDH14(1) 26363493 39 38 39 10 5 13 10 5 6 0 0.013 0.044 185 ST_WNT_BETA_CATENIN_PATHWAY Beta-catenin is degraded in the absence of Wnt signaling; when extracellular Wnt binds Frizzled receptors, beta-catenin accumulates in the nucleus and may promote cell survival. AKT1, AKT2, AKT3, ANKRD6, APC, AXIN1, AXIN2, C22orf2, CER1, CSNK1A1, CTNNB1, DACT1, DKK1, DKK2, DKK3, DKK4, DVL1, FRAT1, FSTL1, GSK3A, GSK3B, IDAX, LAMR1, LRP1, MVP, NKD1, NKD2, PIN1, PSEN1, PTPRA, SENP2, SFRP1, TSHB, WIF1 28 AKT1(12), AKT2(1), AKT3(2), ANKRD6(4), APC(3), AXIN1(1), CER1(1), DKK4(1), GSK3A(1), LRP1(7), MVP(1), NKD1(1), PTPRA(1), SFRP1(2), WIF1(1) 28312908 39 38 29 11 8 17 6 3 5 0 0.013 0.045 186 HSA05050_DENTATORUBROPALLIDOLUYSIAN_ATROPHY Genes involved in dentatorubropallidoluysian atrophy (DRPLA) ATN1, BAIAP2, CASP1, CASP3, CASP7, CASP8, GAPDH, INS, INSR, ITCH, MAGI1, MAGI2, RERE, WWP1, WWP2 14 ATN1(8), BAIAP2(1), CASP1(1), CASP8(2), INSR(2), MAGI1(3), MAGI2(6), RERE(1), WWP2(4) 17024046 28 25 26 7 6 9 4 1 8 0 0.014 0.046 187 HSA04730_LONG_TERM_DEPRESSION Genes involved in long-term depression ARAF, BRAF, C7orf16, CACNA1A, CRH, CRHR1, GNA11, GNA12, GNA13, GNAI1, GNAI2, GNAI3, GNAO1, GNAQ, GNAS, GNAZ, GRIA1, GRIA2, GRIA3, GRID2, GRM1, GRM5, GUCY1A2, GUCY1A3, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, HRAS, IGF1, IGF1R, ITPR1, ITPR2, ITPR3, KRAS, LYN, MAP2K1, MAP2K2, MAPK1, MAPK3, NOS1, NOS2A, NOS3, NPR1, NPR2, NRAS, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCB1, PLCB2, PLCB3, PLCB4, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, PRKCA, PRKCB1, PRKCG, PRKG1, PRKG2, RAF1, RYR1 73 ARAF(1), BRAF(2), C7orf16(1), CACNA1A(5), CRHR1(3), GNAI1(1), GNAI2(1), GNAO1(1), GNAQ(1), GNAS(4), GRIA1(6), GRIA2(1), GRIA3(2), GRID2(2), GRM1(2), GRM5(1), GUCY1A2(2), GUCY2C(5), GUCY2D(1), GUCY2F(2), IGF1(1), IGF1R(1), ITPR1(7), ITPR3(4), KRAS(1), LYN(3), MAP2K1(1), MAPK1(1), MAPK3(1), NOS1(3), NOS3(2), NPR1(1), NPR2(2), PLA2G2D(1), PLA2G2F(1), PLA2G3(3), PLA2G4A(6), PLA2G6(2), PLCB1(3), PLCB2(2), PLCB3(1), PLCB4(6), PPP2CB(2), PRKCG(1), PRKG1(1), PRKG2(4), RAF1(1), RYR1(5) 80529852 111 96 108 24 33 34 22 9 13 0 0.014 0.047 188 PANTOTHENATE_AND_COA_BIOSYNTHESIS BCAT1, COASY, DPYD, DPYS, ENPP1, ENPP3, PANK1, PANK2, PANK3, PANK4, PPCS, UPB1 12 BCAT1(3), COASY(3), DPYD(1), DPYS(1), ENPP1(3), ENPP3(2), PANK2(1), PANK4(1), UPB1(3) 9672546 18 18 18 3 3 2 5 4 4 0 0.015 0.048 189 NUCLEAR_RECEPTORS ALK, AR, ESR1, ESR2, ESRRA, HNF4A, NPM1, NR0B1, NR1D2, NR1H2, NR1H3, NR1I2, NR1I3, NR2C2, NR2E1, NR2F1, NR2F2, NR2F6, NR3C1, NR4A1, NR4A2, NR5A1, NR5A2, PGR, PPARA, PPARD, PPARG, RARA, RARB, RARG, ROR1, RORA, RORC, RXRA, RXRB, RXRG, THRA, THRA, NR1D1, THRB, VDR 38 ALK(3), AR(3), ESR1(2), ESR2(2), HNF4A(2), NR1D1(1), NR1D2(1), NR1H2(3), NR2E1(1), NR4A1(1), NR4A2(1), NR5A2(4), PGR(2), PPARA(1), PPARG(1), RARA(1), RARB(4), RARG(2), ROR1(6), RORC(2), THRB(1) 29827317 44 42 44 16 12 14 6 0 10 2 0.015 0.049 190 NO2IL12PATHWAY Macrophages activate NK cells by releasing IL-12, which induces NK cytotoxic activity in coordination with NO produced by inducible nitric oxide synthase II. CCR5, CD2, CD3D, CD3E, CD3G, CD3Z, CD4, CXCR3, IFNG, IL12A, IL12B, IL12RB1, IL12RB2, JAK2, NOS2A, STAT4, TYK2 14 CD2(2), CD3E(1), CD3G(1), CD4(1), IL12A(1), IL12B(1), IL12RB1(2), JAK2(2), STAT4(5), TYK2(3) 10578555 19 18 18 5 3 2 7 1 6 0 0.018 0.057 191 EPOPATHWAY Erythropoietin, which activates the MAPK pathway, stimulates erythrocyte production and is an effective treatment for anemia. CSNK2A1, ELK1, EPO, EPOR, FOS, GRB2, HRAS, JAK2, JUN, MAP2K1, MAPK3, MAPK8, PLCG1, PTPN6, RAF1, SHC1, SOS1, STAT5A, STAT5B 19 CSNK2A1(1), ELK1(2), EPOR(1), GRB2(1), JAK2(2), JUN(1), MAP2K1(1), MAPK3(1), MAPK8(2), PLCG1(4), RAF1(1), SHC1(1), SOS1(3), STAT5B(4) 15806232 25 24 25 2 2 10 4 1 8 0 0.018 0.059 192 PEPTIDE_GPCRS AGTR1, AGTR2, ATP8A1, AVPR1A, AVPR1B, AVPR2, BDKRB1, BDKRB2, BLR1, BRS3, C3AR1, C5R1, CCKAR, CCKBR, CCR1, CCR10, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CX3CR1, CXCR3, CXCR4, CXCR6, EDNRA, EDNRB, ELA3A, FPR1, FPRL1, FPRL2, FSHR, FY, GALR1, GALR2, GALR3, GALT, GHSR, GNB2L1, GNRHR, GPR77, GRPR, IL8RA, IL8RB, LHCGR, MC1R, MC2R, MC3R, MC4R, MC5R, NMBR, NPY1R, NPY2R, NPY5R, NPY6R, NTSR1, NTSR2, OPRD1, OPRK1, OPRL1, OPRM1, OXTR, PPYR1, SSTR1, SSTR2, SSTR3, SSTR4, TAC4, TACR1, TACR2, TACR3, TRHR, TSHR 63 ATP8A1(2), AVPR1B(1), BDKRB1(2), BRS3(1), CCR2(4), CCR3(1), CCR7(2), CX3CR1(2), EDNRB(1), FPR1(1), FSHR(3), GALR1(2), GALR2(1), GALT(1), GHSR(1), GPR77(2), GRPR(1), LHCGR(4), MC2R(1), MC3R(2), MC4R(1), NPY1R(3), NPY2R(1), NTSR2(1), OPRD1(1), OPRK1(2), OPRM1(5), SSTR2(1), SSTR3(1), TACR2(1), TSHR(3) 36079134 55 51 55 22 5 25 11 7 7 0 0.019 0.059 193 HSA05110_CHOLERA_INFECTION Genes involved in cholera - infection ACTG1, ACTG2, ADCY3, ADCY9, AK1, ARF1, ARF3, ARF4, ARF5, ARF6, ARL4D, ATP6V0A1, ATP6V0A2, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0D1, ATP6V0D2, ATP6V0E1, ATP6V1A, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1E2, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, ERO1L, GNAS, PDIA4, PLCG1, PLCG2, PRKCA, SEC61A1, SEC61A2, SEC61B, SEC61G, TRIM23 41 ACTG1(1), ACTG2(2), ADCY3(2), ADCY9(5), ARF1(1), ATP6V0A2(1), ATP6V0A4(2), ATP6V0B(1), ATP6V0D2(1), ATP6V0E1(1), ATP6V1C1(1), ATP6V1G2(1), ATP6V1H(1), ERO1L(2), GNAS(4), PDIA4(2), PLCG1(4), PLCG2(2), SEC61A1(1), TRIM23(2) 26759460 37 35 37 5 5 10 10 5 7 0 0.020 0.065 194 NICOTINATE_AND_NICOTINAMIDE_METABOLISM AOX1, CD38, ENPP1, ENPP3, NADSYN1, NMNAT1, NMNAT2, NNMT, NNT, NP, NT5C, NT5E, NT5M, QPRT 13 AOX1(3), CD38(2), ENPP1(3), ENPP3(2), NMNAT1(1), NMNAT2(1), NNT(4), NT5E(3) 10647507 19 19 19 2 2 3 10 3 1 0 0.021 0.067 195 ETSPATHWAY The Ets transcription factors are activated by Ras and promote macrophage differentiation. CSF1, CSF1R, DDX20, E2F1, E2F4, ETS1, ETS2, ETV3, FOS, HDAC2, HDAC5, HRAS, JUN, NCOR2, RBL1, RBL2, SIN3A, SIN3B 18 CSF1(2), DDX20(2), E2F1(2), E2F4(2), ETS1(2), ETS2(3), ETV3(1), HDAC2(2), JUN(1), NCOR2(3), RBL1(1), RBL2(1), SIN3A(2), SIN3B(2) 17046354 26 26 26 9 6 5 7 2 6 0 0.021 0.068 196 GPCRDB_CLASS_A_RHODOPSIN_LIKE ADORA1, ADORA2A, ADORA2B, ADORA3, ADRA1A, ADRA1B, ADRA1D, ADRA2A, ADRA2C, ADRB1, ADRB2, ADRB3, AGTR1, AGTR2, AGTRL1, AVPR1A, AVPR1B, AVPR2, BDKRB1, BDKRB2, BLR1, BRS3, C3AR1, C5R1, CCBP2, CCKAR, CCKBR, CCR1, CCR10, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CCRL1, CCRL2, CHML, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, CMKLR1, CMKOR1, CNR1, CNR2, CX3CR1, CXCR3, CXCR4, DRD1, DRD2, DRD3, DRD4, DRD5, EDNRA, EDNRB, ELA3A, F2R, F2RL1, F2RL2, F2RL3, FPR1, FPRL1, FPRL2, FSHR, GALR1, GALR2, GALR3, GALT, GHSR, GNB2L1, GPR10, GPR147, GPR17, GPR173, GPR174, GPR23, GPR24, GPR27, GPR3, GPR30, GPR35, GPR37, GPR37L1, GPR4, GPR44, GPR50, GPR6, GPR63, GPR74, GPR77, GPR83, GPR85, GPR87, GPR92, GRPR, HCRTR1, HCRTR2, HRH1, HRH2, HRH3, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, HTR7, LOC93164, IL8RA, IL8RB, LHCGR, LTB4R, MAS1, MC1R, MC3R, MC4R, MC5R, MLNR, MTNR1A, MTNR1B, NMBR, NMUR1, NMUR2, NPY1R, NPY2R, NPY5R, NPY6R, NTSR1, NTSR2, OPN1SW, OPN3, OPRD1, OPRK1, OPRL1, OPRM1, OR10A5, OR11A1, OR12D3, OR1C1, OR1F1, OR1Q1, OR2H1, OR5V1, OR5V1, OR12D3, OR7A5, OR7C1, OR8B8, OXTR, P2RY1, P2RY10, P2RY11, P2RY12, P2RY13, P2RY14, P2RY2, P2RY5, P2RY6, PPYR1, PTAFR, PTGDR, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, Rgr, RGR, RHO, RRH, SSTR1, SSTR2, SSTR3, SSTR4, SUCNR1, TBXA2R, TRHR 148 ADORA1(1), ADORA3(1), ADRA1A(1), ADRA1B(1), AVPR1B(1), BDKRB1(2), BRS3(1), CCR2(4), CCR3(1), CCR7(2), CCRL1(1), CHML(2), CHRM1(2), CHRM2(2), CHRM3(1), CHRM5(2), CMKLR1(1), CNR1(1), CX3CR1(2), DRD2(1), DRD3(1), EDNRB(1), F2R(2), F2RL2(1), FPR1(1), FSHR(3), GALR1(2), GALR2(1), GALT(1), GHSR(1), GPR37(2), GPR50(2), GPR6(1), GPR63(1), GPR77(2), GPR83(3), GRPR(1), HCRTR1(1), HCRTR2(1), HRH2(2), HTR1A(1), HTR1B(1), HTR1E(2), HTR1F(1), HTR2A(3), HTR2B(1), HTR2C(1), HTR5A(3), LHCGR(4), MAS1(2), MC3R(2), MC4R(1), NMUR1(1), NMUR2(1), NPY1R(3), NPY2R(1), NTSR2(1), OPRD1(1), OPRK1(2), OPRM1(5), OR12D3(4), OR7A5(1), P2RY1(1), P2RY10(1), P2RY11(1), P2RY13(2), P2RY2(1), PTGDR(1), PTGFR(1), RHO(2), SSTR2(1), SSTR3(1) 82767243 114 97 113 41 18 43 25 11 17 0 0.022 0.068 197 CREMPATHWAY The transcription factor CREM activates a post-meiotic transcriptional cascade culminating in spermatogenesis. ADCY1, CREM, FHL5, FSHB, FSHR, GNAS, XPO1 7 ADCY1(3), CREM(1), FHL5(1), FSHR(3), GNAS(4), XPO1(2) 6646770 14 14 14 1 3 4 4 1 2 0 0.022 0.068 198 GLYCEROPHOSPHOLIPID_METABOLISM ACHE, AGPAT1, AGPAT2, AGPAT3, AGPAT4, AGPS, CDIPT, CDS1, CDS2, CHAT, CHKA, CHKB, CHKB, CPT1B, CLC, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKQ, DGKZ, ETNK1, GNPAT, GPD1, GPD2, LCAT, LGALS13, LYPLA1, LYPLA2, LYPLA2, LYPLA2P1, LOC388499, LYPLA3, PAFAH1B1, PAFAH2, PCYT1A, PCYT1B, PEMT, PISD, PLA2G1B, PLA2G2A, PLA2G2E, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCB2, PLCG1, PLCG2, PPAP2A, PPAP2B, PPAP2C 47 ACHE(2), AGPAT3(2), AGPS(1), CDS1(2), CLC(1), DGKA(3), DGKD(1), DGKE(1), DGKG(4), DGKH(1), ETNK1(3), GNPAT(1), GPD1(2), GPD2(1), LCAT(1), PAFAH1B1(1), PCYT1A(1), PCYT1B(2), PLA2G3(3), PLA2G4A(6), PLA2G6(2), PLCB2(2), PLCG1(4), PLCG2(2), PPAP2A(1) 34307169 50 46 47 9 7 17 11 9 6 0 0.022 0.070 199 METHANE_METABOLISM ADH5, ATP6V0C, SHMT1, CAT, EPX, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, SHMT1, SHMT2, TPO 13 EPX(1), LPO(5), MPO(1), PRDX1(1), TPO(6) 8287929 14 14 14 1 2 5 3 0 4 0 0.024 0.074 200 GPCRPATHWAY G-protein coupled receptors activate adenylyl cyclase, which converts ATP to cAMP, to activate second messenger pathways. ADCY1, CALM1, CALM2, CALM3, CREB1, ELK1, FOS, GNAI1, GNAQ, GNAS, GNB1, GNGT1, HRAS, JUN, MAP2K1, MAPK3, NFATC1, NFATC2, NFATC3, NFATC4, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, RAF1, RPS6KA3, SYT1 34 ADCY1(3), ELK1(2), GNAI1(1), GNAQ(1), GNAS(4), GNB1(1), JUN(1), MAP2K1(1), MAPK3(1), NFATC3(3), NFATC4(3), PLCG1(4), PPP3CA(3), PPP3CB(2), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), RAF1(1), RPS6KA3(2) 24281244 36 34 36 6 8 9 13 1 5 0 0.024 0.074 201 CALCIUM_REGULATION_IN_CARDIAC_CELLS ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ADRA1A, ADRA1B, ADRA1D, ADRB1, ADRB2, ADRB3, ANXA6, ARRB1, ARRB2, ATP1A4, ATP1B1, ATP1B2, ATP1B3, ATP2A2, ATP2A3, ATP2B1, ATP2B2, ATP2B3, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1S, CACNB1, CACNB3, CALM1, CALM2, CALM3, CALR, CAMK1, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, CASQ1, CASQ2, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, FXYD2, GJA1, GJA12, GJA4, GJA5, GJB1, GJB2, GJB3, GJB4, GJB5, GJB6, GNA11, GNAI2, GNAI3, GNAO1, GNAQ, GNAZ, GNB1, GNB2, GNB3, GNB4, GNB5, GNG12, GNG13, GNG2, GNG3, GNG4, GNG5, GNG7, GNGT1, GRK4, GRK5, GRK6, ITPR1, ITPR2, ITPR3, KCNB1, KCNJ3, KCNJ5, MGC11266, MYCBP, NME7, PEA15, PKIA, PKIB, PKIG, PLCB3, PLN, PRKACA, PRKACB, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCQ, PRKCZ, PRKD1, RGS1, RGS10, RGS11, RGS14, RGS16, RGS17, RGS18, RGS19, RGS2, RGS20, RGS3, RGS4, RGS5, RGS6, RGS7, RGS9, RYR1, RYR2, RYR3, SARA1, SFN, SLC8A1, SLC8A3, USP5, YWHAB, YWHAH, YWHAQ, YWHAQ, MIB1 135 ADCY1(3), ADCY3(2), ADCY4(1), ADCY5(3), ADCY7(1), ADCY8(2), ADCY9(5), ADRA1A(1), ADRA1B(1), ANXA6(1), ARRB1(1), ATP1A4(5), ATP1B1(1), ATP2B1(4), ATP2B2(4), ATP2B3(4), CACNA1A(5), CACNA1B(1), CACNA1C(4), CACNA1D(4), CACNA1E(8), CACNA1S(1), CACNB1(1), CALR(1), CAMK1(1), CAMK2A(1), CAMK2D(3), CASQ2(1), CHRM1(2), CHRM2(2), CHRM3(1), CHRM5(2), GJA1(2), GJA4(1), GJB2(1), GJB3(2), GJB4(1), GJB5(1), GNAI2(1), GNAO1(1), GNAQ(1), GNB1(1), GNB3(2), GRK4(3), GRK6(1), ITPR1(7), ITPR3(4), KCNJ3(1), MIB1(2), NME7(2), PKIG(1), PLCB3(1), PRKACA(1), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), PRKCG(1), PRKCH(1), PRKCQ(2), PRKCZ(1), PRKD1(1), RGS1(1), RGS14(1), RGS17(2), RGS20(1), RGS3(2), RGS4(3), RGS5(1), RGS7(5), RGS9(2), RYR1(5), RYR2(13), RYR3(11), USP5(4), YWHAB(1) 139403706 175 130 175 79 43 52 44 8 24 4 0.025 0.075 202 DCPATHWAY Dendritic cells internalize and present antigen, after which they migrate to lymphocyte-rich tissues and induce T and B cell differentiation. ANPEP, CD2, CD33, CD5, CD7, CSF2, IFNA1, IFNB1, IFNG, IL10, IL12A, IL12B, IL13, IL3, IL4, IL5, ITGAX, TLR2, TLR4, TLR7, TLR9, TNFRSF5 21 ANPEP(3), CD2(2), CD33(1), CD5(2), IFNB1(1), IL12A(1), IL12B(1), ITGAX(2), TLR2(1), TLR4(7), TLR7(3) 14010945 24 21 23 7 5 6 4 1 8 0 0.025 0.077 203 GLYCOLYSISPATHWAY Glycolysis is an evolutionarily conserved pathway by which one glucose molecule is converted to two pyruvate molecules for a gain of 2 ATP. ALDOB, ENO1, GAPD, GPI, HK1, PFKL, PGAM1, PGK1, PKLR, TPI1 8 ALDOB(2), ENO1(1), GPI(2), HK1(1), PGK1(2) 5463939 8 8 8 0 1 3 2 0 2 0 0.027 0.082 204 HSA00533_KERATAN_SULFATE_BIOSYNTHESIS Genes involved in keratan sulfate biosynthesis B3GNT1, B3GNT2, B3GNT7, B4GALT1, B4GALT2, B4GALT3, B4GALT4, CHST1, CHST2, CHST4, CHST6, FUT8, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4 15 B3GNT1(1), B3GNT2(1), B3GNT7(1), B4GALT1(2), B4GALT3(1), CHST1(1), CHST2(3), ST3GAL1(1), ST3GAL3(1), ST3GAL4(1) 8156109 13 13 13 1 3 6 0 1 3 0 0.028 0.085 205 SMOOTH_MUSCLE_CONTRACTION ACTA1, ACTA2, ACTC, ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ADM, ADMR, ARRB1, ARRB2, ATF1, ATF2, ATF3, ATF4, ATF5, ATP2A2, ATP2A3, CACNB3, CALCA, CALM1, CALM2, CALM3, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CMKOR1, CNN1, CNN2, CORIN, CREB3, CREBL1, CREBL1, TNXB, CRH, CRHR1, DGKZ, EDG2, ETS2, FOS, GABPA, GABPB2, GBA2, GJA1, GNAQ, GNB1, GNB2, GNB3, GNB4, GNB5, GNG12, GNG13, GNG2, GNG3, GNG4, GNG5, GNG7, GNGT1, GRK4, GRK5, GRK6, GSTO1, GUCA2A, GUCA2B, GUCY1A3, HEAB, IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP6, IL1B, IL6, ITPR1, ITPR2, ITPR3, JUN, LGR7, LGR8, MAFF, MGC11266, MYL2, MYL4, MYLK2, NFKB1, NOS1, NOS3, OXT, OXTR, PDE4B, PDE4D, PKIA, PKIB, PKIG, PLCB3, PLCD1, PLCG1, PLCG2, PRKACA, PRKACB, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCH, PRKCQ, PRKCZ, PRKD1, RAMP1, RAMP2, RAMP3, RCP9, RGS1, RGS10, RGS11, RGS14, RGS16, RGS17, RGS18, RGS19, RGS2, RGS20, RGS3, RGS4, RGS5, RGS6, RGS7, RGS9, RLN1, RYR1, RYR2, RYR3, SARA1, SFN, SLC8A1, SP1, USP5, YWHAB, YWHAH, YWHAQ, YWHAQ, MIB1 135 ACTA2(1), ADCY1(3), ADCY3(2), ADCY4(1), ADCY5(3), ADCY7(1), ADCY8(2), ADCY9(5), ARRB1(1), ATF3(1), ATF4(1), ATF5(2), CALCA(1), CAMK2A(1), CAMK2D(3), CORIN(1), CREB3(1), CRHR1(3), ETS2(3), GABPA(1), GJA1(2), GNAQ(1), GNB1(1), GNB3(2), GRK4(3), GRK6(1), IGFBP3(1), IL6(2), ITPR1(7), ITPR3(4), JUN(1), MIB1(2), NFKB1(1), NOS1(3), NOS3(2), PDE4B(2), PDE4D(3), PKIG(1), PLCB3(1), PLCD1(1), PLCG1(4), PLCG2(2), PRKACA(1), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), PRKCH(1), PRKCQ(2), PRKCZ(1), PRKD1(1), RAMP3(1), RGS1(1), RGS14(1), RGS17(2), RGS20(1), RGS3(2), RGS4(3), RGS5(1), RGS7(5), RGS9(2), RLN1(1), RYR1(5), RYR2(13), RYR3(11), SP1(1), TNXB(3), USP5(4), YWHAB(1) 127673754 151 122 151 64 35 43 42 6 25 0 0.029 0.087 206 PENTOSE_PHOSPHATE_PATHWAY ALDOA, ALDOB, ALDOC, FBP1, FBP2, G6PD, GPI, H6PD, PFKM, PFKP, PGD, PGLS, PGM1, PGM3, PRPS1, PRPS1L1, PRPS2, RBKS, RPE, RPE, LOC440001, RPIA, TAL1, TALDO1, TALDO1, HSUP1, TKT 23 ALDOA(3), ALDOB(2), G6PD(1), GPI(2), H6PD(2), PFKM(3), PFKP(2), PGD(2), PGLS(2), PGM1(1), PGM3(1), PRPS2(1), TKT(1) 14669031 23 23 23 4 7 5 3 4 4 0 0.029 0.087 207 HSA04610_COMPLEMENT_AND_COAGULATION_CASCADES Genes involved in complement and coagulation cascades A2M, BDKRB1, BDKRB2, C1QA, C1QB, C1QC, C1R, C1S, C2, C3, C3AR1, C4A, C4B, C4BPA, C4BPB, C5, C5AR1, C6, C7, C8A, C8B, C8G, C9, CD46, CD55, CD59, CFB, CFD, CFH, CFI, CPB2, CR1, CR2, F10, F11, F12, F13A1, F13B, F2, F2R, F3, F5, F7, F8, F9, FGA, FGB, FGG, KLKB1, KNG1, MASP1, MASP2, MBL2, PLAT, PLAU, PLAUR, PLG, PROC, PROS1, SERPINA1, SERPINA5, SERPINC1, SERPIND1, SERPINE1, SERPINF2, SERPING1, TFPI, THBD, VWF 64 A2M(3), BDKRB1(2), C2(1), C3(2), C4BPA(1), C4BPB(1), C5(3), C6(4), C7(3), C9(1), CD55(2), CFB(1), CFH(4), CPB2(1), CR1(6), CR2(2), F12(1), F13A1(3), F2(2), F2R(2), F5(7), F8(1), FGA(3), KLKB1(1), KNG1(1), MASP1(1), MASP2(1), MBL2(1), PLAT(1), PLAU(2), PLG(2), PROC(1), SERPINA1(1), SERPINA5(3), SERPINC1(2), SERPIND1(1), SERPINE1(1), TFPI(1), VWF(6) 66437787 82 75 81 25 11 27 21 12 11 0 0.029 0.087 208 HSA00360_PHENYLALANINE_METABOLISM Genes involved in phenylalanine metabolism ABP1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, ARD1A, DDC, EPX, ESCO1, ESCO2, GOT1, GOT2, HPD, LPO, LYCAT, MAOA, MAOB, MIF, MPO, MYST3, MYST4, NAT5, NAT6, PNPLA3, PRDX6, SH3GLB1, TAT, TPO 26 ALDH3B1(2), ALDH3B2(2), AOC2(1), AOC3(2), DDC(1), EPX(1), ESCO1(3), GOT2(1), HPD(1), LPO(5), MAOA(2), MPO(1), MYST3(1), MYST4(5), PNPLA3(4), TPO(6) 25210575 38 35 38 7 8 10 6 4 7 3 0.032 0.094 209 ERBB3PATHWAY Neuregulins bind to the receptor tyrosine kinases ErbB3 and ErbB4, surface-localized receptors whose overexpression induces tumor formation. EGF, EGFR, ERBB3, NRG1, UBE2D1 5 EGF(2), EGFR(4), ERBB3(8) 7630857 14 14 14 2 1 2 2 8 1 0 0.033 0.098 210 ST_PAC1_RECEPTOR_PATHWAY The signaling peptide PACAP binds to its receptor, PAC1R, which activates adenylyl cyclase and phospholipase C. ASAH1, CAMP, DAG1, GAS, GNAQ, ITPKA, ITPKB, PACAP 5 GNAQ(1), ITPKB(7) 3916575 8 8 8 0 1 2 0 3 2 0 0.035 0.10 211 GALACTOSE_METABOLISM AKR1B1, B4GALT1, B4GALT2, FBP2, G6PC, GAA, GALE, GALK1, GALK2, GALT, GANAB, GCK, GLA, GLB1, HK1, HK2, HK3, LALBA, LCT, MGAM, PFKM, PFKP, PGM1, PGM3 24 AKR1B1(2), B4GALT1(2), GAA(2), GALT(1), GCK(2), GLA(2), GLB1(1), HK1(1), HK3(2), LCT(3), MGAM(8), PFKM(3), PFKP(2), PGM1(1), PGM3(1) 22943778 33 32 33 10 5 11 7 5 5 0 0.036 0.11 212 GPCRDB_CLASS_B_SECRETIN_LIKE ADCYAP1R1, CALCR, CALCRL, CD97, CRHR1, CRHR2, ELTD1, EMR1, EMR2, GCGR, GHRHR, GIPR, GLP1R, GLP2R, GPR64, LPHN1, LPHN2, LPHN3, PTHR1, PTHR2, SCTR, VIPR1, VIPR2 20 ADCYAP1R1(3), CALCR(1), CALCRL(1), CD97(5), CRHR1(3), CRHR2(1), ELTD1(2), EMR1(2), EMR2(3), GHRHR(1), GIPR(1), GPR64(3), LPHN1(2), LPHN2(3), LPHN3(4) 19996080 35 31 35 10 4 8 10 4 6 3 0.036 0.11 213 ERKPATHWAY Cell growth is promoted by Ras activation of the anti-apoptotic p44/42 MAP kinase pathway. DPM2, EGFR, ELK1, GNAS, GNB1, GNGT1, GRB2, HRAS, IGF1R, ITGB1, KLK2, MAP2K1, MAP2K2, MAPK1, MAPK3, MKNK1, MKNK2, MYC, NGFB, NGFR, PDGFRA, PPP2CA, PTPRR, RAF1, RPS6KA1, RPS6KA5, SHC1, SOS1, SRC, STAT3 28 EGFR(4), ELK1(2), GNAS(4), GNB1(1), GRB2(1), IGF1R(1), ITGB1(2), KLK2(2), MAP2K1(1), MAPK1(1), MAPK3(1), MYC(1), NGFR(1), PDGFRA(3), PTPRR(1), RAF1(1), RPS6KA1(1), SHC1(1), SOS1(3), STAT3(1) 23317944 33 33 33 6 4 13 9 4 3 0 0.038 0.11 214 HSA00030_PENTOSE_PHOSPHATE_PATHWAY Genes involved in pentose phosphate pathway ALDOA, ALDOB, ALDOC, DERA, FBP1, FBP2, G6PD, GPI, H6PD, PFKL, PFKM, PFKP, PGD, PGLS, PGM1, PGM3, PRPS1, PRPS1L1, PRPS2, RBKS, RPE, RPIA, TALDO1, TKT, TKTL1, TKTL2 25 ALDOA(3), ALDOB(2), G6PD(1), GPI(2), H6PD(2), PFKM(3), PFKP(2), PGD(2), PGLS(2), PGM1(1), PGM3(1), PRPS2(1), TKT(1), TKTL1(1), TKTL2(1) 16685877 25 25 25 4 7 6 4 4 4 0 0.039 0.11 215 MONOAMINE_GPCRS ADRA1A, ADRA1B, ADRA1D, ADRA2A, ADRA2C, ADRB1, ADRB2, ADRB3, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, DRD1, DRD2, DRD3, DRD4, DRD5, HRH1, HRH2, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, HTR7, LOC93164 27 ADRA1A(1), ADRA1B(1), CHRM1(2), CHRM2(2), CHRM3(1), CHRM5(2), DRD2(1), DRD3(1), HRH2(2), HTR1A(1), HTR1B(1), HTR1E(2), HTR1F(1), HTR2A(3), HTR2B(1), HTR2C(1), HTR5A(3) 16994640 26 25 26 10 9 8 3 0 6 0 0.040 0.11 216 HSA04540_GAP_JUNCTION Genes involved in gap junction ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ADRB1, CDC2, CSNK1D, DRD1, DRD2, EDG2, EGF, EGFR, GJA1, GJD2, GNA11, GNAI1, GNAI2, GNAI3, GNAQ, GNAS, GRB2, GRM1, GRM5, GUCY1A2, GUCY1A3, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, HRAS, HTR2A, HTR2B, HTR2C, ITPR1, ITPR2, ITPR3, KRAS, LOC643224, LOC654264, MAP2K1, MAP2K2, MAP2K5, MAP3K2, MAPK1, MAPK3, MAPK7, NPR1, NPR2, NRAS, PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, PDGFRB, PLCB1, PLCB2, PLCB3, PLCB4, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKG1, PRKG2, PRKX, PRKY, RAF1, SOS1, SOS2, SRC, TJP1, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, TUBB8 90 ADCY1(3), ADCY3(2), ADCY4(1), ADCY5(3), ADCY7(1), ADCY8(2), ADCY9(5), DRD2(1), EGF(2), EGFR(4), GJA1(2), GNAI1(1), GNAI2(1), GNAQ(1), GNAS(4), GRB2(1), GRM1(2), GRM5(1), GUCY1A2(2), GUCY2C(5), GUCY2D(1), GUCY2F(2), HTR2A(3), HTR2B(1), HTR2C(1), ITPR1(7), ITPR3(4), KRAS(1), MAP2K1(1), MAP2K5(1), MAPK1(1), MAPK3(1), NPR1(1), NPR2(2), PDGFB(1), PDGFRA(3), PDGFRB(2), PLCB1(3), PLCB2(2), PLCB3(1), PLCB4(6), PRKACA(1), PRKCG(1), PRKG1(1), PRKG2(4), RAF1(1), SOS1(3), SOS2(1), TJP1(4), TUBA1B(1), TUBA3C(1), TUBA3D(1), TUBAL3(1), TUBB(1), TUBB2B(1), TUBB2C(2), TUBB4(1) 95638452 114 93 113 36 26 41 20 10 17 0 0.041 0.12 217 GLYCINE_SERINE_AND_THREONINE_METABOLISM ABP1, AGXT, AGXT2, ALAS1, ALAS2, AMT, AOC2, AOC3, ATP6V0C, SHMT1, BHMT, CBS, CHDH, CHKA, CHKB, CHKB, CPT1B, CTH, DAO, DLD, DMGDH, GAMT, GARS, GATM, GCAT, GLDC, MAOA, MAOB, PEMT, PISD, PLCB2, PLCG1, PLCG2, PSPH, SARDH, SARS, SHMT1, SHMT2, TARS 36 AGXT(1), AGXT2(1), ALAS2(1), AMT(1), AOC2(1), AOC3(2), BHMT(1), CBS(1), CTH(1), DAO(1), DLD(1), DMGDH(3), GARS(1), GATM(3), GCAT(2), MAOA(2), PLCB2(2), PLCG1(4), PLCG2(2), SARDH(2), SARS(2), TARS(4) 29933280 39 37 39 17 7 16 6 2 8 0 0.043 0.12 218 STRIATED_MUSCLE_CONTRACTION ACTA1, ACTA2, ACTC, ACTN2, ACTN3, ACTN4, C9orf97, DES, DES, FAM48A, DMD, MYBPC1, MYBPC2, MYBPC3, MYH3, MYH6, MYH6, MYH7, MYH8, MYL1, MYL2, MYL3, MYL4, MYL9, MYOM1, NEB, TCAP, TMOD1, TNNC2, TNNI1, TNNI2, TNNI3, TNNT1, TNNT2, TNNT3, TPM1, TPM2, TPM3, TPM4, TPM4, TTN, VIM 35 ACTA2(1), ACTN2(4), ACTN3(1), ACTN4(4), DMD(11), MYBPC1(2), MYBPC2(1), MYBPC3(1), MYH3(1), MYH6(7), MYH7(6), MYH8(4), MYL1(1), MYOM1(2), NEB(13), TMOD1(1), TNNC2(1), TNNI3(1), TPM1(2), TPM2(1), TPM3(1), TTN(77) 104159094 143 112 143 25 26 35 45 13 20 4 0.044 0.13 219 SA_DIACYLGLYCEROL_SIGNALING DAG (diacylglycerol) signaling activity ESR1, ESR2, ITPKA, PDE1A, PDE1B, PLCB1, PLCB2, PRL, TRH, VIP 9 ESR1(2), ESR2(2), PDE1A(2), PDE1B(1), PLCB1(3), PLCB2(2), VIP(1) 7870668 13 13 13 2 9 2 1 0 1 0 0.046 0.13 220 HSA00680_METHANE_METABOLISM Genes involved in methane metabolism ADH5, CAT, EPX, LPO, MPO, MTHFR, PRDX6, SHMT1, SHMT2, TPO 10 EPX(1), LPO(5), MPO(1), TPO(6) 8250918 13 13 13 1 2 5 3 0 3 0 0.048 0.14 221 BIOPEPTIDESPATHWAY Extracellular signaling peptides exert biological effects via G-protein coupled receptors (GPCRs), which activate intracellular GTPases. AGT, AGTR2, BDK, CALM1, CALM2, CALM3, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CDK5, F2, FYN, GNA11, GNAI1, GNB1, GNGT1, GRB2, HRAS, JAK2, MAP2K1, MAP2K2, MAPK1, MAPK14, MAPK3, MAPK8, MAPT, MYLK, PLCG1, PRKCA, PRKCB1, PTK2B, RAF1, SHC1, SOS1, STAT1, STAT3, STAT5A, SYT1 36 AGT(3), CAMK2A(1), CAMK2D(3), CDK5(1), F2(2), GNAI1(1), GNB1(1), GRB2(1), JAK2(2), MAP2K1(1), MAPK1(1), MAPK14(1), MAPK3(1), MAPK8(2), MAPT(1), MYLK(5), PLCG1(4), PTK2B(3), RAF1(1), SHC1(1), SOS1(3), STAT1(1), STAT3(1) 30070170 41 39 41 11 6 17 8 2 8 0 0.050 0.14 222 FRUCTOSE_AND_MANNOSE_METABOLISM AKR1B1, ALDOA, ALDOB, ALDOC, FBP1, FBP2, FPGT, GCK, GMDS, GMPPA, GMPPB, HK1, HK2, HK3, KHK, MPI, PFKFB1, PFKFB3, PFKFB4, PFKM, PFKP, PMM1, PMM2, SORD, TPI1 25 AKR1B1(2), ALDOA(3), ALDOB(2), GCK(2), GMDS(2), HK1(1), HK3(2), KHK(1), PFKFB1(1), PFKFB3(1), PFKFB4(1), PFKM(3), PFKP(2) 17381988 23 23 23 4 4 11 2 2 4 0 0.050 0.14 223 HSA00591_LINOLEIC_ACID_METABOLISM Genes involved in linoleic acid metabolism AKR1B10, ALOX15, ALOX5, CYP1A2, CYP2C18, CYP2C19, CYP2C8, CYP2C9, CYP2E1, CYP2J2, CYP3A4, CYP3A43, CYP3A5, CYP3A7, HSD3B7, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, RDH11, RDH12, RDH13, RDH14 31 CYP2C18(2), CYP2C19(1), CYP2C8(1), CYP2C9(2), CYP3A4(3), CYP3A7(4), PLA2G2D(1), PLA2G2F(1), PLA2G3(3), PLA2G4A(6), PLA2G6(2), RDH11(2), RDH12(1), RDH14(1) 17358159 30 27 28 6 5 8 7 4 6 0 0.054 0.15 224 HSA00361_GAMMA_HEXACHLOROCYCLOHEXANE_DEGRADATION Genes involved in gamma-hexachlorocyclohexane degradation ACP1, ACP2, ACP5, ACP6, ACPP, ACPT, ALPI, ALPL, ALPP, ALPPL2, CMBL, CYP3A4, CYP3A43, CYP3A5, CYP3A7, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, PON1, PON2, PON3 23 ACP5(1), ACP6(1), ACPP(1), ACPT(2), ALPI(2), ALPL(1), ALPP(2), ALPPL2(3), CYP3A4(3), CYP3A7(4), DHRS2(2), DHRS7(1), PON1(1), PON3(1) 12883377 25 20 24 6 6 6 6 3 4 0 0.058 0.16 225 HSA00760_NICOTINATE_AND_NICOTINAMIDE_METABOLISM Genes involved in nicotinate and nicotinamide metabolism AOX1, BST1, C9orf95, CD38, ENPP1, ENPP3, NADK, NADSYN1, NMNAT1, NMNAT2, NMNAT3, NNMT, NNT, NP, NT5C, NT5C1A, NT5C1B, NT5C2, NT5C3, NT5E, NT5M, NUDT12, PBEF1, QPRT 22 AOX1(3), CD38(2), ENPP1(3), ENPP3(2), NADK(1), NMNAT1(1), NMNAT2(1), NNT(4), NT5C1B(3), NT5C3(1), NT5E(3) 15745899 24 24 24 3 4 4 12 3 1 0 0.059 0.16 226 FIBRINOLYSISPATHWAY Thrombin cleavage of fibrinogen results in rapid formation of fibrin threads that form a mesh to capture platelets and other blood cells into a clot. CPB2, F13A1, F2, F2R, FGA, FGB, FGG, PLAT, PLAU, PLG, SERPINB2, SERPINE1 12 CPB2(1), F13A1(3), F2(2), F2R(2), FGA(3), PLAT(1), PLAU(2), PLG(2), SERPINE1(1) 10074597 17 17 17 5 3 7 3 3 1 0 0.059 0.16 227 HSA00440_AMINOPHOSPHONATE_METABOLISM Genes involved in aminophosphonate metabolism CARM1, CHPT1, HEMK1, LCMT1, LCMT2, METTL2B, METTL6, PCYT1A, PCYT1B, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, WBSCR22 16 CARM1(1), CHPT1(1), LCMT1(1), LCMT2(3), METTL2B(2), PCYT1A(1), PCYT1B(2), PRMT3(2), PRMT5(2), PRMT6(2), PRMT7(1), PRMT8(1) 10125297 19 16 19 3 2 6 6 1 4 0 0.063 0.17 228 IONPATHWAY Activated phospholipase C hydrolyzes the lipid PIP3 into second messengers DAG, which activates protein kinase C, and IP3, which induces calcium influx into the cytoplasm. P2RY2, PLCG1, PRKCA, PRKCB1, PTK2B 4 P2RY2(1), PLCG1(4), PTK2B(3) 5011695 8 8 8 0 3 2 1 0 2 0 0.065 0.17 229 CARDIACEGFPATHWAY Cardiac hypertrophy, a response to high blood pressure, is stimulated by GPCR ligands such as angiotensin II that activate the EGF pathway. ADAM12, AGT, AGTR2, ARHA, EDN1, EDNRA, EDNRB, EGF, EGFR, FOS, HRAS, JUN, MYC, NFKB1, PLCG1, PRKCA, PRKCB1, RELA 16 ADAM12(1), AGT(3), EDN1(2), EDNRB(1), EGF(2), EGFR(4), JUN(1), MYC(1), NFKB1(1), PLCG1(4), RELA(1) 15368184 21 21 21 4 5 6 1 5 4 0 0.065 0.17 230 HSA04340_HEDGEHOG_SIGNALING_PATHWAY Genes involved in Hedgehog signaling pathway BMP2, BMP4, BMP5, BMP6, BMP7, BMP8A, BMP8B, BTRC, CSNK1A1, CSNK1A1L, CSNK1D, CSNK1E, CSNK1G1, CSNK1G2, CSNK1G3, DHH, FBXW11, GAS1, GLI1, GLI2, GLI3, GSK3B, HHIP, IHH, LRP2, PRKACA, PRKACB, PRKACG, PRKX, PRKY, PTCH1, PTCH2, RAB23, SHH, SMO, STK36, SUFU, WNT1, WNT10A, WNT10B, WNT11, WNT16, WNT2, WNT2B, WNT3, WNT3A, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A, WNT8B, WNT9A, WNT9B, ZIC2 54 BMP2(2), BMP4(2), BMP5(1), BMP6(1), BMP8B(1), CSNK1A1L(2), CSNK1E(1), DHH(1), GLI1(2), GLI2(2), GLI3(3), LRP2(17), PRKACA(1), PTCH1(3), SMO(2), SUFU(2), WNT10B(1), WNT11(2), WNT2B(1), WNT3A(1), WNT5B(1), WNT6(1), WNT7A(5), WNT8B(1), WNT9A(1), ZIC2(1) 42390270 58 52 58 23 13 21 10 8 6 0 0.065 0.17 231 HSA00626_NAPHTHALENE_AND_ANTHRACENE_DEGRADATION Genes involved in naphthalene and anthracene degradation CARM1, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, HEMK1, LCMT1, LCMT2, METTL2B, METTL6, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, WBSCR22 18 CARM1(1), DHRS2(2), DHRS7(1), LCMT1(1), LCMT2(3), METTL2B(2), PRMT3(2), PRMT5(2), PRMT6(2), PRMT7(1), PRMT8(1) 10633311 18 16 18 4 3 4 6 1 4 0 0.066 0.18 232 IL5PATHWAY Pro-inflammatory IL-5 is secretes by activated T cells, eosinophils, and mast cells, and stimulates the proliferation and activation of eosinophils in bone marrow. CCL11, CCR3, CD4, HLA-DRA, HLA-DRB1, IL1B, IL4, IL5, IL5RA, IL6 10 CCL11(1), CCR3(1), CD4(1), HLA-DRB1(2), IL5RA(1), IL6(2) 4083885 8 8 8 3 0 3 1 1 3 0 0.068 0.18 233 FOLATE_BIOSYNTHESIS ALPI, ALPL, ALPP, ALPP, ALPPL2, ALPPL2, DHFR, FPGS, GCH1, GGH, SPR 9 ALPI(2), ALPL(1), ALPP(2), ALPPL2(3), GCH1(1) 4283643 9 8 8 2 2 2 3 1 1 0 0.071 0.19 234 PLCEPATHWAY Gs-coupled receptors activate adenylyl cyclase, which activates Epac1, leading to the stimulation of PLC and subsequent DAG and IP3 production. ADCY1, ADRB2, GNAS, PLCE1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTGER1, RAP2B 11 ADCY1(3), GNAS(4), PLCE1(5), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), RAP2B(1) 10122762 16 16 16 4 5 4 3 1 3 0 0.071 0.19 235 HSA04330_NOTCH_SIGNALING_PATHWAY Genes involved in Notch signaling pathway ADAM17, APH1A, CIR, CREBBP, CTBP1, CTBP2, DLL1, DLL3, DLL4, DTX1, DTX2, DTX3, DTX3L, DTX4, DVL1, DVL2, DVL3, EP300, GCN5L2, HDAC1, HDAC2, HES1, JAG1, JAG2, LFNG, LOC652788, MAML1, MAML2, MAML3, MFNG, NCOR2, NCSTN, NOTCH1, NOTCH2, NOTCH3, NOTCH4, NUMB, NUMBL, PCAF, PSEN1, PSEN2, PSENEN, PTCRA, RBPJ, RBPJL, RFNG, SNW1 37 CREBBP(2), DTX1(3), DTX2(1), DTX4(1), DVL3(1), EP300(3), HDAC1(2), HDAC2(2), JAG1(1), MAML1(1), MAML2(1), MAML3(1), NCOR2(3), NCSTN(1), NOTCH2(4), NOTCH3(3), NOTCH4(6), NUMB(1), NUMBL(3), PSEN2(2), PTCRA(1), RBPJL(3), SNW1(2) 42009006 48 43 46 17 11 12 9 2 12 2 0.072 0.19 236 TUBBYPATHWAY Tubby is activated by phospholipase C activity and hydrolysis of PIP2, after which it enters the nucleus and regulates transcription. CHRM1, GNAQ, GNB1, GNGT1, HTR2C, PLCB1, TUB 7 CHRM1(2), GNAQ(1), GNB1(1), HTR2C(1), PLCB1(3), TUB(2) 5256069 10 10 10 1 4 4 2 0 0 0 0.073 0.19 237 INTEGRIN_MEDIATED_CELL_ADHESION_KEGG AKT1, AKT3, BCAR1, CAPN1, CAPN10, CAPN11, CAPN2, CAPN3, CAPN5, CAPN6, CAPN7, CAPN9, CAPNS1, CAV1, CAV2, CAV3, CDC42, CRK, CSK, DKFZp434E1119, DOCK1, FLJ14825, FLJ40125, FYN, GIT2, GRB2, ILK, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAD, ITGAE, ITGAL, ITGAM, ITGAV, ITGAX, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, LOC283874, PDPK1, MAP2K1, MAP2K2, MAP2K3, MAP2K6, MAPK10, MAPK12, MAPK4, MAPK6, MAPK7, MGC17301, MYLK2, PAK1, PAK2, PAK3, PAK4, PAK6, PDPK1, PIK3R2, PTK2, PXN, RAC1, RAC2, RAC3, RAP1B, RAPGEF1, RHO, ROCK1, ROCK2, SDCCAG8, SEPP1, SHC1, SHC3, SORBS1, SOS1, SRC, TLN1, TNS, TNS1, VASP, VAV2, VAV3, VCL, ZYX 86 AKT1(12), AKT3(2), CAPN1(3), CAPN10(1), CAPN11(1), CAPN2(2), CAPN6(1), CAV1(1), GRB2(1), ILK(2), ITGA10(1), ITGA11(4), ITGA2(2), ITGA2B(2), ITGA4(1), ITGA6(3), ITGA7(5), ITGA8(2), ITGAD(1), ITGAL(1), ITGAM(1), ITGAV(3), ITGAX(2), ITGB1(2), ITGB2(3), ITGB3(2), ITGB4(4), ITGB5(2), ITGB8(1), MAP2K1(1), MAP2K3(1), MAPK10(1), MAPK4(2), MAPK6(1), PAK1(2), PAK2(1), PAK3(1), PTK2(1), PXN(1), RAPGEF1(3), RHO(2), ROCK1(1), ROCK2(2), SDCCAG8(3), SHC1(1), SHC3(1), SORBS1(4), SOS1(3), TLN1(7), TNS1(4), VAV3(1), VCL(3) 96464862 115 94 105 35 21 36 27 9 22 0 0.075 0.19 238 HSA01040_POLYUNSATURATED_FATTY_ACID_BIOSYNTHESIS Genes involved in polyunsaturated fatty acid biosynthesis ACAA1, ACOX1, ACOX3, ELOVL2, ELOVL5, ELOVL6, FADS1, FADS2, FASN, GPSN2, HADHA, HSD17B12, PECR, SCD 12 ACAA1(1), ACOX1(2), ACOX3(1), ELOVL5(2), ELOVL6(2), FADS2(4), SCD(1) 7883850 13 13 13 4 0 3 4 4 2 0 0.075 0.20 239 GPCRDB_OTHER ADORA3, ALG6, C5R1, CCKBR, CCR2, CCR3, CCR5, CELSR1, CELSR2, CELSR3, CHRM2, CHRM3, CIDEB, CXCR3, DRD4, EBI2, EDG1, EDNRA, ELA3A, EMR2, EMR3, F2R, FSHR, FY, GHRHR, GNRHR, GPR, GPR116, GPR132, GPR133, GPR135, GPR143, GPR145, GPR17, GPR18, GPR55, GPR56, GPR61, GPR73L1, GPR77, GPR84, GPR88, GRCA, GRM1, GRPR, HRH4, IL8RA, IL8RB, LGR6, LGR7, LPHN2, LPHN3, LTB4R2, MASS1, NTSR1, OR2A9P, OR2M4, OR5E1P, OR7E19P, OR7E47P, OR7E37P, OR7E18P, OR7E35P, LOC441453, OR8G1, LOC442754, OR8G2, P2RY11, P2RY13, PTGFR, RLN3R1, SMO, SSTR2, TAAR5, TSHR, VN1R1 48 ADORA3(1), ALG6(1), CCR2(4), CCR3(1), CELSR2(1), CELSR3(4), CHRM2(2), CHRM3(1), EMR2(3), EMR3(2), F2R(2), FSHR(3), GHRHR(1), GPR132(1), GPR133(1), GPR143(2), GPR56(1), GPR77(2), GPR84(2), GRM1(2), GRPR(1), HRH4(1), LGR6(2), LPHN2(3), LPHN3(4), LTB4R2(1), P2RY11(1), P2RY13(2), PTGFR(1), SMO(2), SSTR2(1), TAAR5(3), TSHR(3) 43026048 62 55 62 13 12 25 14 5 6 0 0.080 0.21 240 MCALPAINPATHWAY In integrin-mediated cell migration, calpains digest links between the actin cytoskeleton and focal adhesion proteins. ACTA1, CAPN1, CAPN2, CAPNS1, CAPNS2, CXCR3, EGF, EGFR, HRAS, ITGA1, ITGB1, MAPK1, MAPK3, MYL2, MYLK, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTK2, PXN, TLN1, VIL2 24 CAPN1(3), CAPN2(2), EGF(2), EGFR(4), ITGA1(3), ITGB1(2), MAPK1(1), MAPK3(1), MYLK(5), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), PTK2(1), PXN(1), TLN1(7) 24248796 35 33 35 12 5 13 6 8 3 0 0.083 0.21 241 INTEGRINPATHWAY Integrins are cell surface receptors commonly present at focal adhensions that interact with the extracellular matrix and transduce extracellular signaling. ACTA1, ACTN1, ACTN2, ACTN3, ARHA, BCAR1, BCR, CAPN1, CAPNS1, CAPNS2, CAV1, CRKL, CSK, FYN, GRB2, GRF2, HRAS, ITGA1, ITGB1, JUN, MAP2K1, MAP2K2, MAPK1, MAPK3, MAPK8, PPP1R12B, PTK2, PXN, RAF1, RAP1A, ROCK1, SHC1, SOS1, SRC, TLN1, TNS, VCL, ZYX 33 ACTN2(4), ACTN3(1), BCR(1), CAPN1(3), CAV1(1), CRKL(1), GRB2(1), ITGA1(3), ITGB1(2), JUN(1), MAP2K1(1), MAPK1(1), MAPK3(1), MAPK8(2), PTK2(1), PXN(1), RAF1(1), ROCK1(1), SHC1(1), SOS1(3), TLN1(7), VCL(3) 32807463 41 40 41 12 3 13 13 2 10 0 0.084 0.22 242 HSA00564_GLYCEROPHOSPHOLIPID_METABOLISM Genes involved in glycerophospholipid metabolism ACHE, AGPAT1, AGPAT2, AGPAT3, AGPAT4, AGPAT6, ARD1A, CDIPT, CDS1, CDS2, CHAT, CHKA, CHKB, CHPT1, CRLS1, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKI, DGKQ, DGKZ, ESCO1, ESCO2, ETNK1, ETNK2, GNPAT, GPAM, GPD1, GPD1L, GPD2, LCAT, LYCAT, LYPLA1, LYPLA2, LYPLA3, MYST3, MYST4, NAT5, NAT6, PCYT1A, PCYT1B, PEMT, PHOSPHO1, PISD, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLD1, PLD2, PNPLA3, PPAP2A, PPAP2B, PPAP2C, PTDSS1, PTDSS2, SH3GLB1 61 ACHE(2), AGPAT3(2), AGPAT6(1), CDS1(2), CHPT1(1), DGKA(3), DGKD(1), DGKE(1), DGKG(4), DGKH(1), DGKI(5), ESCO1(3), ETNK1(3), ETNK2(1), GNPAT(1), GPD1(2), GPD1L(1), GPD2(1), LCAT(1), MYST3(1), MYST4(5), PCYT1A(1), PCYT1B(2), PLA2G2D(1), PLA2G2F(1), PLA2G3(3), PLA2G4A(6), PLA2G6(2), PLD1(1), PNPLA3(4), PPAP2A(1), PTDSS2(1) 45749145 65 57 62 13 12 20 13 10 7 3 0.086 0.22 243 TERPENOID_BIOSYNTHESIS FDFT1, FDPS, FDPS, LOC402397, IDI1, SQLE 4 FDFT1(1), FDPS(1), IDI1(2), SQLE(1) 2398617 5 5 5 3 2 2 0 0 1 0 0.087 0.22 244 SA_MMP_CYTOKINE_CONNECTION Cytokines can induce activation of matrix metalloproteinases, which degrade extracellular matrix. ACE, CD44, CSF1, FCGR3A, IL1B, IL6R, SELL, SPN, TGFB1, TGFB2, TNF, TNFRSF1A, TNFRSF1B, TNFRSF8, TNFSF8 15 ACE(3), CSF1(2), IL6R(1), SELL(4), SPN(2), TNFRSF1A(1), TNFRSF8(1) 9757722 14 14 13 4 4 2 3 2 3 0 0.10 0.25 245 HSA03320_PPAR_SIGNALING_PATHWAY Genes involved in PPAR signaling pathway ACAA1, ACADL, ACADM, ACOX1, ACOX2, ACOX3, ACSL1, ACSL3, ACSL4, ACSL5, ACSL6, ADIPOQ, ANGPTL4, APOA1, APOA2, APOA5, APOC3, AQP7, CD36, CPT1A, CPT1B, CPT1C, CPT2, CYP27A1, CYP4A11, CYP4A22, CYP7A1, CYP8B1, DBI, EHHADH, FABP1, FABP2, FABP3, FABP4, FABP5, FABP5L1, FABP6, FABP7, FADS2, GK, GK2, HMGCS2, ILK, LOC642956, LPL, ME1, MMP1, NR1H3, OLR1, PCK1, PCK2, PDPK1, PLIN, PLTP, PPARA, PPARD, PPARG, RXRA, RXRB, RXRG, SCD, SCP2, SLC27A1, SLC27A2, SLC27A4, SLC27A5, SLC27A6, SORBS1, UBC, UCP1 65 ACAA1(1), ACOX1(2), ACOX3(1), ACSL3(1), ACSL4(1), ACSL5(1), ACSL6(2), APOA5(1), AQP7(2), CD36(1), CPT1A(2), CPT1C(2), CPT2(1), CYP27A1(1), CYP8B1(1), EHHADH(2), FABP1(1), FABP2(1), FABP4(1), FABP6(1), FADS2(4), GK2(1), HMGCS2(1), ILK(2), LPL(1), PCK1(1), PCK2(1), PLTP(1), PPARA(1), PPARG(1), SCD(1), SLC27A2(1), SLC27A4(2), SLC27A5(2), SORBS1(4), UBC(6) 47968791 56 52 56 18 8 15 14 5 14 0 0.10 0.26 246 C21_STEROID_HORMONE_METABOLISM AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 11 AKR1C4(1), CYP11A1(1), CYP11B1(2), CYP11B2(3), CYP17A1(1), CYP21A2(2), HSD3B2(2) 6722313 12 12 12 1 4 3 4 1 0 0 0.10 0.26 247 HSA00140_C21_STEROID_HORMONE_METABOLISM Genes involved in C21-steroid hormone metabolism AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 11 AKR1C4(1), CYP11A1(1), CYP11B1(2), CYP11B2(3), CYP17A1(1), CYP21A2(2), HSD3B2(2) 6722313 12 12 12 1 4 3 4 1 0 0 0.10 0.26 248 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_LACTOSERIES ABO, FUT1, FUT2, FUT3, FUT5, FUT6, SIAT6, ST3GAL3 6 FUT2(2), FUT3(2), ST3GAL3(1) 3254940 5 5 4 0 3 0 0 0 2 0 0.11 0.26 249 HSA00260_GLYCINE_SERINE_AND_THREONINE_METABOLISM Genes involved in glycine, serine and threonine metabolism ABP1, AGXT, AGXT2, AKR1B10, ALAS1, ALAS2, AMT, AOC2, AOC3, BHMT, CBS, CHDH, CHKA, CHKB, CTH, DAO, DLD, DMGDH, GAMT, GARS, GATM, GCAT, GLDC, GNMT, HSD3B7, MAOA, MAOB, PEMT, PHGDH, PIPOX, PISD, PSAT1, PSPH, RDH11, RDH12, RDH13, RDH14, SARDH, SARS, SARS2, SDS, SHMT1, SHMT2, TARS, TARS2 44 AGXT(1), AGXT2(1), ALAS2(1), AMT(1), AOC2(1), AOC3(2), BHMT(1), CBS(1), CTH(1), DAO(1), DLD(1), DMGDH(3), GARS(1), GATM(3), GCAT(2), MAOA(2), PIPOX(1), RDH11(2), RDH12(1), RDH14(1), SARDH(2), SARS(2), SARS2(2), TARS(4), TARS2(2) 30761211 40 38 40 20 7 16 8 2 7 0 0.11 0.26 250 RIBOFLAVIN_METABOLISM ACP1, ACP2, ACP5, ACPP, ACPT, ENPP1, ENPP3, FLAD1, RFK, TYR 10 ACP5(1), ACPP(1), ACPT(2), ENPP1(3), ENPP3(2), TYR(3) 7215117 12 12 12 4 2 4 3 2 1 0 0.11 0.26 251 HSA01030_GLYCAN_STRUCTURES_BIOSYNTHESIS_1 Genes involved in glycan structures - biosynthesis 1 A4GNT, ALG1, ALG10, ALG10B, ALG11, ALG12, ALG13, ALG14, ALG2, ALG3, ALG6, ALG8, ALG9, B3GALT6, B3GNT1, B3GNT2, B3GNT6, B3GNT7, B4GALT1, B4GALT2, B4GALT3, B4GALT4, B4GALT5, B4GALT7, C1GALT1, C1GALT1C1, ChGn, CHPF, CHST1, CHST11, CHST12, CHST13, CHST14, CHST2, CHST3, CHST4, CHST6, CHST7, CHSY-2, CHSY1, CSGlcA-T, DAD1, DDOST, DPAGT1, EXT1, EXT2, EXTL1, EXTL2, EXTL3, FUT11, FUT8, GALNAC4S-6ST, GALNACT-2, GALNT1, GALNT10, GALNT11, GALNT12, GALNT13, GALNT14, GALNT17, GALNT2, GALNT3, GALNT4, GALNT5, GALNT6, GALNT7, GALNT8, GALNT9, GALNTL1, GALNTL2, GALNTL4, GALNTL5, GANAB, GCNT1, GCNT3, GCNT4, GCS1, HS2ST1, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, HS3ST5, HS6ST1, HS6ST2, HS6ST3, LOC728969, MAN1A1, MAN1A2, MAN1B1, MAN1C1, MAN2A1, MGAT1, MGAT2, MGAT3, MGAT4A, MGAT4B, MGAT5, MGAT5B, NDST1, NDST2, NDST3, NDST4, OGT, RPN1, RPN2, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4, ST6GAL1, ST6GALNAC1, STT3B, UST, WBSCR17, XYLT1, XYLT2 103 ALG1(1), ALG10(1), ALG10B(3), ALG11(1), ALG13(2), ALG2(1), ALG6(1), ALG9(1), B3GNT1(1), B3GNT2(1), B3GNT7(1), B4GALT1(2), B4GALT3(1), C1GALT1(1), C1GALT1C1(1), CHPF(1), CHST1(1), CHST11(1), CHST2(3), CHST3(1), DPAGT1(2), EXT1(3), EXT2(2), EXTL3(3), FUT11(1), GALNT10(2), GALNT11(3), GALNT13(1), GALNT3(1), GALNT4(1), GALNT5(2), GALNT7(2), GALNTL1(1), GALNTL5(1), GCNT4(1), HS2ST1(1), HS3ST2(1), HS3ST5(3), HS6ST2(3), HS6ST3(1), MAN1A2(1), MAN1B1(1), MAN2A1(3), MGAT3(1), MGAT5(2), MGAT5B(4), NDST3(1), OGT(2), RPN1(1), ST3GAL1(1), ST3GAL3(1), ST3GAL4(1), ST6GALNAC1(2), UST(1), WBSCR17(4), XYLT2(1) 78611871 88 79 88 39 22 25 17 6 18 0 0.11 0.27 252 HSA00500_STARCH_AND_SUCROSE_METABOLISM Genes involved in starch and sucrose metabolism AGL, AMY1A, AMY1B, AMY1C, AMY2A, AMY2B, ASCC3, ASCC3L1, ATP13A2, DDX18, DDX19A, DDX23, DDX4, DDX41, DDX47, DDX50, DDX51, DDX52, DDX54, DDX55, DDX56, DHX58, ENPP1, ENPP3, ENTPD7, EP400, ERCC2, ERCC3, G6PC, G6PC2, GAA, GANC, GBA, GBA3, GBE1, GCK, GPI, GUSB, GYS1, GYS2, HK1, HK2, HK3, IFIH1, LYZL1, MGAM, MOV10L1, NUDT5, NUDT8, PGM1, PGM3, PYGB, PYGL, PYGM, RAD54B, RAD54L, RUVBL2, SETX, SI, SKIV2L2, SMARCA2, SMARCA5, TREH, UGDH, UGP2, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, UXS1 79 AGL(3), AMY2A(1), ASCC3(1), ATP13A2(1), DDX41(1), DDX50(3), DDX55(3), DDX56(1), DHX58(2), ENPP1(3), ENPP3(2), ENTPD7(1), ERCC3(2), G6PC2(1), GAA(2), GANC(1), GBE1(3), GCK(2), GPI(2), GUSB(1), GYS1(5), GYS2(1), HK1(1), HK3(2), IFIH1(1), MGAM(8), NUDT8(1), PGM1(1), PGM3(1), PYGB(3), PYGL(1), PYGM(2), RAD54B(4), RAD54L(2), SETX(6), SI(4), SKIV2L2(1), SMARCA2(3), SMARCA5(1), TREH(1), UGT1A10(1), UGT1A6(2), UGT2A1(1), UGT2B10(2), UGT2B15(2), UGT2B28(1), UGT2B4(1), UXS1(2) 89551410 97 86 97 21 20 24 27 10 16 0 0.11 0.28 253 CDK5PATHWAY Cdk5, a regulatory kinase implicated in neuronal development, represses Mek1, which downregulates the MAP kinase pathway. CDK5, CDK5R1, DPM2, EGR1, HRAS, KLK2, MAP2K1, MAP2K2, MAPK1, MAPK3, NGFB, NGFR, RAF1 11 CDK5(1), EGR1(1), KLK2(2), MAP2K1(1), MAPK1(1), MAPK3(1), NGFR(1), RAF1(1) 5585112 9 9 9 2 0 5 2 1 1 0 0.11 0.28 254 BIOGENIC_AMINE_SYNTHESIS AANAT, ACHE, CHAT, COMT, DBH, DDC, DXYS155E, GAD1, GAD2, HDC, MAOA, PAH, PNMT, SLC18A3, TH, TPH1 13 ACHE(2), DBH(4), DDC(1), GAD1(2), GAD2(3), MAOA(2), PAH(1) 9864699 15 15 15 1 3 5 5 0 2 0 0.12 0.28 255 HSA00601_GLYCOSPHINGOLIPID_BIOSYNTHESIS_LACTOSERIES Genes involved in glycosphingolipid biosynthesis - lactoseries ABO, B3GALT1, B3GALT2, B3GALT5, B3GNT5, FUT1, FUT2, FUT3, ST3GAL3, ST3GAL4 10 B3GALT1(1), B3GALT5(1), FUT2(2), FUT3(2), ST3GAL3(1), ST3GAL4(1) 5462925 8 8 7 0 3 2 1 0 2 0 0.12 0.28 256 HSA00603_GLYCOSPHINGOLIPID_BIOSYNTHESIS_GLOBOSERIES Genes involved in glycosphingolipid biosynthesis - globoseries A4GALT, B3GALNT1, B3GALT5, FUT1, FUT2, FUT9, GBGT1, GLA, HEXA, HEXB, NAGA, ST3GAL1, ST3GAL2, ST8SIA1 14 B3GALNT1(1), B3GALT5(1), FUT2(2), GLA(2), HEXB(1), ST3GAL1(1), ST8SIA1(1) 7540104 9 9 8 1 2 0 3 1 3 0 0.12 0.28 257 EXTRINSICPATHWAY The extrinsic prothrombin activation pathway requires the release of thromboplastin from damaged tissues to activate the blood clotting cascade. F10, F2, F2R, F3, F5, F7, FGA, FGB, FGG, PROC, PROS1, SERPINC1, TFPI 13 F2(2), F2R(2), F5(7), FGA(3), PROC(1), SERPINC1(2), TFPI(1) 11751246 18 18 18 6 2 6 2 5 3 0 0.12 0.29 258 O_GLYCAN_BIOSYNTHESIS GALNT1, GALNT10, GALNT2, GALNT3, GALNT4, GALNT6, GALNT7, GALNT8, GALNT9, GCNT1, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, WBSCR17 14 GALNT10(2), GALNT3(1), GALNT4(1), GALNT7(2), ST3GAL1(1), ST3GAL4(1), WBSCR17(4) 10584639 12 12 12 6 2 3 2 0 5 0 0.12 0.29 259 HSA00550_PEPTIDOGLYCAN_BIOSYNTHESIS Genes involved in peptidoglycan biosynthesis GLUL, PGLYRP2 2 PGLYRP2(3) 1383603 3 3 3 1 1 1 0 0 1 0 0.12 0.29 260 G_PROTEIN_SIGNALING ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, AKAP1, AKAP10, AKAP11, AKAP12, AKAP2, PALM2_AKAP2, AKAP3, AKAP4, AKAP5, AKAP6, AKAP7, AKAP8, AKAP9, ARHGEF1, CALM1, CALM2, CALM3, CHMP1B, GNA11, GNA12, GNA13, GNA14, GNA15, GNAI2, GNAI3, GNAL, GNAO1, GNAQ, GNAZ, GNB1, GNB2, GNB3, GNB5, GNG10, GNG10, LOC552891, GNG12, GNG13, GNG3, GNG4, GNG5, GNG7, GNGT1, GNGT2, HRAS, IL18BP, ITPR1, KCNJ3, KRAS, MGC11266, NRAS, PALM2, PALM2_AKAP2, PALM2_AKAP2, PDE1A, PDE1B, PDE1C, PDE4A, PDE4B, PDE4C, PDE4D, PDE7A, PDE7B, PDE8A, PDE8B, PLCB3, PPP3CA, PPP3CC, PRKACA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCI, PRKCQ, PRKCZ, PRKD1, PRKD3, RHOA, RRAS, SARA1, SLC9A1, USP5 92 ADCY1(3), ADCY3(2), ADCY4(1), ADCY5(3), ADCY7(1), ADCY8(2), ADCY9(5), AKAP1(1), AKAP11(5), AKAP12(2), AKAP3(2), AKAP6(3), AKAP8(1), AKAP9(7), ARHGEF1(5), GNAI2(1), GNAO1(1), GNAQ(1), GNB1(1), GNB3(2), ITPR1(7), KCNJ3(1), KRAS(1), PDE1A(2), PDE1B(1), PDE4A(1), PDE4B(2), PDE4C(3), PDE4D(3), PLCB3(1), PPP3CA(3), PRKACA(1), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), PRKCG(1), PRKCH(1), PRKCI(1), PRKCQ(2), PRKCZ(1), PRKD1(1), RHOA(2), USP5(4) 85302243 91 81 91 36 22 23 25 8 13 0 0.13 0.30 261 TCRMOLECULE T Cell Receptor and CD3 Complex CD3D, CD3E, CD3G, CD3Z, TRA@, TRB@ 3 CD3E(1), CD3G(1) 864942 2 2 2 0 0 1 1 0 0 0 0.13 0.30 262 LAIRPATHWAY The local acute inflammatory response is mediated by activated macrophages and mast cells or by complement activation. BDK, C3, C5, C6, C7, ICAM1, IL1A, IL6, IL8, ITGA4, ITGAL, ITGB1, ITGB2, SELP, SELPLG, TNF, VCAM1 16 C3(2), C5(3), C6(4), C7(3), IL1A(1), IL6(2), ITGA4(1), ITGAL(1), ITGB1(2), ITGB2(3), SELP(3), SELPLG(1), VCAM1(2) 17954898 28 25 28 6 8 5 6 4 5 0 0.13 0.31 263 EOSINOPHILSPATHWAY Recruitment of eosinophils in the inflammatory response observed in asthma occurs via the chemoattractant eotaxin binding to the CCR3 receptor. CCL11, CCL5, CCR3, CSF2, HLA-DRA, HLA-DRB1, IL3, IL5 8 CCL11(1), CCR3(1), HLA-DRB1(2) 2298231 4 4 4 1 0 1 1 1 1 0 0.13 0.31 264 VALINE_LEUCINE_AND_ISOLEUCINE_BIOSYNTHESIS BCAT1, IARS, LARS, LARS2, PDHA1, PDHA2, PDHB 7 BCAT1(3), IARS(5), LARS2(2), PDHA1(1), PDHA2(1), PDHB(1) 7556328 13 12 13 4 2 5 4 0 2 0 0.13 0.31 265 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 DAO(1) 549588 1 1 1 1 0 0 0 0 1 0 0.13 0.31 266 BLOOD_CLOTTING_CASCADE F10, F11, F12, F13B, F2, F5, F7, F8, F8A1, F9, FGA, FGB, FGG, LPA, PLG, PLAT, PLAU, PLG, SERPINB2, SERPINE1, SERPINF2, VWF 20 F12(1), F2(2), F5(7), F8(1), FGA(3), LPA(5), PLAT(1), PLAU(2), PLG(2), SERPINE1(1), VWF(6) 25646088 31 31 30 12 3 12 7 5 4 0 0.13 0.31 267 ALANINE_AND_ASPARTATE_METABOLISM AARS, ABAT, ADSL, ADSS, AGXT, AGXT2, ASL, ASNS, ASPA, ASS, CAD, CRAT, DARS, DDO, GAD1, GAD2, GOT1, GOT2, GPT, GPT2, NARS, PC 20 ABAT(3), ADSL(1), AGXT(1), AGXT2(1), ASL(3), ASPA(1), CAD(7), CRAT(3), DARS(1), GAD1(2), GAD2(3), GOT2(1), GPT2(2), NARS(1), PC(1) 18343767 31 28 31 4 7 13 5 3 3 0 0.14 0.31 268 HSA00430_TAURINE_AND_HYPOTAURINE_METABOLISM Genes involved in taurine and hypotaurine metabolism BAAT, CDO1, CSAD, GAD1, GAD2, GGT1, GGTL3, GGTL4 6 BAAT(1), CDO1(1), GAD1(2), GAD2(3), GGT1(1) 4305951 8 8 8 0 2 3 3 0 0 0 0.14 0.31 269 GLOBOSIDE_METABOLISM A4GALT, FUT1, FUT2, FUT9, GBGT1, GLA, HEXA, HEXB, NAGA, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, ST8SIA1 13 FUT2(2), GLA(2), HEXB(1), ST3GAL1(1), ST3GAL4(1), ST8SIA1(1) 7070115 8 8 7 1 2 1 2 0 3 0 0.14 0.32 270 HSA00051_FRUCTOSE_AND_MANNOSE_METABOLISM Genes involved in fructose and mannose metabolism AKR1B1, AKR1B10, ALDOA, ALDOB, ALDOC, FBP1, FBP2, FPGT, FUK, GMDS, GMPPA, GMPPB, HK1, HK2, HK3, HSD3B7, KHK, LHPP, MPI, MTMR1, MTMR2, MTMR6, PFKFB1, PFKFB2, PFKFB3, PFKFB4, PFKL, PFKM, PFKP, PGM2, PHPT1, PMM1, PMM2, RDH11, RDH12, RDH13, RDH14, SORD, TPI1, TSTA3, UGCGL1, UGCGL2 39 AKR1B1(2), ALDOA(3), ALDOB(2), FUK(2), GMDS(2), HK1(1), HK3(2), KHK(1), MTMR6(1), PFKFB1(1), PFKFB3(1), PFKFB4(1), PFKM(3), PFKP(2), RDH11(2), RDH12(1), RDH14(1) 25502100 28 27 28 8 4 11 4 3 6 0 0.14 0.33 271 IL18PATHWAY Pro-inflammatory IL-18 is activated in macrophages by caspase-1 cleavage and, in conjunction with IL-12, stimulates Th1 cell differentiation. CASP1, IFNG, IL12A, IL12B, IL18, IL2 6 CASP1(1), IL12A(1), IL12B(1), IL2(1) 2321046 4 4 4 1 0 0 2 1 1 0 0.14 0.33 272 CCR5PATHWAY CCR5 is a G-protein coupled receptor expressed in macrophages that recognizes chemokine ligands and is targeted by the HIV envelope protein GP120. CALM1, CALM2, CALM3, CCL2, CCL4, CCR5, CXCL12, CXCR4, FOS, GNAQ, JUN, MAPK14, MAPK8, PLCG1, PRKCA, PRKCB1, PTK2B, SYT1 16 GNAQ(1), JUN(1), MAPK14(1), MAPK8(2), PLCG1(4), PTK2B(3) 9682686 12 12 12 2 3 4 1 0 4 0 0.16 0.36 273 CHREBPPATHWAY Carbohydrate responsive element binding protein (chREBP) is a transcription factor inhibited by cAMP and activated by high carbohydrate levels. ADCY1, BG1, BUCS1, GNAS, GNB1, GNGT1, PPP2CA, PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKACB, PRKACG, PRKAG1, PRKAG2, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, WBSCR14 17 ADCY1(3), GNAS(4), GNB1(1), PRKAA2(2), PRKAB1(1), PRKAG2(1), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1) 10483239 15 15 15 6 6 3 3 1 2 0 0.16 0.36 274 HSA00930_CAPROLACTAM_DEGRADATION Genes involved in caprolactam degradation AKR1A1, ASAHL, ECHS1, EHHADH, HADH, HADHA, HSD17B10, HSD17B4, NTAN1, SIRT1, SIRT2, SIRT5, SIRT7, VNN2, VNN3 12 ECHS1(1), EHHADH(2), HADH(1), HSD17B10(1), HSD17B4(3), NTAN1(1), VNN2(3) 8264100 12 12 12 5 2 2 6 1 1 0 0.16 0.36 275 IL6PATHWAY IL-6 binding to its receptor activates JAK kinases and a variety of transcription factors, with effects in neuronal differentiation, bone loss, and inflammation. CEBPB, CSNK2A1, ELK1, FOS, GRB2, HRAS, IL6, IL6R, IL6ST, JAK1, JAK2, JAK3, JUN, MAP2K1, MAPK3, PTPN11, RAF1, SHC1, SOS1, SRF, STAT3 20 CSNK2A1(1), ELK1(2), GRB2(1), IL6(2), IL6R(1), IL6ST(3), JAK1(1), JAK2(2), JAK3(1), JUN(1), MAP2K1(1), MAPK3(1), RAF1(1), SHC1(1), SOS1(3), SRF(1), STAT3(1) 17464629 24 23 24 3 1 6 7 3 7 0 0.16 0.36 276 HSA00062_FATTY_ACID_ELONGATION_IN_MITOCHONDRIA Genes involved in fatty acid elongation in mitochondria ACAA2, ECHS1, HADH, HADHA, HADHB, HSD17B10, HSD17B4, MECR, PPT1, PPT2 10 ACAA2(1), ECHS1(1), HADH(1), HADHB(1), HSD17B10(1), HSD17B4(3), PPT2(1) 6138756 9 9 9 3 3 2 1 2 1 0 0.16 0.36 277 HIFPATHWAY Under normal conditions, hypoxia inducible factor HIF-1 is degraded; under hypoxic conditions, it activates transcription of genes controlled by hpoxic response elements (HREs). ARNT, ASPH, COPS5, CREB1, EDN1, EP300, EPO, HIF1A, HSPCA, JUN, LDHA, NOS3, P4HB, VEGF, VHL 13 ARNT(2), ASPH(3), EDN1(2), EP300(3), JUN(1), NOS3(2) 11883066 13 13 12 4 4 1 1 1 6 0 0.17 0.37 278 HSA00251_GLUTAMATE_METABOLISM Genes involved in glutamate metabolism ABAT, ADC, ALDH4A1, ALDH5A1, CAD, CPS1, EARS2, EPRS, GAD1, GAD2, GCLC, GCLM, GFPT1, GFPT2, GLS, GLS2, GLUD1, GLUD2, GLUL, GMPS, GNPNAT1, GOT1, GOT2, GPT, GPT2, GSR, GSS, NADSYN1, NAGK, PPAT, QARS 30 ABAT(3), ADC(1), ALDH5A1(1), CAD(7), CPS1(2), EARS2(3), EPRS(2), GAD1(2), GAD2(3), GCLC(1), GCLM(1), GFPT2(3), GLS(1), GLUD2(1), GMPS(1), GNPNAT1(1), GOT2(1), GPT2(2), GSS(1), NAGK(1), PPAT(1), QARS(2) 28367664 41 37 41 5 7 11 17 3 3 0 0.17 0.38 279 BLYMPHOCYTEPATHWAY B cells express the major histocompatibility complex (class II MHC), immunoglobulins, adhesion proteins, and other factors on their cell surface. CD80, CR1, CR2, FCGR2B, HLA-DRA, HLA-DRB1, ICAM1, ITGAL, ITGB2, PTPRC, TNFRSF5 10 CR1(6), CR2(2), HLA-DRB1(2), ITGAL(1), ITGB2(3), PTPRC(1) 11272638 15 15 15 7 3 2 5 4 1 0 0.17 0.38 280 ALTERNATIVEPATHWAY The alternative complement pathway is an antibody-independent mechanism of immune activation that results in cell lysis via the membrane attack complex. BF, C3, C5, C6, C7, C8A, C9, DF, PFC 6 C3(2), C5(3), C6(4), C7(3), C9(1) 9174165 13 13 13 3 2 4 3 2 2 0 0.17 0.38 281 CARM_ERPATHWAY Methyltransferase CARM1 methylates CBP and co-activates estrogen receptors via Grip1. BRCA1, CARM1, CCND1, CREBBP, EP300, ERCC3, ESR1, GRIP1, GTF2A1, GTF2E1, GTF2F1, HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HIST2H3C, MEF2C, NCOR2, NR0B1, NRIP1, PELP1, POLR2A, PPARBP, PPARGC1, REA, SHARP, SRA1, TBP 25 BRCA1(8), CARM1(1), CCND1(1), CREBBP(2), EP300(3), ERCC3(2), ESR1(2), HDAC1(2), HDAC2(2), HDAC3(1), HDAC6(2), MEF2C(2), NCOR2(3), POLR2A(2), TBP(1) 32082453 34 32 33 9 7 5 7 1 14 0 0.18 0.38 282 MONOCYTEPATHWAY Monocytes are a class of immune phagocytes that can develop into macrophages and express LFA-1, CD44, and other surface signaling proteins. CD44, ICAM1, ITGA4, ITGAL, ITGAM, ITGB1, ITGB2, PECAM1, SELE, SELL, SELP 11 ITGA4(1), ITGAL(1), ITGAM(1), ITGB1(2), ITGB2(3), SELE(1), SELL(4), SELP(3) 12912783 16 16 16 2 4 1 5 3 3 0 0.18 0.38 283 CALCINEURINPATHWAY Increased intracellular calcium activates the phosphatase calcineurin in differentiating keratinocytes. CALM1, CALM2, CALM3, CDKN1A, GNAQ, MARCKS, NFATC1, NFATC2, NFATC3, NFATC4, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCA, PRKCB1, SP1, SP3, SYT1 17 GNAQ(1), NFATC3(3), NFATC4(3), PLCG1(4), PPP3CA(3), PPP3CB(2), SP1(1), SP3(3) 14787669 20 18 20 3 2 4 9 0 5 0 0.18 0.39 284 BOTULINPATHWAY Blockade of Neurotransmitter Relase by Botulinum Toxin CHRM1, CHRNA1, SNAP25, STX1A, VAMP2 5 CHRM1(2), CHRNA1(1), SNAP25(1) 2437656 4 4 4 1 1 1 1 1 0 0 0.18 0.39 285 REELINPATHWAY Reelin is secreted by neurons and recognized by receptors including cadherin related neuronal receptors, which promote phosphorylation of Dab1. CDK5, CDK5R1, DAB1, FYN, LRP8, RELN, VLDLR 7 CDK5(1), DAB1(2), LRP8(1), RELN(10), VLDLR(2) 10596300 16 16 15 3 4 5 4 0 3 0 0.18 0.39 286 HSA00565_ETHER_LIPID_METABOLISM Genes involved in ether lipid metabolism AGPAT1, AGPAT2, AGPAT3, AGPAT4, AGPAT6, AGPS, CHPT1, ENPP2, ENPP6, LYCAT, PAFAH1B1, PAFAH1B2, PAFAH1B3, PAFAH2, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLD1, PLD2, PPAP2A, PPAP2B, PPAP2C 29 AGPAT3(2), AGPAT6(1), AGPS(1), CHPT1(1), ENPP2(3), PAFAH1B1(1), PAFAH1B3(1), PLA2G2D(1), PLA2G2F(1), PLA2G3(3), PLA2G4A(6), PLA2G6(2), PLD1(1), PPAP2A(1) 16270137 25 23 23 3 5 6 7 5 2 0 0.19 0.40 287 UCALPAINPATHWAY Calpains promote formation of integrin adhesion clusters which recruit Rac to enable the formation of mature focal adhesions that do not contain calpain. ACTA1, ACTN1, ACTN2, ACTN3, ARHA, CAPN1, CAPNS1, CAPNS2, ITGA1, ITGB1, ITGB3, PTK2, PXN, RAC1, SPTAN1, SRC, TLN1, VIL2 16 ACTN2(4), ACTN3(1), CAPN1(3), ITGA1(3), ITGB1(2), ITGB3(2), PTK2(1), PXN(1), SPTAN1(2), TLN1(7) 21083595 26 26 26 8 2 9 9 2 4 0 0.19 0.40 288 FLUMAZENILPATHWAY Flumazenil is a benzodiazepine receptor antagonist that may induce protective preconditioning in ischemic cardiomyocytes. GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GPX1, PRKCE, SOD1 9 GABRA1(2), GABRA3(3), GABRA6(3), SOD1(1) 5944068 9 9 9 4 2 5 2 0 0 0 0.19 0.40 289 SARSPATHWAY The SARS coronavirus has a 30kb RNA genome containing rep, a large gene encoding viral protease Mpro. ANPEP, CKM, EIF4E, FBL, GPT, LDHA, LDHB, LDHC, MAPK14, NCL 9 ANPEP(3), FBL(2), LDHC(1), MAPK14(1), NCL(1) 6315699 8 8 8 1 2 4 1 0 1 0 0.19 0.41 290 KERATAN_SULFATE_BIOSYNTHESIS B3GNT1, B4GALT1, B4GALT2, B4GALT3, B4GALT5, FUT8, SIAT4A, SIAT4B, SIAT6, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4 10 B3GNT1(1), B4GALT1(2), B4GALT3(1), ST3GAL1(1), ST3GAL3(1), ST3GAL4(1) 5528328 7 7 7 0 2 2 0 1 2 0 0.19 0.41 291 GLUCONEOGENESIS ACYP1, ACYP2, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, AKR1A1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH9A1, ALDOA, ALDOB, ALDOC, BPGM, DLAT, DLD, ENO1, ENO2, ENO3, FBP1, FBP2, G6PC, GAPDH, GCK, GPI, HK1, HK2, HK3, LDHA, LDHB, LDHC, PDHA1, PDHA2, PDHB, PFKM, PFKP, PGAM1, PGK1, PGM1, PGM3, PKLR, PKM2, TPI1 53 ACYP1(1), ADH1A(1), ADH7(2), ADHFE1(1), ALDH1A1(2), ALDH1A2(1), ALDH1B1(1), ALDH3B1(2), ALDH3B2(2), ALDH9A1(1), ALDOA(3), ALDOB(2), DLD(1), ENO1(1), ENO3(1), GCK(2), GPI(2), HK1(1), HK3(2), LDHC(1), PDHA1(1), PDHA2(1), PDHB(1), PFKM(3), PFKP(2), PGK1(2), PGM1(1), PGM3(1) 35244612 42 39 42 10 6 21 5 7 3 0 0.19 0.41 292 GLYCOLYSIS ACYP1, ACYP2, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, AKR1A1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH9A1, ALDOA, ALDOB, ALDOC, BPGM, DLAT, DLD, ENO1, ENO2, ENO3, FBP1, FBP2, G6PC, GAPDH, GCK, GPI, HK1, HK2, HK3, LDHA, LDHB, LDHC, PDHA1, PDHA2, PDHB, PFKM, PFKP, PGAM1, PGK1, PGM1, PGM3, PKLR, PKM2, TPI1 53 ACYP1(1), ADH1A(1), ADH7(2), ADHFE1(1), ALDH1A1(2), ALDH1A2(1), ALDH1B1(1), ALDH3B1(2), ALDH3B2(2), ALDH9A1(1), ALDOA(3), ALDOB(2), DLD(1), ENO1(1), ENO3(1), GCK(2), GPI(2), HK1(1), HK3(2), LDHC(1), PDHA1(1), PDHA2(1), PDHB(1), PFKM(3), PFKP(2), PGK1(2), PGM1(1), PGM3(1) 35244612 42 39 42 10 6 21 5 7 3 0 0.19 0.41 293 LDLPATHWAY Low density lipoproteins (LDL) are present in blood plasma, contain cholesterol and triglycerides, and contribute to atherogenic plaque formation. ACAT1, CCL2, CSF1, IL6, LDLR, LPL 6 ACAT1(1), CSF1(2), IL6(2), LDLR(1), LPL(1) 3979443 7 7 7 5 2 2 1 0 2 0 0.19 0.41 294 HSA00602_GLYCOSPHINGOLIPID_BIOSYNTHESIS_NEO_LACTOSERIES Genes involved in glycosphingolipid biosynthesis - neo-lactoseries ABO, B3GNT1, B3GNT2, B3GNT3, B3GNT4, B3GNT5, B4GALT1, B4GALT2, B4GALT3, B4GALT4, FUT1, FUT2, FUT3, FUT4, FUT5, FUT6, FUT7, FUT9, GCNT2, ST3GAL6, ST8SIA1 18 B3GNT1(1), B3GNT2(1), B3GNT3(1), B3GNT4(1), B4GALT1(2), B4GALT3(1), FUT2(2), FUT3(2), ST3GAL6(1), ST8SIA1(1) 10440651 13 13 12 2 6 1 1 2 3 0 0.19 0.41 295 CACAMPATHWAY Calcium functions as a second messenger activating the calcium/calmodulin-dependent kinases, which phosphorylate targets such as CREB. CALM1, CALM2, CALM3, CAMK1, CAMK1G, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, CAMKK1, CAMKK2, CREB1, SYT1 14 CAMK1(1), CAMK1G(1), CAMK2A(1), CAMK2D(3), CAMKK1(3), CAMKK2(2) 8115042 11 11 11 5 2 2 4 0 3 0 0.20 0.41 296 SPPAPATHWAY Thrombin cleaves protease-activated receptors PAR1 and PAR4 to induce calcium influx and activate platelet aggregation, a process inhibited by aspirin. F2, F2R, F2RL3, GNAI1, GNB1, GNGT1, HRAS, ITGA1, ITGB1, MAP2K1, MAPK1, MAPK3, PLA2G4A, PLCB1, PRKCA, PRKCB1, PTGS1, PTK2, RAF1, SRC, SYK, TBXAS1 20 F2(2), F2R(2), GNAI1(1), GNB1(1), ITGA1(3), ITGB1(2), MAP2K1(1), MAPK1(1), MAPK3(1), PLA2G4A(6), PLCB1(3), PTK2(1), RAF1(1), TBXAS1(1) 17665908 26 24 25 5 5 10 7 4 0 0 0.20 0.41 297 MPRPATHWAY Progesterone binding to its intracellular receptor activates the MAPK pathway and induces oocyte maturation; binding to membrane receptor inhibits adenylyl cyclase. ACTA1, ADCY1, CAP1, CCNB1, CDC2, CDC25C, GNAI1, GNAS, GNB1, GNGT1, HRAS, MAPK1, MAPK3, MYT1, PIN1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RPS6KA1, SRC 22 ADCY1(3), CAP1(2), CCNB1(2), GNAI1(1), GNAS(4), GNB1(1), MAPK1(1), MAPK3(1), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), RPS6KA1(1) 13810173 19 18 19 5 5 6 4 2 2 0 0.20 0.41 298 HSA04360_AXON_GUIDANCE Genes involved in axon guidance ABL1, ABLIM1, ABLIM2, ABLIM3, ARHGEF12, CDC42, CDK5, CFL1, CFL2, CHP, CXCL12, CXCR4, DCC, DPYSL2, DPYSL5, EFNA1, EFNA2, EFNA3, EFNA4, EFNA5, EFNB1, EFNB2, EFNB3, EPHA1, EPHA2, EPHA3, EPHA4, EPHA5, EPHA6, EPHA7, EPHA8, EPHB1, EPHB2, EPHB3, EPHB4, EPHB6, FES, FYN, GNAI1, GNAI2, GNAI3, GSK3B, HRAS, ITGB1, KRAS, L1CAM, LIMK1, LIMK2, LRRC4C, MAPK1, MAPK3, MET, NCK1, NCK2, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NGEF, NRAS, NRP1, NTN1, NTN2L, NTN4, NTNG1, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PLXNA1, PLXNA2, PLXNA3, PLXNB1, PLXNB2, PLXNB3, PLXNC1, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PTK2, RAC1, RAC2, RAC3, RASA1, RGS3, RHOA, RHOD, RND1, ROBO1, ROBO2, ROBO3, ROCK1, ROCK2, SEMA3A, SEMA3B, SEMA3C, SEMA3D, SEMA3E, SEMA3F, SEMA3G, SEMA4A, SEMA4B, SEMA4C, SEMA4D, SEMA4F, SEMA4G, SEMA5A, SEMA5B, SEMA6A, SEMA6B, SEMA6C, SEMA6D, SEMA7A, SLIT1, SLIT2, SLIT3, SRGAP1, SRGAP2, SRGAP3, UNC5A, UNC5B, UNC5C, UNC5D 122 ABL1(2), ARHGEF12(2), CDK5(1), DCC(6), DPYSL2(1), DPYSL5(1), EFNA3(1), EFNB1(1), EFNB2(1), EPHA1(2), EPHA2(2), EPHA3(2), EPHA4(1), EPHA5(5), EPHA6(2), EPHA7(2), EPHB1(2), EPHB2(1), EPHB3(1), EPHB4(1), EPHB6(2), FES(1), GNAI1(1), GNAI2(1), ITGB1(2), KRAS(1), L1CAM(1), LIMK1(3), LIMK2(1), MAPK1(1), MAPK3(1), MET(4), NFAT5(1), NFATC3(3), NFATC4(3), NGEF(2), NRP1(3), NTNG1(2), PAK1(2), PAK2(1), PAK3(1), PAK7(1), PLXNA1(3), PLXNA2(4), PLXNA3(3), PLXNB1(1), PLXNC1(1), PPP3CA(3), PPP3CB(2), PTK2(1), RASA1(2), RGS3(2), RHOA(2), ROBO1(2), ROBO2(3), ROCK1(1), ROCK2(2), SEMA3A(2), SEMA3B(1), SEMA3C(1), SEMA3D(1), SEMA3E(1), SEMA3F(1), SEMA4A(1), SEMA4F(5), SEMA4G(1), SEMA5A(3), SEMA5B(2), SEMA6A(1), SEMA7A(1), SLIT1(1), SLIT2(2), SLIT3(1), SRGAP1(5), SRGAP3(1), UNC5B(1), UNC5C(3), UNC5D(6) 136224816 148 120 148 44 34 47 33 8 23 3 0.20 0.41 299 MYOSINPATHWAY Myosin light chain kinase phosphorylates myosin and promotes muscle contraction and platelet formation; myosin phosphatase antagonizes these processes. ARHGAP5, ARHGEF1, GNA12, GNA13, GNAQ, GNB1, GNGT1, MYL2, MYLK, PLCB1, PPP1R12B, PRKCA, PRKCB1, PRKCL1, ROCK1 13 ARHGAP5(3), ARHGEF1(5), GNAQ(1), GNB1(1), MYLK(5), PLCB1(3), ROCK1(1) 15472119 19 19 19 5 5 9 1 1 3 0 0.20 0.42 300 STREPTOMYCIN_BIOSYNTHESIS GCK, HK1, HK2, HK3, IMPA1, PGM1, PGM3, TGDS 8 GCK(2), HK1(1), HK3(2), IMPA1(1), PGM1(1), PGM3(1), TGDS(2) 7469631 10 10 10 2 1 4 2 2 1 0 0.20 0.42 301 GLUTATHIONE_METABOLISM ANPEP, G6PD, GCLC, GCLM, GGT1, GPX1, GPX2, GPX3, GPX4, GPX5, GSS, GSTA1, GSTA2, GSTA3, GSTA4, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, IDH1, IDH2, MGST1, MGST2, MGST3, PGD 29 ANPEP(3), G6PD(1), GCLC(1), GCLM(1), GGT1(1), GPX5(1), GSS(1), GSTA1(1), GSTA4(1), GSTO2(1), GSTZ1(1), IDH1(1), PGD(2) 13306722 16 16 16 2 5 3 6 0 2 0 0.21 0.43 302 WNT_SIGNALING Wnt signaling genes APC, ARHA, AXIN1, C2orf31, CCND1, CCND2, CCND3, CSNK1E, CSNK1E, LOC400927, CTNNB1, DIPA, DVL1, DVL2, DVL3, FBXW2, FOSL1, FRAT1, FZD1, FZD10, FZD2, FZD3, FZD5, FZD6, FZD7, FZD8, FZD9, GSK3B, JUN, LDLR, MAPK10, MAPK9, MYC, PAFAH1B1, PLAU, PPP2R5C, PPP2R5E, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCI, PRKCM, PRKCQ, PRKCZ, PRKD1, RAC1, RHOA, SFRP4, TCF7, WNT1, WNT10A, WNT10B, WNT11, WNT16, WNT2, WNT2B, WNT3, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B 55 APC(3), AXIN1(1), CCND1(1), CCND3(5), CSNK1E(1), DVL3(1), FBXW2(1), FZD1(1), FZD3(2), FZD6(2), FZD9(1), JUN(1), LDLR(1), MAPK10(1), MYC(1), PAFAH1B1(1), PLAU(2), PPP2R5C(1), PPP2R5E(1), PRKCG(1), PRKCH(1), PRKCI(1), PRKCQ(2), PRKCZ(1), PRKD1(1), RHOA(2), SFRP4(1), TCF7(3), WNT10B(1), WNT11(2), WNT2B(1), WNT5B(1), WNT6(1), WNT7A(5) 40121952 52 46 52 21 11 17 10 6 5 3 0.21 0.43 303 ST_WNT_CA2_CYCLIC_GMP_PATHWAY Some Wnt glycoprotein/Frizzled receptor interactions increase intracellular calcium and decrease cGMP. BF, CAMK2A, CAMK2B, CAMK2D, CAMK2G, DAG1, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, NFAT5, PDE6A, PDE6B, PDE6C, PDE6D, PDE6G, PDE6H, SLC6A13, TF 18 CAMK2A(1), CAMK2D(3), ITPKB(7), ITPR1(7), ITPR3(4), NFAT5(1), PDE6A(1), PDE6B(2), PDE6C(2), PDE6G(1), SLC6A13(1), TF(1) 25751037 31 31 31 11 7 6 6 4 8 0 0.21 0.43 304 SA_BONE_MORPHOGENETIC Bone morphogenetic protein binds to its receptor to induce ectopic bone formation and promote development of the viscera. BMP1, BMPR1A, BMPR1B, BMPR2, MADH1, MADH4, MADH6 4 BMP1(1), BMPR1B(2), BMPR2(2) 4549818 5 5 4 3 1 1 0 0 3 0 0.21 0.43 305 HSA00900_TERPENOID_BIOSYNTHESIS Genes involved in terpenoid biosynthesis FDFT1, FDPS, GGPS1, IDI1, IDI2, SQLE 6 FDFT1(1), FDPS(1), IDI1(2), SQLE(1) 3217422 5 5 5 4 2 2 0 0 1 0 0.22 0.43 306 RANKLPATHWAY RANK is a TNF-type receptor that promotes osteoclast differentiation and consequent bone resorbtion on binding RANK ligand produced by osteoblasts. FOS, FOSL1, FOSL2, IFNAR1, IFNAR2, IFNB1, ISGF3G, MAPK8, NFKB1, PRKR, RELA, TNFRSF11A, TNFSF11, TRAF6 12 FOSL2(2), IFNAR2(1), IFNB1(1), MAPK8(2), NFKB1(1), RELA(1), TNFRSF11A(2), TRAF6(1) 8257002 11 11 11 3 3 4 1 1 2 0 0.22 0.44 307 HSA00643_STYRENE_DEGRADATION Genes involved in styrene degradation FAH, GSTZ1, HGD 2 FAH(1), GSTZ1(1) 983073 2 2 2 1 0 2 0 0 0 0 0.22 0.44 308 SHHPATHWAY Sonic hedgehog (Shh) signaling in the developing CNS induces neuronal proliferation via interaction with the patched (Ptc-1) and smoothened receptors. DYRK1A, DYRK1B, GLI, GLI2, GLI3, GSK3B, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTCH, SHH, SMO, SUFU 14 DYRK1A(5), DYRK1B(1), GLI2(2), GLI3(3), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), SMO(2), SUFU(2) 11675703 18 16 18 8 4 5 4 4 1 0 0.22 0.44 309 HSA00410_BETA_ALANINE_METABOLISM Genes involved in beta-alanine metabolism ABAT, ABP1, ACADM, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, AOC2, AOC3, CNDP1, DPYD, DPYS, ECHS1, EHHADH, GAD1, GAD2, HADHA, HIBCH, MLYCD, SMS, SRM, UPB1 25 ABAT(3), ALDH1B1(1), ALDH9A1(1), AOC2(1), AOC3(2), CNDP1(2), DPYD(1), DPYS(1), ECHS1(1), EHHADH(2), GAD1(2), GAD2(3), HIBCH(2), MLYCD(2), UPB1(3) 19599099 27 25 27 8 2 9 9 3 4 0 0.22 0.44 310 HSA00950_ALKALOID_BIOSYNTHESIS_I Genes involved in alkaloid biosynthesis I DDC, GOT1, GOT2, TAT, TYR 5 DDC(1), GOT2(1), TYR(3) 3468894 5 5 5 2 1 3 1 0 0 0 0.23 0.45 311 FEEDERPATHWAY Sugars such as mannose, galactose, and fructose are enzymatically converted to glucose via feeder pathways that lead to glycolysis. HK1, KHK, LCT, MPI, PGM1, PYGL, PYGM, TPI1, TREH 9 HK1(1), KHK(1), LCT(3), PGM1(1), PYGL(1), PYGM(2), TREH(1) 9918441 10 10 10 0 0 3 0 2 5 0 0.23 0.45 312 AGPCRPATHWAY G-protein coupled receptors (GPCRs) transduce extracellular signals across the plasma membrane; attenuation occurs by signal molecule degradation or receptor-mediated endocytosis. ARRB1, GNAS, GNB1, GNGT1, GPRK2L, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1 11 ARRB1(1), GNAS(4), GNB1(1), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1) 6444477 9 9 9 3 3 2 2 1 1 0 0.23 0.45 313 BBCELLPATHWAY Fas ligand expression by T cells induces apoptosis in Fas-expressing, inactive B cells. CD28, CD4, HLA-DRA, HLA-DRB1, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 4 CD4(1), HLA-DRB1(2) 1837368 3 3 3 2 0 1 1 1 0 0 0.23 0.45 314 BETA_ALANINE_METABOLISM ABAT, ABP1, ACADL, ACADM, ACADSB, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, AOC2, AOC3, CNDP1, DPYD, DPYS, ECHS1, EHHADH, GAD1, GAD2, HADHA, MLYCD, SDS, SMS, UPB1 27 ABAT(3), ACADSB(1), ALDH1A1(2), ALDH1A2(1), ALDH1B1(1), ALDH9A1(1), AOC2(1), AOC3(2), CNDP1(2), DPYD(1), DPYS(1), ECHS1(1), EHHADH(2), GAD1(2), GAD2(3), MLYCD(2), UPB1(3) 21314787 29 27 29 10 2 12 7 4 4 0 0.23 0.45 315 HSA00330_ARGININE_AND_PROLINE_METABOLISM Genes involved in arginine and proline metabolism ALDH4A1, ARG1, ARG2, ASL, ASS1, CKB, CKM, CKMT1A, CKMT1B, CKMT2, CPS1, DAO, EPRS, GAMT, GATM, GLUD1, GLUD2, GOT1, GOT2, LAP3, NOS1, NOS2A, NOS3, OAT, OTC, P4HA1, P4HA2, P4HA3, PARS2, PRODH, PYCR1, PYCR2, PYCRL, RARS, RARS2 31 ARG1(2), ARG2(1), ASL(3), ASS1(1), CKMT2(1), CPS1(2), DAO(1), EPRS(2), GATM(3), GLUD2(1), GOT2(1), NOS1(3), NOS3(2), P4HA3(1), PARS2(1), PYCRL(3), RARS(1), RARS2(1) 24333972 30 29 29 6 5 12 10 1 2 0 0.23 0.45 316 SULFUR_METABOLISM BPNT1, PAPSS1, PAPSS2, SULT1A2, SULT1A3, SULT1A3, SULT1A4, SULT1E1, SULT2A1, SUOX 7 PAPSS1(2), SULT1E1(2), SUOX(3) 4623840 7 7 7 2 1 4 1 0 1 0 0.23 0.45 317 ETCPATHWAY Energy is extracted from carbohydrates via oxidation and transferred to the mitochondrial electron transport chain, which couples ATP synthesis to the reduction of oxygen to water. ATP5A1, CYCS, GPD2, MTCO1, NDUFA1, SDHA, SDHB, SDHC, SDHD, UQCRC1 9 ATP5A1(1), GPD2(1), NDUFA1(1), SDHA(1), SDHB(1), UQCRC1(2) 4941729 7 7 7 3 0 2 1 3 1 0 0.23 0.45 318 NEUROTRANSMITTERSPATHWAY Biosynthesis of neurotransmitters DBH, GAD1, HDC, PNMT, TH, TPH1 5 DBH(4), GAD1(2) 3937869 6 6 6 1 1 2 2 0 1 0 0.23 0.45 319 HSA00902_MONOTERPENOID_BIOSYNTHESIS Genes involved in monoterpenoid biosynthesis CYP2C19, CYP2C9 2 CYP2C19(1), CYP2C9(2) 1530126 3 3 3 1 1 1 1 0 0 0 0.23 0.45 320 ST_TYPE_I_INTERFERON_PATHWAY Type I interferon is an antiviral cytokine that induces a JAK-STAT type pathway leading to ISGF3 activation and a cellular antiviral response. IFNAR1, IFNB1, ISGF3G, JAK1, PTPRU, REG1A, STAT1, STAT2, TYK2 8 IFNB1(1), JAK1(1), PTPRU(5), STAT1(1), STAT2(1), TYK2(3) 9173151 12 12 11 5 2 3 3 2 2 0 0.24 0.46 321 IL3PATHWAY IL-3 promotes proliferation and differentiation of hematopoietic cells via a heterodimeric receptor that activates the Stat5 and MAP kinase pathways. CSF2RB, FOS, GRB2, HRAS, IL3, IL3RA, JAK2, MAP2K1, MAPK3, PTPN6, RAF1, SHC1, SOS1, STAT5A, STAT5B 15 CSF2RB(2), GRB2(1), IL3RA(1), JAK2(2), MAP2K1(1), MAPK3(1), RAF1(1), SHC1(1), SOS1(3), STAT5B(4) 12693759 17 17 17 2 1 7 3 1 5 0 0.24 0.46 322 HSA00660_C5_BRANCHED_DIBASIC_ACID_METABOLISM Genes involved in C5-branched dibasic acid metabolism ILVBL, SUCLA2 2 ILVBL(2), SUCLA2(1) 1601106 3 3 3 0 2 0 1 0 0 0 0.24 0.46 323 INOSITOL_METABOLISM ALDH6A1, ALDOA, ALDOB, ALDOC, TPI1 5 ALDOA(3), ALDOB(2) 2934009 5 5 5 0 1 3 0 1 0 0 0.24 0.46 324 GABAPATHWAY Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter whose receptor is regulated by Plic-1, gephyrin, and GABARAP, which promote receptor clustering. DNM1, GABARAP, GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GPHN, NSF, SRC, UBQLN1 12 DNM1(2), GABRA1(2), GABRA3(3), GABRA6(3), GPHN(1), UBQLN1(1) 8917116 12 12 12 4 2 7 1 1 1 0 0.24 0.46 325 PARKINPATHWAY In Parkinson's disease, dopaminergic neurons contain Lewy bodies consisting of alpha-synuclein and parkin, an E3 ubiquitin ligase that targets glycosylated alpha-synuclein. GPR37, PARK2, PNUTL1, SNCA, SNCAIP, UBE2E2, UBE2F, UBE2G1, UBE2G2, UBE2L3, UBE2L6, UBL1 10 GPR37(2), PARK2(3), SNCAIP(2) 4594434 7 7 7 2 2 2 2 1 0 0 0.25 0.47 326 HSA00521_STREPTOMYCIN_BIOSYNTHESIS Genes involved in streptomycin biosynthesis GCK, HK1, HK2, HK3, IMPA1, IMPA2, ISYNA1, PGM1, PGM3, TGDS 9 GCK(2), HK1(1), HK3(2), IMPA1(1), PGM1(1), PGM3(1), TGDS(2) 7846839 10 10 10 2 1 4 2 2 1 0 0.25 0.47 327 LYSINE_BIOSYNTHESIS AADAT, AASDH, AASDHPPT, AASS, KARS 5 AASDH(1), AASDHPPT(2), AASS(3) 5207904 6 6 6 3 0 2 2 0 2 0 0.25 0.47 328 ST_ERK1_ERK2_MAPK_PATHWAY The Erk1 and Erk2 MAP kinase pathways are regulated by Raf, Mos, and Tpl-2. ARAF1, ATF1, BAD, BRAF, COPEB, CREB1, CREB3, CREB5, DUSP4, DUSP6, DUSP9, EEF2K, EIF4E, GRB2, HTATIP, MAP2K1, MAP2K2, MAP3K8, MAPK1, MAPK3, MKNK1, MKNK2, MOS, NFKB1, RAP1A, RPS6KA1, RPS6KA2, RPS6KA3, SHC1, SOS1, SOS2, TRAF3 28 BAD(1), BRAF(2), CREB3(1), DUSP6(1), DUSP9(1), EEF2K(2), GRB2(1), MAP2K1(1), MAP3K8(2), MAPK1(1), MAPK3(1), MOS(2), NFKB1(1), RPS6KA1(1), RPS6KA2(2), RPS6KA3(2), SHC1(1), SOS1(3), SOS2(1) 21150519 27 27 27 4 6 9 8 1 3 0 0.25 0.47 329 GLYCOLYSIS_AND_GLUCONEOGENESIS Genes involved in glycolysis and gluconeogenesis ALDOA, ALDOB, ALDOC, DLAT, DLD, ENO1, ENO2, ENO3, FBP1, FBP2, G6PC, GAPDH, GAPDHS, GAPDS, GCK, GOT1, GOT2, GPI, HK1, HK2, HK3, LDHA, LDHAL6B, LDHB, LDHC, MDH1, MDH2, PC, PCK1, PDHA1, PDHA2, PDHB, PDHX, PFKL, PFKM, PFKP, PGAM1, PGAM2, PGK1, PGK2, PKLR, PKM2, TNFAIP1, TPI1 42 ALDOA(3), ALDOB(2), DLD(1), ENO1(1), ENO3(1), GCK(2), GOT2(1), GPI(2), HK1(1), HK3(2), LDHC(1), MDH2(2), PC(1), PCK1(1), PDHA1(1), PDHA2(1), PDHB(1), PDHX(1), PFKM(3), PFKP(2), PGK1(2) 29427801 32 31 32 7 6 15 4 4 3 0 0.26 0.48 330 IL22BPPATHWAY IL-22 is produced by T cells and induces the acute phase inflammatory response in hepatocytes. IL10RA, IL22, IL22RA1, IL22RA2, JAK1, JAK2, JAK3, SOCS3, STAT1, STAT3, STAT5A, STAT5B, TYK2 13 IL10RA(1), IL22(1), IL22RA1(1), IL22RA2(1), JAK1(1), JAK2(2), JAK3(1), STAT1(1), STAT3(1), STAT5B(4), TYK2(3) 13375674 17 16 16 3 2 4 4 2 5 0 0.26 0.48 331 HSA00534_HEPARAN_SULFATE_BIOSYNTHESIS Genes involved in heparan sulfate biosynthesis EXT1, EXT2, EXTL1, EXTL2, EXTL3, GLCE, HS2ST1, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, HS3ST5, HS6ST1, HS6ST2, HS6ST3, LOC728969, NDST1, NDST2, NDST3, NDST4 17 EXT1(3), EXT2(2), EXTL3(3), GLCE(2), HS2ST1(1), HS3ST2(1), HS3ST5(3), HS6ST2(3), HS6ST3(1), NDST3(1) 14650272 20 19 20 7 3 5 7 1 4 0 0.26 0.48 332 GLUCOCORTICOID_MINERALOCORTICOID_METABOLISM CPN2, CYP11A1, CYP11B2, CYP17A1, HSD11B1, HSD11B2, HSD3B1, HSD3B2 8 CPN2(1), CYP11A1(1), CYP11B2(3), CYP17A1(1), HSD3B2(2) 5218551 8 8 8 1 4 2 1 1 0 0 0.26 0.49 333 INFLAMPATHWAY Interleukins and TNF serve as signals to coordinate the inflammatory response, in which macrophages recruit and activate neutrophils, fibroblasts, and T cells. CD4, CSF1, CSF2, CSF3, HLA-DRA, HLA-DRB1, IFNA1, IFNB1, IFNG, IL10, IL11, IL12A, IL12B, IL13, IL15, IL1A, IL2, IL3, IL4, IL5, IL6, IL7, IL8, LTA, PDGFA, TGFB1, TGFB2, TGFB3, TNF 27 CD4(1), CSF1(2), HLA-DRB1(2), IFNB1(1), IL12A(1), IL12B(1), IL15(1), IL1A(1), IL2(1), IL6(2), TGFB3(1) 9781044 14 13 14 6 4 2 3 2 3 0 0.26 0.49 334 HSA00300_LYSINE_BIOSYNTHESIS Genes involved in lysine biosynthesis AADAT, AASDHPPT, AASS, KARS 4 AASDHPPT(2), AASS(3) 3507933 5 5 5 3 0 2 2 0 1 0 0.26 0.49 335 LYMPHOCYTEPATHWAY B and T cell lymphocytes interact with other cells via transmembrane adhesion proteins such as CD44, which interacts with endothelial cells. CD44, ICAM1, ITGA4, ITGAL, ITGB1, ITGB2, PECAM1, SELE, SELL 9 ITGA4(1), ITGAL(1), ITGB1(2), ITGB2(3), SELE(1), SELL(4) 9914385 12 12 12 2 2 1 4 3 2 0 0.27 0.49 336 RHOPATHWAY RhoA is a G protein whose active form stabilizes actin structures such as focal adhesions and activates Rock1, which phosphorylates myosin light chains. ACTR2, ACTR3, ARHA, ARHGAP1, ARHGAP4, ARHGAP5, ARHGAP6, ARHGEF1, ARHGEF11, ARHGEF5, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, BAIAP2, CFL1, DIAPH1, GSN, LIMK1, MYL2, MYLK, OPHN1, PFN1, PIP5K1A, PIP5K1B, PPP1R12B, ROCK1, SRC, TLN1, VCL 30 ARHGAP5(3), ARHGAP6(1), ARHGEF1(5), ARHGEF11(1), ARPC1A(1), ARPC1B(1), ARPC2(2), BAIAP2(1), GSN(1), LIMK1(3), MYLK(5), OPHN1(2), PIP5K1A(1), ROCK1(1), TLN1(7), VCL(3) 34057725 38 34 38 17 7 10 7 3 11 0 0.27 0.49 337 HSA00750_VITAMIN_B6_METABOLISM Genes involved in vitamin B6 metabolism AOX1, PDXK, PDXP, PNPO, PSAT1 5 AOX1(3), PNPO(2) 3425799 5 5 5 1 0 2 2 0 1 0 0.27 0.49 338 UREA_CYCLE_AND_METABOLISM_OF_AMINO_GROUPS ACY1, ALDH18A1, ARG1, ARG2, ASL, ASS, CKB, CKM, CKMT1, CKMT1B, CKMT1A, CKMT2, CPS1, GAMT, GATM, GLUD1, NAGS, OAT, ODC1, OTC, PYCR1, SMS 16 ACY1(2), ALDH18A1(1), ARG1(2), ARG2(1), ASL(3), CKMT2(1), CPS1(2), GATM(3) 11416119 15 15 15 3 2 7 4 1 1 0 0.27 0.50 339 STEMPATHWAY In the absence of infection, bone marrow stromal cells release hematopoietic cytokines; activated macrophages and Th cells induce hematopoiesis during infection. CD4, CD8A, CSF1, CSF2, CSF3, EPO, IL11, IL2, IL3, IL4, IL5, IL6, IL7, IL8, IL9 14 CD4(1), CD8A(1), CSF1(2), IL2(1), IL6(2) 4508751 7 7 7 2 1 2 2 0 2 0 0.27 0.50 340 HSA00512_O_GLYCAN_BIOSYNTHESIS Genes involved in O-glycan biosynthesis B3GNT6, B4GALT5, C1GALT1, C1GALT1C1, GALNT1, GALNT10, GALNT11, GALNT12, GALNT13, GALNT14, GALNT17, GALNT2, GALNT3, GALNT4, GALNT5, GALNT6, GALNT7, GALNT8, GALNT9, GALNTL1, GALNTL2, GALNTL4, GALNTL5, GCNT1, GCNT3, GCNT4, OGT, ST3GAL1, ST3GAL2, ST6GALNAC1, WBSCR17 29 C1GALT1(1), C1GALT1C1(1), GALNT10(2), GALNT11(3), GALNT13(1), GALNT3(1), GALNT4(1), GALNT5(2), GALNT7(2), GALNTL1(1), GALNTL5(1), GCNT4(1), OGT(2), ST3GAL1(1), ST6GALNAC1(2), WBSCR17(4) 23704785 26 24 26 11 9 5 4 2 6 0 0.28 0.50 341 HSA00650_BUTANOATE_METABOLISM Genes involved in butanoate metabolism AACS, AADAC, ABAT, ACADS, ACAT1, ACAT2, ACSM1, AKR1B10, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH5A1, ALDH7A1, ALDH9A1, BDH1, BDH2, DDHD1, ECHS1, EHHADH, GAD1, GAD2, HADH, HADHA, HMGCL, HMGCS1, HMGCS2, HSD17B10, HSD17B4, HSD3B7, ILVBL, L2HGDH, OXCT1, OXCT2, PDHA1, PDHA2, PDHB, PLA1A, PPME1, PRDX6, RDH11, RDH12, RDH13, RDH14 45 AADAC(1), ABAT(3), ACAT1(1), ACSM1(1), ALDH1B1(1), ALDH5A1(1), ALDH9A1(1), ECHS1(1), EHHADH(2), GAD1(2), GAD2(3), HADH(1), HMGCS1(1), HMGCS2(1), HSD17B10(1), HSD17B4(3), ILVBL(2), L2HGDH(1), OXCT1(1), OXCT2(1), PDHA1(1), PDHA2(1), PDHB(1), PLA1A(2), RDH11(2), RDH12(1), RDH14(1) 29395353 38 36 38 14 8 11 13 3 3 0 0.28 0.50 342 HSA00232_CAFFEINE_METABOLISM Genes involved in caffeine metabolism CYP1A2, CYP2A13, CYP2A6, CYP2A7, NAT1, NAT2, XDH 7 CYP2A13(4), CYP2A6(1), CYP2A7(1), XDH(3) 6075381 9 9 9 1 3 2 3 1 0 0 0.29 0.51 343 HSA00220_UREA_CYCLE_AND_METABOLISM_OF_AMINO_GROUPS Genes involved in urea cycle and metabolism of amino groups ABP1, ACY1, ADC, AGMAT, ALDH18A1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, AMD1, AOC2, AOC3, ARG1, ARG2, ASL, ASS1, CPS1, GATM, MAOA, MAOB, NAGS, ODC1, OTC, SAT1, SAT2, SMS, SRM 29 ACY1(2), ADC(1), AGMAT(1), ALDH18A1(1), ALDH1B1(1), ALDH9A1(1), AMD1(1), AOC2(1), AOC3(2), ARG1(2), ARG2(1), ASL(3), ASS1(1), CPS1(2), GATM(3), MAOA(2), SAT1(1), SAT2(1) 21234681 27 27 27 5 3 13 7 1 3 0 0.29 0.52 344 HSA00252_ALANINE_AND_ASPARTATE_METABOLISM Genes involved in alanine and aspartate metabolism AARS, AARS2, ABAT, ACY3, ADSL, ADSS, ADSSL1, AGXT, AGXT2, ASL, ASNS, ASPA, ASRGL1, ASS1, CAD, CRAT, DARS, DARS2, DDO, DLAT, DLD, GAD1, GAD2, GOT1, GOT2, GPT, GPT2, NARS, NARS2, PC, PDHA1, PDHA2, PDHB 32 AARS2(2), ABAT(3), ADSL(1), AGXT(1), AGXT2(1), ASL(3), ASPA(1), ASS1(1), CAD(7), CRAT(3), DARS(1), DARS2(1), DLD(1), GAD1(2), GAD2(3), GOT2(1), GPT2(2), NARS(1), NARS2(1), PC(1), PDHA1(1), PDHA2(1), PDHB(1) 26791908 40 35 40 6 7 17 9 4 3 0 0.29 0.52 345 UREACYCLEPATHWAY Ammonia released from amino acid deamination is used to produce carbamoyl phosphate, which is used to convert ornithine to citrulline, from which urea is eventually formed. ARG1, ASL, ASS, CPS1, GLS, GLUD1, GOT1 6 ARG1(2), ASL(3), CPS1(2), GLS(1) 5560776 8 8 8 0 1 3 2 1 1 0 0.29 0.52 346 NEUTROPHILPATHWAY Neutrophils are phagocytotic leukocytes that destroy foreign cells with reactive oxygen species or enzymatic digestion and express CD11 and CD18. CD44, ICAM1, ITGAL, ITGAM, ITGB2, PECAM1, SELE, SELL 8 ITGAL(1), ITGAM(1), ITGB2(3), SELE(1), SELL(4) 8792901 10 10 10 1 2 1 3 1 3 0 0.30 0.53 347 MSPPATHWAY Macrophage stimulating protein is synthesized as pro-MSP by the liver and, on proteolysis, binds to monocyte receptor kinase RON to induce macrophage development. CCL2, CSF1, IL1B, MST1, MST1R, TNF 6 CSF1(2), MST1(3) 4472247 5 5 5 0 1 1 1 1 1 0 0.30 0.54 348 PTC1PATHWAY The binding of extracellular signaling protein Sonic hedgehog to the Patched receptor (Ptc1) allows progression through G1 and may inhibit the G2/M transition. CCNB1, CCNH, CDC2, CDC25A, CDC25B, CDC25C, CDK7, MNAT1, PTCH, SHH, XPO1 9 CCNB1(2), CDC25B(3), CDK7(1), MNAT1(1), XPO1(2) 6424704 9 9 9 3 2 3 1 2 1 0 0.31 0.54 349 ACE_INHIBITOR_PATHWAY_PHARMGKB ACE, AGT, AGTR1, AGTR2, BDKRB2, KNG1, NOS3, REN 8 ACE(3), AGT(3), KNG1(1), NOS3(2) 6494670 9 9 9 2 3 2 2 0 2 0 0.31 0.54 350 HSA00290_VALINE_LEUCINE_AND_ISOLEUCINE_BIOSYNTHESIS Genes involved in valine, leucine and isoleucine biosynthesis BCAT1, BCAT2, IARS, IARS2, ILVBL, LARS, LARS2, PDHA1, PDHA2, PDHB, VARS, VARS2 12 BCAT1(3), BCAT2(2), IARS(5), IARS2(2), ILVBL(2), LARS2(2), PDHA1(1), PDHA2(1), PDHB(1) 13871013 19 18 19 6 5 8 4 0 2 0 0.31 0.54 351 IL2PATHWAY IL-2 promotes proliferation via JAK and MAP kinase and has surface receptors on activated B cells, LPS-treated monocytes, and many T cells. CSNK2A1, ELK1, FOS, GRB2, HRAS, IL2, IL2RA, IL2RB, IL2RG, JAK1, JAK3, JUN, LCK, MAP2K1, MAPK3, MAPK8, RAF1, SHC1, SOS1, STAT5A, STAT5B, SYK 22 CSNK2A1(1), ELK1(2), GRB2(1), IL2(1), IL2RG(1), JAK1(1), JAK3(1), JUN(1), MAP2K1(1), MAPK3(1), MAPK8(2), RAF1(1), SHC1(1), SOS1(3), STAT5B(4) 17205552 22 21 22 6 1 9 5 2 5 0 0.31 0.54 352 AMIPATHWAY Endogenous anti-thrombosis pathways are overwhelmed in plaque-narrowed blood vessels, resulting in potentially lethal myocardial infarction. ADCY1, CD3D, CD3E, CD3G, CD3Z, CD4, CREBBP, CSK, GNAS, GNB1, GNGT1, HLA-DRA, HLA-DRB1, LCK, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTPRC, TRA@, TRB@, ZAP70 21 ADCY1(3), CD3E(1), CD3G(1), CD4(1), CREBBP(2), GNAS(4), GNB1(1), HLA-DRB1(2), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), PTPRC(1), ZAP70(1) 15967458 20 20 20 8 6 4 5 3 2 0 0.31 0.54 353 CSKPATHWAY Csk inhibits T-cell activation by phosphorylating Lck; Csk is regulated by cAMP-dependent kinases and is opposed by the T-cell activator CD45. ADCY1, CD3D, CD3E, CD3G, CD3Z, CD4, CREBBP, CSK, GNAS, GNB1, GNGT1, HLA-DRA, HLA-DRB1, LCK, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTPRC, TRA@, TRB@, ZAP70 21 ADCY1(3), CD3E(1), CD3G(1), CD4(1), CREBBP(2), GNAS(4), GNB1(1), HLA-DRB1(2), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), PTPRC(1), ZAP70(1) 15967458 20 20 20 8 6 4 5 3 2 0 0.31 0.54 354 ST_MYOCYTE_AD_PATHWAY Cardiac myocytes have a variety of adrenergic receptors that induce subtype-specific signaling effects. ADRB1, AKT1, APC, ASAH1, BF, CAMP, CAV3, DAG1, DLG4, EPHB2, GAS, GNAI1, GNAQ, HTATIP, ITPR1, ITPR2, ITPR3, KCNJ3, KCNJ5, KCNJ9, MAPK1, PITX2, PLB, PTX1, PTX3, RAC1, RHO, RYR1 23 AKT1(12), APC(3), EPHB2(1), GNAI1(1), GNAQ(1), ITPR1(7), ITPR3(4), KCNJ3(1), MAPK1(1), PITX2(1), PTX3(1), RHO(2), RYR1(5) 34497294 40 38 30 13 7 19 6 1 7 0 0.31 0.54 355 S1PPATHWAY At low cholesterol concentrations, sterol-regulatory element binding proteins (SREBPs) act as transcription factors to promote cholesterol uptake and biosynthesis. EPLIN, HMGCS1, LDLR, MBTPS1, MBTPS2, SCAP, SREBF1, SREBF2 7 HMGCS1(1), LDLR(1), MBTPS1(1), MBTPS2(1), SCAP(3), SREBF2(3) 7526922 10 10 10 6 2 3 2 2 1 0 0.31 0.54 356 TCAPOPTOSISPATHWAY HIV infection upregulates Fas ligand in macrophages and CD4 in helper T cells, leading to widespread Fas-induced T cell apoptosis. CCR5, CD28, CD3D, CD3E, CD3G, CD3Z, CD4, TNFRSF6, TNFSF6, TRA@, TRB@ 5 CD3E(1), CD3G(1), CD4(1) 1925586 3 3 3 1 0 2 1 0 0 0 0.31 0.54 357 AKAPCENTROSOMEPATHWAY Protein Kinase A at the Centrosome AKAP9, ARHA, CDC2, MAP2, PCNT1, PCNT2, PPP1CA, PPP2CA, PRKACB, PRKACG, PRKAG1, PRKAR2A, PRKAR2B, PRKCE, PRKCL1 10 AKAP9(7), MAP2(7), PRKAR2A(1), PRKAR2B(1) 13720941 16 16 16 6 2 5 0 7 2 0 0.32 0.55 358 HSA04742_TASTE_TRANSDUCTION Genes involved in taste transduction ACCN1, ADCY4, ADCY6, ADCY8, CACNA1A, CACNA1B, GNAS, GNAT3, GNB1, GNB3, GNG13, GNG3, GRM4, ITPR3, KCNB1, PDE1A, PLCB2, PRKACA, PRKACB, PRKACG, PRKX, PRKY, SCNN1A, SCNN1B, SCNN1G, TAS1R1, TAS1R2, TAS1R3, TAS2R1, TAS2R10, TAS2R13, TAS2R14, TAS2R16, TAS2R3, TAS2R38, TAS2R39, TAS2R4, TAS2R40, TAS2R41, TAS2R42, TAS2R43, TAS2R44, TAS2R45, TAS2R46, TAS2R48, TAS2R49, TAS2R5, TAS2R50, TAS2R60, TAS2R7, TAS2R8, TAS2R9, TRPM5 46 ADCY4(1), ADCY8(2), CACNA1A(5), CACNA1B(1), GNAS(4), GNB1(1), GNB3(2), GRM4(1), ITPR3(4), PDE1A(2), PLCB2(2), PRKACA(1), TAS1R1(1), TAS1R2(1), TAS2R1(1), TAS2R10(1), TAS2R13(1), TAS2R14(1), TAS2R16(2), TAS2R3(1), TAS2R43(3), TAS2R46(1), TAS2R8(1), TAS2R9(2) 40245660 42 39 42 24 7 13 9 4 9 0 0.32 0.55 359 CDC25PATHWAY The protein phosphatase Cdc25 is phosphorylated by Chk1 and activates Cdc2 to stimulate eukaryotic cells into M phase. ATM, CDC2, CDC25A, CDC25B, CDC25C, CHEK1, MYT1, WEE1, YWHAH 8 ATM(9), CDC25B(3) 10220106 12 11 12 3 0 5 0 3 4 0 0.32 0.55 360 ALKPATHWAY Activin receptor-like kinase 3 (ALK3) is required during gestation for cardiac muscle development. ACVR1, APC, ATF2, AXIN1, BMP10, BMP2, BMP4, BMP5, BMP7, BMPR1A, BMPR2, CHRD, CTNNB1, DVL1, FZD1, GATA4, GSK3B, MADH1, MADH4, MADH5, MADH6, MAP3K7, MEF2C, MYL2, NKX2-5, NOG, NPPA, NPPB, RFC1, TCF1, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3, WNT1 30 ACVR1(1), APC(3), AXIN1(1), BMP10(1), BMP2(2), BMP4(2), BMP5(1), BMPR2(2), CHRD(2), FZD1(1), MEF2C(2), NPPA(1), RFC1(2), TGFB3(1), TGFBR1(2), TGFBR3(2) 25249107 26 25 25 16 2 13 4 3 4 0 0.32 0.55 361 HSA00450_SELENOAMINO_ACID_METABOLISM Genes involved in selenoamino acid metabolism AHCY, CARM1, CBS, CTH, GGT1, GGTL3, GGTL4, HEMK1, KIAA0828, LCMT1, LCMT2, MARS, MARS2, MAT1A, MAT2B, METTL2B, METTL6, PAPSS1, PAPSS2, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, SCLY, SEPHS1, SEPHS2, WBSCR22 26 AHCY(1), CARM1(1), CBS(1), CTH(1), GGT1(1), LCMT1(1), LCMT2(3), MAT2B(1), METTL2B(2), PAPSS1(2), PRMT3(2), PRMT5(2), PRMT6(2), PRMT7(1), PRMT8(1), SEPHS1(1) 17718636 23 20 23 7 2 10 7 0 4 0 0.33 0.57 362 GLYOXYLATE_AND_DICARBOXYLATE_METABOLISM ACO1, ACO2, CS, GRHPR, HAO1, HAO2, HYI, MDH1, MDH2, MTHFD1, MTHFD1L, MTHFD2 12 ACO1(1), ACO2(2), CS(1), HAO1(3), HAO2(1), MDH2(2), MTHFD1(4), MTHFD1L(1) 9514869 15 13 15 2 4 6 3 1 1 0 0.33 0.57 363 BENZOATE_DEGRADATION_VIA_COA_LIGATION ACAT1, ACAT2, ACYP1, ACYP2, ECHS1, EHHADH, GCDH, HADHA, SDHB, SDS 10 ACAT1(1), ACYP1(1), ECHS1(1), EHHADH(2), GCDH(1), SDHB(1) 5613504 7 7 7 5 0 2 3 2 0 0 0.34 0.57 364 HSA00920_SULFUR_METABOLISM Genes involved in sulfur metabolism BPNT1, CHST11, CHST12, CHST13, PAPSS1, PAPSS2, SULT1A1, SULT1A2, SULT1A3, SULT1A4, SULT1E1, SULT2A1, SULT2B1, SUOX 11 CHST11(1), PAPSS1(2), SULT1A1(1), SULT1E1(2), SUOX(3) 6736002 9 9 9 5 2 4 2 0 1 0 0.34 0.58 365 STEROID_BIOSYNTHESIS CYP17A1, F13B, HSD17B1, HSD17B2, HSD17B3, HSD17B4, HSD17B7, HSD3B1, HSD3B2 9 CYP17A1(1), HSD17B1(1), HSD17B2(1), HSD17B4(3), HSD3B2(2) 6020625 8 8 8 1 4 1 1 1 1 0 0.34 0.58 366 EPHA4PATHWAY Eph Kinases and ephrins support platelet aggregation ACTA1, EPHA4, EPHB1, FYN, ITGA1, ITGB1, L1CAM, LYN, RAP1B, SELP 10 EPHA4(1), EPHB1(2), ITGA1(3), ITGB1(2), L1CAM(1), LYN(3), SELP(3) 12027054 15 15 15 4 4 6 4 1 0 0 0.34 0.58 367 HSA00363_BISPHENOL_A_DEGRADATION Genes involved in bisphenol A degradation AKR1B10, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, HSD3B7, PON1, PON2, PON3, RDH11, RDH12, RDH13, RDH14 14 DHRS2(2), DHRS7(1), PON1(1), PON3(1), RDH11(2), RDH12(1), RDH14(1) 6518499 9 8 9 3 2 1 2 1 3 0 0.35 0.59 368 HSA00280_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION Genes involved in valine, leucine and isoleucine degradation ABAT, ACAA1, ACAA2, ACADM, ACADS, ACAT1, ACAT2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH6A1, ALDH7A1, ALDH9A1, AOX1, AUH, BCAT1, BCAT2, BCKDHA, BCKDHB, DBT, DLD, ECHS1, EHHADH, HADH, HADHA, HADHB, HIBADH, HIBCH, HMGCL, HMGCS1, HMGCS2, HSD17B10, HSD17B4, IVD, MCCC1, MCCC2, MCEE, MUT, OXCT1, OXCT2, PCCA, PCCB 44 ABAT(3), ACAA1(1), ACAA2(1), ACAT1(1), ALDH1B1(1), ALDH9A1(1), AOX1(3), BCAT1(3), BCAT2(2), BCKDHA(1), DLD(1), ECHS1(1), EHHADH(2), HADH(1), HADHB(1), HIBCH(2), HMGCS1(1), HMGCS2(1), HSD17B10(1), HSD17B4(3), MCCC1(2), OXCT1(1), OXCT2(1), PCCA(1) 31026879 36 36 36 11 5 14 12 2 3 0 0.35 0.59 369 HSA00632_BENZOATE_DEGRADATION_VIA_COA_LIGATION Genes involved in benzoate degradation via CoA ligation ACAT1, ACAT2, ACOT11, ACYP1, ACYP2, ARD1A, CARKL, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ECHS1, EHHADH, ESCO1, ESCO2, FN3K, GCDH, HADHA, ITGB1BP3, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1, YOD1 24 ACAT1(1), ACOT11(2), ACYP1(1), DHRS2(2), DHRS7(1), ECHS1(1), EHHADH(2), ESCO1(3), GCDH(1), ITGB1BP3(1), MYST3(1), MYST4(5), PNPLA3(4) 19064214 25 22 25 8 6 4 6 4 2 3 0.35 0.59 370 HSA00740_RIBOFLAVIN_METABOLISM Genes involved in riboflavin metabolism ACP1, ACP2, ACP5, ACP6, ACPP, ACPT, ENPP1, ENPP3, FLAD1, LHPP, MTMR1, MTMR2, MTMR6, PHPT1, RFK, TYR 16 ACP5(1), ACP6(1), ACPP(1), ACPT(2), ENPP1(3), ENPP3(2), MTMR6(1), TYR(3) 11073894 14 14 14 4 3 4 4 2 1 0 0.35 0.59 371 ST_STAT3_PATHWAY The transcription factor STAT3 is involved in cell growth regulation and is commonly upregulated in tumors. CISH, IL6, IL6R, JAK1, JAK2, JAK3, PIAS3, PTPRU, REG1A, SRC, STAT3 11 IL6(2), IL6R(1), JAK1(1), JAK2(2), JAK3(1), PTPRU(5), STAT3(1) 11162112 13 13 13 6 1 4 0 2 6 0 0.36 0.60 372 CCR3PATHWAY CCR3 is a G-protein coupled receptor that recruits eosinophils to inflammation sites via chemokine ligands. ARHA, CCL11, CCR3, CFL1, GNAQ, GNAS, GNB1, GNGT1, HRAS, LIMK1, MAP2K1, MAPK1, MAPK3, MYL2, NOX1, PIK3C2G, PLCB1, PPP1R12B, PRKCA, PRKCB1, PTK2, RAF1, ROCK2 21 CCL11(1), CCR3(1), GNAQ(1), GNAS(4), GNB1(1), LIMK1(3), MAP2K1(1), MAPK1(1), MAPK3(1), NOX1(1), PIK3C2G(1), PLCB1(3), PTK2(1), RAF1(1), ROCK2(2) 18579015 23 22 23 4 3 11 7 0 2 0 0.37 0.60 373 TCYTOTOXICPATHWAY Cytotoxic T cells release perforin and granzyme to lyse foreign cell targets and express Fas ligand to promote Fas-induced apoptosis. CD2, CD28, CD3D, CD3E, CD3G, CD3Z, CD8A, ICAM1, ITGAL, ITGB2, PTPRC, THY1, TRA@, TRB@ 11 CD2(2), CD3E(1), CD3G(1), CD8A(1), ITGAL(1), ITGB2(3), PTPRC(1) 7738848 10 10 10 1 2 3 3 0 2 0 0.37 0.61 374 RABPATHWAY Rab family GTPases regulate vesicle transport, endocytosis and exocytosis, and vesicle docking via interactions with the rabphilins. ACTA1, MEL, RAB11A, RAB1A, RAB2, RAB27A, RAB3A, RAB4A, RAB5A, RAB6A, RAB7, RAB9A 9 RAB11A(1), RAB1A(1), RAB6A(1) 3261024 3 3 3 0 0 0 1 0 2 0 0.37 0.61 375 HSA00480_GLUTATHIONE_METABOLISM Genes involved in glutathione metabolism ANPEP, G6PD, GCLC, GCLM, GGT1, GGTL3, GGTL4, GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, GSR, GSS, GSTA1, GSTA2, GSTA3, GSTA4, GSTA5, GSTK1, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, IDH1, IDH2, MGST1, MGST2, MGST3, OPLAH, TXNDC12 34 ANPEP(3), G6PD(1), GCLC(1), GCLM(1), GGT1(1), GPX5(1), GSS(1), GSTA1(1), GSTA4(1), GSTK1(1), GSTO2(1), GSTZ1(1), IDH1(1), TXNDC12(1) 14852058 16 16 16 2 4 4 6 0 2 0 0.38 0.62 376 PGC1APATHWAY PCG-1a is expressed in skeletal muscle, heart muscle, and brown fat, and is a coactivator for receptors such as glucocorticoid receptor and thyroid hormone receptor. CALM1, CALM2, CALM3, CAMK1, CAMK1G, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, ESRRA, HDAC5, MEF2A, MEF2B, MEF2C, MEF2D, PPARA, PPARGC1, PPP3CA, PPP3CB, PPP3CC, SLC2A4, SYT1, YWHAH 23 CAMK1(1), CAMK1G(1), CAMK2A(1), CAMK2D(3), MEF2A(1), MEF2C(2), PPARA(1), PPP3CA(3), PPP3CB(2), SLC2A4(1) 14370408 16 16 16 7 2 3 7 0 4 0 0.38 0.62 377 SODDPATHWAY Some members of the tumor necrosis factor receptor family have cytoplasmic death domains that promote apoptosis when active and are repressed by silencers called SODDs. BAG4, BIRC3, CASP8, FADD, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TRADD, TRAF2 9 BAG4(1), CASP8(2), RIPK1(3), TNFRSF1A(1) 5788419 7 7 7 2 0 3 1 0 3 0 0.38 0.62 378 HSA03010_RIBOSOME Genes involved in ribosome C15orf15, FAU, hCG_1644323, hCG_1984468, hCG_2041321, hCG_21078, hCG_26523, LOC283412, LOC284064, LOC284230, LOC284288, LOC284393, LOC285053, LOC342994, LOC347292, LOC388720, LOC389342, LOC390876, LOC391656, LOC400652, LOC402057, LOC439992, LOC440055, LOC440589, LOC440733, LOC440737, LOC441377, LOC441876, LOC441907, MRPL13, MRPS7, RPL10A, RPL10L, RPL11, RPL12, RPL13, RPL13A, RPL14, RPL18, RPL18A, RPL19, RPL21, RPL22L1, RPL23A, RPL23AP2, RPL24, RPL26, RPL27, RPL27A, RPL28, RPL29, RPL3, RPL30, RPL31, RPL32, RPL34, RPL35, RPL35A, RPL36A, RPL36AL, RPL37, RPL37A, RPL38, RPL39, RPL3L, RPL41, RPL6, RPL7, RPL8, RPL9, RPS10, RPS11, RPS12, RPS13, RPS15A, RPS16, RPS18, RPS2, RPS20, RPS21, RPS23, RPS24, RPS25, RPS26, RPS26P10, RPS27, RPS28, RPS29, RPS3, RPS3A, RPS4Y1, RPS5, RPS6, RPS7, RPS8, RPS9, RPSA, tcag7.23 65 MRPL13(1), MRPS7(2), RPL13A(2), RPL18(1), RPL18A(1), RPL19(1), RPL26(1), RPL29(1), RPL35(2), RPL3L(1), RPL41(1), RPS10(1), RPS2(1), RPS21(1), RPS27(1), RPS5(2), RPS6(1) 15928419 21 20 21 6 5 5 6 4 1 0 0.38 0.62 379 FXRPATHWAY The nuclear receptor transcription factors FXR and LXR are activated by cholesterol metabolites and regulate cholesterol homeostasis. FABP6, LDLR, NR0B2, NR1H3, NR1H4, RXRA 6 FABP6(1), LDLR(1), NR0B2(2), NR1H4(1) 3914547 5 5 5 4 0 2 3 0 0 0 0.38 0.62 380 ASBCELLPATHWAY B cells require interaction with helper T cells to produce antigen-specific immunoglobulins as a key element of the human immune response. CD28, CD4, CD80, HLA-DRA, HLA-DRB1, IL10, IL2, IL4, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 8 CD4(1), HLA-DRB1(2), IL2(1) 3054168 4 4 4 3 0 1 2 1 0 0 0.38 0.62 381 UBIQUITIN_MEDIATED_PROTEOLYSIS CDC34, HIP2, NRF1, UBE1, UBE2A, UBE2B, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2E1, UBE2E3, UBE2G1, UBE2G2, UBE2G2, TAX1BP3, UBE2H, UBE2I, UBE2J1, UBE2J2, UBE2L3, UBE2L6, UBE2M, UBE2N, UBE2S, UBE3A 22 NRF1(1), UBE2A(1), UBE2D2(2), UBE2J1(3), UBE2J2(1), UBE3A(1) 7147179 9 9 9 1 0 3 3 0 3 0 0.38 0.62 382 D4GDIPATHWAY D4-GDI inhibits the pro-apoptotic Rho GTPases and is cleaved by caspase-3. ADPRT, APAF1, ARHGAP5, ARHGDIB, CASP1, CASP10, CASP3, CASP8, CASP9, CYCS, GZMB, JUN, PRF1 12 APAF1(1), ARHGAP5(3), ARHGDIB(1), CASP1(1), CASP8(2), JUN(1), PRF1(2) 9689784 11 11 11 2 0 5 2 0 4 0 0.39 0.64 383 HSA00630_GLYOXYLATE_AND_DICARBOXYLATE_METABOLISM Genes involved in glyoxylate and dicarboxylate metabolism ACO1, ACO2, AFMID, CS, GRHPR, HAO1, HAO2, HYI, LOC441996, MDH1, MDH2, MTHFD1, MTHFD1L, MTHFD2 13 ACO1(1), ACO2(2), CS(1), HAO1(3), HAO2(1), MDH2(2), MTHFD1(4), MTHFD1L(1) 9980295 15 13 15 2 4 6 3 1 1 0 0.40 0.64 384 BUTANOATE_METABOLISM AACS, ABAT, ACADS, ACAT1, ACAT2, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH5A1, ALDH9A1, BDH, BUCS1, ECHS1, EHHADH, GAD1, GAD2, HADHA, HMGCL, L2HGDH, OXCT1, PDHA1, PDHA2, PDHB, SDHB, SDS 27 ABAT(3), ACAT1(1), ALDH1A1(2), ALDH1A2(1), ALDH1B1(1), ALDH5A1(1), ALDH9A1(1), ECHS1(1), EHHADH(2), GAD1(2), GAD2(3), L2HGDH(1), OXCT1(1), PDHA1(1), PDHA2(1), PDHB(1), SDHB(1) 18572424 24 23 24 10 2 11 9 2 0 0 0.40 0.64 385 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_NEOLACTOSERIES ABO, B3GNT1, FUT1, FUT2, FUT9, GCNT2, ST8SIA1 7 B3GNT1(1), FUT2(2), ST8SIA1(1) 4510272 4 4 3 1 2 0 0 0 2 0 0.40 0.64 386 HSA02010_ABC_TRANSPORTERS_GENERAL Genes involved in ABC transporters - general ABCA1, ABCA10, ABCA12, ABCA13, ABCA2, ABCA3, ABCA4, ABCA5, ABCA6, ABCA7, ABCA8, ABCA9, ABCB1, ABCB10, ABCB11, ABCB4, ABCB5, ABCB6, ABCB7, ABCB8, ABCB9, ABCC1, ABCC10, ABCC11, ABCC12, ABCC2, ABCC3, ABCC4, ABCC5, ABCC6, ABCC8, ABCC9, ABCD1, ABCD2, ABCD3, ABCD4, ABCG1, ABCG2, ABCG4, ABCG5, ABCG8, CFTR, TAP1, TAP2 42 ABCA1(5), ABCA10(2), ABCA12(4), ABCA13(13), ABCA3(2), ABCA4(5), ABCA5(3), ABCA6(1), ABCA8(4), ABCA9(3), ABCB1(3), ABCB10(1), ABCB11(4), ABCB6(1), ABCB7(1), ABCB8(2), ABCC1(3), ABCC10(2), ABCC11(1), ABCC12(3), ABCC2(3), ABCC4(3), ABCC5(1), ABCC6(2), ABCC8(7), ABCC9(3), ABCD1(2), ABCD2(1), ABCD3(2), ABCG5(1), CFTR(6), TAP1(1) 83159154 95 83 95 28 25 29 23 6 12 0 0.40 0.64 387 HSA00785_LIPOIC_ACID_METABOLISM Genes involved in lipoic acid metabolism LIAS, LIPT1, LOC387787 2 LIAS(1) 1124019 1 1 1 0 0 0 0 0 1 0 0.40 0.64 388 HBXPATHWAY Hbx is a hepatitis B protein that activates a number of transcription factors, possibly by inducing calcium release from the mitochondrion to the cytoplasm. CREB1, GRB2, HBXIP, HRAS, PTK2B, SHC1, SOS1, SRC 8 GRB2(1), PTK2B(3), SHC1(1), SOS1(3) 6313671 8 8 8 1 2 2 3 0 1 0 0.41 0.65 389 HSA03060_PROTEIN_EXPORT Genes involved in protein export OXA1L, SEC61A2, SRP19, SRP54, SRP68, SRP72, SRP9, SRPR 8 SRP68(1), SRP72(1), SRPR(7) 5603871 9 7 9 3 1 2 2 2 2 0 0.41 0.65 390 STAT3PATHWAY The STAT transcription factors are phosphorylated and activated by JAK kinases in response to cytokine signaling. FRAP1, JAK1, JAK2, JAK3, MAPK1, MAPK3, STAT3, TYK2 7 JAK1(1), JAK2(2), JAK3(1), MAPK1(1), MAPK3(1), STAT3(1), TYK2(3) 8584017 10 9 9 2 0 3 3 1 3 0 0.41 0.65 391 FATTY_ACID_BIOSYNTHESIS_PATH_2 ACAA1, ACAA2, ACAT1, ACAT2, ECHS1, EHHADH, HADHA, HADHB, SDS 9 ACAA1(1), ACAA2(1), ACAT1(1), ECHS1(1), EHHADH(2), HADHB(1) 6045975 7 7 7 5 1 2 2 1 1 0 0.42 0.66 392 METHIONINEPATHWAY Catabolic Pathways for Methionine, Isoleucine, Threonine and Valine BCKDHB, BCKDK, CBS, CTH, MUT 5 BCKDK(2), CBS(1), CTH(1) 3350763 4 4 4 0 0 2 0 0 2 0 0.42 0.66 393 MRNA_PROCESSING_REACTOME BRUNOL4, C10orf9, C20orf14, CD2BP2, CDC40, CLK2, CLK3, CLK4, COL2A1, CPSF1, CPSF2, CPSF3, CPSF4, CSTF1, CSTF2, CSTF2T, CSTF3, CUGBP1, CUGBP2, DDIT3, DDX1, DDX20, DHX15, DHX16, DHX38, DHX8, DHX9, DICER1, DNAJC8, FLJ10748, FNBP3, FUS, FUSIP1, GIPC1, HEAB, HNRPA2B1, HNRPA3, HNRPA3P1, HNRPA3, LOC387933, HNRPA3P1, HNRPA3, LOC389395, HNRPAB, HNRPC, HNRPC, HNRPCL1, LOC390615, LOC440563, HNRPD, HNRPH1, HNRPH2, HNRPL, HNRPR, HNRPU, HRMT1L2, LSM2, LSM7, METTL3, NCBP1, NCBP2, NONO, NUDT21, NXF1, PABPN1, PAPOLA, PHF5A, POLR2A, PPM1G, PRPF18, PRPF3, PRPF4, PRPF4B, PRPF8, PSKH1, PTBP1, PTBP2, RBM17, RBM5, RNGTT, RNMT, RNPC2, RNPS1, SF3A1, SF3A2, SF3A3, SF3B1, SF3B2, SF3B4, SF3B5, SF4, SFRS10, SFRS12, SFRS14, SFRS16, SFRS2, SFRS4, SFRS5, SFRS6, SFRS7, SFRS8, SFRS9, SMC1L1, SNRP70, SNRPA, SNRPA1, SNRPB, SNRPB2, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, SNRPN, SNRPN, PAR1, SNRPN, SNURF, SPOP, SRPK1, SRPK2, SRRM1, SUPT5H, TMP21, TXNL4A, U2AF1, U2AF2, WDR57, XRN2 89 CD2BP2(1), CLK4(1), COL2A1(3), CPSF1(2), CPSF3(1), CPSF4(2), CSTF2T(1), CSTF3(3), DDX20(2), DHX15(1), DHX16(1), DHX38(2), DHX8(1), DICER1(1), FUS(1), GIPC1(1), NCBP1(1), NUDT21(1), NXF1(2), PABPN1(1), PAPOLA(1), POLR2A(2), PRPF4(2), PRPF4B(3), PRPF8(5), PSKH1(2), PTBP1(2), RBM17(1), RBM5(1), SF3B1(10), SF3B2(1), SF3B4(1), SF4(4), SFRS16(3), SFRS2(1), SFRS4(2), SFRS5(1), SFRS9(1), SNRPB(1), SPOP(1), SRPK1(1), SRRM1(1), SUPT5H(4), TXNL4A(1), XRN2(3) 77043213 84 73 80 17 15 24 26 4 13 2 0.42 0.66 394 PELP1PATHWAY Pelp1 acts downstream of activated estrogen receptor to promote cell proliferation and is overexpressed in many breast tumors. CREBBP, EP300, ESR1, MAPK1, MAPK3, PELP1, SRC 7 CREBBP(2), EP300(3), ESR1(2), MAPK1(1), MAPK3(1) 10444200 9 9 8 2 2 2 0 1 4 0 0.43 0.66 395 BIOSYNTHESIS_OF_STEROIDS DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, IDI1, LSS, MVD, MVK, NQO1, NQO2, PMVK, SC5DL, SQLE, VKORC1 14 FDFT1(1), FDPS(1), IDI1(2), NQO1(1), PMVK(1), SQLE(1), VKORC1(1) 7224750 8 8 8 7 2 4 1 0 1 0 0.43 0.66 396 NUCLEOTIDE_SUGARS_METABOLISM GALE, GALT, TGDS, UGDH, UXS1 5 GALT(1), TGDS(2), UXS1(2) 3016650 5 4 5 0 2 1 0 2 0 0 0.43 0.67 397 ONE_CARBON_POOL_BY_FOLATE ALDH1L1, AMT, ATIC, ATP6V0C, SHMT1, DHFR, GART, MTHFD1, MTHFD1L, MTHFD2, MTHFR, MTHFS, MTR, SHMT1, SHMT2, TYMS 15 ALDH1L1(1), AMT(1), ATIC(3), MTHFD1(4), MTHFD1L(1), MTHFS(1), MTR(5) 13366041 16 15 16 7 3 4 2 2 5 0 0.43 0.67 398 TSP1PATHWAY Thrombospondin-1 (TSP-1) inhibits angiogenesis by inducing caspase-dependent apoptosis in microvascular endothelial cells. CASP3, CD36, FOS, FYN, JUN, MAPK14, THBS1 7 CD36(1), JUN(1), MAPK14(1), THBS1(3) 5522244 6 5 6 3 0 3 0 1 2 0 0.44 0.67 399 GLUTAMATE_METABOLISM ABAT, ALDH4A1, ALDH5A1, CAD, CPS1, EPRS, GAD1, GAD2, GCLC, GCLM, GFPT1, GLS, GLS2, GLUD1, GLUL, GMPS, GOT1, GOT2, GPT, GPT2, GSS, NADSYN1, PPAT, QARS 23 ABAT(3), ALDH5A1(1), CAD(7), CPS1(2), EPRS(2), GAD1(2), GAD2(3), GCLC(1), GCLM(1), GLS(1), GMPS(1), GOT2(1), GPT2(2), GSS(1), PPAT(1), QARS(2) 23776272 31 28 31 3 4 11 11 2 3 0 0.44 0.67 400 CARBON_FIXATION ALDOA, ALDOB, ALDOC, FBP1, FBP2, GOT1, GOT2, GPT, GPT2, MDH1, MDH2, ME1, ME2, ME3, PGK1, PKLR, PKM2, RPE, RPE, LOC440001, RPIA, TKT, TPI1 20 ALDOA(3), ALDOB(2), GOT2(1), GPT2(2), MDH2(2), ME2(1), ME3(1), PGK1(2), TKT(1) 12363702 15 15 15 2 4 9 1 1 0 0 0.44 0.67 401 NKTPATHWAY T cell differentiation into Th1 and Th2 cells occurs by differential chemokine receptor expression, which mediates tissue localization and immune response. CCL3, CCL4, CCR1, CCR2, CCR3, CCR4, CCR5, CCR7, CD28, CD4, CSF2, CXCR3, CXCR4, IFNG, IFNGR1, IFNGR2, IL12A, IL12B, IL12RB1, IL12RB2, IL18R1, IL2, IL4, IL4R, IL5, TGFB1, TGFB2, TGFB3, TNFSF5 27 CCR2(4), CCR3(1), CCR7(2), CD4(1), IL12A(1), IL12B(1), IL12RB1(2), IL18R1(1), IL2(1), TGFB3(1) 14461668 15 15 15 7 1 6 2 1 5 0 0.44 0.67 402 THELPERPATHWAY Helper T cells coordinate the actions of B cells, macrophages, and other immune cells via surface molecules such as T cell receptor/CD3 and their characteristic marker CD4. CD2, CD28, CD3D, CD3E, CD3G, CD3Z, CD4, ICAM1, ITGAL, ITGB2, PTPRC, THY1, TRA@, TRB@ 11 CD2(2), CD3E(1), CD3G(1), CD4(1), ITGAL(1), ITGB2(3), PTPRC(1) 8179431 10 10 10 2 2 3 3 0 2 0 0.44 0.67 403 MEF2DPATHWAY Mef2 transcription factors promote calcium-induced apoptosis in T cells and are regulated by MAP kinases and histone deacetylases. CABIN1, CALM1, CALM2, CALM3, CAPN2, CAPNS1, CAPNS2, EP300, HDAC1, HDAC2, MEF2D, NFATC1, NFATC2, PPP3CA, PPP3CB, PPP3CC, PRKCA, PRKCB1, SYT1, TRA@, TRB@ 18 CABIN1(5), CAPN2(2), EP300(3), HDAC1(2), HDAC2(2), PPP3CA(3), PPP3CB(2) 17211129 19 17 18 7 4 5 4 0 6 0 0.45 0.68 404 HSA00980_METABOLISM_OF_XENOBIOTICS_BY_CYTOCHROME_P450 Genes involved in metabolism of xenobiotics by cytochrome P450 ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, AKR1C1, AKR1C2, AKR1C3, AKR1C4, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, CYP1A1, CYP1A2, CYP1B1, CYP2B6, CYP2C18, CYP2C19, CYP2C8, CYP2C9, CYP2E1, CYP2F1, CYP2S1, CYP3A4, CYP3A43, CYP3A5, CYP3A7, DHDH, EPHX1, GSTA1, GSTA2, GSTA3, GSTA4, GSTA5, GSTK1, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, MGST1, MGST2, MGST3, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7 69 ADH1A(1), ADH7(2), ADHFE1(1), AKR1C1(1), AKR1C2(2), AKR1C3(1), AKR1C4(1), ALDH3B1(2), ALDH3B2(2), CYP1B1(1), CYP2B6(2), CYP2C18(2), CYP2C19(1), CYP2C8(1), CYP2C9(2), CYP2F1(1), CYP2S1(3), CYP3A4(3), CYP3A7(4), EPHX1(1), GSTA1(1), GSTA4(1), GSTK1(1), GSTO2(1), GSTZ1(1), UGT1A10(1), UGT1A6(2), UGT2A1(1), UGT2B10(2), UGT2B15(2), UGT2B28(1), UGT2B4(1) 41307825 49 46 49 19 10 14 13 4 8 0 0.45 0.68 405 HSA04614_RENIN_ANGIOTENSIN_SYSTEM Genes involved in renin-angiotensin system ACE, ACE2, AGT, AGTR1, AGTR2, ANPEP, CMA1, CPA3, CTSA, CTSG, ENPEP, LNPEP, MAS1, MME, NLN, REN, THOP1 16 ACE(3), ACE2(1), AGT(3), ANPEP(3), CTSA(1), CTSG(1), ENPEP(1), MAS1(2) 14904786 15 15 15 6 4 4 2 1 4 0 0.45 0.68 406 HSA00625_TETRACHLOROETHENE_DEGRADATION Genes involved in tetrachloroethene degradation AKR1B10, EPHX2, HSD3B7, RDH11, RDH12, RDH13, RDH14 7 RDH11(2), RDH12(1), RDH14(1) 3500328 4 4 4 2 0 1 2 0 1 0 0.45 0.68 407 HSA00642_ETHYLBENZENE_DEGRADATION Genes involved in ethylbenzene degradation ARD1A, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ESCO1, ESCO2, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1 12 DHRS2(2), DHRS7(1), ESCO1(3), MYST3(1), MYST4(5), PNPLA3(4) 12283089 16 14 16 3 5 2 2 2 2 3 0.45 0.68 408 METHIONINE_METABOLISM AHCY, BHMT, CBS, CTH, DNMT1, DNMT2, DNMT3A, DNMT3B, MARS, MARS2, MAT1A, MAT2B, MTR 12 AHCY(1), BHMT(1), CBS(1), CTH(1), DNMT3A(3), DNMT3B(1), MAT2B(1), MTR(5) 12459018 14 13 14 4 1 5 3 3 2 0 0.46 0.69 409 NDKDYNAMINPATHWAY Endocytotic role of NDK, Phosphins and Dynamin AMPH, AP2A1, AP2M1, BIN1, CALM1, CALM2, CALM3, DNM1, EPN1, EPS15, NME1, NME2, PICALM, PPP3CA, PPP3CB, PPP3CC, SYNJ1, SYNJ2, SYT1 19 AMPH(2), AP2A1(3), AP2M1(2), BIN1(1), DNM1(2), EPS15(1), PPP3CA(3), PPP3CB(2), SYNJ2(1) 15971007 17 17 17 6 0 7 4 1 5 0 0.46 0.69 410 EPONFKBPATHWAY The cytokine erythropoietin (Epo) prevents stress-induced neuronal apoptosis by stimulating anti-apoptotic pathways through JAK2 kinase and NF-kB. ARNT, CDKN1A, EPO, EPOR, GRIN1, HIF1A, JAK2, NFKB1, NFKBIA, RELA, SOD2 11 ARNT(2), EPOR(1), GRIN1(1), JAK2(2), NFKB1(1), RELA(1) 9009390 8 8 8 3 0 2 0 2 4 0 0.47 0.70 411 HSA00670_ONE_CARBON_POOL_BY_FOLATE Genes involved in one carbon pool by folate ALDH1L1, AMT, ATIC, DHFR, FTCD, GART, MTFMT, MTHFD1, MTHFD1L, MTHFD2, MTHFR, MTHFS, MTR, SHMT1, SHMT2, TYMS 15 ALDH1L1(1), AMT(1), ATIC(3), MTHFD1(4), MTHFD1L(1), MTHFS(1), MTR(5) 13668213 16 15 16 7 3 4 2 2 5 0 0.47 0.70 412 HSA00604_GLYCOSPHINGOLIPID_BIOSYNTHESIS_GANGLIOSERIES Genes involved in glycosphingolipid biosynthesis - ganglioseries B3GALT4, B4GALNT1, GLB1, HEXA, HEXB, LCT, SLC33A1, ST3GAL1, ST3GAL2, ST3GAL5, ST6GALNAC3, ST6GALNAC4, ST6GALNAC5, ST6GALNAC6, ST8SIA1, ST8SIA5 16 B3GALT4(2), GLB1(1), HEXB(1), LCT(3), ST3GAL1(1), ST3GAL5(2), ST6GALNAC4(1), ST8SIA1(1) 12058488 12 12 12 0 2 5 3 0 2 0 0.47 0.70 413 TOB1PATHWAY TGF-beta signaling activates SMADs, which interact with intracellular Tob to maintain unstimulated T cells by repressing IL-2 expression. CD28, CD3D, CD3E, CD3G, CD3Z, IFNG, IL2, IL2RA, IL4, MADH3, MADH4, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3, TOB1, TOB2, TRA@, TRB@ 16 CD3E(1), CD3G(1), IL2(1), TGFB3(1), TGFBR1(2), TGFBR3(2), TOB1(1) 7884864 9 9 9 3 0 6 3 0 0 0 0.48 0.71 414 HSA00190_OXIDATIVE_PHOSPHORYLATION Genes involved in oxidative phosphorylation ATP12A, ATP4A, ATP4B, ATP5A1, ATP5B, ATP5C1, ATP5D, ATP5E, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5H, ATP5I, ATP5J, ATP5J2, ATP5L, ATP5O, ATP6, ATP6AP1, ATP6V0A1, ATP6V0A2, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0D1, ATP6V0D2, ATP6V0E1, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1E2, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, ATP8, COX1, COX10, COX15, COX17, COX2, COX3, COX4I1, COX4I2, COX5A, COX5B, COX6A1, COX6A2, COX6B1, COX6B2, COX6C, COX7A1, COX7A2, COX7B, COX7B2, COX7C, COX8A, COX8C, CYC1, CYTB, LHPP, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA1, NDUFA10, NDUFA11, NDUFA12, NDUFA13, NDUFA2, NDUFA3, NDUFA4, NDUFA4L2, NDUFA5, NDUFA6, NDUFA7, NDUFA8, NDUFA9, NDUFAB1, NDUFB1, NDUFB10, NDUFB11, NDUFB2, NDUFB3, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFB8, NDUFB9, NDUFC1, NDUFC2, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS5, NDUFS6, NDUFS7, NDUFS8, NDUFV1, NDUFV2, NDUFV3, PPA1, PPA2, SDHA, SDHB, SDHC, SDHD, TCIRG1, UCRC, UQCR, UQCRB, UQCRC1, UQCRC2, UQCRFS1, UQCRH, UQCRQ 107 ATP12A(3), ATP4A(4), ATP5A1(1), ATP5B(1), ATP5C1(1), ATP5F1(1), ATP6V0A2(1), ATP6V0A4(2), ATP6V0B(1), ATP6V0D2(1), ATP6V0E1(1), ATP6V1B2(1), ATP6V1C1(1), ATP6V1G2(1), ATP6V1H(1), COX10(2), COX4I2(1), COX5A(1), COX6C(1), COX7B2(1), NDUFA1(1), NDUFA10(1), NDUFA13(1), NDUFA2(1), NDUFA3(1), NDUFB9(1), NDUFS2(1), NDUFS3(1), NDUFV1(1), NDUFV2(1), PPA1(1), SDHA(1), SDHB(1), TCIRG1(1), UQCRC1(2), UQCRC2(1) 39958698 44 42 44 8 6 10 11 9 8 0 0.48 0.71 415 ST_INTERFERON_GAMMA_PATHWAY The interferon gamma pathway resembles the JAK-STAT pathway and activates STAT transcription factors. CISH, IFNG, IFNGR1, JAK1, JAK2, PLA2G2A, PTPRU, REG1A, STAT1, STATIP1 9 JAK1(1), JAK2(2), PTPRU(5), STAT1(1) 8494785 9 9 9 4 1 3 0 1 4 0 0.48 0.71 416 REDUCTIVE_CARBOXYLATE_CYCLE_CO2_FIXATION ACO1, ACO2, FH, IDH1, IDH2, MDH1, MDH2, SDHB, SUCLA2 9 ACO1(1), ACO2(2), IDH1(1), MDH2(2), SDHB(1), SUCLA2(1) 6645249 8 8 8 2 2 2 4 0 0 0 0.48 0.71 417 MITRPATHWAY The MyoD/MEF2 transcription factors induce muscle cell differentiation and are repressed by the transcriptional repressor MITR. CAMK1, CAMK1G, HDAC9, MEF2A, MEF2B, MEF2C, MEF2D, MYOD1, YWHAH 9 CAMK1(1), CAMK1G(1), HDAC9(1), MEF2A(1), MEF2C(2) 5971446 6 6 6 2 1 1 1 0 3 0 0.48 0.71 418 ST_G_ALPHA_S_PATHWAY The G-alpha-s protein activates adenylyl cyclases, which catalyze cAMP formation. ASAH1, BF, BFAR, BRAF, CAMP, CREB1, CREB3, CREB5, EPAC, GAS, GRF2, MAPK1, RAF1, SNX13, SRC, TERF2IP 12 BFAR(1), BRAF(2), CREB3(1), MAPK1(1), RAF1(1), SNX13(1), TERF2IP(2) 8413665 9 9 9 1 1 2 5 0 1 0 0.49 0.72 419 MITOCHONDRIAPATHWAY Pro-apoptotic signaling induces mitochondria to release cytochrome c, which stimulates Apaf-1 to activate caspase 9. APAF1, BAK1, BAX, BCL2, BCL2L1, BID, BIK, BIRC2, BIRC3, BIRC4, CASP3, CASP6, CASP7, CASP8, CASP9, CYCS, DFFA, DFFB, DIABLO, ENDOG, PDCD8 18 APAF1(1), BAK1(1), BID(4), CASP6(1), CASP8(2), DFFB(2) 9767355 11 11 11 0 2 4 1 0 4 0 0.49 0.72 420 CIRCADIAN_EXERCISE ARNTL, AZIN1, BTG1, C10orf110, C1orf1, CBX3, CEBPB, CLDN5, CLOCK, CRY1, CRY2, DAZAP2, DAZAP2, LOC401029, DNAJA1, EIF4G2, ETV6, G0S2, GENX_3414, GFRA1, GSTM3, GSTP1, HERPUD1, HLA_DMA, HSPA8, IDI1, KLF9, MAP3K7IP2, MYF6, NCKAP1, NCOA4, NR1D2, OAZIN, PER1, PER2, PIGF, PPP1R3C, PPP2CB, PSMA4, PURA, SF3A3, SUMO3, TOB1, TUBB3, UCP3, UGP2, VAPA, ZFR 37 ARNTL(1), AZIN1(1), CBX3(1), CRY1(1), EIF4G2(1), ETV6(1), HSPA8(3), IDI1(2), MYF6(1), NCKAP1(3), NR1D2(1), PER1(2), PER2(3), PPP2CB(2), TOB1(1), UCP3(1), VAPA(1), ZFR(4) 26284401 30 28 30 11 7 9 5 3 6 0 0.49 0.72 421 MTA3PATHWAY The estrogen receptor regulates proliferation in mammary epithelia via MTA3 activation; loss of either protein is implicated in breast cancer. ALDOA, CTSD, ESR1, GAPD, GREB1, HSPB1, HSPB2, MTA1, MTA3, PDZK1, TUBA1, TUBA2, TUBA3, TUBA4, TUBA6, TUBA8 9 ALDOA(3), ESR1(2), GREB1(1), MTA3(1) 7239960 7 7 7 3 2 2 1 1 1 0 0.49 0.72 422 HSA00531_GLYCOSAMINOGLYCAN_DEGRADATION Genes involved in glycosaminoglycan degradation ARSB, GALNS, GLB1, GNS, GUSB, HEXA, HEXB, HGSNAT, HPSE, HPSE2, HYAL1, HYAL2, IDS, IDUA, LCT, NAGLU, SPAM1 16 ARSB(3), GLB1(1), GUSB(1), HEXB(1), HGSNAT(1), HPSE(3), HPSE2(1), HYAL2(1), IDS(2), LCT(3), NAGLU(1) 14409954 18 17 18 3 3 7 6 0 2 0 0.50 0.73 423 ERYTHPATHWAY Erythropoietin selectively stimulates erythrocyte differentiation from CFU-GEMM cells in bone marrow. CCL3, CSF2, CSF3, EPO, FLT3, IGF1, IL11, IL1A, IL3, IL6, IL9, KITLG, TGFB1, TGFB2, TGFB3 14 FLT3(2), IGF1(1), IL1A(1), IL6(2), KITLG(2), TGFB3(1) 6119490 9 7 9 4 3 1 3 0 2 0 0.50 0.73 424 GLYCOSAMINOGLYCAN_DEGRADATION ARSB, GALNS, GLB1, GNS, GUSB, HEXA, HEXB, IDS, IDUA, LCT, NAGLU 10 ARSB(3), GLB1(1), GUSB(1), HEXB(1), IDS(2), LCT(3), NAGLU(1) 9843912 12 12 12 1 2 5 4 0 1 0 0.51 0.74 425 RARRXRPATHWAY RXR and RAR suppress transcription in the absence of ligand and, on binding trans- or 9-cis-retinoic acid, are ubiquitinated to allow transcription to proceed. ERCC3, GTF2A1, GTF2B, GTF2E1, GTF2F1, HDAC3, NCOA1, NCOA2, NCOA3, NCOR2, PCAF, POLR2A, RARA, RXRA, TBP 14 ERCC3(2), HDAC3(1), NCOA1(1), NCOA2(1), NCOA3(4), NCOR2(3), POLR2A(2), RARA(1), TBP(1) 17054973 16 16 16 7 2 4 5 1 4 0 0.51 0.74 426 PURINE_METABOLISM 1_Sep, ADA, ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADK, ADSL, ADSS, AK1, AK2, AK5, ALLC, AMPD1, AMPD2, AMPD3, APRT, ATIC, ATP1B1, ATP5A1, ATP5B, ATP5C1, ATP5D, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5H, ATP5I, ATP5J, ATP5J2, CANT1, DCK, DGUOK, ECGF1, ENPP1, ENPP3, ENTPD1, ENTPD2, FHIT, GART, GDA, GMPS, GUCY1A2, GUCY1A3, GUCY1B2, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, GUK1, HPRT1, IMPDH1, IMPDH2, ITPA, NME1, NME2, NP, NPR1, NPR2, NT5C, NT5E, NT5M, NUDT2, PAICS, PAPSS1, PAPSS2, PDE1A, PDE4A, PDE4B, PDE4C, PDE4D, PDE5A, PDE6B, PDE6C, PDE6G, PDE7B, PDE8A, PDE9A, PFAS, PKLR, PKM2, POLA, POLB, POLD1, POLD2, POLE, POLG, POLL, POLQ, POLR1B, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLRMT, POLS, PPAT, PRPS1, PRPS1L1, PRPS2, PRUNE, RRM1, RRM2, SAC 106 ADA(2), ADCY1(3), ADCY3(2), ADCY4(1), ADCY5(3), ADCY7(1), ADCY8(2), ADK(1), ADSL(1), AK2(1), AK5(1), AMPD1(3), ATIC(3), ATP1B1(1), ATP5A1(1), ATP5B(1), ATP5C1(1), ATP5F1(1), ENPP1(3), ENPP3(2), ENTPD1(2), FHIT(1), GMPS(1), GUCY1A2(2), GUCY2C(5), GUCY2D(1), GUCY2F(2), IMPDH1(2), IMPDH2(1), NPR1(1), NPR2(2), NT5E(3), PAICS(1), PAPSS1(2), PDE1A(2), PDE4A(1), PDE4B(2), PDE4C(3), PDE4D(3), PDE5A(1), PDE6B(2), PDE6C(2), PDE6G(1), PDE9A(3), PFAS(1), POLB(1), POLD2(1), POLG(1), POLL(1), POLQ(4), POLR1B(2), POLR2A(2), POLR2B(3), POLR2H(1), PPAT(1), PRPS2(1), PRUNE(3), RRM2(1) 91146939 103 85 102 35 22 28 25 10 18 0 0.51 0.74 427 HSA00271_METHIONINE_METABOLISM Genes involved in methionine metabolism AHCY, AMD1, BHMT, CBS, CTH, DNMT1, DNMT3A, DNMT3B, KIAA0828, MARS, MARS2, MAT1A, MAT2B, MTAP, MTFMT, MTR, SRM, TAT 17 AHCY(1), AMD1(1), BHMT(1), CBS(1), CTH(1), DNMT3A(3), DNMT3B(1), MAT2B(1), MTAP(1), MTR(5) 14677650 16 15 16 4 1 7 3 3 2 0 0.52 0.74 428 ST_IL_13_PATHWAY Like IL-4, IL-13 is produced by Th2 cells on activation of the T cell antigen receptor, and by mast and basophil cells on activation of the IgE receptor. IL13, IL13RA1, IL13RA2, IL4R, JAK1, JAK2, TYK2 7 IL13RA1(1), IL13RA2(2), JAK1(1), JAK2(2), TYK2(3) 7770282 9 8 8 2 1 0 4 2 2 0 0.52 0.74 429 ST_INTERLEUKIN_13_PATHWAY IL-13 is produced by Th2 cells on activation of the T cell antigen receptor, and by mast and basophil cells on activation of the IgE receptor. IL13, IL13RA1, IL13RA2, IL4R, JAK1, JAK2, TYK2 7 IL13RA1(1), IL13RA2(2), JAK1(1), JAK2(2), TYK2(3) 7770282 9 8 8 2 1 0 4 2 2 0 0.52 0.74 430 HSA00340_HISTIDINE_METABOLISM Genes involved in histidine metabolism ABP1, ACY3, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH7A1, ALDH9A1, AMDHD1, AOC2, AOC3, ASPA, CARM1, CNDP1, DDC, FTCD, HAL, HARS, HARS2, HDC, HEMK1, HNMT, LCMT1, LCMT2, MAOA, MAOB, METTL2B, METTL6, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, PRPS1, PRPS2, UROC1, WBSCR22 40 ALDH1B1(1), ALDH3B1(2), ALDH3B2(2), ALDH9A1(1), AMDHD1(1), AOC2(1), AOC3(2), ASPA(1), CARM1(1), CNDP1(2), DDC(1), HAL(2), LCMT1(1), LCMT2(3), MAOA(2), METTL2B(2), PRMT3(2), PRMT5(2), PRMT6(2), PRMT7(1), PRMT8(1), PRPS2(1) 28319499 34 29 34 10 6 8 10 4 6 0 0.52 0.74 431 COMPPATHWAY Both the classic and alternative immune complement pathways promote inflammation, foreign cell lysis, and phagocytosis. BF, C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C9, DF, MASP1, MASP2, MBL2 14 C2(1), C3(2), C5(3), C6(4), C7(3), C9(1), MASP1(1), MASP2(1), MBL2(1) 15790008 17 17 17 4 2 6 4 2 3 0 0.52 0.75 432 HSA00710_CARBON_FIXATION Genes involved in carbon fixation ALDOA, ALDOB, ALDOC, FBP1, FBP2, GOT1, GOT2, GPT, GPT2, MDH1, MDH2, ME1, ME3, PGK1, PGK2, PKLR, PKM2, RPE, RPIA, TKT, TKTL1, TKTL2, TPI1 22 ALDOA(3), ALDOB(2), GOT2(1), GPT2(2), MDH2(2), ME3(1), PGK1(2), TKT(1), TKTL1(1), TKTL2(1) 13850733 16 16 16 4 4 10 1 1 0 0 0.52 0.75 433 CLASSICPATHWAY The classic complement pathway is initiated by antibodies and promotes phagocytosis and lysis of foreign cells as well as activating the inflammatory response. C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C9 11 C2(1), C3(2), C5(3), C6(4), C7(3), C9(1) 13106457 14 14 14 4 2 5 3 2 2 0 0.53 0.75 434 DREAMPATHWAY The transcription factor DREAM blocks expression of the prodynorphin gene, which encodes the ligand of an opioid receptor that blocks pain signaling. CREB1, CREM, CSEN, FOS, JUN, MAPK3, OPRK1, POLR2A, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B 13 CREM(1), JUN(1), MAPK3(1), OPRK1(2), POLR2A(2), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1) 9177714 10 10 10 3 3 2 2 2 1 0 0.53 0.75 435 CHOLESTEROL_BIOSYNTHESIS C10orf110, CYP51A1, DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, HMGCS1, IDI1, LSS, MVD, MVK, NSDHL, PMVK, SC4MOL, SC5DL, SQLE 15 FDFT1(1), FDPS(1), HMGCS1(1), IDI1(2), NSDHL(1), PMVK(1), SC4MOL(1), SQLE(1) 8798478 9 9 9 8 2 3 2 0 2 0 0.53 0.75 436 HSA00061_FATTY_ACID_BIOSYNTHESIS Genes involved in fatty acid biosynthesis ACACA, ACACB, FASN, MCAT, OLAH, OXSM 5 ACACA(1), ACACB(8), MCAT(1) 8967816 10 10 10 1 5 5 0 0 0 0 0.53 0.75 437 HSA00590_ARACHIDONIC_ACID_METABOLISM Genes involved in arachidonic acid metabolism AKR1C3, ALOX12, ALOX12B, ALOX15, ALOX15B, ALOX5, CBR1, CBR3, CYP2B6, CYP2C18, CYP2C19, CYP2C8, CYP2C9, CYP2E1, CYP2J2, CYP2U1, CYP4A11, CYP4A22, CYP4F2, CYP4F3, DHRS4, EPHX2, GGT1, GGTL3, GGTL4, GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, LTA4H, LTC4S, PGDS, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PTGDS, PTGES, PTGES2, PTGIS, PTGS1, PTGS2, TBXAS1 49 AKR1C3(1), ALOX12(1), CBR3(1), CYP2B6(2), CYP2C18(2), CYP2C19(1), CYP2C8(1), CYP2C9(2), CYP4F2(1), DHRS4(1), GGT1(1), GPX5(1), PLA2G2D(1), PLA2G2F(1), PLA2G3(3), PLA2G4A(6), PLA2G6(2), PTGDS(1), PTGS2(1), TBXAS1(1) 27431742 31 30 29 5 6 10 8 3 4 0 0.53 0.75 438 CK1PATHWAY Caseine kinase 1 (CK1) and cdk5 phosphorylate DARPP32 in the dopamine signaling pathway. CDK5, CDK5R1, CSNK1D, DRD1, DRD2, GRM1, PLCB1, PPP1CA, PPP1R1B, PPP2CA, PPP3CA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B 17 CDK5(1), DRD2(1), GRM1(2), PLCB1(3), PPP3CA(3), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1) 11477466 13 13 13 6 7 2 3 1 0 0 0.53 0.75 439 SPRYPATHWAY Four members of the Sprouty protein family block proliferative EGF signals by binding Grb-2, preventing Ras and MAP kinase activation. CBL, EGF, EGFR, GRB2, HRAS, MAP2K1, MAPK1, MAPK3, PTPRB, RAF1, RASA1, SHC1, SOS1, SPRY1, SPRY2, SPRY3, SPRY4, SRC 18 EGF(2), EGFR(4), GRB2(1), MAP2K1(1), MAPK1(1), MAPK3(1), PTPRB(2), RAF1(1), RASA1(2), SHC1(1), SOS1(3) 18580536 19 19 19 7 2 6 4 4 3 0 0.54 0.75 440 PEPIPATHWAY Proepithelin (PEPI) induces epithelial cells to secrete IL-8, which promotes elastase secretion by neutrophils. ELA1, ELA2, ELA2A, ELA2B, ELA3B, GRN, IL8, SLPI 3 GRN(1) 1294371 1 1 1 1 1 0 0 0 0 0 0.54 0.75 441 HSA00530_AMINOSUGARS_METABOLISM Genes involved in aminosugars metabolism AMDHD2, CHIA, CHIT1, CMAS, CTBS, CYB5R1, CYB5R3, GFPT1, GFPT2, GNE, GNPDA1, GNPDA2, GNPNAT1, HEXA, HEXB, HK1, HK2, HK3, LHPP, MTMR1, MTMR2, MTMR6, NAGK, NANS, NPL, PGM3, PHPT1, RENBP, UAP1 29 AMDHD2(1), CHIA(2), CTBS(1), CYB5R1(2), GFPT2(3), GNE(3), GNPNAT1(1), HEXB(1), HK1(1), HK3(2), MTMR6(1), NAGK(1), NANS(1), PGM3(1), RENBP(1) 20888907 22 21 22 2 4 5 8 2 3 0 0.54 0.75 442 ALKALOID_BIOSYNTHESIS_II ABP1, AOC2, AOC3, CES1, ESD 5 AOC2(1), AOC3(2), CES1(1), ESD(1) 4679610 5 5 5 2 0 3 1 0 1 0 0.54 0.75 443 STATIN_PATHWAY_PHARMGKB ABCA1, APOA1, APOA1, LOC440837, APOA4, APOC1, APOC2, APOC3, APOC3, LOC440838, APOE, CETP, CYP7A1, DGAT1, HMGCR, LCAT, LDLR, LIPC, LPL, LRP1, SCARB1, SOAT1 14 ABCA1(5), CETP(1), LCAT(1), LDLR(1), LPL(1), LRP1(7), SCARB1(2), SOAT1(1) 18633264 19 19 19 8 10 3 3 0 3 0 0.54 0.75 444 HSA00903_LIMONENE_AND_PINENE_DEGRADATION Genes involved in limonene and pinene degradation ACOT11, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, ARD1A, CYP2C19, CYP2C9, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ECHS1, EHHADH, ESCO1, ESCO2, HADHA, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1, YOD1 26 ACOT11(2), ALDH1B1(1), ALDH9A1(1), CYP2C19(1), CYP2C9(2), DHRS2(2), DHRS7(1), ECHS1(1), EHHADH(2), ESCO1(3), MYST3(1), MYST4(5), PNPLA3(4) 22605609 26 24 26 9 6 5 7 3 2 3 0.55 0.76 445 UBIQUINONE_BIOSYNTHESIS NDUFA1, NDUFA10, NDUFA11, NDUFA4, NDUFA5, NDUFA8, NDUFB2, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFS1, NDUFS2, NDUFV1, NDUFV2 12 NDUFA1(1), NDUFA10(1), NDUFS2(1), NDUFV1(1), NDUFV2(1) 4791657 5 5 5 1 0 2 2 0 1 0 0.55 0.76 446 ARAPPATHWAY ADP-ribosylation factors (ARFs), members of the Ras superfamily, regulate eukaryotic vesicular trafficking and activate phospholipase D's. ARF1, ARFGAP1, ARFGAP3, ARFGEF2, BIG1, CENTD1, CENTD2, CLTA, CLTB, COP, COPA, DDEF1, DDEF2, GBF1, GPLD1, KDELR1, KDELR2, KDELR3, PSCD1, PSCD2, PSCD3, PSCD4 12 ARF1(1), ARFGAP1(1), ARFGAP3(1), ARFGEF2(2), COPA(1), GBF1(4), GPLD1(2), KDELR3(1) 11684322 13 13 13 0 3 2 3 3 2 0 0.55 0.76 447 HSA00230_PURINE_METABOLISM Genes involved in purine metabolism ADA, ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ADK, ADSL, ADSS, ADSSL1, AK1, AK2, AK3L1, AK5, AK7, ALLC, AMPD1, AMPD2, AMPD3, APRT, ATIC, CANT1, DCK, DGUOK, ECGF1, ENPP1, ENPP3, ENTPD1, ENTPD2, ENTPD3, ENTPD4, ENTPD5, ENTPD6, ENTPD8, FHIT, GART, GDA, GMPR, GMPR2, GMPS, GUCY1A2, GUCY1A3, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, GUK1, HPRT1, IMPDH1, IMPDH2, ITPA, NME1, NME2, NME4, NME6, NME7, NP, NPR1, NPR2, NT5C, NT5C1A, NT5C1B, NT5C2, NT5C3, NT5E, NT5M, NUDT2, NUDT5, NUDT9, PAICS, PAPSS1, PAPSS2, PDE10A, PDE11A, PDE1A, PDE1C, PDE2A, PDE3B, PDE4A, PDE4B, PDE4C, PDE4D, PDE5A, PDE6D, PDE6G, PDE6H, PDE7A, PDE7B, PDE8A, PDE8B, PDE9A, PFAS, PKLR, PKM2, PNPT1, POLA1, POLA2, POLD1, POLD2, POLD3, POLD4, POLE, POLE2, POLE3, POLE4, POLR1A, POLR1B, POLR1C, POLR1D, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLR3A, POLR3B, POLR3G, POLR3GL, POLR3H, POLR3K, PPAT, PRIM1, PRIM2, PRPS1, PRPS1L1, PRPS2, PRUNE, RFC5, RRM1, RRM2, RRM2B, SAC, XDH, ZNRD1 138 ADA(2), ADCY1(3), ADCY3(2), ADCY4(1), ADCY5(3), ADCY7(1), ADCY8(2), ADCY9(5), ADK(1), ADSL(1), AK2(1), AK5(1), AK7(1), AMPD1(3), ATIC(3), ENPP1(3), ENPP3(2), ENTPD1(2), ENTPD4(1), ENTPD6(1), FHIT(1), GMPR2(1), GMPS(1), GUCY1A2(2), GUCY2C(5), GUCY2D(1), GUCY2F(2), IMPDH1(2), IMPDH2(1), NME6(1), NME7(2), NPR1(1), NPR2(2), NT5C1B(3), NT5C3(1), NT5E(3), PAICS(1), PAPSS1(2), PDE10A(1), PDE11A(1), PDE1A(2), PDE2A(3), PDE3B(1), PDE4A(1), PDE4B(2), PDE4C(3), PDE4D(3), PDE5A(1), PDE6G(1), PDE9A(3), PFAS(1), POLA1(4), POLD2(1), POLD4(1), POLE2(1), POLE3(1), POLR1A(1), POLR1B(2), POLR1C(2), POLR1D(1), POLR2A(2), POLR2B(3), POLR2H(1), POLR3A(1), POLR3B(2), POLR3GL(2), PPAT(1), PRPS2(1), PRUNE(3), RRM2(1), XDH(3) 118570569 128 102 127 46 27 35 38 9 19 0 0.55 0.76 448 SETPATHWAY Cytotoxic T cells release perforin, which to allow entry into target cells of granzyme B, which activates caspases, and granzyme A, which induces caspase-independent apoptosis. ANP32A, APEX1, CREBBP, DFFA, DFFB, GZMA, GZMB, HMGB2, NME1, PRF1, SET 11 APEX1(1), CREBBP(2), DFFB(2), HMGB2(1), PRF1(2), SET(1) 7647588 9 8 9 3 2 2 0 2 3 0 0.55 0.76 449 ARENRF2PATHWAY Nrf1 and nrf2 are transcription factors that bind to antioxidant response elements (AREs), promoters of genes involved in oxidative damage control. CREB1, FOS, FXYD2, JUN, KEAP1, MAFF, MAFG, MAFK, MAPK1, MAPK14, MAPK8, NFE2L2, PRKCA, PRKCB1 9 JUN(1), KEAP1(2), MAPK1(1), MAPK14(1), MAPK8(2) 6141291 7 6 7 1 0 3 0 0 2 2 0.56 0.77 450 SA_CASPASE_CASCADE Apoptosis is mediated by caspases, cysteine proteases arranged in a proteolytic cascade. ADPRT, APAF1, BIRC2, BIRC3, BIRC4, CASP10, CASP3, CASP7, CASP8, CASP9, DFFA, DFFB, GZMB, PRF1, SCAP, SREBF1, SREBF2, TNFRSF6, TNFSF6 15 APAF1(1), CASP8(2), DFFB(2), PRF1(2), SCAP(3), SREBF2(3) 12415416 13 13 13 2 2 5 1 2 3 0 0.56 0.77 451 P35ALZHEIMERSPATHWAY p35, a neuron-specific activator of cyclin-dependent kinase 5, is cleaved to p25 in Alzheimer's disease and promotoes hyperphosphorylated tau formation and apoptosis. APP, CAPN1, CAPNS1, CAPNS2, CDK5, CDK5R1, CSNK1A1, CSNK1D, GSK3B, MAPT, PPP2CA 11 APP(2), CAPN1(3), CDK5(1), MAPT(1) 6567678 7 7 7 1 0 4 1 1 1 0 0.56 0.77 452 1_AND_2_METHYLNAPHTHALENE_DEGRADATION ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1 7 ADH1A(1), ADH7(2), ADHFE1(1) 4275531 4 4 4 1 0 3 1 0 0 0 0.57 0.77 453 HSA00010_GLYCOLYSIS_AND_GLUCONEOGENESIS Genes involved in glycolysis and gluconeogenesis ACSS1, ACSS2, ACYP1, ACYP2, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, AKR1A1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH7A1, ALDH9A1, ALDOA, ALDOB, ALDOC, BPGM, DLAT, DLD, ENO1, ENO2, ENO3, FBP1, FBP2, G6PC, G6PC2, GALM, GAPDH, GAPDHS, GCK, GPI, HK1, HK2, HK3, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, PDHA1, PDHA2, PDHB, PFKL, PFKM, PFKP, PGAM1, PGAM2, PGAM4, PGK1, PGK2, PGM1, PGM3, PKLR, PKM2, TPI1 62 ACYP1(1), ADH1A(1), ADH7(2), ADHFE1(1), ALDH1B1(1), ALDH3B1(2), ALDH3B2(2), ALDH9A1(1), ALDOA(3), ALDOB(2), DLD(1), ENO1(1), ENO3(1), G6PC2(1), GCK(2), GPI(2), HK1(1), HK3(2), LDHC(1), PDHA1(1), PDHA2(1), PDHB(1), PFKM(3), PFKP(2), PGK1(2), PGM1(1), PGM3(1) 40754688 40 37 40 11 6 19 5 7 3 0 0.57 0.77 454 SRCRPTPPATHWAY Activation of Src by Protein-tyrosine phosphatase alpha CCNB1, CDC2, CDC25A, CDC25B, CDC25C, CSK, GRB2, PRKCA, PRKCB1, PTPRA, SRC 9 CCNB1(2), CDC25B(3), GRB2(1), PTPRA(1) 6812559 7 7 7 2 0 4 0 2 1 0 0.57 0.77 455 IFNAPATHWAY Interferon alpha, active in the immune response, binds to the IFN receptor and activates Jak1 and Tyk2, which phosphorylate Stat1 and Stat2. IFNA1, IFNAR1, IFNAR2, IFNB1, ISGF3G, JAK1, STAT1, STAT2, TYK2 8 IFNAR2(1), IFNB1(1), JAK1(1), STAT1(1), STAT2(1), TYK2(3) 8103381 8 8 7 3 2 0 3 2 1 0 0.57 0.78 456 FREEPATHWAY Neutrophils release superoxide to induce lysis in invading bacteria; in neighboring endothelial cells, superoxide dismutase scavenges radicals but produces pro-apoptotic peroxides. GPX1, GSR, GSS, IL8, NFKB1, NOX1, RELA, SOD1, TNF, XDH 10 GSS(1), NFKB1(1), NOX1(1), RELA(1), SOD1(1), XDH(3) 7579143 8 8 8 0 2 1 4 0 1 0 0.58 0.78 457 ST_JAK_STAT_PATHWAY The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway transduces extracellular signals to promote gene activation. CISH, JAK1, JAK2, JAK3, PIAS1, PIAS3, PTPRU, REG1A, SOAT1 9 JAK1(1), JAK2(2), JAK3(1), PTPRU(5), SOAT1(1) 10227711 10 10 10 5 2 3 0 1 4 0 0.58 0.78 458 CAPROLACTAM_DEGRADATION AKR1A1, ECHS1, EHHADH, HADHA, SDS 5 ECHS1(1), EHHADH(2) 3434418 3 3 3 4 0 0 2 1 0 0 0.58 0.78 459 TRYPTOPHAN_METABOLISM AANAT, ABP1, ACAT1, ACAT2, ACMSD, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, AOC2, AOC3, AOX1, ASMT, CAT, CYP19A1, CYP1A1, CYP1A2, CYP2A6, CYP2A6, CYP2A7, CYP2A7P1, CYP2A13, CYP2B6, CYP2C18, CYP2C19, CYP2C19, CYP2C9, CYP2C8, CYP2C9, CYP2D6, CYP2E1, CYP2F1, CYP2J2, CYP3A4, CYP3A5, CYP3A7, CYP4B1, CYP4F8, CYP51A1, DDC, ECHS1, EHHADH, GCDH, HAAO, HADHA, INDO, KMO, KYNU, MAOA, MAOB, SDS, TDO2, TPH1, WARS, WARS2 54 ACAT1(1), ALDH1A1(2), ALDH1A2(1), ALDH1B1(1), ALDH9A1(1), AOC2(1), AOC3(2), AOX1(3), CYP2A13(4), CYP2A6(1), CYP2A7(1), CYP2B6(2), CYP2C18(2), CYP2C19(1), CYP2C8(1), CYP2C9(2), CYP2D6(2), CYP2F1(1), CYP3A4(3), CYP3A7(4), CYP4B1(2), CYP4F8(2), DDC(1), ECHS1(1), EHHADH(2), GCDH(1), KYNU(1), MAOA(2), WARS2(1) 41060916 49 43 49 19 5 18 13 5 8 0 0.59 0.78 460 TH1TH2PATHWAY Helper T subtype Th1 produces pro-inflammatory cytokines that stimulate phagocytosis, while Th2 cells promote antibody production and activate eosinophils. CD28, CD86, HLA-DRA, HLA-DRB1, IFNG, IFNGR1, IFNGR2, IL12A, IL12B, IL12RB1, IL12RB2, IL18, IL18R1, IL2, IL2RA, IL4, IL4R, TNFRSF5, TNFSF5 17 CD86(1), HLA-DRB1(2), IL12A(1), IL12B(1), IL12RB1(2), IL18R1(1), IL2(1) 9572667 9 9 9 6 1 0 3 3 2 0 0.59 0.78 461 LEPTINPATHWAY Leptin is a peptide secreted by adipose tissue that, in skeletal muscle, promotes fatty acid oxidation, decreases cells' lipid content, and promotes insulin sensitivity. ACACA, CPT1A, LEP, LEPR, PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKAG1, PRKAG2 10 ACACA(1), CPT1A(2), LEPR(3), PRKAA2(2), PRKAB1(1), PRKAG2(1) 10819887 10 10 10 5 4 3 1 0 2 0 0.59 0.78 462 EEA1PATHWAY The FYVE-finger proteins EEA1 and HRS are localized to endosome membranes and regulate sorting and ubiquitination in the vesicle transport system. EEA1, EGF, EGFR, HGS, RAB5A, TF, TFRC 7 EEA1(1), EGF(2), EGFR(4), TF(1), TFRC(1) 9514362 9 9 9 4 1 2 2 4 0 0 0.59 0.78 463 HSA04130_SNARE_INTERACTIONS_IN_VESICULAR_TRANSPORT Genes involved in SNARE interactions in vesicular transport BET1, BET1L, BNIP1, C1orf142, GOSR1, GOSR2, SEC22B, SNAP23, SNAP25, SNAP29, STX10, STX11, STX12, STX16, STX17, STX18, STX19, STX2, STX3, STX4, STX5, STX6, STX7, STX8, TSNARE1, USE1, VAMP1, VAMP2, VAMP3, VAMP4, VAMP5, VAMP7, VAMP8, VTI1A, VTI1B, YKT6 35 SNAP23(2), SNAP25(1), STX10(1), STX17(1), STX3(1), STX6(1), STX7(1), TSNARE1(3), USE1(1) 12155832 12 12 12 9 3 2 1 3 3 0 0.59 0.79 464 IL10PATHWAY The cytokine IL-10 inhibits the inflammatory response by macrophages via activation of heme oxygenase 1. BLVRA, BLVRB, HMOX1, IL10, IL10RA, IL10RB, IL1A, IL6, JAK1, STAT1, STAT3, STAT5A, TNF 13 IL10RA(1), IL10RB(3), IL1A(1), IL6(2), JAK1(1), STAT1(1), STAT3(1) 9056034 10 9 10 1 3 2 1 1 3 0 0.60 0.80 465 PROSTAGLANDIN_SYNTHESIS_REGULATION ANXA1, ANXA2, ANXA3, ANXA4, ANXA5, ANXA6, ANXA8, CYP11A1, EDN1, EDNRA, EDNRB, HPGD, HSD11B1, HSD11B2, PLA2G4A, PRL, PTGDR, PTGDS, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, PTGIS, PTGS1, PTGS2, S100A6, SCGB1A1, TBXAS1 27 ANXA3(1), ANXA4(1), ANXA6(1), CYP11A1(1), EDN1(2), EDNRB(1), PLA2G4A(6), PTGDR(1), PTGDS(1), PTGFR(1), PTGS2(1), S100A6(1), TBXAS1(1) 15335229 19 18 18 3 6 5 6 2 0 0 0.61 0.80 466 ANDROGEN_AND_ESTROGEN_METABOLISM AKR1C4, AKR1D1, ARSB, ARSD, ARSE, CYP11B1, CYP11B2, HSD11B1, HSD11B2, HSD17B2, HSD17B3, HSD17B8, HSD3B1, HSD3B2, SRD5A1, SRD5A2, STS, SULT1E1, SULT2A1, UGT1A10, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A9, UGT2B15, UGT2B4 30 AKR1C4(1), ARSB(3), ARSE(1), CYP11B1(2), CYP11B2(3), HSD17B2(1), HSD3B2(2), SRD5A1(1), SRD5A2(2), SULT1E1(2), UGT1A10(1), UGT1A6(2), UGT2B15(2), UGT2B4(1) 19720779 24 21 24 6 6 7 6 3 2 0 0.61 0.81 467 HSA00520_NUCLEOTIDE_SUGARS_METABOLISM Genes involved in nucleotide sugars metabolism GALE, GALT, TGDS, UGDH, UGP2, UXS1 6 GALT(1), TGDS(2), UXS1(2) 3811119 5 4 5 0 2 1 0 2 0 0 0.61 0.81 468 HSA00072_SYNTHESIS_AND_DEGRADATION_OF_KETONE_BODIES Genes involved in synthesis and degradation of ketone bodies ACAT1, ACAT2, BDH1, BDH2, HMGCL, HMGCS1, HMGCS2, OXCT1, OXCT2 9 ACAT1(1), HMGCS1(1), HMGCS2(1), OXCT1(1), OXCT2(1) 5172414 5 5 5 2 0 2 2 1 0 0 0.62 0.81 469 NITROGEN_METABOLISM AMT, ASNS, CA1, CA12, CA14, CA2, CA3, CA4, CA5A, CA5B, CA6, CA7, CA8, CA9, CPS1, CTH, GLS, GLS2, GLUD1, GLUL, HAL 21 AMT(1), CA2(1), CA4(1), CA6(2), CA9(3), CPS1(2), CTH(1), GLS(1), HAL(2) 14028690 14 14 14 3 2 5 3 1 3 0 0.62 0.81 470 ACETYLCHOLINE_SYNTHESIS ACHE, CHAT, CHKA, PCYT1A, PDHA1, PDHA2, PEMT, SLC18A3 8 ACHE(2), PCYT1A(1), PDHA1(1), PDHA2(1) 5048199 5 5 5 1 0 4 1 0 0 0 0.62 0.81 471 HSA00400_PHENYLALANINE_TYROSINE_AND_TRYPTOPHAN_BIOSYNTHESIS Genes involved in phenylalanine, tyrosine and tryptophan biosynthesis FARS2, FARSA, FARSB, GOT1, GOT2, PAH, TAT, YARS, YARS2 9 FARS2(1), FARSA(1), FARSB(3), GOT2(1), PAH(1) 6516471 7 7 7 0 1 3 2 1 0 0 0.62 0.81 472 HSA00071_FATTY_ACID_METABOLISM Genes involved in fatty acid metabolism ACAA1, ACAA2, ACADL, ACADM, ACADS, ACADSB, ACADVL, ACAT1, ACAT2, ACOX1, ACOX3, ACSL1, ACSL3, ACSL4, ACSL5, ACSL6, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, CPT1A, CPT1B, CPT1C, CPT2, CYP4A11, CYP4A22, DCI, ECHS1, EHHADH, GCDH, HADH, HADHA, HADHB, HSD17B10, HSD17B4, PECI 47 ACAA1(1), ACAA2(1), ACADSB(1), ACADVL(2), ACAT1(1), ACOX1(2), ACOX3(1), ACSL3(1), ACSL4(1), ACSL5(1), ACSL6(2), ADH1A(1), ADH7(2), ADHFE1(1), ALDH1B1(1), ALDH9A1(1), CPT1A(2), CPT1C(2), CPT2(1), ECHS1(1), EHHADH(2), GCDH(1), HADH(1), HADHB(1), HSD17B10(1), HSD17B4(3), PECI(1) 35644128 36 35 36 13 6 15 6 5 4 0 0.62 0.81 473 RELAPATHWAY Acetylated NF-kB proteins are immune to IkB regulation and promote transcription until the histone deacetylase HDAC3 deacetylates the RelA subunit of NF-kB. CHUK, CREBBP, EP300, FADD, HDAC3, IKBKB, IKBKG, NFKB1, NFKBIA, RELA, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TRADD, TRAF6 14 CREBBP(2), EP300(3), HDAC3(1), IKBKB(2), NFKB1(1), RELA(1), RIPK1(3), TNFRSF1A(1), TRAF6(1) 16086096 15 15 14 3 1 8 0 1 5 0 0.63 0.82 474 NUCLEOTIDE_GPCRS ADORA1, ADORA2A, ADORA2B, ADORA3, GPR23, LTB4R, P2RY1, P2RY2, P2RY5, P2RY6 8 ADORA1(1), ADORA3(1), P2RY1(1), P2RY2(1) 4245111 4 4 4 2 1 3 0 0 0 0 0.63 0.82 475 AMINOSUGARS_METABOLISM CMAS, CYB5R3, GCK, GFPT1, GNE, GNPDA1, GNPDA2, HEXA, HEXB, HK1, HK2, HK3, PGM3, RENBP, UAP1 15 GCK(2), GNE(3), HEXB(1), HK1(1), HK3(2), PGM3(1), RENBP(1) 12357618 11 11 11 2 2 4 3 0 2 0 0.63 0.82 476 HSA00150_ANDROGEN_AND_ESTROGEN_METABOLISM Genes involved in androgen and estrogen metabolism AKR1C4, AKR1D1, ARSD, ARSE, CARM1, CYP11B1, CYP11B2, CYP19A1, HEMK1, HSD11B1, HSD11B2, HSD17B1, HSD17B12, HSD17B2, HSD17B3, HSD17B7, HSD17B8, HSD3B1, HSD3B2, LCMT1, LCMT2, METTL2B, METTL6, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, SRD5A1, SRD5A2, STS, SULT1E1, SULT2A1, SULT2B1, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, WBSCR22 54 AKR1C4(1), ARSE(1), CARM1(1), CYP11B1(2), CYP11B2(3), HSD17B1(1), HSD17B2(1), HSD3B2(2), LCMT1(1), LCMT2(3), METTL2B(2), PRMT3(2), PRMT5(2), PRMT6(2), PRMT7(1), PRMT8(1), SRD5A1(1), SRD5A2(2), SULT1E1(2), UGT1A10(1), UGT1A6(2), UGT2A1(1), UGT2B10(2), UGT2B15(2), UGT2B28(1), UGT2B4(1) 35708010 41 36 41 14 9 10 14 3 5 0 0.64 0.82 477 CASPASEPATHWAY Caspases are cysteine proteases active in apoptosis; caspase-8 and 9 cleave and activate other caspases, while 3, 6, and 7 cleave cellular targets. ADPRT, APAF1, ARHGDIB, BIRC2, BIRC3, BIRC4, CASP1, CASP10, CASP2, CASP3, CASP4, CASP6, CASP7, CASP8, CASP9, CYCS, DFFA, DFFB, GZMB, LMNA, LMNB1, LMNB2, PRF1 20 APAF1(1), ARHGDIB(1), CASP1(1), CASP2(2), CASP6(1), CASP8(2), DFFB(2), LMNB1(1), PRF1(2) 13661115 13 13 13 2 1 5 2 2 3 0 0.64 0.82 478 ARGININE_AND_PROLINE_METABOLISM ABP1, AGMAT, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH4A1, ALDH9A1, AMD1, AOC2, AOC3, ARG1, ARG2, ASL, ASS, CKB, CKM, CKMT1, CKMT1B, CKMT1A, CKMT2, CPS1, DAO, GAMT, GATM, GLUD1, GOT1, GOT2, MAOA, MAOB, NOS1, NOS2A, NOS3, OAT, ODC1, OTC, P4HA1, P4HA2, P4HA3, P4HB, PYCR1, RARS, SAT, SMS 40 AGMAT(1), ALDH1A1(2), ALDH1A2(1), ALDH1B1(1), ALDH9A1(1), AMD1(1), AOC2(1), AOC3(2), ARG1(2), ARG2(1), ASL(3), CKMT2(1), CPS1(2), DAO(1), GATM(3), GOT2(1), MAOA(2), NOS1(3), NOS3(2), P4HA3(1), RARS(1) 30495543 33 30 33 10 5 17 7 1 3 0 0.64 0.82 479 SA_FAS_SIGNALING The TNF-type receptor Fas induces apoptosis on ligand binding. BCL2, CASP3, CASP8, CFL1, CFLAR, P11, PDE6D, TNFRSF6, TNFSF6 6 CASP8(2) 2765178 2 2 2 0 0 0 1 0 1 0 0.64 0.82 480 TCRAPATHWAY The kinases Lck and Fyn phosphorylate and activate the T cell receptor, which recognizes antigen-bound MHCII and leads to T cell activation. CD3D, CD3E, CD3G, CD3Z, CD4, FYN, HLA-DRA, HLA-DRB1, LCK, PTPRC, TRA@, TRB@, ZAP70 10 CD3E(1), CD3G(1), CD4(1), HLA-DRB1(2), PTPRC(1), ZAP70(1) 6755775 7 7 7 5 2 2 2 1 0 0 0.64 0.83 481 GPCRDB_CLASS_A_RHODOPSIN_LIKE2 CYSLTR1, CYSLTR2, GPR109B, GPR161, GPR171, GPR18, GPR34, GPR39, GPR41, GPR42, GPR45, GPR65, GPR68, GPR75, GPR81, LYPDC1 13 CYSLTR1(1), CYSLTR2(1), GPR109B(1), GPR161(2), GPR34(1), GPR75(1) 7405749 7 7 7 7 0 2 2 3 0 0 0.65 0.83 482 SELENOAMINO_ACID_METABOLISM AHCY, CBS, CTH, GGT1, MARS, MARS2, MAT1A, MAT2B, PAPSS1, PAPSS2, SCLY, SEPHS1 12 AHCY(1), CBS(1), CTH(1), GGT1(1), MAT2B(1), PAPSS1(2), SEPHS1(1) 8761974 8 8 8 4 0 6 1 0 1 0 0.65 0.83 483 ST_T_CELL_SIGNAL_TRANSDUCTION On activation of the T cell receptor, phospholipase C is activated to produce second messengers DAG and PIP3, both required for T cell activation. CBL, CD28, CD3D, CSK, CTLA4, DAG1, DTYMK, EPHB2, FBXW7, GRAP2, GRB2, ITK, ITPKA, ITPKB, LAT, LCK, LCP2, MAPK1, NCK1, NFAT5, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PAG, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PLCG1, PTPRC, RAF1, RASGRP1, RASGRP2, RASGRP3, RASGRP4, SOS1, SOS2, VAV1, ZAP70 42 EPHB2(1), FBXW7(1), GRB2(1), ITK(3), ITPKB(7), LAT(1), LCP2(1), MAPK1(1), NFAT5(1), NFKB1(1), NFKB2(4), PAK1(2), PAK2(1), PAK3(1), PAK7(1), PLCG1(4), PTPRC(1), RAF1(1), RASGRP2(2), RASGRP4(1), SOS1(3), SOS2(1), VAV1(1), ZAP70(1) 39911547 42 37 42 12 10 13 4 6 6 3 0.65 0.83 484 HISTIDINE_METABOLISM ABP1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH9A1, AOC2, AOC3, ASPA, CNDP1, DDC, HAL, HARS, HARSL, HDC, HNMT, MAOA, MAOB, PRPS1, PRPS2 24 ALDH1A1(2), ALDH1A2(1), ALDH1B1(1), ALDH3B1(2), ALDH3B2(2), ALDH9A1(1), AOC2(1), AOC3(2), ASPA(1), CNDP1(2), DDC(1), HAL(2), MAOA(2), PRPS2(1) 18196230 21 19 21 7 4 7 3 4 3 0 0.65 0.83 485 INTRINSICPATHWAY The intrinsic prothrombin activation pathway is activated by traumatized blood vessels and induces clot formation. COL4A1, COL4A2, COL4A3, COL4A4, COL4A5, COL4A6, F10, F11, F12, F2, F2R, F5, F8, F9, FGA, FGB, FGG, KLKB1, KNG, PROC, PROS1, SERPINC1, SERPING1 22 COL4A1(4), COL4A2(2), COL4A3(1), COL4A4(1), COL4A5(4), COL4A6(3), F12(1), F2(2), F2R(2), F5(7), F8(1), FGA(3), KLKB1(1), PROC(1), SERPINC1(2) 33025473 35 34 35 11 6 11 8 6 4 0 0.65 0.83 486 SA_PROGRAMMED_CELL_DEATH Programmed cell death, or apoptosis, eliminates damaged or unneeded cells. APAF1, BAD, BAK1, BAX, BCL10, BCL2, BCL2L1, BCL2L11, BID, CASP8AP2, CASP9, CES1 12 APAF1(1), BAD(1), BAK1(1), BCL2L11(1), BID(4), CES1(1) 8450676 9 9 9 0 3 4 0 0 2 0 0.65 0.83 487 FOSBPATHWAY FOSB gene expression and drug abuse CDK5, FOSB, GRIA2, JUND, PPP1R1B 4 CDK5(1), GRIA2(1) 2589249 2 2 2 1 1 1 0 0 0 0 0.66 0.83 488 ACTINYPATHWAY The Arp 2/3 complex localizes to the Y-junction of polymerizing actin fibers that enable lamellipod extension and consequent cell motility. ABI-2, ACTA1, ACTR2, ACTR3, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, NCK1, NCKAP1, NTRK1, PIR, PSMA7, RAC1, WASF1, WASF2, WASF3, WASL 18 ARPC1A(1), ARPC1B(1), ARPC2(2), NCKAP1(3), NTRK1(1), PIR(1), WASF1(1), WASF3(1), WASL(1) 11461749 12 12 12 5 6 1 4 0 1 0 0.66 0.83 489 HSA00561_GLYCEROLIPID_METABOLISM Genes involved in glycerolipid metabolism ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, AGK, AGPAT1, AGPAT2, AGPAT3, AGPAT4, AGPAT6, AKR1A1, AKR1B1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, CEL, DAK, DGAT1, DGAT2, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKI, DGKQ, DGKZ, GK, GK2, GLA, GLB1, GPAM, LCT, LIPA, LIPC, LIPF, LIPG, LPL, LYCAT, MGLL, PNLIP, PNLIPRP1, PNLIPRP2, PNPLA3, PPAP2A, PPAP2B, PPAP2C, UGCGL1, UGCGL2 52 ADH1A(1), ADH7(2), ADHFE1(1), AGK(2), AGPAT3(2), AGPAT6(1), AKR1B1(2), ALDH1B1(1), ALDH9A1(1), CEL(1), DAK(2), DGKA(3), DGKD(1), DGKE(1), DGKG(4), DGKH(1), DGKI(5), GK2(1), GLA(2), GLB1(1), LCT(3), LPL(1), PNLIP(1), PNLIPRP1(2), PNPLA3(4), PPAP2A(1) 41479191 47 41 46 13 9 16 8 4 7 3 0.66 0.83 490 PYRIMIDINE_METABOLISM AK3, AK3L1, AK3L1, AK3L2, CAD, CANT1, CDA, CMPK, CTPS, CTPS2, DCK, DCTD, DHODH, DPYD, DPYS, DTYMK, DUT, ECGF1, ENTPD1, ITPA, NME1, NME2, NP, NT5C, NT5E, NT5M, NUDT2, POLA, POLB, POLD1, POLD2, POLE, POLG, POLL, POLQ, POLR1B, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLRMT, POLS, RRM1, RRM2, TK1, TK2, TXNRD1, TYMS, UCK1, UCK2, UMPS, UNG, UPB1, UPP1 53 CAD(7), CTPS2(2), DPYD(1), DPYS(1), ENTPD1(2), NT5E(3), POLB(1), POLD2(1), POLG(1), POLL(1), POLQ(4), POLR1B(2), POLR2A(2), POLR2B(3), POLR2H(1), RRM2(1), TK2(1), UCK2(2), UMPS(1), UPB1(3), UPP1(2) 40676103 42 38 42 12 7 10 10 4 11 0 0.66 0.83 491 PKCPATHWAY Gq-coupled receptors promote hydrolysis of PIP2 to DAG and IP3, which causes calcium influx and activates protein kinase C. GNAQ, NFKB1, NFKBIA, PLCB1, PRKCA, PRKCB1, RELA 6 GNAQ(1), NFKB1(1), PLCB1(3), RELA(1) 6134700 6 6 6 1 2 3 0 0 1 0 0.66 0.83 492 BILE_ACID_BIOSYNTHESIS ACAA1, ACAA2, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, AKR1C4, AKR1D1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, BAAT, CEL, CYP27A1, CYP7A1, HADHB, SOAT2, SRD5A1, SRD5A2 27 ACAA1(1), ACAA2(1), ADH1A(1), ADH7(2), ADHFE1(1), AKR1C4(1), ALDH1A1(2), ALDH1A2(1), ALDH1B1(1), ALDH9A1(1), BAAT(1), CEL(1), CYP27A1(1), HADHB(1), SRD5A1(1), SRD5A2(2) 17098068 19 17 19 5 1 12 3 1 2 0 0.67 0.83 493 HSA00624_1_AND_2_METHYLNAPHTHALENE_DEGRADATION Genes involved in 1- and 2-methylnaphthalene degradation ACAD8, ACAD9, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, ARD1A, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ESCO1, ESCO2, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1 22 ADH1A(1), ADH7(2), ADHFE1(1), DHRS2(2), DHRS7(1), ESCO1(3), MYST3(1), MYST4(5), PNPLA3(4) 18603351 20 18 20 4 5 5 3 2 2 3 0.67 0.83 494 SA_G2_AND_M_PHASES Cdc25 activates the cdc2/cyclin B complex to induce the G2/M transition. CDC2, CDC25A, CDC25B, CDK7, CDKN1A, CHEK1, NEK1, WEE1 7 CDC25B(3), CDK7(1), NEK1(1) 5474079 5 5 5 2 1 2 0 2 0 0 0.67 0.83 495 COMPLEMENT_ACTIVATION_CLASSICAL C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C8B, C9, DAF, MASP1 13 C2(1), C3(2), C5(3), C6(4), C7(3), C9(1), MASP1(1) 15607488 15 15 15 4 2 5 3 2 3 0 0.67 0.83 496 HSA00532_CHONDROITIN_SULFATE_BIOSYNTHESIS Genes involved in chondroitin sulfate biosynthesis B3GALT6, B3GAT1, B3GAT2, B3GAT3, B4GALT7, ChGn, CHPF, CHST11, CHST12, CHST13, CHST14, CHST3, CHST7, CHSY-2, CHSY1, CSGlcA-T, DSE, GALNAC4S-6ST, GALNACT-2, UST, XYLT1, XYLT2 15 B3GAT3(1), CHPF(1), CHST11(1), CHST3(1), DSE(4), UST(1), XYLT2(1) 9839856 10 10 10 7 3 4 2 0 1 0 0.67 0.83 497 CYTOKINEPATHWAY Intercellular signaling in the immune system occurs via secretion of cytokines, which promote antigen-dependent B and T cell response. IFNA1, IFNB1, IFNG, IL10, IL12A, IL12B, IL13, IL14, IL15, IL16, IL17, IL18, IL1A, IL2, IL3, IL4, IL5, IL6, IL8, IL9, LTA, TNF 20 IFNB1(1), IL12A(1), IL12B(1), IL15(1), IL1A(1), IL2(1), IL6(2) 7624773 8 7 8 4 3 0 1 1 3 0 0.68 0.84 498 HSA00120_BILE_ACID_BIOSYNTHESIS Genes involved in bile acid biosynthesis ACAA1, ACAA2, ACAD8, ACAD9, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, AKR1B10, AKR1C4, AKR1D1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, BAAT, CEL, CYP27A1, CYP7A1, HADHB, HSD3B7, LIPA, RDH11, RDH12, RDH13, RDH14, SLC27A5, SOAT1, SOAT2, SRD5A1, SRD5A2 38 ACAA1(1), ACAA2(1), ADH1A(1), ADH7(2), ADHFE1(1), AKR1C4(1), ALDH1B1(1), ALDH9A1(1), BAAT(1), CEL(1), CYP27A1(1), HADHB(1), RDH11(2), RDH12(1), RDH14(1), SLC27A5(2), SOAT1(1), SRD5A1(1), SRD5A2(2) 23033517 23 22 23 6 2 11 5 1 4 0 0.68 0.84 499 HSA00910_NITROGEN_METABOLISM Genes involved in nitrogen metabolism AMT, ASNS, ASRGL1, CA1, CA12, CA13, CA14, CA2, CA3, CA4, CA5A, CA5B, CA6, CA7, CA8, CA9, CPS1, CTH, GLS, GLS2, GLUD1, GLUD2, GLUL, HAL 24 AMT(1), CA2(1), CA4(1), CA6(2), CA9(3), CPS1(2), CTH(1), GLS(1), GLUD2(1), HAL(2) 15598362 15 15 15 4 2 5 4 1 3 0 0.68 0.84 500 CARM1PATHWAY The methyltransferase CARM1 interacts with transcription factors such as CBP/p300 and methylates histones H3 and H4. CARM1, CREB1, CREBBP, EP300, NCOA3, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RARA, RXRA 13 CARM1(1), CREBBP(2), EP300(3), NCOA3(4), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), RARA(1) 14774487 14 12 13 5 4 1 0 3 6 0 0.69 0.85 501 CDMACPATHWAY Cadmium 2+ promotes cell proliferation in cultured macrophages by entering the cell via calcium channels and activating the MAP kinase pathway. CUZD1, FOS, HRAS, JUN, MAP2K1, MAPK1, MAPK3, MYC, NFKB1, NFKBIA, PLCB1, PRKCA, PRKCB1, RAF1, RELA, TNF 15 JUN(1), MAP2K1(1), MAPK1(1), MAPK3(1), MYC(1), NFKB1(1), PLCB1(3), RAF1(1), RELA(1) 11420682 11 11 11 3 2 6 1 0 2 0 0.69 0.85 502 HSA04710_CIRCADIAN_RHYTHM Genes involved in circadian rhythm ARNTL, BHLHB2, BHLHB3, CLOCK, CRY1, CRY2, CSNK1D, CSNK1E, NPAS2, NR1D1, PER1, PER2, PER3 11 ARNTL(1), CRY1(1), CSNK1E(1), NPAS2(1), NR1D1(1), PER1(2), PER2(3), PER3(2) 11869884 12 12 12 7 4 4 1 0 3 0 0.69 0.85 503 HSA00780_BIOTIN_METABOLISM Genes involved in biotin metabolism BTD, HLCS, SPCS1, SPCS3 4 BTD(1), HLCS(1) 2248545 2 2 2 0 1 0 1 0 0 0 0.70 0.86 504 HSA00790_FOLATE_BIOSYNTHESIS Genes involved in folate biosynthesis ALPI, ALPL, ALPP, ALPPL2, ASCC3, ASCC3L1, ATP13A2, DDX18, DDX19A, DDX23, DDX4, DDX41, DDX47, DDX50, DDX51, DDX52, DDX54, DDX55, DDX56, DHFR, DHX58, ENTPD7, EP400, ERCC2, ERCC3, FPGS, GCH1, GGH, IFIH1, MOV10L1, NUDT5, NUDT8, PTS, QDPR, RAD54B, RAD54L, RUVBL2, SETX, SKIV2L2, SMARCA2, SMARCA5, SPR 40 ALPI(2), ALPL(1), ALPP(2), ALPPL2(3), ASCC3(1), ATP13A2(1), DDX41(1), DDX50(3), DDX55(3), DDX56(1), DHX58(2), ENTPD7(1), ERCC3(2), GCH1(1), IFIH1(1), NUDT8(1), RAD54B(4), RAD54L(2), SETX(6), SKIV2L2(1), SMARCA2(3), SMARCA5(1) 45087510 43 38 42 6 9 9 12 6 7 0 0.70 0.86 505 HSA00100_BIOSYNTHESIS_OF_STEROIDS Genes involved in biosynthesis of steroids CYP27B1, CYP51A1, DHCR24, DHCR7, EBP, FDFT1, FDPS, GGCX, GGPS1, HMGCR, HSD17B7, IDI1, IDI2, LSS, MVD, MVK, NQO1, NSDHL, PMVK, SC4MOL, SC5DL, SQLE, TM7SF2, VKORC1 24 DHCR24(1), EBP(1), FDFT1(1), FDPS(1), IDI1(2), NQO1(1), NSDHL(1), PMVK(1), SC4MOL(1), SQLE(1), VKORC1(1) 13375167 12 12 12 10 3 5 2 0 2 0 0.71 0.86 506 HSA01031_GLYCAN_STRUCTURES_BIOSYNTHESIS_2 Genes involved in glycan structures - biosynthesis 2 A4GALT, ABO, B3GALNT1, B3GALT1, B3GALT2, B3GALT4, B3GALT5, B3GNT1, B3GNT2, B3GNT3, B3GNT4, B3GNT5, B4GALNT1, B4GALT1, B4GALT2, B4GALT3, B4GALT4, B4GALT6, FUT1, FUT2, FUT3, FUT4, FUT5, FUT6, FUT7, FUT9, GBGT1, GCNT2, PIGA, PIGB, PIGC, PIGF, PIGG, PIGH, PIGK, PIGL, PIGM, PIGN, PIGO, PIGP, PIGQ, PIGS, PIGT, PIGU, PIGV, PIGX, PIGZ, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4, ST3GAL5, ST3GAL6, ST6GALNAC3, ST6GALNAC4, ST6GALNAC5, ST6GALNAC6, ST8SIA1, ST8SIA5, UGCG, UGCGL1, UGCGL2 56 B3GALNT1(1), B3GALT1(1), B3GALT4(2), B3GALT5(1), B3GNT1(1), B3GNT2(1), B3GNT3(1), B3GNT4(1), B4GALT1(2), B4GALT3(1), B4GALT6(1), FUT2(2), FUT3(2), PIGA(1), PIGB(1), PIGG(1), ST3GAL1(1), ST3GAL3(1), ST3GAL4(1), ST3GAL5(2), ST3GAL6(1), ST6GALNAC4(1), ST8SIA1(1) 32978829 28 28 27 5 9 7 4 4 4 0 0.71 0.86 507 ARGININECPATHWAY Related catabolic pathways process arginine, histidine, glutamine, and proline through glutamate to alpha-ketoglutamate, which feeds into the citric acid cycle. ALDH4A1, ARG1, GLS, GLUD1, OAT, PRODH 6 ARG1(2), GLS(1) 3483090 3 3 3 1 0 1 0 1 1 0 0.72 0.88 508 HSA00401_NOVOBIOCIN_BIOSYNTHESIS Genes involved in novobiocin biosynthesis GOT1, GOT2, TAT 3 GOT2(1) 1909869 1 1 1 0 0 1 0 0 0 0 0.72 0.88 509 TRANSLATION_FACTORS ANKHD1, ANKHD1, MASK_BP3, EEF1A2, EEF1B2, EEF1D, EEF1G, EEF2, EEF2K, EIF1AX, EIF1AY, EIF2AK1, EIF2AK2, EIF2AK3, EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5, EIF2S1, EIF2S2, EIF2S3, EIF3S1, EIF3S10, EIF3S2, EIF3S3, EIF3S4, EIF3S5, EIF3S6, EIF3S7, EIF3S8, EIF3S9, EIF4A1, EIF4A2, EIF4E, EIF4EBP1, EIF4EBP2, EIF4G1, EIF4G3, EIF5, EIF5A, EIF5B, ETF1, GSPT2, ITGB4BP, KIAA0664, PABPC1, PABPC3, PABPC1, LOC341315, PAIP1, PAIP1, LOC388345, SLC35A4, SUI1, WBSCR1 35 EEF1D(1), EEF2(1), EEF2K(2), EIF1AX(2), EIF2AK1(1), EIF2AK3(1), EIF2B5(1), EIF2S1(1), EIF2S2(1), EIF4A2(3), EIF4G3(2), EIF5(1), EIF5B(2), ETF1(1), GSPT2(2), PABPC1(3), PABPC3(1), SLC35A4(2) 30443322 28 27 28 12 4 5 7 5 7 0 0.73 0.88 510 SALMONELLAPATHWAY Salmonella induces membrane ruffling in infected cells via bacterial proteins including SipA, SipC, and SopE, which alter actin structure. ACTA1, ACTR2, ACTR3, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, CDC42, RAC1, WASF1, WASL 12 ARPC1A(1), ARPC1B(1), ARPC2(2), WASF1(1), WASL(1) 6118476 6 6 6 5 3 0 2 0 1 0 0.73 0.88 511 CELL2CELLPATHWAY Epithelial cell adhesion proteins such as cadherins transduce signals into the cell via catenins, which alter cell shape and motility. ACTN1, ACTN2, ACTN3, BCAR1, CSK, CTNNA1, CTNNA2, CTNNB1, PECAM1, PTK2, PXN, SRC, VCL 12 ACTN2(4), ACTN3(1), CTNNA1(1), CTNNA2(2), PTK2(1), PXN(1), VCL(3) 14072292 13 13 13 10 4 4 2 0 3 0 0.73 0.88 512 GLYCEROLIPID_METABOLISM ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, AGPAT1, AGPAT2, AGPAT3, AGPAT4, AKR1A1, AKR1B1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, CEL, DGAT1, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKQ, DGKZ, GK, GLA, GLB1, LCT, LIPC, LIPF, LIPG, LPL, PNLIP, PNLIPRP1, PNLIPRP2, PPAP2A, PPAP2B, PPAP2C 42 ADH1A(1), ADH7(2), ADHFE1(1), AGPAT3(2), AKR1B1(2), ALDH1A1(2), ALDH1A2(1), ALDH1B1(1), ALDH9A1(1), CEL(1), DGKA(3), DGKD(1), DGKE(1), DGKG(4), DGKH(1), GLA(2), GLB1(1), LCT(3), LPL(1), PNLIP(1), PNLIPRP1(2), PPAP2A(1) 33672405 35 33 34 12 4 17 6 3 5 0 0.74 0.89 513 HSA00960_ALKALOID_BIOSYNTHESIS_II Genes involved in alkaloid biosynthesis II AADAC, ABP1, AOC2, AOC3, ARD1A, CES1, CES7, DDHD1, ESCO1, ESCO2, LIPA, LYCAT, MYST3, MYST4, NAT5, NAT6, PLA1A, PNPLA3, PPME1, PRDX6, SH3GLB1 18 AADAC(1), AOC2(1), AOC3(2), CES1(1), CES7(1), ESCO1(3), MYST3(1), MYST4(5), PLA1A(2), PNPLA3(4) 19069284 21 19 21 8 6 6 2 1 3 3 0.74 0.89 514 LIMONENE_AND_PINENE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, ECHS1, EHHADH, HADHA, SDS 12 ALDH1A1(2), ALDH1A2(1), ALDH1B1(1), ALDH9A1(1), ECHS1(1), EHHADH(2) 8614437 8 8 8 7 0 5 2 1 0 0 0.74 0.89 515 MRPPATHWAY Cancer cells resistant to numerous drugs are called multidrug-resistant (MDR) and express ATP-binding cassette transporter proteins that pump the drugs out of cells. ABCB1, ABCB11, ABCB4, ABCC1, ABCC3, GSTP1 6 ABCB1(3), ABCB11(4), ABCC1(3) 11039418 10 10 10 9 1 3 4 1 1 0 0.74 0.89 516 HSA00600_SPHINGOLIPID_METABOLISM Genes involved in sphingolipid metabolism ARSA, ARSD, ARSE, ASAH1, ASAH3L, B4GALT6, CERK, DEGS1, DEGS2, ENPP7, FVT1, GAL3ST1, GALC, GBA, GLA, GLB1, LCT, NEU1, NEU2, NEU3, NEU4, PHCA, PPAP2A, PPAP2B, PPAP2C, SGMS1, SGMS2, SGPP1, SGPP2, SMPD1, SMPD2, SMPD3, SMPD4, SPHK1, SPHK2, SPTLC1, SPTLC2, UGCG, UGT8 33 ARSE(1), B4GALT6(1), CERK(1), DEGS1(2), ENPP7(1), GLA(2), GLB1(1), LCT(3), NEU2(1), PPAP2A(1), SGMS1(1), SGPP1(1), SGPP2(1), SMPD2(2), SPHK2(2), SPTLC1(1), SPTLC2(2), UGT8(1) 23712897 25 24 25 7 4 8 8 1 4 0 0.74 0.89 517 HSA00970_AMINOACYL_TRNA_BIOSYNTHESIS Genes involved in aminoacyl-tRNA biosynthesis AARS, AARS2, CARS, CARS2, DARS, DARS2, EARS2, EPRS, FARS2, FARSA, FARSB, GARS, HARS, HARS2, IARS, IARS2, KARS, LARS, LARS2, MARS, MARS2, MTFMT, NARS, NARS2, PARS2, QARS, RARS, RARS2, SARS, SARS2, TARS, TARS2, VARS, VARS2, WARS, WARS2, YARS, YARS2 38 AARS2(2), CARS2(1), DARS(1), DARS2(1), EARS2(3), EPRS(2), FARS2(1), FARSA(1), FARSB(3), GARS(1), IARS(5), IARS2(2), LARS2(2), NARS(1), NARS2(1), PARS2(1), QARS(2), RARS(1), RARS2(1), SARS(2), SARS2(2), TARS(4), TARS2(2), WARS2(1) 40526031 43 39 43 9 7 14 14 3 5 0 0.75 0.89 518 HSA01032_GLYCAN_STRUCTURES_DEGRADATION Genes involved in degradation of glycan structures AGA, ARSB, FLJ21865, FUCA1, FUCA2, GALNS, GBA, GLB1, GNS, GUSB, HEXA, HEXB, HGSNAT, HPSE, HPSE2, HYAL1, HYAL2, IDS, IDUA, LCT, MAN2B1, MAN2B2, MAN2C1, MANBA, NAGLU, NEU1, NEU2, NEU3, NEU4, SPAM1 27 ARSB(3), GLB1(1), GUSB(1), HEXB(1), HGSNAT(1), HPSE(3), HPSE2(1), HYAL2(1), IDS(2), LCT(3), MAN2B1(2), MAN2B2(3), MANBA(1), NAGLU(1), NEU2(1) 24132186 25 24 25 7 3 7 11 1 3 0 0.75 0.89 519 CIRCADIANPATHWAY A heterodimer composed of Bmal1 and Clock acts as a transcription factor for proteins that regulate circadian rhythms, such as Per and Cry. ARNTL, CLOCK, CRY1, CRY2, CSNK1E, PER1 6 ARNTL(1), CRY1(1), CSNK1E(1), PER1(2) 5832021 5 5 5 4 1 3 0 0 1 0 0.76 0.90 520 OXIDATIVE_PHOSPHORYLATION ATP12A, ATP4B, ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, ATP7A, ATP7B, COX10, COX4I1, COX5A, COX5B, COX6A1, COX6A2, COX6B1, COX6C, COX7A1, COX7A2, COX7B, COX7C, COX8A, NDUFA1, NDUFA10, NDUFA11, NDUFA4, NDUFA5, NDUFA8, NDUFB2, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFS1, NDUFS2, NDUFV1, NDUFV2, PP, PPA2, SDHA, SDHA, SDHAL2, SDHB, UQCRB, UQCRC1, UQCRFS1, UQCRH 55 ATP12A(3), ATP6V0A4(2), ATP6V0B(1), ATP6V1B2(1), ATP6V1C1(1), ATP6V1G2(1), ATP6V1H(1), ATP7B(1), COX10(2), COX5A(1), COX6C(1), NDUFA1(1), NDUFA10(1), NDUFS2(1), NDUFV1(1), NDUFV2(1), SDHA(1), SDHB(1), UQCRC1(2) 25584234 24 23 24 8 5 6 5 2 6 0 0.76 0.90 521 RECKPATHWAY RECK is a membrane-anchored inhibitor of matrix metalloproteinases, which are expressed by tumor cells and promote metastasis. HRAS, MMP14, MMP2, MMP9, RECK, TIMP1, TIMP2, TIMP3, TIMP4 9 MMP14(3), MMP9(1) 5542524 4 4 3 4 1 3 0 0 0 0 0.76 0.90 522 HSA03020_RNA_POLYMERASE Genes involved in RNA polymerase POLR1A, POLR1B, POLR1C, POLR1D, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLR3A, POLR3B, POLR3G, POLR3GL, POLR3H, POLR3K, ZNRD1 23 POLR1A(1), POLR1B(2), POLR1C(2), POLR1D(1), POLR2A(2), POLR2B(3), POLR2H(1), POLR3A(1), POLR3B(2), POLR3GL(2) 17322162 17 16 17 8 3 3 6 1 4 0 0.77 0.91 523 VITCBPATHWAY Vitamin C (ascorbic acid), in addition to its role in collagen modification, serves as an antioxidant and is imported into cells by Svct2 in the brain and Svct1 in intestinal epithelium. COL4A1, COL4A2, COL4A3, COL4A4, COL4A5, COL4A6, P4HB, SLC23A1, SLC23A2, SLC2A1, SLC2A3 11 COL4A1(4), COL4A2(2), COL4A3(1), COL4A4(1), COL4A5(4), COL4A6(3), SLC23A1(2), SLC2A3(2) 18875103 19 18 19 9 3 6 7 1 2 0 0.77 0.91 524 PHENYLALANINE_TYROSINE_AND_TRYPTOPHAN_BIOSYNTHESIS ENO1, ENO2, ENO3, FARS2, FARSLB, GOT1, GOT2, PAH, TAT, YARS 9 ENO1(1), ENO3(1), FARS2(1), GOT2(1), PAH(1) 6207201 5 5 5 0 0 2 1 2 0 0 0.77 0.91 525 RNA_POLYMERASE POLR1B, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLRMT 13 POLR1B(2), POLR2A(2), POLR2B(3), POLR2H(1) 8445606 8 7 8 5 3 0 2 0 3 0 0.78 0.91 526 HSA00720_REDUCTIVE_CARBOXYLATE_CYCLE Genes involved in reductive carboxylate cycle (CO2 fixation) ACLY, ACO1, ACO2, ACSS1, ACSS2, FH, IDH1, IDH2, LOC441996, MDH1, MDH2, SUCLA2 11 ACLY(2), ACO1(1), ACO2(2), IDH1(1), MDH2(2), SUCLA2(1) 9951396 9 9 9 2 2 4 3 0 0 0 0.78 0.91 527 SYNTHESIS_AND_DEGRADATION_OF_KETONE_BODIES ACAT1, ACAT2, BDH, HMGCL, OXCT1 4 ACAT1(1), OXCT1(1) 2475174 2 2 2 1 0 1 1 0 0 0 0.78 0.92 528 HYPERTROPHY_MODEL ADAM10, ANKRD1, ATF3, CYR61, DUSP14, EIF4E, EIF4EBP1, GDF8, HBEGF, IFNG, IFRD1, IL18, IL1A, IL1R1, JUND, MYOG, NR4A3, TCF8, VEGF, WDR1 16 ADAM10(1), ATF3(1), CYR61(1), IFRD1(1), IL1A(1), IL1R1(1) 7695246 6 6 6 2 1 1 3 1 0 0 0.80 0.93 529 1_2_DICHLOROETHANE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A1(2), ALDH1A2(1), ALDH1B1(1), ALDH9A1(1) 5692089 5 5 5 3 0 5 0 0 0 0 0.80 0.93 530 ASCORBATE_AND_ALDARATE_METABOLISM ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A1(2), ALDH1A2(1), ALDH1B1(1), ALDH9A1(1) 5692089 5 5 5 3 0 5 0 0 0 0 0.80 0.93 531 HSA00240_PYRIMIDINE_METABOLISM Genes involved in pyrimidine metabolism AICDA, AK3, CAD, CANT1, CDA, CMPK, CTPS, CTPS2, DCK, DCTD, DHODH, DPYD, DPYS, DTYMK, DUT, ECGF1, ENTPD1, ENTPD3, ENTPD4, ENTPD5, ENTPD6, ENTPD8, ITPA, NME1, NME2, NME4, NME6, NME7, NP, NT5C, NT5C1A, NT5C1B, NT5C2, NT5C3, NT5E, NT5M, NUDT2, PNPT1, POLA1, POLA2, POLD1, POLD2, POLD3, POLD4, POLE, POLE2, POLE3, POLE4, POLR1A, POLR1B, POLR1C, POLR1D, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLR3A, POLR3B, POLR3G, POLR3GL, POLR3H, POLR3K, PRIM1, PRIM2, RFC5, RRM1, RRM2, RRM2B, TK1, TK2, TXNRD1, TXNRD2, TYMS, UCK1, UCK2, UMPS, UPB1, UPP1, UPP2, UPRT, ZNRD1 83 CAD(7), CTPS2(2), DPYD(1), DPYS(1), ENTPD1(2), ENTPD4(1), ENTPD6(1), NME6(1), NME7(2), NT5C1B(3), NT5C3(1), NT5E(3), POLA1(4), POLD2(1), POLD4(1), POLE2(1), POLE3(1), POLR1A(1), POLR1B(2), POLR1C(2), POLR1D(1), POLR2A(2), POLR2B(3), POLR2H(1), POLR3A(1), POLR3B(2), POLR3GL(2), RRM2(1), TK2(1), UCK2(2), UMPS(1), UPB1(3), UPP1(2), UPRT(1) 59012265 61 53 61 19 11 14 19 5 12 0 0.80 0.93 532 HSA04140_REGULATION_OF_AUTOPHAGY Genes involved in regulation of autophagy ATG12, ATG3, ATG5, ATG7, BECN1, GABARAP, GABARAPL1, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNG, INS, LOC441925, PIK3C3, PIK3R4, PRKAA1, PRKAA2, ULK1, ULK2, ULK3 27 ATG7(2), IFNA10(1), IFNA14(1), IFNA2(2), IFNA4(1), PIK3C3(2), PIK3R4(3), PRKAA2(2) 14310582 14 13 14 5 4 3 3 2 2 0 0.80 0.93 533 ST_GA12_PATHWAY G-alpha-12 promotes cell survival and proliferation, is involved in the stress response, and activates JNK. BF, BTK, DLG4, EPHB2, F2, F2RL1, F2RL2, F2RL3, JUN, MAP2K5, MAPK1, MAPK7, MAPK8, MYEF2, PLD1, PLD2, PLD3, PTK2, RAF1, RASAL1, SRC, TEC, VAV1 21 BTK(2), EPHB2(1), F2(2), F2RL2(1), JUN(1), MAP2K5(1), MAPK1(1), MAPK8(2), MYEF2(1), PLD1(1), PLD3(1), PTK2(1), RAF1(1), RASAL1(1), TEC(1), VAV1(1) 19738524 19 18 19 5 1 9 3 3 3 0 0.81 0.93 534 IFNGPATHWAY IFN gamma signaling pathway IFNG, IFNGR1, IFNGR2, JAK1, JAK2, STAT1 6 JAK1(1), JAK2(2), STAT1(1) 6231537 4 4 4 1 0 0 0 1 3 0 0.81 0.93 535 KREBS_TCA_CYCLE ACO2, CGI_48, CS, DLAT, DLD, DLST, DLST, DLSTP, FH, IDH2, IDH3A, IDH3B, IDH3G, KIAA1348, MDH1, MDH2, OGDH, PC, PDHA1, PDHA2, PDHB, PDHX, PDK1, PDK2, PDK3, PDK4, PDP2, PPM2C, SDHA, SDHA, SDHAL2, SDHB, SDHC, SDHD, SUCLA2, SUCLG1, SUCLG2, WDR50 30 ACO2(2), CS(1), DLD(1), IDH3A(1), IDH3G(1), MDH2(2), OGDH(1), PC(1), PDHA1(1), PDHA2(1), PDHB(1), PDHX(1), PDK1(1), PDK2(1), PDK4(1), PDP2(1), SDHA(1), SDHB(1), SUCLA2(1) 20894484 21 20 21 6 4 8 7 2 0 0 0.81 0.93 536 CITRATE_CYCLE_TCA_CYCLE ACO1, ACO2, CS, DLD, DLST, DLSTP, FH, IDH1, IDH2, IDH3A, IDH3B, IDH3G, MDH1, MDH2, PC, PCK1, SDHA, SDHA, SDHAL2, SDHB, SUCLA2, SUCLG1, SUCLG2 20 ACO1(1), ACO2(2), CS(1), DLD(1), IDH1(1), IDH3A(1), IDH3G(1), MDH2(2), PC(1), PCK1(1), SDHA(1), SDHB(1), SUCLA2(1) 15259179 15 14 15 3 2 6 6 1 0 0 0.81 0.93 537 HSA00510_N_GLYCAN_BIOSYNTHESIS Genes involved in N-glycan biosynthesis ALG1, ALG10, ALG10B, ALG11, ALG12, ALG13, ALG14, ALG2, ALG3, ALG5, ALG6, ALG8, ALG9, B4GALT1, B4GALT2, B4GALT3, DAD1, DDOST, DHDDS, DOLPP1, DPAGT1, DPM1, FUT8, GANAB, GCS1, MAN1A1, MAN1A2, MAN1B1, MAN1C1, MAN2A1, MGAT1, MGAT2, MGAT3, MGAT4A, MGAT4B, MGAT5, MGAT5B, RFT1, RPN1, RPN2, ST6GAL1, STT3B 41 ALG1(1), ALG10(1), ALG10B(3), ALG11(1), ALG13(2), ALG2(1), ALG6(1), ALG9(1), B4GALT1(2), B4GALT3(1), DPAGT1(2), MAN1A2(1), MAN1B1(1), MAN2A1(3), MGAT3(1), MGAT5(2), MGAT5B(4), RPN1(1) 30462588 29 28 29 13 5 8 6 3 7 0 0.81 0.93 538 LYSINE_DEGRADATION AADAT, AASDH, AASDHPPT, AASS, ACAT1, ACAT2, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, ATP6V0C, SHMT1, BAT8, BBOX1, DLST, DLSTP, DOT1L, ECHS1, EHHADH, EHMT1, EHMT2, GCDH, HADHA, PLOD1, PLOD2, PLOD3, SDS, SHMT1, SHMT2, TMLHE 31 AASDH(1), AASDHPPT(2), AASS(3), ACAT1(1), ALDH1A1(2), ALDH1A2(1), ALDH1B1(1), ALDH9A1(1), DOT1L(3), ECHS1(1), EHHADH(2), GCDH(1), PLOD1(1), PLOD2(1), PLOD3(1) 25485369 22 21 22 14 1 9 5 3 4 0 0.82 0.93 539 PLCDPATHWAY Phospholipase C (PLC-d1) hydrolyzes the membrane lipid PIP2 to DAG and IP3, which induce calcium influx and activates protein kinase C. ADRA1B, PLCD1, PRKCA, PRKCB1, TGM2 4 ADRA1B(1), PLCD1(1) 3752814 2 2 2 3 0 0 0 0 2 0 0.82 0.94 540 HSA00471_D_GLUTAMINE_AND_D_GLUTAMATE_METABOLISM Genes involved in D-glutamine and D-glutamate metabolism GLS, GLS2, GLUD1, GLUD2 4 GLS(1), GLUD2(1) 3079011 2 2 2 1 0 0 1 0 1 0 0.82 0.94 541 PHOTOSYNTHESIS ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, FDXR 22 ATP6V0A4(2), ATP6V0B(1), ATP6V1B2(1), ATP6V1C1(1), ATP6V1G2(1), ATP6V1H(1), FDXR(3) 11895234 10 10 9 3 2 2 3 1 2 0 0.82 0.94 542 CYSTEINE_METABOLISM CARS, CTH, GOT1, GOT2, LDHA, LDHB, LDHC, MPST 7 CTH(1), GOT2(1), LDHC(1) 4869228 3 3 3 0 0 2 0 0 1 0 0.82 0.94 543 CHONDROITIN B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 7 B3GAT3(1), HS3ST2(1), XYLT2(1) 4417998 3 3 3 2 1 1 1 0 0 0 0.83 0.94 544 HEPARAN_SULFATE_BIOSYNTHESIS B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 7 B3GAT3(1), HS3ST2(1), XYLT2(1) 4417998 3 3 3 2 1 1 1 0 0 0 0.83 0.94 545 PENTOSE_AND_GLUCURONATE_INTERCONVERSIONS AKR1B1, DCXR, GUSB, RPE, RPE, LOC440001, UCHL1, UCHL3, UGDH, UGT1A10, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A9, UGT2B15, UGT2B4 18 AKR1B1(2), GUSB(1), UCHL3(1), UGT1A10(1), UGT1A6(2), UGT2B15(2), UGT2B4(1) 12038715 10 10 10 5 2 2 3 1 2 0 0.83 0.94 546 ACE2PATHWAY Angiotensin-converting enzyme 2 (ACE2) digests the blood-pressure regulator angiotensin II (AGT) ultimately to the vasodilator AGT1-7. ACE2, AGT, AGTR1, AGTR2, CMA1, COL4A1, COL4A2, COL4A3, COL4A4, COL4A5, COL4A6, REN 12 ACE2(1), AGT(3), COL4A1(4), COL4A2(2), COL4A3(1), COL4A4(1), COL4A5(4), COL4A6(3) 19148376 19 17 19 8 3 7 6 0 3 0 0.83 0.94 547 MALATEXPATHWAY The tricarboxylate transfer pathway shuttles acetyl groups of acetyl-CoA between mitochondria and the cytoplasm. ACLY, CS, MDH1, ME1, PC, PDHA1, SLC25A1, SLC25A11 8 ACLY(2), CS(1), PC(1), PDHA1(1) 6708624 5 5 5 2 0 3 1 1 0 0 0.83 0.94 548 AMINOACYL_TRNA_BIOSYNTHESIS AARS, CARS, DARS, EPRS, FARS2, FARSLB, GARS, HARS, HARSL, IARS, KARS, LARS, LARS2, MARS, MARS2, NARS, QARS, RARS, SARS, TARS, WARS, WARS2, YARS 21 DARS(1), EPRS(2), FARS2(1), GARS(1), IARS(5), LARS2(2), NARS(1), QARS(2), RARS(1), SARS(2), TARS(4), WARS2(1) 23973495 23 22 23 6 3 7 7 2 4 0 0.84 0.94 549 CBLPATHWAY Activated EGF receptors undergo endocytosis into clathrin-coated vesicles, where they are recycled to the membrane or ubiquitinated by Cbl. CBL, CSF1R, EGF, EGFR, GRB2, MET, PDGFRA, PRKCA, PRKCB1, SH3GLB1, SH3GLB2, SH3KBP1, SRC 12 EGF(2), EGFR(4), GRB2(1), MET(4), PDGFRA(3) 14554956 14 12 14 4 3 3 1 4 0 3 0.84 0.94 550 HSA00791_ATRAZINE_DEGRADATION Genes involved in atrazine degradation ADAR, APOBEC1, APOBEC2, APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3F, APOBEC3G, APOBEC4 9 ADAR(1), APOBEC2(1), APOBEC3B(1), APOBEC4(1) 5493345 4 4 4 1 0 2 1 0 1 0 0.84 0.94 551 HSA00511_N_GLYCAN_DEGRADATION Genes involved in N-glycan degradation AGA, FLJ21865, FUCA1, FUCA2, GLB1, HEXA, HEXB, LCT, MAN2B1, MAN2B2, MAN2C1, MANBA, NEU1, NEU2, NEU3, NEU4 14 GLB1(1), HEXB(1), LCT(3), MAN2B1(2), MAN2B2(3), MANBA(1), NEU2(1) 14468259 12 12 12 4 0 2 7 1 2 0 0.84 0.94 552 HSA00020_CITRATE_CYCLE Genes involved in citrate cycle (TCA cycle) ACLY, ACO1, ACO2, CLYBL, CS, DLD, DLST, FH, IDH1, IDH2, IDH3A, IDH3B, IDH3G, LOC283398, LOC441996, MDH1, MDH2, OGDH, OGDHL, PC, PCK1, PCK2, SDHA, SDHB, SDHC, SDHD, SUCLA2, SUCLG1, SUCLG2 27 ACLY(2), ACO1(1), ACO2(2), CLYBL(2), CS(1), DLD(1), IDH1(1), IDH3A(1), IDH3G(1), MDH2(2), OGDH(1), OGDHL(1), PC(1), PCK1(1), PCK2(1), SDHA(1), SDHB(1), SUCLA2(1) 22200516 22 20 22 5 2 11 7 2 0 0 0.84 0.94 553 HSA00130_UBIQUINONE_BIOSYNTHESIS Genes involved in ubiquinone biosynthesis COQ2, COQ3, COQ5, COQ6, COQ7, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA12, NDUFA13, NDUFB11 8 COQ3(1), NDUFA13(1) 2989272 2 2 2 0 0 2 0 0 0 0 0.85 0.95 554 BETAOXIDATIONPATHWAY Beta-Oxidation of Fatty Acids ACADL, ACADM, ACADS, ACAT1, ECHS1, HADHA 6 ACAT1(1), ECHS1(1) 3846609 2 2 2 3 0 1 0 1 0 0 0.86 0.95 555 VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION ACAA1, ACAA2, ACADL, ACADM, ACADS, ACADSB, ACAT1, ACAT2, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH6A1, ALDH9A1, AOX1, BCAT1, BCKDHA, BCKDHB, ECHS1, EHHADH, HADHA, HADHB, HIBADH, HMGCL, IVD, MCCC1, MCCC2, MCEE, MUT, OXCT1, PCCA, PCCB, SDS 36 ACAA1(1), ACAA2(1), ACADSB(1), ACAT1(1), ALDH1A1(2), ALDH1A2(1), ALDH1B1(1), ALDH9A1(1), AOX1(3), BCAT1(3), BCKDHA(1), ECHS1(1), EHHADH(2), HADHB(1), MCCC1(2), OXCT1(1), PCCA(1) 25785513 24 23 24 10 3 10 7 2 2 0 0.86 0.96 556 EIF2PATHWAY Eukaryotic initiation factor 2 (EIF2) initiates translation by transferring Met-tRNA to the 40S ribosome in a GTP-dependent process. EIF2AK3, EIF2AK4, EIF2B5, EIF2S1, EIF2S2, EIF2S3, EIF5, GSK3B, HRI, PPP1CA, PRKR 9 EIF2AK3(1), EIF2B5(1), EIF2S1(1), EIF2S2(1), EIF5(1) 8609367 5 5 5 3 2 1 1 0 1 0 0.86 0.96 557 ERBB4PATHWAY ErbB4 (aka HER4) is a receptor tyrosine kinase that binds neuregulins as well as members of the EGF family, which also target EGF receptors. ADAM17, ERBB4, NRG2, NRG3, PRKCA, PRKCB1, PSEN1 6 ERBB4(4), NRG3(1) 6545370 5 5 5 2 2 2 1 0 0 0 0.87 0.96 558 DNA_REPLICATION_REACTOME ASK, CDC45L, CDC6, CDC7, CDK2, CDT1, DIAPH2, GMNN, MCM10, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, NACA, NACA, FKSG17, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, POLA, POLA2, POLD1, POLD2, POLD3, POLD4, POLE, POLE2, PRIM1, PRIM2A, RFC1, RFC2, RFC3, RFC4, RFC5, RPA1, RPA2, RPA3, RPA4, RPS27A, RPS27A, LOC388720, LOC389425, UBA52, UBB, UBC 41 CDC7(1), CDK2(1), MCM10(1), MCM2(1), MCM3(1), MCM4(2), MCM6(2), MCM7(2), NACA(3), ORC2L(1), ORC3L(1), POLD2(1), POLD4(1), POLE2(1), RFC1(2), RFC4(3), RPA1(1), UBC(6) 36393981 31 30 31 8 7 7 9 1 5 2 0.88 0.97 559 HSA00380_TRYPTOPHAN_METABOLISM Genes involved in tryptophan metabolism AADAT, AANAT, ABP1, ACAT1, ACAT2, ACMSD, AFMID, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, AOC2, AOC3, AOX1, ASMT, CARM1, CAT, CYP1A1, CYP1A2, CYP1B1, DDC, ECHS1, EHHADH, GCDH, HAAO, HADH, HADHA, HEMK1, HSD17B10, HSD17B4, INDO, INDOL1, INMT, KMO, KYNU, LCMT1, LCMT2, LNX1, MAOA, MAOB, METTL2B, METTL6, NFX1, OGDH, OGDHL, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, TDO2, TPH1, TPH2, WARS, WARS2, WBSCR22 58 ACAT1(1), ALDH1B1(1), ALDH9A1(1), AOC2(1), AOC3(2), AOX1(3), CARM1(1), CYP1B1(1), DDC(1), ECHS1(1), EHHADH(2), GCDH(1), HADH(1), HSD17B10(1), HSD17B4(3), INMT(1), KYNU(1), LCMT1(1), LCMT2(3), LNX1(1), MAOA(2), METTL2B(2), OGDH(1), OGDHL(1), PRMT3(2), PRMT5(2), PRMT6(2), PRMT7(1), PRMT8(1), WARS2(1) 44382780 43 38 43 20 5 15 14 2 7 0 0.88 0.97 560 HSA03050_PROTEASOME Genes involved in proteasome PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMC2, PSMC3, PSMD1, PSMD11, PSMD12, PSMD13, PSMD2, PSMD6 22 PSMA5(1), PSMB6(1), PSMD1(4), PSMD2(1), PSMD6(2) 11864814 9 9 9 3 2 2 3 0 2 0 0.88 0.97 561 GLYCOSPHINGOLIPID_METABOLISM ARSA, ARSB, ARSD, ARSE, ASAH1, GAL3ST1, GALC, GBA, GBAP, GLA, GLB1, LCT, NEU1, NEU2, NEU3, NEU4, PPAP2A, PPAP2B, PPAP2C, SMPD1, SMPD2, SPTLC1, SPTLC2, UGCG 20 ARSB(3), ARSE(1), GLA(2), GLB1(1), LCT(3), NEU2(1), PPAP2A(1), SMPD2(2), SPTLC1(1), SPTLC2(2) 16675230 17 14 17 2 3 6 5 1 2 0 0.88 0.97 562 RANPATHWAY RanGEF (aka RCC1) and RanGFP regulate the GTP- or GDP-bound state of Ran, creating a Ran gradient across the nuclear membrane that is used in nuclear import. CHC1, RAN, RANBP1, RANBP2, RANGAP1 4 RAN(1), RANBP2(1), RANGAP1(2) 6114420 4 4 4 0 1 0 1 1 1 0 0.88 0.97 563 HSA04740_OLFACTORY_TRANSDUCTION Genes involved in olfactory transduction ADCY3, ADRBK2, ARRB2, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CLCA1, CLCA2, CLCA4, CNGA3, CNGA4, CNGB1, GNAL, GUCA1A, GUCA1B, GUCA1C, PDC, PDE1C, PRKACA, PRKACB, PRKACG, PRKG1, PRKG2, PRKX, PRKY 30 ADCY3(2), CAMK2A(1), CAMK2D(3), CNGA3(3), CNGA4(2), GUCA1A(1), GUCA1C(1), PRKACA(1), PRKG1(1), PRKG2(4) 22180743 19 19 19 10 4 4 5 4 2 0 0.89 0.97 564 PPARGPATHWAY PPAR-gamma is a nuclear hormone receptor that is activated by fatty acids and regulates transcription through co-activations like Src-1 and Tif2. CREBBP, EP300, LPL, NCOA1, NCOA2, PPARBP, PPARG, PPARGC1, RXRA 7 CREBBP(2), EP300(3), LPL(1), NCOA1(1), NCOA2(1), PPARG(1) 13479609 9 9 8 4 2 1 1 1 4 0 0.89 0.97 565 VOBESITYPATHWAY The adipose tissue of obese individuals overexpresses a key glucocorticoid-metabolizing enzyme, activating inactive circulating corticosteroids and inducing insulin resistance. APM1, HSD11B1, LPL, NR3C1, PPARG, RETN, RXRA, TNF 7 LPL(1), PPARG(1) 4189848 2 2 2 1 1 0 1 0 0 0 0.89 0.97 566 SLRPPATHWAY Small leucine-rich proteoglycans (SLRPs) interact with and reorganize collagen fibers in the extracellular matrix. BGN, DCN, DSPG3, FMOD, KERA, LUM 5 BGN(1) 2775318 1 1 1 0 1 0 0 0 0 0 0.89 0.97 567 RNA_TRANSCRIPTION_REACTOME CCNH, CDK7, ERCC3, GTF2A2, GTF2B, GTF2E1, GTF2E2, GTF2F2, GTF2H1, GTF2H2, GTF2H4, ILK, MGC9850, MNAT1, POLR1A, POLR1B, POLR2A, POLR2B, POLR2C, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR3B, POLR3D, POLR3E, POLR3H, POLR3K, TAF12, TAF13, TAF5, TAF6, TAF7, TAF9, TBP, VARS2L 36 CDK7(1), ERCC3(2), GTF2E2(1), GTF2F2(1), ILK(2), MNAT1(1), POLR1A(1), POLR1B(2), POLR2A(2), POLR2B(3), POLR2H(1), POLR3B(2), POLR3E(2), TAF6(1), TAF7(1), TBP(1) 26232180 24 22 24 11 4 7 7 0 6 0 0.89 0.97 568 CYANOAMINO_ACID_METABOLISM ATP6V0C, SHMT1, GBA3, GGT1, SHMT1, SHMT2 5 GGT1(1) 3155061 1 1 1 1 0 1 0 0 0 0 0.90 0.97 569 HSA00310_LYSINE_DEGRADATION Genes involved in lysine degradation AADAT, AASDHPPT, AASS, ACAT1, ACAT2, AKR1B10, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, BBOX1, DLST, DOT1L, ECHS1, EHHADH, EHMT1, EHMT2, GCDH, HADH, HADHA, HSD17B10, HSD17B4, HSD3B7, NSD1, OGDH, OGDHL, PIPOX, PLOD1, PLOD2, PLOD3, RDH11, RDH12, RDH13, RDH14, SETD1A, SETD7, SETDB1, SHMT1, SHMT2, SPCS1, SPCS3, SUV39H1, SUV39H2, TMLHE 47 AASDHPPT(2), AASS(3), ACAT1(1), ALDH1B1(1), ALDH9A1(1), DOT1L(3), ECHS1(1), EHHADH(2), GCDH(1), HADH(1), HSD17B10(1), HSD17B4(3), OGDH(1), OGDHL(1), PIPOX(1), PLOD1(1), PLOD2(1), PLOD3(1), RDH11(2), RDH12(1), RDH14(1), SETD7(1), SETDB1(7) 41347878 38 37 37 18 6 14 9 4 5 0 0.90 0.97 570 EICOSANOID_SYNTHESIS ALOX12, ALOX15, ALOX15B, ALOX5, ALOX5AP, DPEP1, GGT1, IPLA2(GAMMA), LTA4H, LTC4S, PLA2G2A, PLA2G6, PTGDS, PTGES, PTGIS, PTGS1, PTGS2, TBXAS1 15 ALOX12(1), GGT1(1), PLA2G6(2), PTGDS(1), PTGS2(1), TBXAS1(1) 9843912 7 7 7 1 0 4 2 0 1 0 0.90 0.97 571 MITOCHONDRIAL_FATTY_ACID_BETAOXIDATION ACADL, ACADM, ACADS, ACADVL, ACSL1, ACSL3, ACSL4, CPT1A, CPT2, DCI, EHHADH, HADHA, HADHSC, MGC5139, PECR, SCP2, SLC25A20 15 ACADVL(2), ACSL3(1), ACSL4(1), CPT1A(2), CPT2(1), EHHADH(2), SLC25A20(1) 12381447 10 10 10 7 1 6 3 0 0 0 0.91 0.98 572 KREBPATHWAY The Krebs (citric acid) cycle takes place in mitochondria, where it extracts energy in the form of electron carriers NADH and FADH2, which drive the electron transport chain. ACO2, CS, FH, IDH2, MDH1, OGDH, SDHA, SUCLA2 8 ACO2(2), CS(1), OGDH(1), SDHA(1), SUCLA2(1) 7055919 6 5 6 2 1 2 2 1 0 0 0.91 0.98 573 N_GLYCAN_BIOSYNTHESIS ALG3, ALG5, B4GALT1, B4GALT2, B4GALT3, B4GALT5, DDOST, DPAGT1, DPM1, FUT8, GCS1, MAN1A1, MAN1B1, MGAT1, MGAT2, MGAT3, MGAT4A, MGAT4B, MGAT5, RPN1, RPN2, ST6GAL1 21 B4GALT1(2), B4GALT3(1), DPAGT1(2), MAN1B1(1), MGAT3(1), MGAT5(2), RPN1(1) 13911066 10 10 10 3 0 4 2 1 3 0 0.92 0.99 574 HSA03030_DNA_POLYMERASE Genes involved in DNA polymerase POLA1, POLA2, POLB, POLD1, POLD2, POLD3, POLD4, POLE, POLE2, POLE3, POLE4, POLG, POLG2, POLH, POLI, POLK, POLL, POLM, POLQ, POLS, PRIM1, PRIM2, REV1, REV3L, RFC5 24 POLA1(4), POLB(1), POLD2(1), POLD4(1), POLE2(1), POLE3(1), POLG(1), POLH(2), POLI(3), POLL(1), POLQ(4), REV1(1), REV3L(4) 31128279 25 24 25 7 3 8 5 3 6 0 0.92 0.99 575 APOPTOSIS_KEGG APAF1, BAD, BAX, BCL2, BCL2A1, BCL2L1, BCL2L2, BOK, CASP1, CASP1, COPl, CASP10, CASP2, CASP3, CASP4, CASP6, CASP7, CASP8, CASP9, CD40, CD40LG, CRADD, CYCS, DAXX, DFFA, DFFB, FADD, FAS, FASLG, HRK, IKBKE, LTA, MCL1, NFKB1, NFKBIA, NGFB, NGFR, NR3C1, NTRK1, PTPN13, RIPK1, SFRS2IP, TFG, TNF, TNFRSF1A, TNFRSF1B, TRADD, TRAF1, TRAF2, TRAF3, TRAF6 45 APAF1(1), BAD(1), CASP1(1), CASP2(2), CASP6(1), CASP8(2), CD40(1), CD40LG(1), DFFB(2), FAS(1), FASLG(1), IKBKE(1), NFKB1(1), NGFR(1), NTRK1(1), PTPN13(4), RIPK1(3), SFRS2IP(1), TNFRSF1A(1), TRAF6(1) 32007924 28 26 28 5 9 9 2 2 6 0 0.92 0.99 576 NUCLEOTIDE_METABOLISM ADSL, ADSS, DHFR, HPRT1, IMPDH1, MTHFD2, NME2, OAZ1, POLA, POLB, POLD1, POLG, PRPS2, RRM1, SAT, SRM 13 ADSL(1), IMPDH1(2), POLB(1), POLG(1), PRPS2(1) 8741187 6 6 6 3 2 2 0 1 1 0 0.93 0.99 577 TALL1PATHWAY APRIL and BAFF bind to BCMA and TACI receptors on B cell surfaces, promoting immunoglobulin production and cell proliferation. CHUK, MAP3K14, MAPK14, MAPK8, NFKB1, RELA, TNFRSF13B, TNFRSF13C, TNFRSF17, TNFSF13, TNFSF13B, TRAF2, TRAF3, TRAF5, TRAF6 14 MAPK14(1), MAPK8(2), NFKB1(1), RELA(1), TNFSF13B(1), TRAF6(1) 10531404 7 7 7 1 1 4 0 0 2 0 0.93 0.99 578 AKAP13PATHWAY A-kinase anchor protein 13 (AKAP13) localizes protein kinase A holoenzyme and is a nucleotide exchange factor for Rho/Rac. AKAP13, ARHA, EDG2, EDG4, EDG7, GNA12, PRKACB, PRKACG, PRKAG1, PRKAR2A, PRKAR2B 7 AKAP13(3), PRKAR2A(1), PRKAR2B(1) 7388004 5 5 5 3 2 2 0 1 0 0 0.93 0.99 579 HSA00272_CYSTEINE_METABOLISM Genes involved in cysteine metabolism CARS, CARS2, CDO1, CTH, GOT1, GOT2, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, MPST, SDS, SULT1B1, SULT1C2, SULT1C4, SULT4A1 16 CARS2(1), CDO1(1), CTH(1), GOT2(1), LDHC(1) 8927256 5 5 5 1 0 2 1 0 2 0 0.93 0.99 580 HSA00641_3_CHLOROACRYLIC_ACID_DEGRADATION Genes involved in 3-chloroacrylic acid degradation ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1 15 ADH1A(1), ADH7(2), ADHFE1(1), ALDH1B1(1), ALDH9A1(1) 9670011 6 6 6 2 0 5 1 0 0 0 0.93 0.99 581 NTHIPATHWAY Hemophilus influenzae infections activate NF-kB via several pathways, inducing the inflammatory response. CHUK, CREBBP, DUSP1, EP300, IKBKB, IL1B, IL8, MADH3, MADH4, MAP2K3, MAP2K6, MAP3K14, MAP3K7, MAPK11, MAPK14, MYD88, NFKB1, NFKBIA, NR3C1, RELA, TGFBR1, TGFBR2, TLR2, TNF 21 CREBBP(2), EP300(3), IKBKB(2), MAP2K3(1), MAPK14(1), NFKB1(1), RELA(1), TGFBR1(2), TLR2(1) 21208317 14 14 13 4 1 6 1 1 5 0 0.94 0.99 582 HSA00640_PROPANOATE_METABOLISM Genes involved in propanoate metabolism ABAT, ACACA, ACACB, ACADM, ACAT1, ACAT2, ACSS1, ACSS2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH6A1, ALDH7A1, ALDH9A1, ECHS1, EHHADH, HADHA, HIBCH, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, LOC283398, MCEE, MLYCD, MUT, PCCA, PCCB, SUCLA2, SUCLG1, SUCLG2 33 ABAT(3), ACACA(1), ACACB(8), ACAT1(1), ALDH1B1(1), ALDH9A1(1), ECHS1(1), EHHADH(2), HIBCH(2), LDHC(1), MLYCD(2), PCCA(1), SUCLA2(1) 29235141 25 24 25 7 4 12 7 1 1 0 0.94 0.99 583 NOTCHPATHWAY Proteolysis and Signaling Pathway of Notch ADAM17, DLL1, FURIN, NOTCH1, PSEN1, RBPSUH 4 FURIN(1) 3715803 1 1 1 2 0 0 0 1 0 0 0.94 0.99 584 IRINOTECAN_PATHWAY_PHARMGKB ABCC1, ABCC2, ABCG2, BCHE, CES1, CES2, CES4, CYP3A4, CYP3A5, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6 17 ABCC1(3), ABCC2(3), BCHE(1), CES1(1), CYP3A4(3), UGT1A10(1), UGT1A6(2) 17340921 14 14 14 6 4 3 6 0 1 0 0.94 0.99 585 HSA03022_BASAL_TRANSCRIPTION_FACTORS Genes involved in basal transcription factors GTF2A1, GTF2A1L, GTF2A2, GTF2B, GTF2E1, GTF2E2, GTF2F1, GTF2F2, GTF2H1, GTF2H2, GTF2H3, GTF2H4, GTF2I, GTF2IRD1, LOC391764, STON1, TAF1, TAF10, TAF12, TAF13, TAF1L, TAF2, TAF4, TAF4B, TAF5, TAF5L, TAF6, TAF6L, TAF7, TAF7L, TAF9, TAF9B, TBPL1, TBPL2 31 GTF2E2(1), GTF2F2(1), TAF1(6), TAF1L(6), TAF4B(2), TAF5L(1), TAF6(1), TAF7(1), TBPL2(2) 26955162 21 21 20 5 4 5 8 0 4 0 0.95 1.00 586 ATP_SYNTHESIS ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H 21 ATP6V0A4(2), ATP6V0B(1), ATP6V1B2(1), ATP6V1C1(1), ATP6V1G2(1), ATP6V1H(1) 11287848 7 7 7 3 2 0 2 1 2 0 0.95 1.00 587 FLAGELLAR_ASSEMBLY ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H 21 ATP6V0A4(2), ATP6V0B(1), ATP6V1B2(1), ATP6V1C1(1), ATP6V1G2(1), ATP6V1H(1) 11287848 7 7 7 3 2 0 2 1 2 0 0.95 1.00 588 TYPE_III_SECRETION_SYSTEM ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H 21 ATP6V0A4(2), ATP6V0B(1), ATP6V1B2(1), ATP6V1C1(1), ATP6V1G2(1), ATP6V1H(1) 11287848 7 7 7 3 2 0 2 1 2 0 0.95 1.00 589 PITX2PATHWAY The bicoid-related transcription factor Pitx2 is activated by Wnt binding to the Frizzled receptor and induces tissue-specific cell proliferation. APC, AXIN1, CREBBP, CTNNB1, DVL1, EP300, FZD1, GSK3B, HDAC1, HTATIP, LDB1, LEF1, PITX2, PPARBP, TRRAP, WNT1 13 APC(3), AXIN1(1), CREBBP(2), EP300(3), FZD1(1), HDAC1(2), PITX2(1), TRRAP(3) 23100948 16 15 15 8 2 3 4 2 5 0 0.96 1.00 590 ACETAMINOPHENPATHWAY Acetaminophen selectively inhibits Cox-3, which is localized to the brain, and yields the toxic metabolite NAPQI when processed by CAR in the liver. CYP1A2, CYP2E1, CYP3A, NR1I3, PTGS1, PTGS2 5 PTGS2(1) 3974880 1 1 1 0 0 1 0 0 0 0 0.96 1.00 591 N_GLYCAN_DEGRADATION AGA, FLJ21865, FUCA1, FUCA2, GLB1, HEXA, HEXB, LCT, MAN2C1, MANBA, NEU1, NEU2, NEU3, NEU4 12 GLB1(1), HEXB(1), LCT(3), MANBA(1), NEU2(1) 11744148 7 7 7 1 0 2 3 0 2 0 0.96 1.00 592 DNAFRAGMENTPATHWAY DNA fragmentation during apoptosis is effected by DFF, a caspase-activated DNAse, and by endonuclease G. CASP3, CASP7, DFFA, DFFB, ENDOG, GZMB, HMGB1, HMGB2, TOP2A, TOP2B 9 DFFB(2), HMGB2(1), TOP2A(1) 7465575 4 4 4 0 2 1 0 1 0 0 0.96 1.00 593 HSA00460_CYANOAMINO_ACID_METABOLISM Genes involved in cyanoamino acid metabolism ASRGL1, GBA, GBA3, GGT1, GGTL3, GGTL4, SHMT1, SHMT2 6 GGT1(1) 4176159 1 1 1 1 0 1 0 0 0 0 0.96 1.00 594 PROTEASOME PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1, PSMB10, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMB8, PSMB9 17 PSMA5(1), PSMB6(1), PSMB8(1) 6472869 3 3 3 0 1 0 2 0 0 0 0.96 1.00 595 DNA_POLYMERASE POLA, POLB, POLD1, POLD2, POLE, POLG, POLL, POLQ, POLS 7 POLB(1), POLD2(1), POLG(1), POLL(1), POLQ(4) 12519351 8 8 8 1 0 5 0 1 2 0 0.97 1.00 596 HSP27PATHWAY Hsp27 oligomers have molecular chaperone activity and protect heat-stressed cells against apoptosis. ACTA1, APAF1, BCL2, CASP3, CASP9, CYCS, DAXX, FAS, FASLG, HSPB1, HSPB2, IL1A, MAPKAPK2, MAPKAPK3, TNF, TNFRSF6 14 APAF1(1), FAS(1), FASLG(1), IL1A(1), MAPKAPK3(1) 8080059 5 5 5 1 4 1 0 0 0 0 0.97 1.00 597 PROPANOATE_METABOLISM ABAT, ACACA, ACADL, ACADM, ACADSB, ACAS2, ACAS2L, ACAT1, ACAT2, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH6A1, ALDH9A1, ECHS1, EHHADH, HADHA, LDHA, LDHB, LDHC, MCEE, MLYCD, MUT, PCCA, PCCB, SDS, SUCLA2, SUCLG1, SUCLG2 31 ABAT(3), ACACA(1), ACADSB(1), ACAT1(1), ALDH1A1(2), ALDH1A2(1), ALDH1B1(1), ALDH9A1(1), ECHS1(1), EHHADH(2), LDHC(1), MLYCD(2), PCCA(1), SUCLA2(1) 24317241 19 18 19 9 1 10 5 2 1 0 0.97 1.00 598 PROTEASOMEPATHWAY Ubiquitinated proteins are targeted for proteolytic degradation by the proteasome, where they are unfolded and degraded to small peptides in an ATP-dependent process. PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMC3, PSMD14, RPN1, RPN2, UBE1, UBE2A, UBE3A 20 PSMA5(1), PSMB6(1), RPN1(1), UBE2A(1), UBE3A(1) 9834279 5 5 5 1 0 1 3 0 1 0 0.97 1.00 599 GPCRDB_CLASS_C_METABOTROPIC_GLUTAMATE_PHEROMONE CASR, GABBR1, GPCR5A, GPR51, GPRC5A, GPRC5B, GPRC5C, GPRC5D, GRM1, GRM2, GRM3, GRM4, GRM5, GRM7, GRM8 13 CASR(3), GRM1(2), GRM2(1), GRM3(3), GRM4(1), GRM5(1), GRM8(1) 15237885 12 11 12 6 6 2 2 1 1 0 0.97 1.00 600 HSA00730_THIAMINE_METABOLISM Genes involved in thiamine metabolism LHPP, MTMR1, MTMR2, MTMR6, NFS1, PHPT1, THTPA, TPK1 8 MTMR6(1), TPK1(1) 4689750 2 2 2 0 1 1 0 0 0 0 0.98 1.00 601 WNTPATHWAY The Wnt glycoprotein binds to membrane-bound receptors such as Frizzled to activate a number of signaling pathways, including that of beta-catenin. APC, AXIN1, BTRC, CCND1, CREBBP, CSNK1A1, CSNK1D, CSNK2A1, CTBP1, CTNNB1, DVL1, FRAT1, FZD1, GSK3B, HDAC1, MADH4, MAP3K7, MAP3K7IP1, MYC, NLK, PPARD, PPP2CA, TCF1, TLE1, WIF1, WNT1 20 APC(3), AXIN1(1), CCND1(1), CREBBP(2), CSNK2A1(1), FZD1(1), HDAC1(2), MYC(1), NLK(1), WIF1(1) 19757283 14 13 14 7 2 5 2 3 2 0 0.98 1.00 602 HSA00620_PYRUVATE_METABOLISM Genes involved in pyruvate metabolism ACACA, ACACB, ACAT1, ACAT2, ACOT12, ACSS1, ACSS2, ACYP1, ACYP2, AKR1B1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, DLAT, DLD, GLO1, GRHPR, HAGH, HAGHL, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, LDHD, MDH1, MDH2, ME1, ME2, ME3, PC, PCK1, PCK2, PDHA1, PDHA2, PDHB, PKLR, PKM2 41 ACACA(1), ACACB(8), ACAT1(1), ACYP1(1), AKR1B1(2), ALDH1B1(1), ALDH9A1(1), DLD(1), LDHC(1), MDH2(2), ME2(1), ME3(1), PC(1), PCK1(1), PCK2(1), PDHA1(1), PDHA2(1), PDHB(1) 33688629 27 26 27 4 6 16 4 0 1 0 0.98 1.00 603 HSA00040_PENTOSE_AND_GLUCURONATE_INTERCONVERSIONS Genes involved in pentose and glucuronate interconversions AKR1B1, DCXR, GUSB, RPE, UGDH, UGP2, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, XYLB 25 AKR1B1(2), GUSB(1), UGT1A10(1), UGT1A6(2), UGT2A1(1), UGT2B10(2), UGT2B15(2), UGT2B28(1), UGT2B4(1) 18672810 13 13 13 8 4 2 5 0 2 0 0.98 1.00 604 SMALL_LIGAND_GPCRS C9orf47, CNR1, CNR2, DNMT1, EDG1, EDG2, EDG5, EDG6, MTNR1A, MTNR1B, PTAFR, PTGDR, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, TBXA2R 11 CNR1(1), PTGDR(1), PTGFR(1) 7365189 3 3 3 5 0 0 3 0 0 0 0.98 1.00 605 DEATHPATHWAY Death receptors such as Fas and DR3, 4, and 5 transduce pro-apoptotic signaling by oligomerizing to activate the caspase cascade. APAF1, BCL2, BID, BIRC2, BIRC3, BIRC4, CASP10, CASP3, CASP6, CASP7, CASP8, CASP9, CFLAR, CHUK, CYCS, DFFA, DFFB, FADD, GAS2, LMNA, MAP3K14, NFKB1, NFKBIA, RELA, RIPK1, SPTAN1, TNFRSF10A, TNFRSF10B, TNFRSF25, TNFSF10, TNFSF12, TRADD, TRAF2 31 APAF1(1), BID(4), CASP6(1), CASP8(2), DFFB(2), NFKB1(1), RELA(1), RIPK1(3), SPTAN1(2) 23946117 17 16 17 2 1 8 2 0 6 0 0.98 1.00 606 HEME_BIOSYNTHESIS ALAD, ALAS1, ALAS2, CPOX, FECH, HMBS, PPOX, UROD, UROS 9 ALAS2(1), PPOX(1) 5778279 2 2 2 2 1 0 1 0 0 0 0.98 1.00 607 HSA00053_ASCORBATE_AND_ALDARATE_METABOLISM Genes involved in ascorbate and aldarate metabolism ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, MIOX, UGDH 9 ALDH1B1(1), ALDH9A1(1) 5833035 2 2 2 1 0 2 0 0 0 0 0.98 1.00 608 HSA00860_PORPHYRIN_AND_CHLOROPHYLL_METABOLISM Genes involved in porphyrin and chlorophyll metabolism ALAD, ALAS1, ALAS2, BLVRA, BLVRB, COX10, COX15, CP, CPOX, EARS2, EPRS, FECH, FTH1, FTMT, GUSB, HCCS, HMBS, HMOX1, HMOX2, MMAB, PPOX, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, UROD, UROS 41 ALAS2(1), COX10(2), CP(2), EARS2(3), EPRS(2), GUSB(1), PPOX(1), UGT1A10(1), UGT1A6(2), UGT2A1(1), UGT2B10(2), UGT2B15(2), UGT2B28(1), UGT2B4(1) 29682822 22 21 22 11 7 2 8 1 4 0 0.99 1.00 609 PYRUVATE_METABOLISM ACACA, ACAS2, ACAS2L, ACAT1, ACAT2, ACYP1, ACYP2, ADH5, AKR1B1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, CACH_1, DLAT, DLD, GLO1, GRHPR, HAGH, HAGHL, LDHA, LDHB, LDHC, LDHD, MDH1, MDH2, ME1, ME2, ME3, PC, PCK1, PDHA1, PDHA2, PDHB, PKLR, PKM2 36 ACACA(1), ACAT1(1), ACYP1(1), AKR1B1(2), ALDH1A1(2), ALDH1A2(1), ALDH1B1(1), ALDH9A1(1), DLD(1), LDHC(1), MDH2(2), ME2(1), ME3(1), PC(1), PCK1(1), PDHA1(1), PDHA2(1), PDHB(1) 26318370 21 19 21 6 3 14 3 0 1 0 0.99 1.00 610 PS1PATHWAY Presenilin is required for gamma-secretase activity to activate Notch signaling; presenilin also inhibits beta-catenin in the Wnt/Frizzled pathway. ADAM17, APC, AXIN1, BTRC, CTNNB1, DLL1, DVL1, FZD1, GSK3B, NOTCH1, PSEN1, RBPSUH, TCF1, WNT1 10 APC(3), AXIN1(1), FZD1(1) 11563656 5 5 5 7 0 2 2 1 0 0 0.99 1.00 611 HSA04120_UBIQUITIN_MEDIATED_PROTEOLYSIS Genes involved in ubiquitin mediated proteolysis ANAPC1, ANAPC10, ANAPC11, ANAPC2, ANAPC4, ANAPC5, ANAPC7, BTRC, CDC16, CDC20, CDC23, CDC26, CDC27, CUL1, CUL2, CUL3, FBXW11, FBXW7, FZR1, ITCH, LOC728919, RBX1, SKP1, SKP2, SMURF1, SMURF2, TCEB1, TCEB2, UBA1, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2D4, UBE2E1, UBE2E2, UBE2E3, VHL, WWP1, WWP2 38 ANAPC1(1), ANAPC5(4), ANAPC7(1), CDC23(1), CDC27(1), CUL1(1), FBXW7(1), SMURF2(1), UBA1(3), UBE2D2(2), WWP2(4) 29671161 20 20 20 7 4 9 3 1 3 0 0.99 1.00 612 PORPHYRIN_AND_CHLOROPHYLL_METABOLISM ALAD, BLVRA, BLVRB, CP, CPOX, EPRS, FECH, GUSB, HCCS, HMBS, HMOX1, HMOX2, PPOX, UGT1A10, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A9, UGT2B15, UGT2B4, UROD, UROS 26 CP(2), EPRS(2), GUSB(1), PPOX(1), UGT1A10(1), UGT1A6(2), UGT2B15(2), UGT2B4(1) 19384638 12 11 12 6 3 2 4 1 2 0 1.00 1.00 613 AHSPPATHWAY Alpha-hemoglobin stabilizing protein (AHSP) prevents precitipation of hemoglobin alpha-subunits. ALAD, ALAS1, ALAS2, CPO, ERAF, FECH, GATA1, HBA1, HBA2, HBB, HMBS, UROD, UROS 10 ALAS2(1) 5981079 1 1 1 2 1 0 0 0 0 0 1.00 1.00 614 HSA00563_GLYCOSYLPHOSPHATIDYLINOSITOL_ANCHOR_BIOSYNTHESIS Genes involved in glycosylphosphatidylinositol(GPI)-anchor biosynthesis GPAA1, GPLD1, PGAP1, PIGA, PIGB, PIGC, PIGF, PIGG, PIGH, PIGK, PIGL, PIGM, PIGN, PIGO, PIGP, PIGQ, PIGS, PIGT, PIGU, PIGV, PIGW, PIGX, PIGZ 22 GPLD1(2), PGAP1(2), PIGA(1), PIGB(1), PIGG(1) 17040270 7 7 7 3 1 3 2 1 0 0 1.00 1.00 615 HSA00031_INOSITOL_METABOLISM Genes involved in inositol metabolism ALDH6A1, TPI1 2 1220856 0 0 0 0 0 0 0 0 0 0 1.00 1.00 616 HSA00627_1,4_DICHLOROBENZENE_DEGRADATION Genes involved in 1,4-dichlorobenzene degradation CMBL 1 384306 0 0 0 0 0 0 0 0 0 0 1.00 1.00