rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p q 1 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 246 ACVR1C(2), AKT1(1), AKT2(1), AKT3(1), ATF2(1), ATF4(1), BDNF(1), BRAF(6), CACNA1A(4), CACNA1B(7), CACNA1C(5), CACNA1D(9), CACNA1E(9), CACNA1F(10), CACNA1G(6), CACNA1H(9), CACNA1I(5), CACNA1S(12), CACNA2D1(8), CACNA2D2(1), CACNA2D3(3), CACNA2D4(1), CACNB2(1), CACNB3(1), CACNG1(1), CACNG2(1), CACNG3(4), CACNG6(1), CACNG7(1), CACNG8(1), CD14(2), CDC25B(1), CHUK(4), DAXX(4), DDIT3(1), DUSP10(1), DUSP14(1), DUSP16(1), DUSP2(2), DUSP4(3), DUSP8(1), DUSP9(1), EGF(3), EGFR(58), ELK1(1), ELK4(1), FGF10(1), FGF13(1), FGF14(2), FGF18(1), FGF2(1), FGF20(2), FGF21(1), FGF23(3), FGF3(1), FGF6(3), FGF9(1), FGFR1(3), FGFR2(3), FGFR3(2), FGFR4(3), FLNA(14), FLNB(4), FLNC(6), FOS(1), GADD45B(1), GNA12(2), IKBKB(2), IL1R1(2), KRAS(1), MAP2K1(1), MAP2K2(1), MAP2K3(1), MAP2K5(1), MAP2K7(1), MAP3K1(5), MAP3K10(3), MAP3K12(5), MAP3K13(2), MAP3K14(2), MAP3K2(1), MAP3K3(4), MAP3K4(2), MAP3K5(1), MAP3K6(5), MAP3K7(2), MAP4K1(1), MAP4K2(1), MAP4K3(1), MAP4K4(5), MAPK1(3), MAPK13(1), MAPK14(1), MAPK3(2), MAPK7(3), MAPK8IP1(3), MAPK8IP2(3), MAPK8IP3(5), MAPK9(2), MAPKAPK2(1), MAPKAPK3(1), MAPT(1), MAX(2), MEF2C(1), MKNK1(1), NF1(31), NFATC2(1), NFATC4(2), NFKB1(1), NFKB2(1), NR4A1(3), NRAS(1), NTF3(1), NTRK1(4), NTRK2(1), PAK1(2), PDGFRA(10), PDGFRB(5), PLA2G12A(3), PLA2G2A(5), PLA2G2F(2), PLA2G3(2), PLA2G4A(4), PLA2G5(1), PLA2G6(3), PPM1B(1), PPP3CB(1), PPP3R1(1), PPP3R2(1), PPP5C(1), PRKACG(1), PRKCA(3), PRKCG(1), PRKX(2), PTPRR(2), RAP1B(2), RAPGEF2(4), RASA2(1), RASGRF1(5), RASGRF2(6), RASGRP1(1), RASGRP2(2), RASGRP3(2), RASGRP4(3), RPS6KA2(2), RPS6KA3(5), RRAS2(3), SOS1(1), SOS2(4), SRF(2), STK3(2), STK4(1), STMN1(1), TAOK1(1), TAOK2(2), TAOK3(2), TGFB1(1), TGFB2(1), TGFBR1(1), TGFBR2(5), TNFRSF1A(2), TP53(89), TRAF2(2), ZAK(1) 111569559 586 213 518 148 184 87 111 98 100 6 <1.00e-15 <1.37e-14 2 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 64 APAF1(1), ATM(7), ATR(9), BAI1(1), BID(4), CCNB3(1), CCND2(1), CCNE1(1), CCNE2(1), CCNG1(2), CDKN1A(1), CDKN2A(3), CHEK1(5), DDB2(1), GADD45B(1), GTSE1(2), IGFBP3(1), MDM2(1), MDM4(2), PERP(3), PPM1D(1), PTEN(80), RFWD2(2), RPRM(1), SERPINB5(2), SERPINE1(1), SESN1(2), SESN2(1), SESN3(3), STEAP3(2), THBS1(3), TP53(89), TP53I3(2), TP73(1), TSC2(2) 25535861 240 158 198 28 44 51 32 39 71 3 <1.00e-15 <1.37e-14 3 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 78 ABL1(1), ACTN1(1), ACTR3(2), AKT1(1), AKT2(1), AKT3(1), ANGPTL2(2), ARHGEF7(1), BRAF(6), CAV1(1), CDKN2A(3), CSE1L(2), DOCK1(9), EPHB2(6), GRB7(1), GRLF1(4), ILK(2), ITGA1(1), ITGA10(3), ITGA11(2), ITGA2(4), ITGA3(2), ITGA4(7), ITGA5(1), ITGA6(2), ITGA7(3), ITGA8(7), ITGA9(1), MAP2K7(1), MAPK1(3), MAPK8IP1(3), MAPK8IP2(3), MAPK8IP3(5), MAPK9(2), MYLK(7), MYLK2(1), PAK1(2), PAK3(2), PAK6(1), PAK7(3), PIK3CA(19), PIK3CB(2), PKLR(4), PLCG1(3), PLCG2(11), PTEN(80), PTK2(2), RALA(1), RHO(1), ROCK1(3), ROCK2(4), SOS1(1), SOS2(4), SRC(2), TERF2IP(3), TLN1(6), TLN2(5), VASP(2), ZYX(2) 48062722 265 143 245 58 68 49 41 50 57 0 <1.00e-15 <1.37e-14 4 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 59 BTK(1), CAD(6), CASP8AP2(3), CD7(2), DAXX(4), DEDD2(2), DFFA(1), DIABLO(1), EGFR(58), EPHB2(6), FAF1(3), FAIM2(1), MAP2K7(1), MAP3K1(5), MAP3K5(1), MAPK1(3), MAPK8IP1(3), MAPK8IP2(3), MAPK8IP3(5), MAPK9(2), MET(5), NFAT5(3), NFKB1(1), NFKB2(1), NFKBIA(2), NFKBIB(1), NFKBIE(1), NFKBIL1(1), NFKBIL2(6), NR0B2(3), PTPN13(4), RALBP1(3), RIPK1(1), ROCK1(3), TNFRSF6B(2), TP53(89), TPX2(1), TRAF2(2), TUFM(1) 28393004 241 142 182 36 57 53 55 36 38 2 <1.00e-15 <1.37e-14 5 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 ACTR3(2), AKT1(1), AKT2(1), AKT3(1), ANGPTL2(2), ARHGAP1(1), ARHGAP4(1), ARHGEF11(3), BTK(1), CFL2(1), INPPL1(4), ITPR1(7), ITPR2(11), ITPR3(11), LIMK1(1), MYLK(7), MYLK2(1), PAK1(2), PAK3(2), PAK6(1), PAK7(3), PIK3CA(19), PIK3CD(2), PIK3CG(12), PIK3R1(17), PTEN(80), RACGAP1(1), RHO(1), ROCK1(3), ROCK2(4), RPS4X(1), WASF1(1) 27707675 205 139 185 32 44 40 31 32 58 0 <1.00e-15 <1.37e-14 6 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(1), BCL2(3), EGFR(58), IGF1R(2), POLR2A(2), PPP2CA(1), PRKCA(3), RB1(21), TEP1(4), TERT(8), TNKS(4), TP53(89), XRCC5(1) 11328048 197 139 135 11 45 40 42 22 46 2 <1.00e-15 <1.37e-14 7 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 AIFM1(4), AKT1(1), AKT2(1), AKT3(1), APAF1(1), ATM(7), BCL2(3), BID(4), BIRC2(1), BIRC3(1), CAPN1(5), CAPN2(1), CASP6(1), CHUK(4), CSF2RB(4), DFFA(1), DFFB(3), IKBKB(2), IL1R1(2), IL1RAP(2), IRAK1(2), IRAK2(3), IRAK3(2), IRAK4(2), MAP3K14(2), NFKB1(1), NFKB2(1), NFKBIA(2), NTRK1(4), PIK3CA(19), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(17), PIK3R2(5), PIK3R5(2), PPP3CB(1), PPP3R1(1), PPP3R2(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1), RIPK1(1), TNFRSF10A(2), TNFRSF1A(2), TNFSF10(5), TP53(89), TRAF2(2) 32877178 234 133 199 39 59 40 36 53 44 2 <1.00e-15 <1.37e-14 8 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 47 FN3K(1), IMPA1(1), INPP1(2), INPP4A(1), INPP4B(1), INPP5A(1), INPP5B(2), INPP5E(1), INPPL1(4), ITGB1BP3(2), ITPKB(2), MINPP1(1), MIOX(1), OCRL(1), PI4KA(1), PI4KB(3), PIK3C3(1), PIK3CA(19), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIP4K2A(3), PIP4K2B(1), PIP4K2C(3), PIP5K1B(2), PIP5K1C(4), PLCB1(3), PLCB2(5), PLCB3(5), PLCB4(3), PLCD1(1), PLCD3(2), PLCD4(2), PLCE1(7), PLCG1(3), PLCG2(11), PLCZ1(1), PTEN(80), SYNJ1(1), SYNJ2(7) 29194980 205 131 187 33 50 41 29 31 53 1 <1.00e-15 <1.37e-14 9 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 109 ABL1(1), ANAPC1(4), ANAPC10(2), ANAPC11(1), ANAPC2(1), ANAPC4(2), ANAPC5(2), ATM(7), ATR(9), BUB1(4), BUB1B(1), CCNA1(1), CCNB3(1), CCND2(1), CCNE1(1), CCNE2(1), CCNH(2), CDC20(2), CDC23(1), CDC25B(1), CDC27(3), CDC7(2), CDKN1A(1), CDKN1B(3), CDKN2A(3), CDKN2B(1), CDKN2C(4), CDKN2D(1), CHEK1(5), CREBBP(8), CUL1(5), E2F2(3), E2F3(2), EP300(5), ESPL1(8), GADD45B(1), GSK3B(1), HDAC1(1), HDAC2(3), MAD1L1(1), MCM2(3), MCM3(3), MCM4(3), MCM5(1), MCM6(1), MCM7(2), MDM2(1), PCNA(1), PKMYT1(1), PLK1(1), PRKDC(5), PTTG2(2), RB1(21), RBL1(3), RBL2(1), SMAD3(1), SMAD4(1), SMC1A(7), SMC1B(3), TGFB1(1), TGFB2(1), TP53(89), YWHAB(1), YWHAE(2) 54445600 261 130 233 42 53 45 52 32 76 3 <1.00e-15 <1.37e-14 10 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(1), AKT2(1), AKT3(1), BRD4(7), CBL(1), CDKN2A(3), FLOT1(2), GSK3B(1), IGFBP1(1), INPPL1(4), IRS1(4), IRS4(3), LNPEP(2), MAPK1(3), MAPK3(2), PARD3(2), PARD6A(1), PIK3CA(19), PIK3CD(2), PIK3R1(17), PPYR1(2), PTEN(80), PTPN1(1), RPS6KA2(2), RPS6KA3(5), RPS6KB1(1), SERPINB6(1), SLC2A4(3), SORBS1(2), SOS1(1), SOS2(4), YWHAB(1), YWHAE(2) 23158627 182 128 162 32 30 35 21 36 60 0 <1.00e-15 <1.37e-14 11 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(1), AKT2(1), AKT3(1), CDKN1B(3), CDKN2A(3), CREB3(1), CREB5(1), ERBB4(1), GAB1(1), GSK3B(1), IGFBP1(1), INPPL1(4), IRS1(4), IRS4(3), MET(5), NOLC1(1), PAK1(2), PAK3(2), PAK6(1), PAK7(3), PARD3(2), PARD6A(1), PIK3CA(19), PIK3CD(2), PREX1(9), PTEN(80), PTK2(2), PTPN1(1), RPS6KA2(2), RPS6KA3(5), RPS6KB1(1), SLC2A4(3), SOS1(1), SOS2(4), TSC1(4), TSC2(2), YWHAB(1), YWHAE(2) 30024023 181 123 164 27 35 33 23 34 56 0 <1.00e-15 <1.37e-14 12 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(1), EIF4A1(4), EIF4E(2), EIF4G1(2), EIF4G2(2), EIF4G3(1), GHR(3), IRS1(4), MAPK1(3), MAPK14(1), MAPK3(2), MKNK1(1), PIK3CA(19), PIK3R1(17), PRKCA(3), PTEN(80), RPS6KB1(1) 11296925 146 118 126 7 19 29 17 32 49 0 <1.00e-15 <1.37e-14 13 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(1), EIF4A1(4), EIF4B(3), EIF4E(2), EIF4G1(2), EIF4G2(2), EIF4G3(1), FKBP1A(1), MKNK1(1), PIK3CA(19), PIK3R1(17), PPP2CA(1), PTEN(80), RPS6KB1(1), TSC1(4), TSC2(2) 10941579 141 117 121 5 15 30 17 25 54 0 <1.00e-15 <1.37e-14 14 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 16 AKT1(1), CDKN1B(3), ILK(2), MAPK1(3), MAPK3(2), PIK3CA(19), PIK3R1(17), PTEN(80), PTK2(2), SOS1(1) 7670831 130 116 110 4 12 30 15 26 47 0 <1.00e-15 <1.37e-14 15 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 16 ABL1(1), CDKN2A(3), MDM2(1), PIK3CA(19), PIK3R1(17), POLR1A(3), POLR1B(1), POLR1C(1), RB1(21), TBX2(1), TP53(89) 8040458 157 113 124 13 28 28 20 25 54 2 <1.00e-15 <1.37e-14 16 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 64 ATM(7), CCNA1(1), CCND2(1), CCNE1(1), CCNE2(1), CCNH(2), CDKN1A(1), CDKN1B(3), CDKN2A(3), CDKN2B(1), CDKN2C(4), CDKN2D(1), CREB3(1), CREB3L1(1), CREB3L3(3), CREB3L4(1), E2F2(3), E2F3(2), MCM2(3), MCM3(3), MCM4(3), MCM5(1), MCM6(1), MCM7(2), MDM2(1), MYT1(7), NACA(7), PCNA(1), POLA2(3), POLE(4), POLE2(2), PRIM1(1), RB1(21), RBL1(3), TFDP2(1), TNXB(6), TP53(89) 29776866 196 110 165 30 50 29 32 22 61 2 <1.00e-15 <1.37e-14 17 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 A1BG(2), AKT1(1), AKT2(1), AKT3(1), BTK(1), CDKN2A(3), GSK3B(1), IARS(4), IGFBP1(1), INPP5D(6), PIK3CA(19), PTEN(80), RPS6KA2(2), RPS6KA3(5), RPS6KB1(1), SOS1(1), SOS2(4), TEC(5), YWHAB(1), YWHAE(2) 14274206 141 109 124 17 23 35 15 23 45 0 <1.00e-15 <1.37e-14 18 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 66 APAF1(1), BCL2(3), BID(4), BIRC2(1), BIRC3(1), BIRC5(1), BNIP3L(1), CASP1(4), CASP2(1), CASP4(1), CASP6(1), CHUK(4), DFFA(1), DFFB(3), GZMB(3), IKBKB(2), IRF2(1), IRF4(2), IRF5(5), IRF6(6), MAP3K1(5), MDM2(1), NFKB1(1), NFKBIA(2), NFKBIB(1), NFKBIE(1), PLEKHG5(2), PRF1(3), RIPK1(1), TNFRSF1A(2), TNFRSF1B(2), TNFRSF25(1), TNFSF10(5), TP53(89), TP73(1), TRAF1(1), TRAF2(2), TRAF3(3) 22658299 169 105 137 33 38 26 30 34 39 2 <1.00e-15 <1.37e-14 19 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(1), AKT2(1), AKT3(1), BPNT1(1), ILK(2), MAPK1(3), MAPK3(2), PIK3CA(19), PIK3CD(2), PTEN(80), PTK2B(1), RBL2(1), SOS1(1) 8079012 115 104 98 7 14 26 13 24 38 0 <1.00e-15 <1.37e-14 20 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(8), DAXX(4), PAX3(3), PML(2), RARA(5), RB1(21), SIRT1(2), SP100(3), TNFRSF1A(2), TNFRSF1B(2), TP53(89) 7623942 141 102 110 11 31 21 20 21 46 2 <1.00e-15 <1.37e-14 21 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 38 AKT1(1), ATF2(1), DLD(1), DUSP10(1), DUSP4(3), DUSP8(1), GAB1(1), GCK(2), IL1R1(2), MAP2K5(1), MAP2K7(1), MAP3K1(5), MAP3K10(3), MAP3K12(5), MAP3K13(2), MAP3K2(1), MAP3K3(4), MAP3K4(2), MAP3K5(1), MAP3K7(2), MAP3K9(2), MAPK7(3), MAPK9(2), NFATC3(1), PAPPA(6), TP53(89), ZAK(1) 20108047 144 101 116 22 46 21 19 24 32 2 <1.00e-15 <1.37e-14 22 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 22 ATM(7), ATR(9), BRCA1(4), CDC25B(1), CDKN1A(1), CDKN2D(1), CHEK1(5), EP300(5), MDM2(1), MYT1(7), PRKDC(5), TP53(89) 16932144 135 97 110 10 34 23 22 21 32 3 <1.00e-15 <1.37e-14 23 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(7), ATR(9), BRCA1(4), BRCA2(7), CHEK1(5), FANCA(4), FANCC(2), FANCD2(4), FANCG(1), MRE11A(3), RAD1(1), RAD17(2), RAD50(2), RAD9A(1), TP53(89) 17966317 141 96 115 9 35 23 18 28 34 3 <1.00e-15 <1.37e-14 24 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 25 ABL1(1), ATM(7), ATR(9), CCNA1(1), CCNE1(1), CDKN1A(1), CDKN1B(3), CDKN2A(3), CDKN2B(1), DHFR(1), GSK3B(1), HDAC1(1), RB1(21), TGFB1(1), TGFB2(1), TP53(89) 12112046 142 96 114 11 30 24 19 17 50 2 <1.00e-15 <1.37e-14 25 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 IFNG(1), IFNGR1(1), IFNGR2(1), IKBKB(2), JAK2(4), NFKB1(1), NFKBIA(2), RB1(21), TNFRSF1A(2), TNFRSF1B(2), TP53(89), USH1C(1), WT1(3) 7240609 130 96 101 10 31 17 17 18 45 2 <1.00e-15 <1.37e-14 26 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(7), CDC25B(1), CHEK1(5), MYT1(7), RB1(21), TP53(89) 7149998 130 95 102 3 30 19 15 17 47 2 <1.00e-15 <1.37e-14 27 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(7), BCL2(3), CCNE1(1), CDKN1A(1), MDM2(1), PCNA(1), RB1(21), TIMP3(2), TP53(89) 7375110 127 93 99 4 27 21 17 16 44 2 <1.00e-15 <1.37e-14 28 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(7), ATR(9), CHEK1(5), TP53(89) 6573020 110 89 84 4 28 19 14 19 28 2 <1.00e-15 <1.37e-14 29 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 19 ABL1(1), ATM(7), BRCA1(4), CDKN1A(1), CHEK1(5), MDM2(1), MRE11A(3), NFKB1(1), NFKBIA(2), RAD50(2), RBBP8(2), TP53(89), TP73(1) 12007050 119 88 94 9 29 23 15 21 29 2 <1.00e-15 <1.37e-14 30 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(1), MAX(2), SP1(6), SP3(1), TP53(89), WT1(3) 2849491 102 86 76 2 27 17 14 14 28 2 <1.00e-15 <1.37e-14 31 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 CHUK(4), DNAJC3(3), EIF2S2(1), MAP3K14(2), NFKB1(1), NFKBIA(2), TP53(89) 3932195 102 84 75 5 24 16 15 18 27 2 <1.00e-15 <1.37e-14 32 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(4), AKT1(1), ATM(7), CDKN1A(1), CPB2(1), FHL2(1), HIF1A(1), IGFBP3(1), MDM2(1), NFKBIB(1), TP53(89) 8064819 108 83 82 5 29 22 13 16 26 2 <1.00e-15 <1.37e-14 33 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 CDKN1A(1), CDKN1B(3), CDKN2A(3), E2F2(3), MDM2(1), TP53(89) 3180125 100 83 74 8 25 20 12 13 28 2 <1.00e-15 <1.37e-14 34 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 ACTA1(1), CAPN1(5), CAPN2(1), CAPNS1(1), CXCR3(2), EGF(3), EGFR(58), ITGA1(1), MAPK1(3), MAPK3(2), MYL2(2), MYLK(7), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PTK2(2), PXN(1), TLN1(6) 12938269 98 72 66 16 22 24 32 17 3 0 <1.00e-15 <1.37e-14 35 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 CBL(1), CSF1R(3), EGF(3), EGFR(58), MET(5), PDGFRA(10), PRKCA(3), SH3GLB1(2), SH3GLB2(4), SH3KBP1(3), SRC(2) 7910833 94 68 62 12 17 27 33 12 5 0 <1.00e-15 <1.37e-14 36 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(3), EGFR(58), MAP2K1(1), MAP3K1(5), MAPK14(1), NCOR2(5), RARA(5), RXRA(3), THRA(1) 6703510 82 66 48 13 14 24 25 14 5 0 <1.00e-15 <1.37e-14 37 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 17 CBL(1), EGF(3), EGFR(58), MAP2K1(1), MAPK1(3), MAPK3(2), PTPRB(4), SOS1(1), SPRY1(1), SPRY2(2), SRC(2) 9691451 78 66 45 14 14 23 26 12 3 0 <1.00e-15 <1.37e-14 38 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 16 AKT1(1), MAP2K1(1), MAP2K2(1), MAP2K3(1), MAP3K1(5), MAPK1(3), MAPK14(1), MAPK3(2), NFKB1(1), PIK3CA(19), PIK3R1(17), RB1(21), SP1(6) 7874439 79 65 72 7 8 14 7 16 34 0 <1.00e-15 <1.37e-14 39 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), AGTR2(1), EDNRA(1), EDNRB(1), EGF(3), EGFR(58), FOS(1), NFKB1(1), PLCG1(3), PRKCA(3) 8308721 76 63 44 18 12 24 26 12 2 0 <1.00e-15 <1.37e-14 40 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(1), CCNE1(1), CDKN1A(1), CDKN1B(3), MAPK1(3), MAPK3(2), NFKB1(1), NFKBIA(2), PAK1(2), PIK3CA(19), PIK3R1(17), RB1(21) 8106529 73 62 66 7 5 13 9 15 31 0 <1.00e-15 <1.37e-14 41 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(2), EGF(3), EGFR(58), HGS(3), TFRC(2) 5146012 68 59 36 9 9 23 25 8 3 0 <1.00e-15 <1.37e-14 42 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(3), EGFR(58), ERBB3(4), NRG1(4) 4194729 69 59 37 7 13 21 26 8 1 0 <1.00e-15 <1.37e-14 43 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 CD28(1), CD3E(1), CD3G(1), HLA-DRA(1), HLA-DRB1(2), IL2(1), ITK(3), PIK3CA(19), PIK3R1(17), PTPN11(6) 5210686 52 45 47 7 5 11 8 17 11 0 <1.00e-15 <1.37e-14 44 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 ACTR3(2), ARPC1B(1), ARPC2(1), ARPC4(1), PAK1(2), PDGFRA(10), PIK3CA(19), PIK3R1(17) 5451834 53 44 48 2 4 11 10 14 14 0 <1.00e-15 <1.37e-14 45 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(1), PIK3CA(19), PIK3R1(17), PLCB1(3), PLCG1(3), PRKCA(3), VAV1(6) 5190925 52 43 47 8 8 12 8 13 10 1 <1.00e-15 <1.37e-14 46 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 34 AKT1(1), APC(7), ASAH1(1), BRAF(6), CCL13(1), CCL15(1), DAG1(2), EGFR(58), GNA11(2), GNA15(4), GNAQ(1), ITPKB(2), ITPR1(7), ITPR2(11), ITPR3(11), KCNJ3(2), KCNJ5(3), MAPK1(3), MAPK14(1), PHKA2(4), PIK3CA(19), PIK3CD(2), PIK3R1(17), SRC(2) 21236766 168 99 128 26 34 42 41 34 17 0 1.11e-15 1.46e-14 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 41 APAF1(1), BCL2(3), BID(4), BIRC2(1), BIRC3(1), CASP2(1), CASP6(1), GZMB(3), MAP3K1(5), MAP3K14(2), MDM2(1), NFKB1(1), NFKBIA(2), PARP1(3), PRF1(3), RIPK1(1), TNFRSF1A(2), TNFRSF1B(2), TNFSF10(5), TP53(89), TRAF1(1), TRAF2(2) 15017861 134 96 105 18 31 20 25 25 31 2 1.11e-15 1.46e-14 48 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(1), EIF2S2(1), EIF2S3(3), EIF4E(2), GSK3B(1), IGF1R(2), INPPL1(4), PIK3CA(19), PIK3R1(17), PPP2CA(1), PTEN(80), RPS6KB1(1) 7893717 132 119 112 4 13 30 14 26 49 0 1.22e-15 1.57e-14 49 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(3), EGF(3), EGFR(58), ELK1(1), FOS(1), JAK1(3), MAP2K1(1), MAP3K1(5), MAPK3(2), PIK3CA(19), PIK3R1(17), PLCG1(3), PRKCA(3), SOS1(1), SRF(2), STAT1(1), STAT3(2), STAT5A(2) 15160099 127 96 90 18 22 36 32 23 14 0 1.55e-15 1.95e-14 50 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(1), CHUK(4), GH1(1), GHR(3), NFKB1(1), NFKBIA(2), PIK3CA(19), PIK3R1(17), PPP2CA(1) 5686812 49 43 43 5 6 10 6 15 12 0 1.78e-15 2.19e-14 51 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(1), AKT2(1), AKT3(1), BCR(1), BTK(1), CD19(2), CDKN2A(3), FLOT1(2), GAB1(1), ITPR1(7), ITPR2(11), ITPR3(11), LYN(1), NR0B2(3), PIK3CA(19), PLCG2(11), PREX1(9), PTEN(80), PTPRC(4), RPS6KA2(2), RPS6KA3(5), RPS6KB1(1), SYK(2), TEC(5), VAV1(6) 21953122 190 130 173 30 42 41 28 30 49 0 1.89e-15 2.24e-14 52 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 28 BRAF(6), EGFR(58), ERBB2(7), ERBB4(1), ETV7(1), FMN2(2), KRAS(1), MAP2K1(1), MAPK1(3), MAPK3(2), NOTCH1(4), NOTCH2(6), NOTCH3(7), NOTCH4(5), PIWIL1(3), PIWIL3(4), PIWIL4(1), SOS1(1), SOS2(4), SPIRE1(3), SPIRE2(4) 20472230 124 88 84 26 24 27 33 25 15 0 1.89e-15 2.24e-14 53 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(1), APAF1(1), ATM(7), BCL2(3), BID(4), CASP6(1), PRKCA(3), PTK2(2), PXN(1), STAT1(1), TLN1(6), TP53(89) 11107554 119 89 90 5 31 19 17 23 27 2 2.11e-15 2.45e-14 54 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 29 EGFR(58), ELK1(1), GNAS(3), GNB1(1), GNGT1(1), IGF1R(2), MAP2K1(1), MAP2K2(1), MAPK1(3), MAPK3(2), MKNK1(1), NGFR(1), PDGFRA(10), PPP2CA(1), PTPRR(2), SOS1(1), SRC(2), STAT3(2) 13280414 93 73 61 15 21 28 31 11 2 0 2.22e-15 2.53e-14 55 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 73 CALM1(1), CDS1(1), DGKB(1), DGKD(6), DGKE(2), DGKG(5), DGKH(3), DGKI(3), DGKQ(1), DGKZ(5), FN3K(1), IMPA1(1), INPP1(2), INPP4A(1), INPP4B(1), INPP5A(1), INPP5B(2), INPP5D(6), INPP5E(1), INPPL1(4), ITGB1BP3(2), ITPKB(2), ITPR1(7), ITPR2(11), ITPR3(11), OCRL(1), PI4KA(1), PI4KB(3), PIK3C2A(3), PIK3C2B(2), PIK3C2G(9), PIK3C3(1), PIK3CA(19), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(17), PIK3R2(5), PIK3R5(2), PIP4K2A(3), PIP4K2B(1), PIP4K2C(3), PIP5K1B(2), PIP5K1C(4), PLCB1(3), PLCB2(5), PLCB3(5), PLCB4(3), PLCD1(1), PLCD3(2), PLCD4(2), PLCE1(7), PLCG1(3), PLCG2(11), PLCZ1(1), PRKCA(3), PRKCG(1), PTEN(80), SYNJ1(1), SYNJ2(7) 49165194 308 168 286 50 81 56 46 51 73 1 2.33e-15 2.61e-14 56 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 35 ACTA1(1), DOCK1(9), ELK1(1), FOS(1), GAB1(1), HGF(4), ITGA1(1), MAP2K1(1), MAP2K2(1), MAP4K1(1), MAPK1(3), MAPK3(2), MET(5), PAK1(2), PIK3CA(19), PIK3R1(17), PTEN(80), PTK2(2), PTK2B(1), PTPN11(6), PXN(1), RAP1B(2), SOS1(1), SRC(2), STAT3(2) 17751751 166 127 146 11 25 35 22 35 49 0 2.89e-15 3.18e-14 57 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 243 ACVR1(3), ACVR2A(5), ACVR2B(1), AMHR2(3), BMPR1A(2), BMPR1B(1), BMPR2(2), CCL13(1), CCL15(1), CCL19(1), CCL2(2), CCL20(1), CCL22(1), CCL24(1), CCL26(1), CCL3(1), CCL5(1), CCL7(1), CCR1(2), CCR3(2), CCR4(1), CCR6(2), CCR7(2), CCR8(1), CCR9(2), CD70(1), CLCF1(1), CNTF(1), CSF1R(3), CSF2RB(4), CSF3R(2), CX3CL1(1), CX3CR1(2), CXCL1(1), CXCL13(1), CXCL6(3), CXCR3(2), CXCR6(1), EDA(3), EGF(3), EGFR(58), EPO(1), EPOR(1), FLT1(2), FLT3(7), FLT3LG(1), FLT4(3), GDF5(2), GH1(1), GH2(2), GHR(3), HGF(4), IFNA13(1), IFNA14(1), IFNA17(1), IFNA21(1), IFNA5(1), IFNA7(2), IFNAR2(1), IFNB1(1), IFNG(1), IFNGR1(1), IFNGR2(1), IFNW1(1), IL10RA(1), IL12B(1), IL12RB1(4), IL12RB2(4), IL13RA1(1), IL15RA(1), IL17RA(9), IL17RB(1), IL18R1(1), IL18RAP(4), IL1R1(2), IL1RAP(2), IL2(1), IL21(1), IL21R(4), IL22(3), IL22RA1(1), IL23R(2), IL24(1), IL26(1), IL28A(1), IL28B(1), IL28RA(1), IL2RA(3), IL2RB(1), IL4(1), IL4R(6), IL5RA(1), IL6(2), IL6R(2), IL7(1), IL7R(1), INHBA(3), INHBB(2), INHBE(1), KDR(10), KIT(3), KITLG(2), LEPR(1), LIFR(1), LTBR(1), MET(5), MPL(2), NGFR(1), OSM(1), OSMR(2), PDGFC(3), PDGFRA(10), PDGFRB(5), PPBP(2), PRL(3), RELT(1), TGFB1(1), TGFB2(1), TGFBR1(1), TGFBR2(5), TNFRSF10A(2), TNFRSF11A(3), TNFRSF12A(2), TNFRSF13B(2), TNFRSF14(1), TNFRSF18(1), TNFRSF1A(2), TNFRSF1B(2), TNFRSF25(1), TNFRSF6B(2), TNFRSF8(3), TNFSF10(5), TNFSF11(4), TNFSF13B(2), TNFSF14(3), TNFSF18(1), TNFSF4(1), TNFSF8(1), TNFSF9(3), TPO(4), VEGFA(2), VEGFC(2), XCL1(2), XCL2(2), XCR1(1) 69038532 355 152 316 86 104 62 92 62 35 0 3.44e-15 3.72e-14 58 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 33 AGT(3), AGTR1(2), ATF2(1), CALM1(1), EGFR(58), ELK1(1), GNAQ(1), MAP2K1(1), MAP2K2(1), MAP3K1(5), MAPK1(3), MAPK3(2), MEF2A(1), MEF2C(1), MEF2D(1), PAK1(2), PRKCA(3), PTK2(2), PTK2B(1), SOS1(1), SRC(2), SYT1(1) 13533119 94 69 62 19 17 27 32 15 3 0 5.88e-15 6.25e-14 59 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(1), MAPK1(3), MAPK3(2), MAPK7(3), MEF2A(1), MEF2C(1), MEF2D(1), NTRK1(4), PIK3CA(19), PIK3R1(17), PLCG1(3) 7509289 55 51 50 11 8 13 8 16 10 0 6.33e-15 6.61e-14 60 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), NFYC(3), RB1(21), SP1(6), SP3(1) 2702392 32 27 30 4 3 2 3 3 21 0 1.48e-14 1.52e-13 61 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 85 ABL1(1), ABL2(1), AKT1(1), AKT2(1), AKT3(1), ARAF(1), AREG(1), BRAF(6), CAMK2B(1), CAMK2D(1), CAMK2G(4), CBL(1), CBLB(1), CBLC(1), CDKN1A(1), CDKN1B(3), EGF(3), EGFR(58), ELK1(1), ERBB2(7), ERBB3(4), ERBB4(1), GAB1(1), GSK3B(1), KRAS(1), MAP2K1(1), MAP2K2(1), MAP2K7(1), MAPK1(3), MAPK3(2), MAPK9(2), NRAS(1), NRG1(4), NRG2(1), NRG3(1), PAK1(2), PAK3(2), PAK6(1), PAK7(3), PIK3CA(19), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(17), PIK3R2(5), PIK3R5(2), PLCG1(3), PLCG2(11), PRKCA(3), PRKCG(1), PTK2(2), RPS6KB1(1), SHC3(1), SHC4(1), SOS1(1), SOS2(4), SRC(2), STAT5A(2), STAT5B(2), TGFA(2) 40950577 223 129 181 52 58 44 49 46 26 0 1.65e-14 1.67e-13 62 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(1), CHUK(4), ELK1(1), H2AFX(1), MAP2K1(1), MAPK3(2), NFKB1(1), PIK3CA(19), PIK3R1(17), RALA(1), RALBP1(3), RALGDS(3), RHOA(1) 7628802 55 48 49 6 7 9 7 17 15 0 2.32e-14 2.31e-13 63 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(1), KLRC1(1), KLRC3(3), MAP2K1(1), MAPK3(2), PAK1(2), PIK3CA(19), PIK3R1(17), PTK2B(1), PTPN6(4), SYK(2), VAV1(6) 7518622 61 48 56 13 10 9 16 13 13 0 2.89e-14 2.82e-13 64 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(1), NTRK1(4), PIK3CA(19), PIK3R1(17), PLCG1(3), PRKCA(3), SOS1(1) 6243278 48 44 43 8 6 11 6 15 10 0 4.52e-14 4.35e-13 65 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 13 AKT1(1), GH1(1), GHR(3), IGF1R(2), PIK3CA(19), PIK3R1(17), SOD3(1) 5298809 44 40 39 5 6 11 5 12 10 0 1.76e-13 1.67e-12 66 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(1), ATM(7), BUB1(4), BUB1B(1), CCNA1(1), CCNB3(1), CCND2(1), CCNE1(1), CCNE2(1), CCNH(2), CDAN1(5), CDC20(2), CDC25B(1), CDC7(2), CDH1(3), CDKN1A(1), CDKN2A(3), CHEK1(5), E2F2(3), E2F3(2), EP300(5), ESPL1(8), GSK3B(1), HDAC1(1), HDAC2(3), HDAC3(1), HDAC4(1), HDAC5(4), HDAC6(3), HDAC8(1), MAD1L1(1), MCM2(3), MCM3(3), MCM4(3), MCM5(1), MCM6(1), MCM7(2), MDM2(1), MPL(2), PCNA(1), PLK1(1), PRKDC(5), PTPRA(4), PTTG2(2), RB1(21), RBL1(3), SMAD4(1), TBC1D8(4), TGFB1(1), TP53(89) 44091931 224 119 196 41 51 38 43 27 62 3 2.44e-13 2.27e-12 67 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 42 AKT1(1), ASAH1(1), BRAF(6), CREB3(1), CREB5(1), CREBBP(8), DAG1(2), EGR1(2), EGR2(3), EGR3(4), ELK1(1), GNAQ(1), MAP1B(9), MAP2K7(1), MAPK1(3), MAPK3(2), MAPK8IP1(3), MAPK8IP2(3), MAPK8IP3(5), MAPK9(2), NTRK1(4), OPN1LW(3), PIK3C2G(9), PIK3CA(19), PIK3CD(2), PIK3R1(17), PTPN11(6), RPS6KA3(5), SRC(2), TERF2IP(3) 19993337 129 80 121 22 27 22 26 36 18 0 4.01e-13 3.69e-12 68 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 42 BCL2(3), CHUK(4), DAXX(4), EGF(3), EGFR(58), FOS(1), HOXA7(2), IKBKB(2), MAP2K1(1), MAP2K3(1), MAP2K7(1), MAP3K1(5), MAP3K14(2), MAP3K5(1), MAPK1(3), MAPK13(1), MAPK14(1), MAPK3(2), NFKB1(1), NFKBIA(2), PPP2CA(1), PRKCA(3), PRKCD(5), PRKCE(1), PRKCG(1), PRKCH(2), PRKCQ(1), RIPK1(1), SP1(6), TNFRSF1A(2), TNFRSF1B(2), TRAF2(2) 19744800 125 82 92 30 25 31 39 20 10 0 7.36e-13 6.67e-12 69 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 47 ACOX1(2), APOA2(1), CD36(2), CREBBP(8), EHHADH(2), EP300(5), HSD17B4(1), MAPK1(3), MAPK3(2), ME1(4), MRPL11(1), NCOA1(3), NCOR1(5), NCOR2(5), NFKBIA(2), NR0B2(3), NR1H3(1), NRIP1(3), PIK3CA(19), PIK3R1(17), PPARA(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PRKCA(3), RB1(21), RXRA(3), SP1(6), STAT5A(2), STAT5B(2) 24558471 130 83 124 26 22 16 24 28 38 2 1.26e-12 1.13e-11 70 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 130 ACTB(1), ACTN1(1), ACTN3(1), ACTN4(4), AKT1(1), AKT2(1), AKT3(1), ASH1L(3), CASK(2), CGN(3), CLDN14(1), CLDN17(1), CLDN18(1), CLDN2(1), CLDN20(1), CLDN23(2), CLDN4(1), CLDN5(2), CLDN6(1), CLDN7(1), CLDN8(1), CRB3(1), CSDA(1), CSNK2A1(3), CTNNA1(1), CTNNA2(2), CTNNA3(1), CTTN(1), EPB41(2), EPB41L1(2), EPB41L2(2), EPB41L3(7), EXOC3(3), EXOC4(1), F11R(1), GNAI2(1), HCLS1(5), INADL(3), JAM2(1), JAM3(1), KRAS(1), LLGL1(1), LLGL2(2), MAGI1(2), MAGI2(4), MAGI3(2), MLLT4(5), MPDZ(5), MPP5(1), MYH1(3), MYH10(3), MYH11(7), MYH13(11), MYH14(6), MYH15(3), MYH2(13), MYH3(6), MYH4(6), MYH6(5), MYH7(3), MYH7B(9), MYH8(8), MYH9(8), MYL2(2), MYLPF(1), NRAS(1), OCLN(1), PARD3(2), PARD6A(1), PARD6B(3), PPP2CA(1), PPP2R1A(1), PPP2R1B(3), PPP2R2A(1), PPP2R2B(1), PPP2R2C(1), PPP2R3A(3), PPP2R4(1), PRKCA(3), PRKCD(5), PRKCE(1), PRKCG(1), PRKCH(2), PRKCI(1), PRKCQ(1), PRKCZ(2), PTEN(80), RHOA(1), RRAS2(3), SPTAN1(6), SRC(2), SYMPK(4), TJAP1(5), TJP1(2), TJP2(3), TJP3(6), ZAK(1) 76298731 336 152 317 107 117 51 55 48 65 0 3.85e-12 3.39e-11 71 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 ARFIP2(1), CDK5R1(1), LIMK1(1), MAP3K1(5), MYL2(2), MYLK(7), PAK1(2), PDGFRA(10), PIK3CA(19), PIK3R1(17), PPP1R12B(6), RALBP1(3), RPS6KB1(1), TRIO(8), VAV1(6), WASF1(1) 14138892 90 62 85 17 16 16 22 20 16 0 5.79e-12 5.02e-11 72 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 ADRB2(1), AKT1(1), CALM1(1), GNAS(3), GNB1(1), GNGT1(1), NFKB1(1), NOS3(5), NR3C1(1), PIK3CA(19), PIK3R1(17), SYT1(1) 7028218 52 43 47 9 8 10 7 14 13 0 7.63e-12 6.53e-11 73 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(1), CHRNB1(1), CHRNG(1), MUSK(1), PIK3CA(19), PIK3R1(17), PTK2(2), PTK2B(1), SRC(2), TERT(8) 6387994 53 41 48 5 12 11 6 12 12 0 9.10e-12 7.68e-11 74 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 143 APC(7), APC2(2), AXIN1(2), AXIN2(1), BTRC(1), CACYBP(1), CAMK2B(1), CAMK2D(1), CAMK2G(4), CCND2(1), CHD8(9), CREBBP(8), CSNK2A1(3), CTBP1(3), CTBP2(4), CUL1(5), CXXC4(2), DAAM1(1), DAAM2(1), DKK1(1), DKK2(3), DVL2(2), EP300(5), FBXW11(2), FZD1(1), FZD10(4), FZD2(1), FZD3(4), FZD4(3), FZD5(2), FZD6(2), FZD7(1), FZD8(1), FZD9(6), GSK3B(1), LEF1(1), LRP5(3), LRP6(4), MAP3K7(2), MAPK9(2), MMP7(2), NFAT5(3), NFATC1(3), NFATC2(1), NFATC3(1), NFATC4(2), NKD2(2), PLCB1(3), PLCB2(5), PLCB3(5), PLCB4(3), PORCN(2), PPP2CA(1), PPP2R1A(1), PPP2R1B(3), PPP2R2A(1), PPP2R2B(1), PPP2R2C(1), PPP3CB(1), PPP3R1(1), PPP3R2(1), PRICKLE2(3), PRKACG(1), PRKCA(3), PRKCG(1), PRKX(2), RHOA(1), ROCK1(3), ROCK2(4), RUVBL1(1), SENP2(2), SFRP1(2), SFRP5(1), SMAD3(1), SMAD4(1), TBL1X(2), TBL1XR1(1), TBL1Y(1), TCF7(3), TCF7L2(3), TP53(89), VANGL1(2), VANGL2(1), WIF1(2), WNT10A(1), WNT11(1), WNT16(1), WNT2(5), WNT2B(1), WNT3(3), WNT3A(1), WNT4(3), WNT5A(1), WNT8A(1), WNT8B(3), WNT9A(3), WNT9B(4) 62996458 309 137 279 71 90 41 65 53 56 4 1.02e-11 8.53e-11 75 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 69 AKT1(1), AKT2(1), AKT3(1), KDR(10), KRAS(1), MAP2K1(1), MAP2K2(1), MAPK1(3), MAPK13(1), MAPK14(1), MAPK3(2), MAPKAPK2(1), MAPKAPK3(1), NFAT5(3), NFATC1(3), NFATC2(1), NFATC3(1), NFATC4(2), NOS3(5), NRAS(1), PIK3CA(19), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(17), PIK3R2(5), PIK3R5(2), PLA2G12A(3), PLA2G2A(5), PLA2G2F(2), PLA2G3(2), PLA2G4A(4), PLA2G5(1), PLA2G6(3), PLCG1(3), PLCG2(11), PPP3CB(1), PPP3R1(1), PPP3R2(1), PRKCA(3), PRKCG(1), PTK2(2), PXN(1), SH2D2A(2), SPHK1(1), SPHK2(2), SRC(2), VEGFA(2) 28188206 153 94 143 39 45 23 25 34 25 1 1.32e-11 1.07e-10 76 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 CCNE1(1), CDKN1B(3), CUL1(5), RB1(21), UBE2M(3) 3464136 33 28 31 4 3 3 5 0 22 0 1.32e-11 1.07e-10 77 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 21 ADCY1(8), AKT1(1), BCL2(3), CSF2RB(4), IGF1R(2), KIT(3), KITLG(2), PIK3CA(19), PIK3R1(17), PRKACG(1), PRKAR2A(1), PRKAR2B(1) 8335460 62 48 57 6 14 11 10 15 12 0 1.74e-11 1.39e-10 78 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(1), EIF2B2(2), EIF2B3(1), EIF2B4(1), EIF2S2(1), EIF2S3(3), ELAVL1(1), FLT1(2), FLT4(3), HIF1A(1), KDR(10), NOS3(5), PIK3CA(19), PIK3R1(17), PLCG1(3), PRKCA(3), PTK2(2), PXN(1), VHL(1) 13402316 77 58 72 13 16 13 10 22 16 0 1.85e-11 1.46e-10 79 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(3), ELK1(1), FOS(1), JAK1(3), MAP2K1(1), MAP3K1(5), MAPK3(2), PDGFRA(10), PIK3CA(19), PIK3R1(17), PLCG1(3), PRKCA(3), SOS1(1), SRF(2), STAT1(1), STAT3(2), STAT5A(2) 13971889 76 59 71 11 13 17 13 18 15 0 3.39e-11 2.64e-10 80 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(8), AKT1(1), ASAH1(1), GNB1(1), GNGT1(1), ITGAV(1), ITGB3(1), MAPK1(3), MAPK3(2), PDGFRA(10), PIK3CA(19), PIK3R1(17), PLCB1(3), PRKCA(3), PTK2(2), SPHK1(1), SRC(2) 10881577 76 53 72 7 16 15 14 17 13 1 3.49e-11 2.69e-10 81 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(1), IGF1R(2), IRS1(4), MAP2K1(1), MAPK1(3), MAPK3(2), PIK3CA(19), PIK3R1(17), SOS1(1) 7508202 50 43 45 4 7 11 5 16 11 0 4.24e-11 3.22e-10 82 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 32 MAP2K7(1), MAPK1(3), MAPK13(1), MAPK14(1), MAPK3(2), MAPK8IP1(3), MAPK8IP2(3), MAPK8IP3(5), MAPK9(2), NFKB1(1), NFKB2(1), NFKBIA(2), NFKBIB(1), NFKBIE(1), NFKBIL1(1), NFKBIL2(6), PIK3CA(19), PIK3CD(2), PIK3R1(17), SYT1(1), TRAF2(2), TRAF3(3), TRAF5(1) 12589180 79 57 74 14 16 12 13 22 16 0 6.46e-11 4.85e-10 83 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 30 AKT1(1), CABIN1(12), CALM1(1), CAMK1(2), HDAC5(4), IGF1R(2), INSR(5), MAPK14(1), MAPK7(3), MEF2A(1), MEF2C(1), MEF2D(1), MYOD1(2), NFATC1(3), NFATC2(1), PIK3CA(19), PIK3R1(17), PPP3CB(1), SYT1(1) 13588372 78 61 73 15 14 16 13 20 15 0 1.20e-10 8.90e-10 84 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 8 CCNE1(1), CUL1(5), FBXW7(2), RB1(21) 3365196 29 26 27 5 4 2 3 0 20 0 1.29e-10 9.46e-10 85 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(3), ELK1(1), FOS(1), MAP2K1(1), MAPK3(2), NGFR(1), PIK3CA(19), PIK3R1(17), PLCG1(3), SOS1(1) 7669216 49 42 44 6 8 10 6 13 12 0 1.36e-10 9.87e-10 86 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 23 GNAQ(1), GNB1(1), GNGT1(1), MAP2K1(1), MAPK1(3), MAPK3(2), NFKB1(1), PIK3C2G(9), PIK3CA(19), PIK3R1(17), PLCG1(3), PRKCA(3), PTK2(2), PTK2B(1), PXN(1) 10996313 65 51 60 11 10 10 10 22 13 0 1.44e-10 1.03e-09 87 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 34 AKT1(1), AKT2(1), AKT3(1), ASAH1(1), BRAF(6), DAG1(2), DRD2(1), EGFR(58), EPHB2(6), ITPKB(2), ITPR1(7), ITPR2(11), ITPR3(11), KCNJ3(2), KCNJ5(3), MAPK1(3), PIK3CB(2), PLCB1(3), PLCB2(5), PLCB3(5), PLCB4(3), SOS1(1), SOS2(4), SRC(2), STAT3(2), TERF2IP(3) 23295208 146 83 110 25 36 42 39 18 10 1 1.95e-10 1.38e-09 88 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 74 AKT1(1), AKT2(1), AKT3(1), BTK(1), FCER1A(3), FCER1G(1), GAB2(3), IL4(1), INPP5D(6), KRAS(1), LYN(1), MAP2K1(1), MAP2K2(1), MAP2K3(1), MAP2K7(1), MAPK1(3), MAPK13(1), MAPK14(1), MAPK3(2), MAPK9(2), NRAS(1), PIK3CA(19), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(17), PIK3R2(5), PIK3R5(2), PLA2G12A(3), PLA2G2A(5), PLA2G2F(2), PLA2G3(2), PLA2G4A(4), PLA2G5(1), PLA2G6(3), PLCG1(3), PLCG2(11), PRKCA(3), PRKCD(5), PRKCE(1), SOS1(1), SOS2(4), SYK(2), VAV1(6), VAV2(3), VAV3(2) 28539793 154 91 145 47 52 24 26 28 23 1 9.22e-10 6.45e-09 89 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 202 ABI2(2), ACTN1(1), ACTN3(1), ACTN4(4), APC(7), APC2(2), ARAF(1), ARHGEF1(2), ARHGEF4(2), ARHGEF7(1), ARPC1B(1), ARPC2(1), ARPC4(1), ARPC5L(1), BDKRB1(1), BDKRB2(3), BRAF(6), CD14(2), CFL2(1), CHRM2(4), CHRM3(3), CYFIP1(2), CYFIP2(1), DIAPH1(2), DIAPH2(3), DIAPH3(4), DOCK1(9), EGF(3), EGFR(58), EZR(3), F2(1), FGD1(2), FGD3(2), FGF10(1), FGF13(1), FGF14(2), FGF18(1), FGF2(1), FGF20(2), FGF21(1), FGF23(3), FGF3(1), FGF6(3), FGF9(1), FGFR1(3), FGFR2(3), FGFR3(2), FGFR4(3), FN1(3), GIT1(2), GNA12(2), GRLF1(4), GSN(2), IQGAP1(2), IQGAP2(4), IQGAP3(5), ITGA1(1), ITGA10(3), ITGA11(2), ITGA2(4), ITGA2B(2), ITGA3(2), ITGA4(7), ITGA5(1), ITGA6(2), ITGA7(3), ITGA8(7), ITGA9(1), ITGAD(7), ITGAE(3), ITGAL(4), ITGAM(8), ITGAV(1), ITGAX(7), ITGB2(5), ITGB3(1), ITGB4(5), ITGB5(2), ITGB6(5), ITGB7(2), ITGB8(3), KRAS(1), LIMK1(1), LIMK2(1), MAP2K1(1), MAP2K2(1), MAPK1(3), MAPK3(2), MSN(1), MYH10(3), MYH14(6), MYH9(8), MYL2(2), MYLK(7), MYLK2(1), MYLPF(1), NCKAP1(2), NCKAP1L(4), NRAS(1), PAK1(2), PAK3(2), PAK6(1), PAK7(3), PDGFRA(10), PDGFRB(5), PIK3CA(19), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(17), PIK3R2(5), PIK3R5(2), PIP4K2A(3), PIP4K2B(1), PIP4K2C(3), PIP5K1B(2), PIP5K1C(4), PPP1CB(1), PPP1CC(1), PPP1R12A(2), PPP1R12B(6), PTK2(2), PXN(1), RHOA(1), ROCK1(3), ROCK2(4), RRAS2(3), SLC9A1(3), SOS1(1), SOS2(4), SSH1(1), SSH2(4), SSH3(2), TIAM1(2), TIAM2(8), TMSL3(2), VAV1(6), VAV2(3), VAV3(2), VCL(2), WASF1(1), WASF2(1) 108426622 484 185 440 143 149 75 113 77 70 0 9.56e-10 6.62e-09 90 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 25 GH1(1), GHR(3), INSR(5), IRS1(4), JAK2(4), MAP2K1(1), MAPK1(3), MAPK3(2), PIK3CA(19), PIK3R1(17), PLCG1(3), PRKCA(3), PTPN6(4), SLC2A4(3), SOCS1(1), SOS1(1), SRF(2), STAT5A(2), STAT5B(2) 13171393 80 56 74 14 19 15 12 21 13 0 1.06e-09 7.24e-09 91 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 21 CSNK2A1(3), ELK1(1), FOS(1), INSR(5), IRS1(4), MAP2K1(1), MAPK3(2), PIK3CA(19), PIK3R1(17), PTPN11(6), SLC2A4(3), SOS1(1), SRF(2) 10143049 65 48 60 9 11 14 9 17 14 0 1.08e-09 7.30e-09 92 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 65 ADAM10(2), ATP6AP1(2), ATP6V0A1(3), ATP6V0A2(1), ATP6V0A4(5), ATP6V0D1(3), ATP6V0D2(1), ATP6V1A(3), ATP6V1B1(1), ATP6V1B2(1), ATP6V1C1(2), ATP6V1C2(2), ATP6V1G1(2), ATP6V1G2(1), ATP6V1H(1), CCL5(1), CHUK(4), CXCL1(1), EGFR(58), F11R(1), GIT1(2), IKBKB(2), JAM2(1), JAM3(1), LYN(1), MAP3K14(2), MAPK13(1), MAPK14(1), MAPK9(2), MET(5), NFKB1(1), NFKB2(1), NFKBIA(2), NOD1(4), PAK1(2), PLCG1(3), PLCG2(11), PTPN11(6), PTPRZ1(3), SRC(2), TCIRG1(2), TJP1(2) 28081300 152 89 119 44 39 35 43 24 11 0 1.77e-09 1.19e-08 93 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(3), ELK1(1), FOS(1), IGF1R(2), IRS1(4), MAP2K1(1), MAPK3(2), PIK3CA(19), PIK3R1(17), PTPN11(6), SOS1(1), SRF(2) 9870015 59 47 54 8 11 12 8 16 12 0 2.97e-09 1.97e-08 94 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 37 BTK(1), CALM1(1), ELK1(1), FCER1A(3), FCER1G(1), FOS(1), LYN(1), MAP2K1(1), MAP2K7(1), MAP3K1(5), MAPK1(3), MAPK3(2), NFATC1(3), NFATC2(1), NFATC3(1), NFATC4(2), PIK3CA(19), PIK3R1(17), PLA2G4A(4), PLCG1(3), PPP3CB(1), SOS1(1), SYK(2), SYT1(1), VAV1(6) 17155914 82 62 77 24 12 18 12 23 16 1 3.05e-09 2.00e-08 95 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 9 CCNA1(1), CCNE1(1), CUL1(5), RB1(21) 3469465 28 24 26 5 4 2 3 0 19 0 3.29e-09 2.13e-08 96 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 22 CCNA1(1), CCND2(1), CCNE1(1), CCNH(2), CDKN1A(1), CDKN1B(3), CDKN2A(3), CDKN2B(1), CDKN2C(4), CDKN2D(1), RB1(21), RBL1(3) 6349452 42 33 40 9 2 5 6 2 27 0 5.25e-09 3.37e-08 97 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 26 AKT1(1), AKT2(1), AKT3(1), BCL2(3), GSK3B(1), IL4R(6), IRS1(4), JAK1(3), JAK3(4), MAP4K1(1), MAPK1(3), MAPK3(2), PIK3CA(19), PIK3CD(2), PIK3R1(17), SOCS1(1), SOS1(1), SOS2(4), STAT6(3) 14130588 77 57 71 12 17 12 13 22 13 0 5.63e-09 3.57e-08 98 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 62 AKT1(1), AKT2(1), AKT3(1), BLNK(2), BTK(1), CARD11(6), CD19(2), CD22(5), CD72(2), CHUK(4), CR2(6), FOS(1), GSK3B(1), IFITM1(1), IKBKB(2), INPP5D(6), KRAS(1), LILRB3(1), LYN(1), MALT1(3), NFAT5(3), NFATC1(3), NFATC2(1), NFATC3(1), NFATC4(2), NFKB1(1), NFKB2(1), NFKBIA(2), NFKBIB(1), NFKBIE(1), NRAS(1), PIK3CA(19), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(17), PIK3R2(5), PIK3R5(2), PLCG2(11), PPP3CB(1), PPP3R1(1), PPP3R2(1), PTPN6(4), RASGRP3(2), SYK(2), VAV1(6), VAV2(3), VAV3(2) 29303434 157 91 150 46 49 23 28 33 24 0 5.92e-09 3.72e-08 99 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(7), GABRA2(2), GABRA3(2), GABRA4(4), GABRA5(3), GABRA6(9), GPX1(2), PRKCE(1) 3156886 30 25 28 9 6 4 10 8 2 0 7.76e-09 4.83e-08 100 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 BCL2(3), CREBBP(8), EP300(5), IL7(1), IL7R(1), JAK1(3), JAK3(4), PIK3CA(19), PIK3R1(17), PTK2B(1), STAT5A(2), STAT5B(2) 11281631 66 49 60 13 9 13 15 15 13 1 8.41e-09 5.18e-08 101 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(1), BCL2(3), BCR(1), FOS(1), JAK2(4), MAP2K1(1), MAP3K1(5), MAPK3(2), PIK3CA(19), PIK3R1(17), SOS1(1), STAT1(1), STAT5A(2), STAT5B(2) 11152516 60 48 54 7 11 13 9 14 13 0 1.04e-08 6.34e-08 102 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 25 AKT1(1), APC(7), AXIN1(2), CD14(2), FZD1(1), GJA1(1), GSK3B(1), IRAK1(2), LBP(2), LEF1(1), LY96(1), NFKB1(1), PIK3CA(19), PIK3R1(17), PPP2CA(1), TLR4(1) 11708184 60 49 55 12 10 12 9 15 14 0 1.05e-08 6.34e-08 103 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 32 ACTR3(2), AKT1(1), ANGPTL2(2), DAG1(2), GCA(1), ITGA9(1), ITPKB(2), ITPR1(7), ITPR2(11), ITPR3(11), MAP2K1(1), MAPK1(3), MAPK3(2), NR1I3(2), PAK1(2), PDE3A(1), PDE3B(4), PIK3C2G(9), PIK3CA(19), PIK3CD(2), PIK3R1(17), PLDN(1), PSME1(1), RIPK3(2), RPS4X(1), VASP(2) 19248819 109 69 104 19 24 19 19 25 22 0 1.06e-08 6.34e-08 104 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 166 ADCY1(8), ADCY2(3), ADCY3(3), ADCY4(2), ADCY7(3), ADCY8(4), ADCY9(5), ADORA2B(1), ADRA1D(1), ADRB1(1), ADRB2(1), AGTR1(2), ATP2A1(4), ATP2A2(2), ATP2A3(4), ATP2B1(2), ATP2B2(4), ATP2B3(8), ATP2B4(1), AVPR1A(3), AVPR1B(1), BDKRB1(1), BDKRB2(3), CACNA1A(4), CACNA1B(7), CACNA1C(5), CACNA1D(9), CACNA1E(9), CACNA1F(10), CACNA1G(6), CACNA1H(9), CACNA1I(5), CACNA1S(12), CALM1(1), CAMK2B(1), CAMK2D(1), CAMK2G(4), CAMK4(1), CCKAR(3), CCKBR(2), CD38(2), CHRM2(4), CHRM3(3), CHRNA7(2), CYSLTR1(1), CYSLTR2(1), DRD1(2), EDNRA(1), EDNRB(1), EGFR(58), ERBB2(7), ERBB3(4), ERBB4(1), GNA11(2), GNA15(4), GNAL(1), GNAQ(1), GNAS(3), GRIN1(3), GRIN2A(13), GRIN2C(2), GRIN2D(2), GRM1(1), GRM5(1), GRPR(1), HRH1(1), HRH2(5), HTR2A(1), HTR2C(2), HTR4(1), HTR5A(4), HTR6(1), HTR7(1), ITPKB(2), ITPR1(7), ITPR2(11), ITPR3(11), LHCGR(1), LTB4R2(2), MYLK(7), MYLK2(1), NOS1(9), NOS3(5), NTSR1(2), OXTR(2), P2RX1(1), P2RX2(3), P2RX4(2), P2RX5(3), P2RX7(2), PDE1A(1), PDE1C(4), PDGFRA(10), PDGFRB(5), PHKA1(3), PHKA2(4), PHKB(2), PLCB1(3), PLCB2(5), PLCB3(5), PLCB4(3), PLCD1(1), PLCD3(2), PLCD4(2), PLCE1(7), PLCG1(3), PLCG2(11), PLCZ1(1), PPID(1), PPP3CB(1), PPP3R1(1), PPP3R2(1), PRKACG(1), PRKCA(3), PRKCG(1), PRKX(2), PTAFR(2), PTGER3(2), PTGFR(2), PTK2B(1), RYR1(14), RYR2(36), RYR3(17), SLC25A5(2), SLC8A1(2), SLC8A3(2), SPHK1(1), SPHK2(2), TACR1(1), TACR3(4), TNNC1(1), TRHR(2), TRPC1(1), VDAC1(1), VDAC2(1) 105231927 541 185 504 153 223 78 113 77 49 1 1.58e-08 9.36e-08 105 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(8), AKT1(1), CAMK2B(1), CAMK2D(1), CAMK2G(4), GNAS(3), MAPK1(3), MAPK14(1), MAPK3(2), PIK3CA(19), PIK3R1(17), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PRKCA(3), SOS1(1) 11432502 67 50 62 13 14 12 9 21 11 0 2.16e-08 1.27e-07 106 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 19 ADCY1(8), ARHGEF1(2), F2(1), F2RL3(1), GNA12(2), GNAQ(1), GNB1(1), GNGT1(1), MAP3K7(2), PIK3CA(19), PIK3R1(17), PLCB1(3), PPP1R12B(6), PRKCA(3), PTK2B(1), ROCK1(3) 10337884 71 46 66 9 16 11 12 19 12 1 2.31e-08 1.34e-07 107 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 44 AKT1(1), AKT2(1), AKT3(1), BRAF(6), CAB39(2), DDIT4(1), EIF4B(3), FIGF(1), HIF1A(1), MAPK1(3), MAPK3(2), PIK3CA(19), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(17), PIK3R2(5), PIK3R5(2), PRKAA2(1), RICTOR(2), RPS6KA2(2), RPS6KA3(5), RPS6KB1(1), TSC1(4), TSC2(2), ULK1(1), ULK2(6), ULK3(1), VEGFA(2), VEGFC(2) 20646165 110 69 102 24 25 21 14 26 24 0 2.95e-08 1.70e-07 108 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 134 ACTB(1), CHAD(1), COL11A1(8), COL11A2(9), COL17A1(3), COL1A1(4), COL1A2(9), COL2A1(2), COL3A1(5), COL4A1(4), COL4A2(8), COL4A4(4), COL4A6(5), COL5A1(3), COL5A2(5), COL5A3(11), COL6A1(5), COL6A2(3), COL6A3(27), COL6A6(7), COMP(1), DES(3), DSC1(5), DSC2(2), DSC3(2), DSG1(4), DSG2(1), DSG3(8), DSG4(10), FN1(3), GJA1(1), GJA10(1), GJA8(1), GJA9(1), GJB1(4), GJB3(2), GJB5(2), GJB6(1), GJB7(1), GJC1(1), GJC2(1), GJC3(1), GJD4(3), INA(2), ITGA6(2), ITGB4(5), KRT1(2), KRT10(1), KRT12(3), KRT13(4), KRT14(3), KRT15(1), KRT16(4), KRT17(3), KRT18(3), KRT19(5), KRT2(3), KRT20(1), KRT23(8), KRT24(1), KRT25(3), KRT28(3), KRT3(1), KRT31(3), KRT32(2), KRT33A(3), KRT33B(2), KRT34(3), KRT36(4), KRT37(2), KRT38(2), KRT4(2), KRT5(1), KRT6A(1), KRT6B(2), KRT6C(1), KRT7(3), KRT72(1), KRT73(1), KRT74(3), KRT75(2), KRT76(2), KRT77(2), KRT78(1), KRT79(2), KRT8(3), KRT81(1), KRT82(1), KRT83(2), KRT84(2), KRT85(2), KRT9(3), LAMA1(17), LAMA2(12), LAMA3(7), LAMA4(4), LAMA5(9), LAMB1(4), LAMB2(3), LAMB3(4), LAMB4(10), LAMC1(2), LAMC2(6), LAMC3(5), LMNB1(1), LMNB2(3), NES(3), RELN(20), SPP1(1), THBS1(3), THBS2(5), THBS3(1), THBS4(2), TNC(7), TNN(5), TNR(2), TNXB(6), VIM(1), VWF(10) 96477536 453 166 442 181 173 84 82 56 57 1 4.21e-08 2.40e-07 109 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 95 ADCY1(8), ADCY2(3), ADCY3(3), ADCY4(2), ADCY5(3), ADCY6(2), ADCY7(3), ADCY8(4), ADCY9(5), ATF4(1), CACNA1C(5), CACNA1D(9), CACNA1F(10), CACNA1S(12), CALM1(1), CAMK2B(1), CAMK2D(1), CAMK2G(4), CGA(1), EGFR(58), ELK1(1), GNA11(2), GNAQ(1), GNAS(3), GNRH1(1), GNRH2(1), ITPR1(7), ITPR2(11), ITPR3(11), KRAS(1), MAP2K1(1), MAP2K2(1), MAP2K3(1), MAP2K7(1), MAP3K1(5), MAP3K2(1), MAP3K3(4), MAP3K4(2), MAPK1(3), MAPK13(1), MAPK14(1), MAPK3(2), MAPK7(3), MAPK9(2), MMP14(4), MMP2(1), NRAS(1), PLA2G12A(3), PLA2G2A(5), PLA2G2F(2), PLA2G3(2), PLA2G4A(4), PLA2G5(1), PLA2G6(3), PLCB1(3), PLCB2(5), PLCB3(5), PLCB4(3), PLD2(1), PRKACG(1), PRKCA(3), PRKCD(5), PRKX(2), PTK2B(1), SOS1(1), SOS2(4), SRC(2) 50785084 265 128 227 68 90 49 62 41 21 2 5.10e-08 2.88e-07 110 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 99 AKT1(1), AKT2(1), AKT3(1), CCL3(1), CCL5(1), CD14(2), CHUK(4), FOS(1), IFNA13(1), IFNA14(1), IFNA17(1), IFNA21(1), IFNA5(1), IFNA7(2), IFNAR2(1), IFNB1(1), IKBKB(2), IL12B(1), IL6(2), IRAK1(2), IRAK4(2), IRF5(5), LBP(2), LY96(1), MAP2K1(1), MAP2K2(1), MAP2K3(1), MAP2K7(1), MAP3K7(2), MAPK1(3), MAPK13(1), MAPK14(1), MAPK3(2), MAPK9(2), NFKB1(1), NFKB2(1), NFKBIA(2), PIK3CA(19), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(17), PIK3R2(5), PIK3R5(2), RIPK1(1), SPP1(1), STAT1(1), TBK1(2), TLR1(2), TLR2(4), TLR4(1), TLR5(4), TLR6(6), TLR7(5), TLR8(3), TLR9(2), TRAF3(3) 35587805 151 89 141 53 32 29 22 38 30 0 2.11e-07 1.18e-06 111 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(3), FOS(1), JAK2(4), MAP2K1(1), MAPK3(2), MPL(2), PIK3CA(19), PIK3R1(17), PLCG1(3), PRKCA(3), SOS1(1), STAT1(1), STAT3(2), STAT5A(2), STAT5B(2), THPO(1) 12039194 64 47 58 8 15 12 10 15 12 0 2.43e-07 1.35e-06 112 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(5), GABRA1(7), GABRA2(2), GABRA3(2), GABRA4(4), GABRA5(3), GABRA6(9), GPHN(1), NSF(1), SRC(2), UBQLN1(2) 4747449 38 29 36 8 10 5 12 8 3 0 2.62e-07 1.44e-06 113 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 125 ARAF(1), BID(4), BRAF(6), CD244(1), FCER1G(1), FCGR3A(1), GZMB(3), HCST(1), HLA-A(1), HLA-B(1), IFNA13(1), IFNA14(1), IFNA17(1), IFNA21(1), IFNA5(1), IFNA7(2), IFNAR2(1), IFNB1(1), IFNG(1), IFNGR1(1), IFNGR2(1), ITGAL(4), ITGB2(5), KIR2DL1(2), KIR2DL4(1), KIR3DL1(1), KLRC1(1), KLRC3(3), KLRK1(1), KRAS(1), MAP2K1(1), MAP2K2(1), MAPK1(3), MAPK3(2), MICB(1), NCR1(2), NCR2(3), NFAT5(3), NFATC1(3), NFATC2(1), NFATC3(1), NFATC4(2), NRAS(1), PAK1(2), PIK3CA(19), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(17), PIK3R2(5), PIK3R5(2), PLCG1(3), PLCG2(11), PPP3CB(1), PPP3R1(1), PPP3R2(1), PRF1(3), PRKCA(3), PRKCG(1), PTK2B(1), PTPN11(6), PTPN6(4), SH2D1B(1), SH3BP2(2), SHC3(1), SHC4(1), SOS1(1), SOS2(4), SYK(2), TNFRSF10A(2), TNFSF10(5), ULBP1(1), VAV1(6), VAV2(3), VAV3(2), ZAP70(5) 44628599 207 112 197 79 55 27 41 49 35 0 2.92e-07 1.59e-06 114 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 34 AKT1(1), BCL2(3), CBL(1), FOS(1), IL2RA(3), IL2RB(1), IRS1(4), JAK1(3), JAK3(4), MAPK1(3), MAPK3(2), PIK3CA(19), PIK3R1(17), PTPN6(4), RPS6KB1(1), SOCS1(1), SOS1(1), STAT5A(2), STAT5B(2), SYK(2) 14353386 75 53 69 13 13 12 15 21 14 0 3.51e-07 1.90e-06 115 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 CALM1(1), CD3E(1), CD3G(1), ELK1(1), FOS(1), MAP2K1(1), MAP3K1(5), MAPK3(2), NFATC1(3), NFATC2(1), NFATC3(1), NFATC4(2), NFKB1(1), NFKBIA(2), PIK3CA(19), PIK3R1(17), PLCG1(3), PPP3CB(1), PRKCA(3), SOS1(1), SYT1(1), VAV1(6), ZAP70(5) 19078846 79 63 74 26 14 15 13 20 17 0 3.94e-07 2.11e-06 116 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 91 ADCY1(8), ADCY2(3), ADCY3(3), ADCY4(2), ADCY5(3), ADCY6(2), ADCY7(3), ADCY8(4), ADCY9(5), ADRB1(1), DRD1(2), DRD2(1), EGF(3), EGFR(58), GJA1(1), GNA11(2), GNAI2(1), GNAQ(1), GNAS(3), GRM1(1), GRM5(1), GUCY1A2(1), GUCY1A3(5), GUCY2C(2), GUCY2D(2), GUCY2F(1), HTR2A(1), HTR2C(2), ITPR1(7), ITPR2(11), ITPR3(11), KRAS(1), MAP2K1(1), MAP2K2(1), MAP2K5(1), MAP3K2(1), MAPK1(3), MAPK3(2), MAPK7(3), NPR1(6), NPR2(1), NRAS(1), PDGFC(3), PDGFD(2), PDGFRA(10), PDGFRB(5), PLCB1(3), PLCB2(5), PLCB3(5), PLCB4(3), PRKACG(1), PRKCA(3), PRKCG(1), PRKG2(5), PRKX(2), SOS1(1), SOS2(4), SRC(2), TJP1(2), TUBA1A(2), TUBA1C(1), TUBA3C(3), TUBA4A(1), TUBA8(4), TUBB1(1), TUBB2A(1), TUBB2C(1), TUBB3(1), TUBB4(2), TUBB4Q(4), TUBB8(1) 52353882 251 127 211 75 79 45 61 38 27 1 5.10e-07 2.71e-06 117 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 CCL2(2), MST1(10), MST1R(6) 2499702 18 17 14 5 6 0 0 4 8 0 5.98e-07 3.15e-06 118 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 51 ACTA1(1), AGT(3), AKT1(1), CALM1(1), CAMK1(2), CAMK4(1), CREBBP(8), ELSPBP1(1), F2(1), FGF2(1), FKBP1A(1), GATA4(2), GSK3B(1), MAP2K1(1), MAPK1(3), MAPK14(1), MAPK3(2), MEF2C(1), MYH2(13), NFATC1(3), NFATC2(1), NFATC3(1), NFATC4(2), PIK3CA(19), PIK3R1(17), PPP3CB(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1), RPS6KB1(1), SYT1(1) 19940572 94 62 89 25 17 17 16 25 19 0 2.25e-06 0.000012 119 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 ACTA1(1), AKT1(1), BDKRB2(3), CALM1(1), CAV1(1), FLT1(2), FLT4(3), KDR(10), NOS3(5), PDE2A(3), PDE3A(1), PDE3B(4), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PRKG2(5), RYR2(36), SLC7A1(2), SYT1(1), TNNI1(2) 15559598 84 56 83 23 38 10 10 18 8 0 2.78e-06 0.000014 120 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(2), DIAPH1(2), GSN(2), ITGA1(1), MAP2K1(1), MAPK1(3), MAPK3(2), MYL2(2), MYLK(7), PIK3CA(19), PIK3R1(17), PTK2(2), PXN(1), ROCK1(3), SRC(2), TLN1(6) 15165527 72 50 67 10 17 12 11 16 16 0 3.11e-06 0.000016 121 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 23 IMPA1(1), INPP1(2), INPP4A(1), INPP4B(1), INPP5A(1), INPPL1(4), ITPKB(2), MIOX(1), OCRL(1), PIK3C2A(3), PIK3C2B(2), PIK3C2G(9), PIK3CA(19), PIK3CB(2), PIK3CG(12), PLCB1(3), PLCB2(5), PLCB3(5), PLCB4(3), PLCD1(1), PLCG1(3), PLCG2(11) 17799899 92 58 89 21 29 16 18 16 12 1 4.00e-06 0.000020 122 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 46 AKT1(1), AKT2(1), AKT3(1), BCL2(3), BCR(1), BLNK(2), BTK(1), CD19(2), CD22(5), CR2(6), DAG1(2), FLOT1(2), GSK3B(1), INPP5D(6), ITPR1(7), ITPR2(11), ITPR3(11), LYN(1), MAP4K1(1), MAPK1(3), MAPK3(2), NFATC1(3), NFATC2(1), NR0B2(3), PIK3CA(19), PIK3CD(2), PIK3R1(17), PLCG2(11), PPP3CB(1), PTPRC(4), SOS1(1), SOS2(4), SYK(2), VAV1(6) 29203279 144 82 138 33 46 22 24 27 25 0 4.02e-06 0.000020 123 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 39 AKT1(1), AKT2(1), AKT3(1), BCR(1), BLNK(2), BTK(1), CD19(2), DAG1(2), EPHB2(6), ITPKB(2), LYN(1), MAP2K1(1), MAP2K2(1), MAPK1(3), NFAT5(3), NFKB1(1), NFKB2(1), NFKBIA(2), NFKBIB(1), NFKBIE(1), NFKBIL1(1), NFKBIL2(6), PIK3CA(19), PIK3CD(2), PIK3R1(17), PLCG2(11), SOS1(1), SOS2(4), SYK(2), VAV1(6) 20579717 103 62 98 29 28 19 15 23 18 0 6.63e-06 0.000033 124 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 233 ADORA1(2), ADORA2B(1), ADORA3(1), ADRA2B(6), ADRA2C(4), ADRB1(1), ADRB2(1), AGTR1(2), AGTR2(1), AVPR1A(3), AVPR1B(1), BDKRB1(1), BDKRB2(3), BRS3(2), C3AR1(1), C5AR1(1), CALCR(6), CALCRL(2), CCKAR(3), CCKBR(2), CGA(1), CHRM2(4), CHRM3(3), CNR1(2), CNR2(3), CRHR1(2), CTSG(4), CYSLTR1(1), CYSLTR2(1), DRD1(2), DRD2(1), DRD3(1), DRD5(4), EDNRA(1), EDNRB(1), F2(1), F2RL3(1), FPR1(1), FSHR(1), GABBR1(1), GABBR2(6), GABRA1(7), GABRA2(2), GABRA3(2), GABRA4(4), GABRA5(3), GABRA6(9), GABRB1(3), GABRB2(7), GABRB3(2), GABRD(2), GABRE(6), GABRG1(2), GABRG2(6), GABRP(4), GABRQ(2), GABRR2(1), GALR1(3), GALR2(1), GH1(1), GH2(2), GHR(3), GHRHR(3), GHSR(4), GIPR(1), GLP1R(1), GLP2R(1), GLRA2(1), GLRA3(3), GLRB(1), GPR156(3), GPR50(3), GPR83(4), GRIA1(4), GRIA3(5), GRIA4(2), GRID1(3), GRID2(1), GRIK1(1), GRIK2(2), GRIK3(3), GRIK4(1), GRIK5(2), GRIN1(3), GRIN2A(13), GRIN2B(4), GRIN2C(2), GRIN2D(2), GRIN3A(1), GRIN3B(1), GRM1(1), GRM2(1), GRM3(9), GRM4(5), GRM5(1), GRM6(6), GRM7(3), GRM8(8), GRPR(1), GZMA(1), HCRTR1(2), HCRTR2(1), HRH1(1), HRH2(5), HRH3(1), HRH4(1), HTR1A(2), HTR1B(3), HTR1D(1), HTR1E(2), HTR1F(2), HTR2A(1), HTR2C(2), HTR4(1), HTR5A(4), HTR6(1), HTR7(1), LEPR(1), LHCGR(1), LTB4R2(2), MC2R(1), MC3R(6), MC4R(3), MC5R(2), MCHR1(2), MCHR2(3), MLNR(1), NMUR1(2), NMUR2(5), NPBWR1(2), NPFFR1(2), NPFFR2(2), NPY5R(4), NR3C1(1), NTSR1(2), OPRK1(1), OPRL1(2), OPRM1(4), OXTR(2), P2RX1(1), P2RX2(3), P2RX4(2), P2RX5(3), P2RX7(2), P2RY1(1), P2RY10(1), P2RY13(3), P2RY14(1), P2RY2(2), P2RY4(2), P2RY6(2), PARD3(2), PPYR1(2), PRL(3), PRSS1(1), PTAFR(2), PTGDR(1), PTGER2(2), PTGER3(2), PTGER4(2), PTGFR(2), PTGIR(1), PTH2R(2), RXFP1(3), RXFP2(1), SCTR(2), SSTR2(1), SSTR3(2), SSTR4(4), SSTR5(2), TAAR2(1), TAAR5(1), TACR1(1), TACR3(4), THRA(1), TRHR(2), TSHB(1), TSHR(1), TSPO(1), UTS2R(1), VIPR2(2) 86690469 427 159 421 170 193 53 68 72 41 0 0.000014 0.000068 125 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 191 ACTB(1), ACTN1(1), ACTN3(1), ACTN4(4), AKT1(1), AKT2(1), AKT3(1), ARHGAP5(2), BCL2(3), BIRC2(1), BIRC3(1), BRAF(6), CAPN2(1), CAV1(1), CAV3(1), CCND2(1), CHAD(1), COL11A1(8), COL11A2(9), COL1A1(4), COL1A2(9), COL2A1(2), COL3A1(5), COL4A1(4), COL4A2(8), COL4A4(4), COL4A6(5), COL5A1(3), COL5A2(5), COL5A3(11), COL6A1(5), COL6A2(3), COL6A3(27), COL6A6(7), COMP(1), DIAPH1(2), DOCK1(9), EGF(3), EGFR(58), ELK1(1), ERBB2(7), FARP2(2), FIGF(1), FLNA(14), FLNB(4), FLNC(6), FLT1(2), FN1(3), GRLF1(4), GSK3B(1), HGF(4), IGF1R(2), ILK(2), ITGA1(1), ITGA10(3), ITGA11(2), ITGA2(4), ITGA2B(2), ITGA3(2), ITGA4(7), ITGA5(1), ITGA6(2), ITGA7(3), ITGA8(7), ITGA9(1), ITGAV(1), ITGB3(1), ITGB4(5), ITGB5(2), ITGB6(5), ITGB7(2), ITGB8(3), KDR(10), LAMA1(17), LAMA2(12), LAMA3(7), LAMA4(4), LAMA5(9), LAMB1(4), LAMB2(3), LAMB3(4), LAMB4(10), LAMC1(2), LAMC2(6), LAMC3(5), MAP2K1(1), MAPK1(3), MAPK3(2), MAPK9(2), MET(5), MYL2(2), MYLK(7), MYLK2(1), MYLPF(1), PAK1(2), PAK3(2), PAK6(1), PAK7(3), PARVB(1), PARVG(2), PDGFC(3), PDGFD(2), PDGFRA(10), PDGFRB(5), PIK3CA(19), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(17), PIK3R2(5), PIK3R5(2), PIP5K1C(4), PPP1CB(1), PPP1CC(1), PPP1R12A(2), PRKCA(3), PRKCG(1), PTEN(80), PTK2(2), PXN(1), RAP1B(2), RELN(20), RHOA(1), ROCK1(3), ROCK2(4), SHC3(1), SHC4(1), SOS1(1), SOS2(4), SPP1(1), SRC(2), THBS1(3), THBS2(5), THBS3(1), THBS4(2), TLN1(6), TLN2(5), TNC(7), TNN(5), TNR(2), TNXB(6), VASP(2), VAV1(6), VAV2(3), VAV3(2), VCL(2), VEGFA(2), VEGFC(2), VWF(10), ZYX(2) 145099378 742 225 676 196 216 144 141 115 125 1 0.000014 0.000071 126 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 92 AKT1(1), AKT2(1), AKT3(1), CARD11(6), CBL(1), CBLB(1), CBLC(1), CD28(1), CD3E(1), CD3G(1), CD4(3), CD8A(1), CD8B(1), CHUK(4), FOS(1), GRAP2(1), IFNG(1), IKBKB(2), IL2(1), IL4(1), ITK(3), KRAS(1), MALT1(3), MAP3K14(2), NFAT5(3), NFATC1(3), NFATC2(1), NFATC3(1), NFATC4(2), NFKB1(1), NFKB2(1), NFKBIA(2), NFKBIB(1), NFKBIE(1), NRAS(1), PAK1(2), PAK3(2), PAK6(1), PAK7(3), PDCD1(1), PIK3CA(19), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(17), PIK3R2(5), PIK3R5(2), PLCG1(3), PPP3CB(1), PPP3R1(1), PPP3R2(1), PRKCQ(1), PTPN6(4), PTPRC(4), RASGRP1(1), RHOA(1), SOS1(1), SOS2(4), TEC(5), VAV1(6), VAV2(3), VAV3(2), ZAP70(5) 40114332 168 95 160 58 45 25 31 41 26 0 0.000019 0.000093 127 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 15 AKT1(1), AKT2(1), AKT3(1), CDKN1A(1), ELK1(1), MAP2K1(1), MAP2K2(1), NGFR(1), NTRK1(4), PIK3CA(19), PIK3CD(2), SOS1(1) 6333919 34 30 32 7 9 8 3 10 4 0 0.000027 0.00013 128 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 109 ACTN1(1), ACTN3(1), ACTN4(4), ARHGAP5(2), CDH5(2), CLDN14(1), CLDN17(1), CLDN18(1), CLDN2(1), CLDN20(1), CLDN23(2), CLDN4(1), CLDN5(2), CLDN6(1), CLDN7(1), CLDN8(1), CTNNA1(1), CTNNA2(2), CTNNA3(1), CYBB(2), ESAM(1), EZR(3), F11R(1), GNAI2(1), GRLF1(4), ITGA4(7), ITGAL(4), ITGAM(8), ITGB2(5), ITK(3), JAM2(1), JAM3(1), MAPK13(1), MAPK14(1), MLLT4(5), MMP2(1), MMP9(2), MSN(1), MYL2(2), MYLPF(1), NCF1(2), NCF4(1), NOX1(2), NOX3(5), OCLN(1), PECAM1(2), PIK3CA(19), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(17), PIK3R2(5), PIK3R5(2), PLCG1(3), PLCG2(11), PRKCA(3), PRKCG(1), PTK2(2), PTK2B(1), PTPN11(6), PXN(1), RAP1B(2), RAPGEF3(1), RAPGEF4(2), RASSF5(2), RHOA(1), RHOH(2), ROCK1(3), ROCK2(4), SIPA1(3), TXK(1), VASP(2), VAV1(6), VAV2(3), VAV3(2), VCL(2) 48981709 218 112 212 81 70 27 47 40 34 0 0.000033 0.00016 129 REDUCTIVE_CARBOXYLATE_CYCLE_CO2_FIXATION ACO1, ACO2, FH, IDH1, IDH2, MDH1, MDH2, SDHB, SUCLA2 9 ACO1(2), ACO2(1), IDH1(15), IDH2(2), MDH2(1), SUCLA2(1) 3614279 22 19 9 7 16 1 5 0 0 0 0.00045 0.0022 130 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 30 ANPEP(3), G6PD(2), GCLC(1), GGT1(2), GPX1(2), GPX2(1), GPX5(2), GSS(1), GSTA1(2), GSTA4(2), GSTM1(1), GSTM3(1), GSTP1(1), GSTT1(1), IDH1(15), IDH2(2), MGST1(1), MGST3(1) 7229533 41 29 27 6 25 2 7 6 1 0 0.00048 0.0023 131 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 24 GUSB(3), RPE(1), UGP2(1), UGT1A1(1), UGT1A10(1), UGT1A3(1), UGT1A5(2), UGT1A6(2), UGT1A9(1), UGT2A1(5), UGT2A3(3), UGT2B10(1), UGT2B11(3), UGT2B17(1), UGT2B28(5), UGT2B4(5), UGT2B7(3), XYLB(4) 9832004 43 32 42 16 12 6 11 10 4 0 0.00052 0.0024 132 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 75 ACTB(1), ACTN1(1), ACTN3(1), ACTN4(4), ACVR1C(2), CDH1(3), CREBBP(8), CSNK2A1(3), CTNNA1(1), CTNNA2(2), CTNNA3(1), EGFR(58), EP300(5), ERBB2(7), FARP2(2), FGFR1(3), IGF1R(2), INSR(5), IQGAP1(2), LEF1(1), LMO7(2), MAP3K7(2), MAPK1(3), MAPK3(2), MET(5), MLLT4(5), PARD3(2), PTPN1(1), PTPN6(4), PTPRB(4), PTPRF(4), PTPRJ(2), PTPRM(3), PVRL1(2), PVRL2(1), PVRL4(5), RHOA(1), SMAD3(1), SMAD4(1), SNAI1(1), SNAI2(1), SORBS1(2), SRC(2), SSX2IP(1), TCF7(3), TCF7L2(3), TGFBR1(1), TGFBR2(5), TJP1(2), VCL(2), WASF1(1), WASF2(1) 47609853 187 104 151 43 50 43 52 26 14 2 0.00060 0.0028 133 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 80 ANPEP(3), CD14(2), CD19(2), CD1B(1), CD1D(2), CD1E(1), CD22(5), CD33(3), CD34(2), CD36(2), CD38(2), CD3E(1), CD3G(1), CD4(3), CD44(4), CD5(2), CD55(2), CD7(2), CD8A(1), CD8B(1), CD9(2), CR1(5), CR2(6), CSF1R(3), CSF3R(2), DNTT(2), EPO(1), EPOR(1), FLT3(7), FLT3LG(1), GP9(1), GYPA(1), HLA-DRA(1), HLA-DRB1(2), HLA-DRB5(2), IL1R1(2), IL2RA(3), IL4(1), IL4R(6), IL5RA(1), IL6(2), IL6R(2), IL7(1), IL7R(1), ITGA1(1), ITGA2(4), ITGA2B(2), ITGA3(2), ITGA4(7), ITGA5(1), ITGA6(2), ITGAM(8), ITGB3(1), KIT(3), KITLG(2), MS4A1(2), TFRC(2), THPO(1), TPO(4) 31730473 140 79 136 52 54 23 28 23 12 0 0.00074 0.0034 134 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 LDLR(4), NR0B2(3), NR1H3(1), NR1H4(3), RXRA(3) 2161711 14 15 15 3 3 2 4 3 2 0 0.00076 0.0035 135 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 CALCR(6), CALCRL(2), CRHR1(2), ELTD1(5), EMR1(4), EMR2(4), GHRHR(3), GIPR(1), GLP1R(1), GLP2R(1), GPR64(2), LPHN1(10), LPHN2(4), LPHN3(2), SCTR(2), VIPR2(2) 10559931 51 34 45 18 16 5 8 16 6 0 0.0012 0.0055 136 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 F10(1), F13B(2), F2(1), F5(9), F7(1), F8(8), F9(4), FGA(3), FGB(1), FGG(4), LPA(6), PLAU(2), PLG(2), SERPINB2(2), SERPINE1(1), SERPINF2(1), VWF(10) 14027949 58 43 58 22 21 10 11 5 11 0 0.0013 0.0058 137 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 49 AGPAT1(2), AGPAT2(2), AGPAT3(2), AGPAT4(1), AGPS(1), CDS1(1), CHAT(3), CHKA(1), CHKB(1), DGKB(1), DGKD(6), DGKE(2), DGKG(5), DGKH(3), DGKQ(1), DGKZ(5), ETNK1(1), GNPAT(4), GPD1(2), GPD2(1), LCAT(1), LGALS13(1), PAFAH2(2), PCYT1A(1), PCYT1B(2), PISD(3), PLA2G2A(5), PLA2G3(2), PLA2G4A(4), PLA2G5(1), PLA2G6(3), PLCB2(5), PLCG1(3), PLCG2(11), PPAP2C(1) 19737442 90 55 84 23 35 10 17 16 11 1 0.0017 0.0075 138 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 86 AGRN(3), CD36(2), CD44(4), CHAD(1), COL11A1(8), COL11A2(9), COL1A1(4), COL1A2(9), COL2A1(2), COL3A1(5), COL4A1(4), COL4A2(8), COL4A4(4), COL4A6(5), COL5A1(3), COL5A2(5), COL5A3(11), COL6A1(5), COL6A2(3), COL6A3(27), COL6A6(7), DAG1(2), FN1(3), FNDC1(1), FNDC3A(2), GP9(1), HMMR(1), HSPG2(16), ITGA1(1), ITGA10(3), ITGA11(2), ITGA2(4), ITGA2B(2), ITGA3(2), ITGA4(7), ITGA5(1), ITGA6(2), ITGA7(3), ITGA8(7), ITGA9(1), ITGAV(1), ITGB3(1), ITGB4(5), ITGB5(2), ITGB6(5), ITGB7(2), ITGB8(3), LAMA1(17), LAMA2(12), LAMA3(7), LAMA4(4), LAMA5(9), LAMB1(4), LAMB2(3), LAMB3(4), LAMB4(10), LAMC1(2), LAMC2(6), LAMC3(5), RELN(20), SDC1(1), SDC2(2), SDC4(1), SPP1(1), SV2B(1), SV2C(2), THBS1(3), THBS2(5), THBS3(1), THBS4(2), TNC(7), TNN(5), TNR(2), TNXB(6), VWF(10) 87660677 361 142 356 132 133 72 59 49 47 1 0.0019 0.0083 139 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 31 ABP1(9), ADH1A(4), ADH1B(3), ADH1C(3), ADH6(2), ADH7(1), ALDH1A3(1), ALDH3A1(3), ALDH3B1(2), ALDH3B2(1), AOC2(2), AOC3(2), AOX1(7), COMT(2), DBH(6), DDC(1), FAH(1), GOT1(1), HPD(1), MAOB(1), PNMT(1), TAT(3), TPO(4), TYR(5) 12332970 66 42 65 14 35 9 9 13 0 0 0.0022 0.0097 140 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 28 ARHGDIB(4), BAG4(1), CASP2(1), CRADD(1), DFFA(1), DFFB(3), LMNB1(1), LMNB2(3), MADD(6), MAP3K1(5), MAP3K7(2), PAK1(2), PRKDC(5), RB1(21), RIPK1(1), SPTAN1(6), TNFRSF1A(2), TRAF2(2) 15466132 67 42 66 13 10 11 11 11 24 0 0.0024 0.010 141 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 36 ANPEP(3), G6PD(2), GCLC(1), GGT1(2), GPX1(2), GPX2(1), GPX5(2), GSR(1), GSS(1), GSTA1(2), GSTA4(2), GSTA5(1), GSTK1(2), GSTM1(1), GSTM3(1), GSTP1(1), GSTT1(1), IDH1(15), IDH2(2), MGST1(1), MGST3(1) 8541689 45 30 31 7 28 2 8 6 1 0 0.0028 0.012 142 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 40 ALAS1(2), ALAS2(1), BLVRA(1), BLVRB(1), COX10(1), COX15(1), CP(4), CPOX(1), EARS2(2), EPRS(2), FECH(3), FTMT(5), GUSB(3), HCCS(3), HMBS(1), HMOX1(2), PPOX(2), UGT1A1(1), UGT1A10(1), UGT1A3(1), UGT1A5(2), UGT1A6(2), UGT1A9(1), UGT2A1(5), UGT2A3(3), UGT2B10(1), UGT2B11(3), UGT2B17(1), UGT2B28(5), UGT2B4(5), UGT2B7(3), UROD(1), UROS(1) 15914536 71 43 70 22 19 6 16 21 9 0 0.0029 0.013 143 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 68 ADH1A(4), ADH1B(3), ADH1C(3), ADH6(2), ADH7(1), AKR1C1(3), AKR1C4(2), ALDH1A3(1), ALDH3A1(3), ALDH3B1(2), ALDH3B2(1), CYP1A1(1), CYP1B1(4), CYP2B6(2), CYP2C18(1), CYP2C8(2), CYP2C9(2), CYP2E1(4), CYP2S1(1), CYP3A4(3), CYP3A43(2), CYP3A7(3), DHDH(1), GSTA1(2), GSTA4(2), GSTA5(1), GSTK1(2), GSTM1(1), GSTM3(1), GSTP1(1), GSTT1(1), MGST1(1), MGST3(1), UGT1A1(1), UGT1A10(1), UGT1A3(1), UGT1A5(2), UGT1A6(2), UGT1A9(1), UGT2A1(5), UGT2A3(3), UGT2B10(1), UGT2B11(3), UGT2B17(1), UGT2B28(5), UGT2B4(5), UGT2B7(3) 21984496 98 57 98 32 38 8 24 25 3 0 0.0032 0.014 144 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 27 ARHGDIB(4), CASP6(1), DAXX(4), DFFA(1), DFFB(3), FAF1(3), LMNB1(1), LMNB2(3), MAP3K1(5), MAP3K7(2), PAK1(2), PRKDC(5), PTPN13(4), RB1(21), RIPK2(1), SPTAN1(6) 16286291 66 41 65 12 6 11 11 13 25 0 0.0037 0.016 145 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 129 ALCAM(1), CADM1(2), CADM3(1), CD22(5), CD226(2), CD274(1), CD276(3), CD28(1), CD34(2), CD4(3), CD58(1), CD6(2), CD8A(1), CD8B(1), CDH1(3), CDH15(3), CDH3(1), CDH4(3), CDH5(2), CLDN14(1), CLDN17(1), CLDN18(1), CLDN2(1), CLDN20(1), CLDN23(2), CLDN4(1), CLDN5(2), CLDN6(1), CLDN7(1), CLDN8(1), CNTN1(5), CNTN2(4), CNTNAP1(3), CNTNAP2(16), ESAM(1), F11R(1), GLG1(4), HLA-A(1), HLA-B(1), HLA-DMA(1), HLA-DMB(1), HLA-DOA(3), HLA-DOB(2), HLA-DPA1(1), HLA-DQA2(1), HLA-DQB1(2), HLA-DRA(1), HLA-DRB1(2), HLA-DRB5(2), HLA-F(2), ICAM3(1), ICOSLG(1), ITGA4(7), ITGA6(2), ITGA8(7), ITGA9(1), ITGAL(4), ITGAM(8), ITGAV(1), ITGB2(5), ITGB7(2), ITGB8(3), JAM2(1), JAM3(1), L1CAM(7), MAG(5), NCAM1(1), NCAM2(1), NEGR1(2), NEO1(5), NFASC(4), NLGN1(3), NLGN2(1), NLGN3(1), NRCAM(1), NRXN1(5), NRXN2(3), NRXN3(3), OCLN(1), PDCD1(1), PECAM1(2), PTPRC(4), PTPRF(4), PTPRM(3), PVR(2), PVRL1(2), PVRL2(1), SDC1(1), SDC2(2), SDC4(1), SELE(1), SELP(2), SELPLG(2), SIGLEC1(1), VCAN(7) 58992771 228 119 226 105 91 30 39 36 31 1 0.0039 0.017 146 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(1), AKT2(1), AKT3(1), IARS(4), IL13RA1(1), IL4(1), IL4R(6), INPP5D(6), JAK1(3), JAK2(4), JAK3(4), NR0B2(3), PIK3CA(19), RPS6KB1(1), SOS1(1), SOS2(4), SRC(2), STAT6(3), TYK2(3) 14689754 68 43 64 16 25 15 8 14 6 0 0.0047 0.020 147 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), GZMB(3), HLA-A(1), ITGAL(4), ITGB2(5), PRF1(3) 3417489 20 15 20 14 6 1 4 1 8 0 0.0052 0.022 148 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 73 B2M(2), CANX(4), CD4(3), CD8A(1), CD8B(1), CIITA(7), CTSS(2), HLA-A(1), HLA-B(1), HLA-DMA(1), HLA-DMB(1), HLA-DOA(3), HLA-DOB(2), HLA-DPA1(1), HLA-DQA2(1), HLA-DQB1(2), HLA-DRA(1), HLA-DRB1(2), HLA-DRB5(2), HLA-F(2), HSP90AA1(1), HSP90AB1(2), HSPA5(2), IFNA13(1), IFNA14(1), IFNA17(1), IFNA21(1), IFNA5(1), IFNA7(2), KIR2DL1(2), KIR2DL4(1), KIR3DL1(1), KLRC1(1), KLRC3(3), LGMN(1), NFYB(1), NFYC(3), PDIA3(1), PSME1(1), PSME2(1), TAP1(4), TAP2(2) 18456357 74 49 71 27 16 11 17 15 15 0 0.0053 0.022 149 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 64 AGTR1(2), AGTR2(1), ATP8A1(3), AVPR1A(3), AVPR1B(1), BDKRB1(1), BDKRB2(3), BRS3(2), C3AR1(1), CCKAR(3), CCKBR(2), CCR1(2), CCR10(1), CCR3(2), CCR4(1), CCR6(2), CCR7(2), CCR8(1), CX3CR1(2), CXCR3(2), CXCR6(1), EDNRA(1), EDNRB(1), FPR1(1), FSHR(1), GALR1(3), GALR2(1), GALT(1), GHSR(4), GNB2L1(1), GRPR(1), LHCGR(1), MC2R(1), MC3R(6), MC4R(3), MC5R(2), NPY5R(4), NTSR1(2), OPRK1(1), OPRL1(2), OPRM1(4), OXTR(2), PPYR1(2), SSTR2(1), SSTR3(2), SSTR4(4), TACR1(1), TACR3(4), TRHR(2), TSHR(1) 19940026 98 57 98 38 43 19 18 14 4 0 0.0053 0.022 150 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 145 AKT1(1), AKT2(1), AKT3(1), CBL(1), CBLB(1), CBLC(1), CCND2(1), CLCF1(1), CNTF(1), CREBBP(8), CSF2RB(4), CSF3R(2), EP300(5), EPO(1), EPOR(1), GH1(1), GH2(2), GHR(3), IFNA13(1), IFNA14(1), IFNA17(1), IFNA21(1), IFNA5(1), IFNA7(2), IFNAR2(1), IFNB1(1), IFNG(1), IFNGR1(1), IFNGR2(1), IFNW1(1), IL10RA(1), IL12B(1), IL12RB1(4), IL12RB2(4), IL13RA1(1), IL15RA(1), IL2(1), IL21(1), IL21R(4), IL22(3), IL22RA1(1), IL23R(2), IL24(1), IL26(1), IL28A(1), IL28B(1), IL28RA(1), IL2RA(3), IL2RB(1), IL4(1), IL4R(6), IL5RA(1), IL6(2), IL6R(2), IL7(1), IL7R(1), IRF9(2), JAK1(3), JAK2(4), JAK3(4), LEPR(1), LIFR(1), MPL(2), OSM(1), OSMR(2), PIAS1(2), PIAS2(1), PIAS3(4), PIAS4(1), PIK3CA(19), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(17), PIK3R2(5), PIK3R5(2), PRL(3), PTPN11(6), PTPN6(4), SOCS1(1), SOCS2(1), SOCS4(2), SOS1(1), SOS2(4), SPRED1(1), SPRED2(1), SPRY1(1), SPRY2(2), STAM2(2), STAT1(1), STAT2(5), STAT3(2), STAT4(1), STAT5A(2), STAT5B(2), STAT6(3), TPO(4), TYK2(3) 56568272 235 109 227 73 74 36 51 45 28 1 0.0064 0.026 151 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 CD34(2), CD3E(1), CD3G(1), CD4(3), CD58(1), CD8A(1), IL6(2), KITLG(2) 2527581 13 12 11 3 4 0 3 4 2 0 0.0066 0.027 152 NEUROTRANSMITTERSPATHWAY Biosynthesis of neurotransmitters DBH, GAD1, HDC, PNMT, TH, TPH1 6 DBH(6), GAD1(4), HDC(3), PNMT(1), TPH1(3) 2333567 17 13 17 6 10 4 2 1 0 0 0.0074 0.030 153 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 CD28(1), CD3E(1), CD3G(1), CD4(3) 1034755 6 6 4 2 1 0 1 3 1 0 0.0076 0.031 154 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 158 ADORA1(2), ADORA2B(1), ADORA3(1), ADRA1D(1), ADRA2C(4), ADRB1(1), ADRB2(1), AGTR1(2), AGTR2(1), AVPR1A(3), AVPR1B(1), BDKRB1(1), BDKRB2(3), BRS3(2), C3AR1(1), CCBP2(1), CCKAR(3), CCKBR(2), CCR1(2), CCR10(1), CCR3(2), CCR4(1), CCR6(2), CCR7(2), CCR8(1), CCR9(2), CHML(2), CHRM2(4), CHRM3(3), CMKLR1(1), CNR1(2), CNR2(3), CX3CR1(2), CXCR3(2), DRD1(2), DRD2(1), DRD3(1), DRD5(4), EDNRA(1), EDNRB(1), F2RL3(1), FPR1(1), FSHR(1), GALR1(3), GALR2(1), GALT(1), GHSR(4), GNB2L1(1), GPR17(1), GPR174(1), GPR27(3), GPR3(1), GPR37(3), GPR4(1), GPR50(3), GPR6(5), GPR83(4), GPR87(1), GRPR(1), HCRTR1(2), HCRTR2(1), HRH1(1), HRH2(5), HRH3(1), HTR1A(2), HTR1B(3), HTR1D(1), HTR1E(2), HTR1F(2), HTR2A(1), HTR2C(2), HTR4(1), HTR5A(4), HTR6(1), HTR7(1), LHCGR(1), MC3R(6), MC4R(3), MC5R(2), MLNR(1), NMUR1(2), NMUR2(5), NPY5R(4), NTSR1(2), OPN1SW(2), OPRK1(1), OPRL1(2), OPRM1(4), OR1F1(2), OR1Q1(1), OR2H1(4), OR7A5(1), OR7C1(1), OXTR(2), P2RY1(1), P2RY10(1), P2RY13(3), P2RY14(1), P2RY2(2), P2RY6(2), PPYR1(2), PTAFR(2), PTGDR(1), PTGER2(2), PTGER4(2), PTGFR(2), PTGIR(1), RHO(1), RRH(1), SSTR2(1), SSTR3(2), SSTR4(4), TRHR(2) 46757547 219 105 217 84 99 27 38 40 15 0 0.0076 0.031 155 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(1), PLA2G12A(3), PLA2G2A(5), PLA2G2F(2), PLA2G3(2), PLA2G4A(4), PLA2G5(1), PLA2G6(3) 4085903 24 17 20 6 7 1 7 4 4 1 0.0094 0.038 156 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), CD33(3), CD5(2), CD7(2), IFNB1(1), IFNG(1), IL12B(1), IL4(1), ITGAX(7), TLR2(4), TLR4(1), TLR7(5), TLR9(2) 7416008 33 24 33 13 13 6 9 3 2 0 0.0097 0.038 157 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(2), ACO2(1), ACSS2(2), IDH1(15), IDH2(2), MDH2(1), SUCLA2(1) 5399865 26 21 13 7 18 1 6 1 0 0 0.0097 0.038 158 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 ALOX15(2), ALOX5(1), CBR1(1), CBR3(2), CYP4F2(5), CYP4F3(5), EPX(6), GGT1(2), LPO(1), LTA4H(1), MPO(3), PLA2G2A(5), PLA2G3(2), PLA2G4A(4), PLA2G5(1), PLA2G6(3), PRDX2(2), PTGIS(1), PTGS1(2), TBXAS1(3), TPO(4) 11050498 56 36 52 18 28 5 11 5 6 1 0.012 0.048 159 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 82 ACVR1(3), ACVRL1(2), AKT1(1), BMPR1A(2), BMPR2(2), BUB1(4), CDKL1(3), CDS1(1), CLK2(2), CLK4(2), CSNK2A1(3), DGKB(1), DGKD(6), DGKE(2), DGKG(5), DGKH(3), DGKQ(1), DGKZ(5), IMPA1(1), INPP1(2), INPP4A(1), INPP4B(1), INPP5A(1), INPPL1(4), ITPKB(2), MAP3K10(3), NEK1(2), NEK3(2), OCRL(1), PIK3C2A(3), PIK3C2B(2), PIK3C2G(9), PIK3CA(19), PIK3CB(2), PIK3CG(12), PIM2(1), PLCB1(3), PLCB2(5), PLCB3(5), PLCB4(3), PLCD1(1), PLCG1(3), PLCG2(11), PLK3(3), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PRKCA(3), PRKCD(5), PRKCE(1), PRKCG(1), PRKCH(2), PRKCQ(1), PRKCZ(2), PRKD1(3), RPS6KA2(2), RPS6KA3(5), RPS6KB1(1), TGFBR1(1) 44743328 180 88 176 46 55 35 28 36 25 1 0.013 0.051 160 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(8), COL4A3(3), COL4A4(4), COL4A5(5), COL4A6(5), F10(1), F2(1), F5(9), F8(8), F9(4), FGA(3), FGB(1), FGG(4), KLKB1(1), PROC(2), SERPINC1(2), SERPING1(5) 17935830 70 45 68 18 20 17 13 10 10 0 0.014 0.052 161 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 52 APAF1(1), ARHGDIB(4), BAG4(1), BCL2(3), BID(4), BIRC2(1), BIRC3(1), CASP2(1), CASP6(1), CHUK(4), CRADD(1), DAXX(4), DFFA(1), DFFB(3), GSN(2), LMNB1(1), LMNB2(3), MAP2K7(1), MAP3K1(5), MAP3K14(2), MAP3K5(1), MDM2(1), NFKB1(1), NFKBIA(2), NUMA1(4), PRKCD(5), PRKDC(5), PSEN2(1), PTK2(2), RB1(21), RIPK1(1), SPTAN1(6), TNFRSF1A(2), TNFRSF1B(2), TRAF1(1), TRAF2(2) 27575538 101 59 96 26 16 12 23 20 30 0 0.014 0.053 162 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 29 ARSB(2), FUCA1(1), GALNS(1), GBA(1), GLB1(1), GUSB(3), HEXA(1), HGSNAT(2), HPSE(3), HPSE2(2), HYAL1(1), HYAL2(1), LCT(8), MAN2B1(4), MAN2B2(2), MAN2C1(2), MANBA(1), NAGLU(1), NEU1(1), NEU2(4), NEU4(4), SPAM1(6) 13554921 52 37 50 16 19 3 10 9 11 0 0.016 0.060 163 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 50 ADORA3(1), CCKBR(2), CCR3(2), CELSR1(10), CELSR2(9), CELSR3(8), CHRM2(4), CHRM3(3), CXCR3(2), EDNRA(1), EMR2(4), EMR3(2), FSHR(1), GHRHR(3), GPR116(9), GPR132(3), GPR133(7), GPR135(3), GPR143(1), GPR17(1), GPR18(1), GPR56(2), GPR61(2), GPR84(1), GPR88(1), GRM1(1), GRPR(1), HRH4(1), LGR6(3), LPHN2(4), LPHN3(2), LTB4R2(2), NTSR1(2), OR2M4(2), OR8G2(1), P2RY13(3), PTGFR(2), SMO(2), SSTR2(1), TAAR5(1), TSHR(1), VN1R1(1) 24966910 113 60 111 45 40 15 21 23 14 0 0.018 0.068 164 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 CCL3(1), EPO(1), FLT3(7), IL6(2), KITLG(2), TGFB1(1), TGFB2(1) 3311320 15 13 15 1 2 3 4 2 4 0 0.018 0.069 165 ACE_INHIBITOR_PATHWAY_PHARMGKB ACE, AGT, AGTR1, AGTR2, BDKRB2, KNG1, NOS3, REN 8 ACE(7), AGT(3), AGTR1(2), AGTR2(1), BDKRB2(3), KNG1(4), NOS3(5), REN(2) 3816834 27 16 27 9 11 5 5 3 3 0 0.019 0.071 166 GPCRDB_CLASS_C_METABOTROPIC_GLUTAMATE_PHEROMONE CASR, GABBR1, GPCR5A, GPR51, GPRC5A, GPRC5B, GPRC5C, GPRC5D, GRM1, GRM2, GRM3, GRM4, GRM5, GRM7, GRM8 13 CASR(5), GABBR1(1), GPRC5A(1), GPRC5C(1), GPRC5D(2), GRM1(1), GRM2(1), GRM3(9), GRM4(5), GRM5(1), GRM7(3), GRM8(8) 8317755 38 28 37 29 22 2 6 4 4 0 0.021 0.077 167 GLUCOCORTICOID_MINERALOCORTICOID_METABOLISM CPN2, CYP11A1, CYP11B2, CYP17A1, HSD11B1, HSD11B2, HSD3B1, HSD3B2 8 CPN2(2), CYP11A1(1), CYP11B2(4), CYP17A1(1), HSD11B1(2), HSD3B2(2) 2753369 12 12 12 5 7 2 1 1 1 0 0.022 0.079 168 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 67 A2M(5), BDKRB1(1), BDKRB2(3), C1QB(1), C1QC(1), C1R(1), C1S(1), C2(2), C3(8), C3AR1(1), C5(1), C5AR1(1), C6(3), C7(6), C8A(3), C8B(5), C9(1), CD55(2), CFB(1), CFH(3), CFI(1), CPB2(1), CR1(5), CR2(6), F10(1), F13A1(5), F13B(2), F2(1), F5(9), F7(1), F8(8), F9(4), FGA(3), FGB(1), FGG(4), KLKB1(1), KNG1(4), MASP1(2), MBL2(1), PLAU(2), PLAUR(1), PLG(2), PROC(2), SERPINA1(3), SERPINA5(1), SERPINC1(2), SERPIND1(1), SERPINE1(1), SERPINF2(1), SERPING1(5), THBD(3), VWF(10) 35749445 144 75 141 68 48 23 33 19 20 1 0.022 0.080 169 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 CD44(4), ITGA4(7), ITGAL(4), ITGAM(8), ITGB2(5), PECAM1(2), SELE(1), SELP(2) 6700687 33 21 32 17 13 2 7 6 5 0 0.023 0.082 170 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 DAO(3) 293806 3 3 3 1 2 1 0 0 0 0 0.023 0.082 171 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(2), ABP1(9), ACADM(2), ACADSB(1), ALDH1A1(4), ALDH1A2(3), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH9A1(1), AOC2(2), AOC3(2), CNDP1(4), DPYD(2), DPYS(2), ECHS1(1), EHHADH(2), GAD1(4), GAD2(3), HADHA(1), MLYCD(1), SDS(4), UPB1(1) 11727333 58 33 58 12 19 13 10 11 5 0 0.024 0.088 172 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(5), F2(1), FGA(3), FGB(1), FGG(4), PLAU(2), PLG(2), SERPINB2(2), SERPINE1(1) 5404654 22 20 22 8 9 5 4 2 2 0 0.025 0.089 173 BIOGENIC_AMINE_SYNTHESIS AANAT, ACHE, CHAT, COMT, DBH, DDC, DXYS155E, GAD1, GAD2, HDC, MAOA, PAH, PNMT, SLC18A3, TH, TPH1 15 AANAT(1), CHAT(3), COMT(2), DBH(6), DDC(1), GAD1(4), GAD2(3), HDC(3), PAH(1), PNMT(1), TPH1(3) 5608230 28 21 28 9 13 5 3 7 0 0 0.027 0.096 174 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 CD28(1), CD4(3), HLA-DRA(1), HLA-DRB1(2) 979062 7 6 5 1 1 2 0 4 0 0 0.027 0.097 175 HSA00950_ALKALOID_BIOSYNTHESIS_I Genes involved in alkaloid biosynthesis I DDC, GOT1, GOT2, TAT, TYR 5 DDC(1), GOT1(1), TAT(3), TYR(5) 1908974 10 9 10 1 1 3 2 4 0 0 0.029 0.10 176 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 43 ABP1(9), AGMAT(1), ALDH1A1(4), ALDH1A2(3), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH4A1(1), ALDH9A1(1), AMD1(1), AOC2(2), AOC3(2), ARG2(2), CKB(1), CKM(1), CKMT1A(3), CKMT1B(2), CPS1(6), DAO(3), GAMT(1), GATM(2), GOT1(1), MAOB(1), NOS1(9), NOS3(5), OAT(1), ODC1(1), OTC(2), P4HA1(1), P4HA2(3), P4HA3(1) 17401829 77 46 75 19 31 17 11 17 1 0 0.029 0.10 177 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(2), ACO2(1), DLD(1), DLST(2), IDH1(15), IDH2(2), IDH3G(2), MDH2(1), PC(3), PCK1(4), SUCLA2(1), SUCLG1(2) 8250379 36 26 23 14 17 5 10 4 0 0 0.030 0.11 178 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 CD44(4), ITGAL(4), ITGAM(8), ITGB2(5), PECAM1(2), SELE(1) 4433802 24 15 23 13 8 2 7 2 5 0 0.035 0.12 179 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 53 AKR1C4(2), ARSD(1), ARSE(1), CARM1(1), CYP11B2(4), CYP19A1(3), HSD11B1(2), HSD17B3(1), HSD17B7(1), HSD17B8(1), HSD3B2(2), LCMT1(1), PRMT6(5), PRMT7(2), PRMT8(1), STS(2), SULT1E1(1), SULT2A1(1), UGT1A1(1), UGT1A10(1), UGT1A3(1), UGT1A5(2), UGT1A6(2), UGT1A9(1), UGT2A1(5), UGT2A3(3), UGT2B10(1), UGT2B11(3), UGT2B17(1), UGT2B28(5), UGT2B4(5), UGT2B7(3) 19047587 66 45 61 32 19 8 22 13 4 0 0.036 0.12 180 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 130 ACACA(8), ACACB(9), AKT1(1), AKT2(1), AKT3(1), ARAF(1), BRAF(6), CALM1(1), CBL(1), CBLB(1), CBLC(1), ELK1(1), EXOC7(2), FASN(7), FBP1(2), FBP2(4), FLOT1(2), FOXO1(1), G6PC(2), GCK(2), GSK3B(1), GYS2(3), IKBKB(2), INPP5D(6), INSR(5), IRS1(4), IRS4(3), KRAS(1), LIPE(1), MAP2K1(1), MAP2K2(1), MAPK1(3), MAPK3(2), MAPK9(2), MKNK1(1), NRAS(1), PCK1(4), PCK2(1), PDE3A(1), PDE3B(4), PFKM(3), PFKP(6), PHKA1(3), PHKA2(4), PHKB(2), PIK3CA(19), PIK3CB(2), PIK3CD(2), PIK3CG(12), PIK3R1(17), PIK3R2(5), PIK3R5(2), PKLR(4), PPARGC1A(2), PPP1CB(1), PPP1CC(1), PPP1R3A(9), PPP1R3C(1), PPP1R3D(2), PRKAA2(1), PRKACG(1), PRKAG1(2), PRKAG2(5), PRKAG3(3), PRKAR2A(1), PRKAR2B(1), PRKCI(1), PRKCZ(2), PRKX(2), PTPN1(1), PTPRF(4), PYGB(4), PYGL(1), PYGM(2), RHOQ(3), RPS6KB1(1), SH2B2(3), SHC3(1), SHC4(1), SLC2A4(3), SOCS1(1), SOCS2(1), SOCS4(2), SORBS1(2), SOS1(1), SOS2(4), SREBF1(2), TRIP10(4), TSC1(4), TSC2(2) 62263160 264 112 255 73 88 39 46 52 39 0 0.038 0.13 181 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 F10(1), F2(1), F5(9), F7(1), FGA(3), FGB(1), FGG(4), PROC(2), SERPINC1(2) 6457793 24 19 24 9 7 5 6 1 5 0 0.039 0.13 182 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 CDK5R1(1), DAB1(2), LRP8(2), RELN(20), VLDLR(2) 5680593 27 18 27 18 10 8 1 3 5 0 0.045 0.15 183 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 17 CARS2(3), CTH(1), GOT1(1), LDHA(2), LDHAL6A(2), LDHAL6B(1), LDHC(1), MPST(1), SDS(4), SULT1B1(4), SULT1C2(2), SULT1C4(1), SULT4A1(1) 5047540 24 16 24 4 3 6 7 4 4 0 0.050 0.17 184 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 CD28(1), CD3E(1), CD3G(1), CD4(3), ITGAL(4), ITGB2(5), PTPRC(4) 4539789 19 14 17 13 4 2 3 3 7 0 0.055 0.18 185 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 34 ALDH4A1(1), ARG2(2), CKB(1), CKM(1), CKMT1A(3), CKMT1B(2), CPS1(6), DAO(3), EPRS(2), GAMT(1), GATM(2), GLUD2(4), GOT1(1), NOS1(9), NOS3(5), OAT(1), OTC(2), P4HA1(1), P4HA2(3), P4HA3(1), PARS2(2), PRODH(1), RARS2(1) 14085749 55 36 53 16 23 8 11 12 1 0 0.056 0.18 186 1_AND_2_METHYLNAPHTHALENE_DEGRADATION ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1 7 ADH1A(4), ADH1B(3), ADH1C(3), ADH6(2), ADH7(1) 2311758 13 9 13 2 8 0 3 2 0 0 0.056 0.18 187 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 ANP32A(2), CREBBP(8), DFFA(1), DFFB(3), GZMA(1), GZMB(3), PRF1(3) 4170990 21 15 21 5 4 3 6 4 4 0 0.060 0.20 188 SLRPPATHWAY Small leucine-rich proteoglycans (SLRPs) interact with and reorganize collagen fibers in the extracellular matrix. BGN, DCN, DSPG3, FMOD, KERA, LUM 5 DCN(2), KERA(2), LUM(3) 1446169 7 7 6 4 2 2 1 0 2 0 0.062 0.20 189 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(8), C5(1), C6(3), C7(6), C8A(3), C9(1) 4933029 22 16 21 14 7 2 6 4 2 1 0.063 0.20 190 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 29 AKT1(1), AKT2(1), AKT3(1), ANKRD6(3), APC(7), AXIN1(2), AXIN2(1), DACT1(5), DKK1(1), DKK2(3), FSTL1(2), GSK3B(1), LRP1(15), MVP(2), NKD2(2), PTPRA(4), SENP2(2), SFRP1(2), TSHB(1), WIF1(2) 15524662 58 37 52 11 18 3 15 14 8 0 0.068 0.22 191 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 64 AGPAT1(2), AGPAT2(2), AGPAT3(2), AGPAT4(1), CDS1(1), CHAT(3), CHKA(1), CHKB(1), DGKB(1), DGKD(6), DGKE(2), DGKG(5), DGKH(3), DGKI(3), DGKQ(1), DGKZ(5), ESCO1(2), ETNK1(1), ETNK2(1), GNPAT(4), GPAM(2), GPD1(2), GPD2(1), LCAT(1), MYST3(4), MYST4(4), PCYT1A(1), PCYT1B(2), PISD(3), PLA2G12A(3), PLA2G2A(5), PLA2G2F(2), PLA2G3(2), PLA2G4A(4), PLA2G5(1), PLA2G6(3), PLD2(1), PNPLA3(1), PPAP2C(1), PTDSS1(1), PTDSS2(1), SH3GLB1(2) 26083469 94 56 88 26 30 11 20 18 14 1 0.069 0.22 192 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(3), CD8A(1), EPO(1), IL2(1), IL4(1), IL6(2), IL7(1) 2405698 10 9 8 2 3 1 0 5 1 0 0.070 0.22 193 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(1), IL4(1), IL4R(6), IRS1(4), JAK1(3), JAK3(4), RPS6KB1(1), STAT6(3) 5883058 23 18 22 6 8 3 3 7 2 0 0.070 0.22 194 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 CCL2(2), IL6(2), LDLR(4) 2160204 8 8 8 3 1 1 3 2 1 0 0.071 0.22 195 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 55 ABP1(9), ADH1A(4), ADH1B(3), ADH1C(3), ADH6(2), ADH7(1), ALDH1A3(1), ALDH3A1(3), ALDH3B1(2), ALDH3B2(1), AOC2(2), AOC3(2), AOX1(7), CARM1(1), COMT(2), DBH(6), DDC(1), ESCO1(2), FAH(1), GOT1(1), HPD(1), LCMT1(1), MAOB(1), MYST3(4), MYST4(4), PNMT(1), PNPLA3(1), PRMT6(5), PRMT7(2), PRMT8(1), SH3GLB1(2), TAT(3), TPO(4), TYR(5), TYRP1(2) 23393403 91 56 86 23 40 11 17 18 5 0 0.072 0.23 196 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 CALM1(1), CHUK(4), EGR2(3), EGR3(4), GNAQ(1), MAP3K1(5), NFATC1(3), NFATC2(1), NFKB1(1), NFKBIA(2), PLCG1(3), PPP3CB(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1), SYT1(1), VIP(1), VIPR2(2) 10901738 36 28 35 16 7 4 4 12 9 0 0.073 0.23 197 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 37 ACTA1(1), ACTA2(2), ACTN3(1), ACTN4(4), DES(3), DMD(11), FAM48A(5), MYBPC1(2), MYBPC2(1), MYBPC3(3), MYH3(6), MYH6(5), MYH7(3), MYH8(8), MYL2(2), MYOM1(3), NEB(11), TNNI1(2), TNNT1(2), TNNT2(1), TPM1(1), TPM3(1), TPM4(1), TTN(110), VIM(1) 50708337 190 87 186 62 65 36 45 31 13 0 0.076 0.24 198 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 AACS(2), ABAT(2), ACADS(4), ALDH1A1(4), ALDH1A2(3), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH5A1(2), ALDH9A1(1), ECHS1(1), EHHADH(2), GAD1(4), GAD2(3), HADHA(1), HMGCL(1), L2HGDH(1), OXCT1(1), PDHA1(1), PDHA2(3), PDHB(1), SDS(4) 10403076 48 28 49 14 13 12 7 9 7 0 0.078 0.24 199 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 20 ACY1(1), ALDH18A1(1), ARG2(2), CKB(1), CKM(1), CKMT1A(3), CKMT1B(2), CPS1(6), GAMT(1), GATM(2), OAT(1), ODC1(1), OTC(2) 6769060 24 19 23 5 7 5 4 7 1 0 0.080 0.25 200 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(3), HLA-DRA(1), HLA-DRB1(2), PTPRC(4), ZAP70(5) 3681922 17 12 15 6 4 4 2 4 3 0 0.081 0.25 201 NICOTINATE_AND_NICOTINAMIDE_METABOLISM AOX1, CD38, ENPP1, ENPP3, NADSYN1, NMNAT1, NMNAT2, NNMT, NNT, NP, NT5C, NT5E, NT5M, QPRT 13 AOX1(7), CD38(2), ENPP3(1), NADSYN1(4), NMNAT2(1), NNMT(1), QPRT(3) 5902823 19 17 16 2 8 2 2 6 1 0 0.082 0.25 202 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(3), JAK2(4), JAK3(4), MAPK1(3), MAPK3(2), STAT3(2), TYK2(3) 4692033 21 16 19 3 9 3 3 5 1 0 0.084 0.26 203 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 CD3E(1), CD3G(1), CD4(3), CXCR3(2), IFNG(1), IL12B(1), IL12RB1(4), IL12RB2(4), JAK2(4), STAT4(1), TYK2(3) 5635956 25 17 22 9 11 1 5 4 4 0 0.086 0.26 204 ALKALOID_BIOSYNTHESIS_II ABP1, AOC2, AOC3, CES1, ESD 5 ABP1(9), AOC2(2), AOC3(2), CES1(2) 2419051 15 10 15 1 8 3 1 3 0 0 0.092 0.28 205 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 47 ACCN1(4), ADCY4(2), ADCY6(2), ADCY8(4), CACNA1A(4), CACNA1B(7), GNAS(3), GNAT3(3), GNB1(1), GNB3(1), GRM4(5), ITPR3(11), KCNB1(3), PDE1A(1), PLCB2(5), PRKACG(1), PRKX(2), SCNN1A(2), SCNN1B(5), SCNN1G(4), TAS1R1(1), TAS1R2(2), TAS2R1(1), TAS2R10(2), TAS2R14(2), TAS2R16(1), TAS2R38(1), TAS2R39(1), TAS2R40(1), TAS2R41(3), TAS2R42(1), TAS2R60(1), TAS2R8(1), TRPM5(1) 21727627 89 53 89 45 39 11 16 14 9 0 0.097 0.29 206 STILBENE_COUMARINE_AND_LIGNIN_BIOSYNTHESIS EPX, GBA3, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TPO, TYR 10 EPX(6), LPO(1), MPO(3), PRDX2(2), TPO(4), TYR(5) 3807130 21 14 21 8 11 1 2 4 3 0 0.098 0.29 207 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 26 CCL3(1), CCR1(2), CCR3(2), CCR4(1), CCR7(2), CD28(1), CD4(3), CXCR3(2), IFNG(1), IFNGR1(1), IFNGR2(1), IL12B(1), IL12RB1(4), IL12RB2(4), IL18R1(1), IL2(1), IL4(1), IL4R(6), TGFB1(1), TGFB2(1) 7533077 37 21 35 7 12 3 8 8 6 0 0.098 0.29 208 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 CCR3(2), CD4(3), HLA-DRA(1), HLA-DRB1(2), IL4(1), IL5RA(1), IL6(2) 2187762 12 8 10 2 2 3 0 5 2 0 0.099 0.29 209 HSA00750_VITAMIN_B6_METABOLISM Genes involved in vitamin B6 metabolism AOX1, PDXK, PDXP, PNPO, PSAT1 5 AOX1(7), PDXK(1) 1952432 8 8 6 1 6 0 1 1 0 0 0.099 0.29 210 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 40 ALK(5), ESR1(3), ESR2(1), ESRRA(2), HNF4A(7), NPM1(1), NR1D1(3), NR1H2(1), NR1H3(1), NR1I3(2), NR2F2(2), NR2F6(1), NR3C1(1), NR4A1(3), NR4A2(2), NR5A1(1), NR5A2(1), PGR(4), PPARA(1), RARA(5), RARG(2), ROR1(2), RORA(1), RORC(3), RXRA(3), RXRB(1), RXRG(1), THRA(1), VDR(2) 16770470 63 41 59 28 20 3 11 16 13 0 0.11 0.31 211 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 IFNG(1), IFNGR1(1), JAK1(3), JAK2(4), PLA2G2A(5), PTPRU(3), STAT1(1) 4635935 18 15 13 1 9 0 6 1 2 0 0.11 0.31 212 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 41 ABP1(9), ACY3(1), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH3B1(2), ALDH3B2(1), ALDH9A1(1), AMDHD1(3), AOC2(2), AOC3(2), CARM1(1), CNDP1(4), DDC(1), FTCD(3), HAL(2), HARS(3), HARS2(1), HDC(3), HNMT(1), LCMT1(1), MAOB(1), PRMT6(5), PRMT7(2), PRMT8(1), PRPS2(2), UROC1(2) 15763597 61 41 58 17 29 5 11 14 2 0 0.11 0.31 213 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(8), C5(1), C6(3), C7(6), IL6(2), ITGA4(7), ITGAL(4), ITGB2(5), SELP(2), SELPLG(2) 9840865 40 25 39 26 13 3 7 8 8 1 0.11 0.31 214 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 17 ARSB(2), GALNS(1), GLB1(1), GUSB(3), HEXA(1), HGSNAT(2), HPSE(3), HPSE2(2), HYAL1(1), HYAL2(1), LCT(8), NAGLU(1), SPAM1(6) 8100775 32 22 31 10 12 2 6 6 6 0 0.11 0.32 215 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(2), ABP1(9), ACADM(2), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH9A1(1), AOC2(2), AOC3(2), CNDP1(4), DPYD(2), DPYS(2), ECHS1(1), EHHADH(2), GAD1(4), GAD2(3), HADHA(1), MLYCD(1), UPB1(1) 10880045 46 28 46 9 17 7 8 11 3 0 0.11 0.32 216 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(2), ACO2(1), CLYBL(3), DLD(1), DLST(2), IDH1(15), IDH2(2), IDH3G(2), MDH2(1), OGDH(1), OGDHL(5), PC(3), PCK1(4), PCK2(1), SUCLA2(1), SUCLG1(2) 11972976 48 31 35 17 22 6 13 6 1 0 0.11 0.32 217 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(8), CD3E(1), CD3G(1), CD4(3), CREBBP(8), GNAS(3), GNB1(1), GNGT1(1), HLA-DRA(1), HLA-DRB1(2), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PTPRC(4), ZAP70(5) 8965084 41 26 39 12 14 8 7 7 5 0 0.11 0.32 218 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(8), CD3E(1), CD3G(1), CD4(3), CREBBP(8), GNAS(3), GNB1(1), GNGT1(1), HLA-DRA(1), HLA-DRB1(2), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PTPRC(4), ZAP70(5) 8965084 41 26 39 12 14 8 7 7 5 0 0.11 0.32 219 CAPROLACTAM_DEGRADATION AKR1A1, ECHS1, EHHADH, HADHA, SDS 5 AKR1A1(1), ECHS1(1), EHHADH(2), HADHA(1), SDS(4) 1940571 9 7 9 2 0 4 1 1 3 0 0.11 0.32 220 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 CALM1(1), DLG4(2), GRIN1(3), GRIN2A(13), GRIN2B(4), GRIN2C(2), GRIN2D(2), NOS1(9), PPP3CB(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PRKCA(3), SYT1(1) 9871541 44 29 42 19 20 3 8 11 2 0 0.12 0.32 221 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(4), ABCB11(2), ABCB4(8), ABCC1(3), ABCC3(5), GSTP1(1) 5751848 23 18 23 12 9 4 2 4 4 0 0.12 0.32 222 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 44 ADH1A(4), ADH1B(3), ADH1C(3), ADH6(2), ADH7(1), AGPAT1(2), AGPAT2(2), AGPAT3(2), AGPAT4(1), AKR1A1(1), ALDH1A1(4), ALDH1A2(3), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH9A1(1), CEL(3), DGKB(1), DGKD(6), DGKE(2), DGKG(5), DGKH(3), DGKQ(1), DGKZ(5), GK(1), GLA(1), GLB1(1), LCT(8), LIPC(1), LIPG(5), PNLIP(2), PNLIPRP1(2), PPAP2C(1) 18858900 84 44 83 21 34 14 17 12 7 0 0.12 0.34 223 TCRMOLECULE T Cell Receptor and CD3 Complex CD3D, CD3E, CD3G, CD3Z, TRA@, TRB@ 3 CD3E(1), CD3G(1) 468602 2 2 2 1 0 0 1 0 1 0 0.12 0.34 224 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 21 ABO(2), B3GNT1(2), B3GNT2(3), B3GNT3(1), B3GNT4(2), B3GNT5(1), B4GALT2(1), B4GALT4(1), FUT1(1), FUT5(2), FUT6(2), FUT7(5), FUT9(1), GCNT2(1), ST3GAL6(2) 6213807 27 18 23 9 8 3 9 6 1 0 0.12 0.34 225 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 CD44(4), ITGA4(7), ITGAL(4), ITGB2(5), PECAM1(2), SELE(1) 5304269 23 14 23 13 7 1 4 6 5 0 0.13 0.34 226 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 51 ALOX12B(1), ALOX15(2), ALOX15B(1), ALOX5(1), CBR1(1), CBR3(2), CYP2B6(2), CYP2C18(1), CYP2C8(2), CYP2C9(2), CYP2E1(4), CYP4A11(3), CYP4A22(4), CYP4F2(5), CYP4F3(5), EPHX2(2), GGT1(2), GPX1(2), GPX2(1), GPX5(2), LTA4H(1), PLA2G12A(3), PLA2G2A(5), PLA2G2F(2), PLA2G3(2), PLA2G4A(4), PLA2G5(1), PLA2G6(3), PTGIS(1), PTGS1(2), TBXAS1(3) 15495569 72 38 67 28 31 6 20 9 5 1 0.13 0.34 227 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(3), GPR161(2), GPR18(1), GPR34(1), GPR45(2), GPR65(1), GPR68(2), GPR81(2) 3922283 16 12 16 5 6 2 2 4 2 0 0.13 0.34 228 HSA00061_FATTY_ACID_BIOSYNTHESIS Genes involved in fatty acid biosynthesis ACACA, ACACB, FASN, MCAT, OLAH, OXSM 6 ACACA(8), ACACB(9), FASN(7), MCAT(1), OXSM(3) 5930850 28 17 28 7 11 1 8 5 3 0 0.13 0.35 229 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 B4GALT2(1), FBP2(4), G6PC(2), GAA(3), GALE(2), GALK1(3), GALK2(5), GALT(1), GCK(2), GLA(1), GLB1(1), HK2(3), HK3(4), LCT(8), MGAM(7), PFKM(3), PFKP(6), PGM3(2) 12777875 58 33 54 16 28 6 10 10 4 0 0.13 0.36 230 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(3), ADRBK2(2), CALM1(1), CAMK2B(1), CAMK2D(1), CAMK2G(4), CLCA1(3), CLCA2(2), CLCA4(2), CNGA3(2), CNGA4(2), CNGB1(5), GNAL(1), GUCA1B(1), GUCA1C(3), PDE1C(4), PRKACG(1), PRKG2(5), PRKX(2) 12240769 45 30 44 22 13 7 11 11 3 0 0.14 0.36 231 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 127 ABL1(1), ABLIM2(1), ABLIM3(2), CFL2(1), DCC(9), DPYSL2(2), DPYSL5(2), EFNA3(2), EFNA5(2), EFNB1(2), EFNB2(2), EFNB3(1), EPHA1(6), EPHA2(2), EPHA3(2), EPHA4(3), EPHA5(4), EPHA6(2), EPHA7(6), EPHA8(6), EPHB1(10), EPHB2(6), EPHB3(1), EPHB4(2), EPHB6(5), FES(3), GNAI2(1), GSK3B(1), KRAS(1), L1CAM(7), LIMK1(1), LIMK2(1), LRRC4C(3), MAPK1(3), MAPK3(2), MET(5), NFAT5(3), NFATC1(3), NFATC2(1), NFATC3(1), NFATC4(2), NRAS(1), NRP1(5), NTN1(3), NTN4(2), PAK1(2), PAK3(2), PAK6(1), PAK7(3), PLXNA1(3), PLXNA2(8), PLXNA3(3), PLXNB1(3), PLXNB2(7), PLXNB3(7), PLXNC1(3), PPP3CB(1), PPP3R1(1), PPP3R2(1), PTK2(2), RGS3(2), RHOA(1), RHOD(1), RND1(1), ROBO1(3), ROBO2(2), ROBO3(1), ROCK1(3), ROCK2(4), SEMA3A(1), SEMA3B(1), SEMA3C(8), SEMA3E(4), SEMA3F(1), SEMA3G(1), SEMA4B(1), SEMA4C(2), SEMA4D(1), SEMA4F(3), SEMA4G(3), SEMA5A(2), SEMA5B(2), SEMA6B(1), SEMA6C(1), SEMA7A(1), SLIT1(4), SLIT2(5), SLIT3(14), SRGAP1(5), SRGAP2(2), SRGAP3(4), UNC5A(4), UNC5D(2) 75489230 269 124 260 90 73 46 60 53 37 0 0.14 0.37 232 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 PLCD1(1), PRKCA(3), TGM2(9) 2026871 13 8 11 4 3 0 4 4 2 0 0.14 0.37 233 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 37 ABP1(9), AGXT2(2), ALAS1(2), ALAS2(1), AMT(2), AOC2(2), AOC3(2), BHMT(3), CBS(1), CHKA(1), CHKB(1), CTH(1), DAO(3), DLD(1), DMGDH(3), GAMT(1), GATM(2), GCAT(1), GLDC(2), MAOB(1), PISD(3), PLCB2(5), PLCG1(3), PLCG2(11), PSPH(2), SARDH(6), SHMT2(1), TARS(2) 16846339 74 40 71 18 29 14 16 8 7 0 0.14 0.37 234 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 CD28(1), CD3E(1), CD3G(1), CD8A(1), ITGAL(4), ITGB2(5), PTPRC(4) 4298928 17 12 17 12 5 2 3 0 7 0 0.15 0.38 235 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 30 AGPAT1(2), AGPAT2(2), AGPAT3(2), AGPAT4(1), AGPS(1), ENPP2(5), PAFAH2(2), PLA2G12A(3), PLA2G2A(5), PLA2G2F(2), PLA2G3(2), PLA2G4A(4), PLA2G5(1), PLA2G6(3), PLD2(1), PPAP2C(1) 9352222 37 24 33 17 13 3 9 5 6 1 0.15 0.38 236 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 22 ACP5(2), ACP6(2), ACPT(3), ALPI(2), ALPL(2), ALPP(2), ALPPL2(2), CMBL(1), CYP3A4(3), CYP3A43(2), CYP3A7(3), DHRS7(1), PON1(4), PON3(2) 6896273 31 19 31 7 12 3 7 8 1 0 0.15 0.38 237 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(3), STAT1(1), STAT2(5), TYK2(3) 4326909 14 12 14 3 4 2 5 1 2 0 0.15 0.39 238 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 30 ADRA1D(1), ADRA2C(4), ADRB1(1), ADRB2(1), CHRM2(4), CHRM3(3), DRD1(2), DRD2(1), DRD3(1), DRD5(4), HRH1(1), HRH2(5), HTR1A(2), HTR1B(3), HTR1D(1), HTR1E(2), HTR1F(2), HTR2A(1), HTR2C(2), HTR4(1), HTR5A(4), HTR6(1), HTR7(1) 9718968 48 29 48 18 23 5 8 8 4 0 0.15 0.39 239 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 CD28(1), CD4(3), HLA-DRA(1), HLA-DRB1(2), IL2(1), IL4(1) 1633088 9 6 7 1 2 2 0 5 0 0 0.15 0.39 240 C21_STEROID_HORMONE_METABOLISM AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 11 AKR1C4(2), CYP11A1(1), CYP11B2(4), CYP17A1(1), HSD11B1(2), HSD3B2(2) 3532572 12 11 12 7 6 3 2 0 1 0 0.15 0.39 241 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(2), CYP11A1(1), CYP11B2(4), CYP17A1(1), HSD11B1(2), HSD3B2(2) 3532572 12 11 12 7 6 3 2 0 1 0 0.15 0.39 242 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 ABP1(9), ALDH1A1(4), ALDH1A2(3), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH3B1(2), ALDH3B2(1), ALDH9A1(1), AOC2(2), AOC3(2), CNDP1(4), DDC(1), HAL(2), HARS(3), HDC(3), HNMT(1), MAOB(1), PRPS2(2) 9896289 48 27 49 9 24 9 5 8 2 0 0.15 0.39 243 HSA00401_NOVOBIOCIN_BIOSYNTHESIS Genes involved in novobiocin biosynthesis GOT1, GOT2, TAT 3 GOT1(1), TAT(3) 1070053 4 4 4 0 1 2 1 0 0 0 0.16 0.39 244 HSA00940_PHENYLPROPANOID_BIOSYNTHESIS Genes involved in phenylpropanoid biosynthesis EPX, GBA, GBA3, LPO, MPO, PRDX6, TPO 7 EPX(6), GBA(1), LPO(1), MPO(3), TPO(4) 3329226 15 12 15 7 11 0 0 1 3 0 0.16 0.39 245 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 17 ACE(7), ACE2(2), AGT(3), AGTR1(2), AGTR2(1), ANPEP(3), CTSA(2), CTSG(4), ENPEP(9), LNPEP(2), NLN(1), REN(2), THOP1(1) 8431879 39 22 39 13 17 5 8 3 6 0 0.16 0.40 246 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 54 ADH1A(4), ADH1B(3), ADH1C(3), ADH6(2), ADH7(1), AGPAT1(2), AGPAT2(2), AGPAT3(2), AGPAT4(1), AKR1A1(1), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH9A1(1), CEL(3), DGAT2(2), DGKB(1), DGKD(6), DGKE(2), DGKG(5), DGKH(3), DGKI(3), DGKQ(1), DGKZ(5), GK(1), GK2(2), GLA(1), GLB1(1), GPAM(2), LCT(8), LIPC(1), LIPG(5), MGLL(2), PNLIP(2), PNLIPRP1(2), PNPLA3(1), PPAP2C(1) 23080983 89 50 88 25 37 11 17 16 8 0 0.16 0.40 247 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 ABP1(9), ALDH1A3(1), ALDH3A1(3), ALDH3B1(2), ALDH3B2(1), AOC2(2), AOC3(2), DDC(1), EPX(6), GOT1(1), HPD(1), LPO(1), MAOB(1), MPO(3), PRDX2(2), TAT(3), TPO(4) 8803849 43 26 44 10 23 5 4 8 3 0 0.16 0.40 248 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 CD28(1), HLA-DRA(1), HLA-DRB1(2), IFNG(1), IFNGR1(1), IFNGR2(1), IL12B(1), IL12RB1(4), IL12RB2(4), IL18R1(1), IL2(1), IL2RA(3), IL4(1), IL4R(6) 5130651 28 15 28 4 12 5 4 5 2 0 0.16 0.41 249 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(6), AP2A1(2), AP2M1(4), BIN1(1), CALM1(1), DNM1(5), EPN1(1), EPS15(1), PICALM(2), PPP3CB(1), SYNJ1(1), SYNJ2(7), SYT1(1) 8612476 33 21 32 7 9 6 8 3 7 0 0.17 0.41 250 FOLATE_BIOSYNTHESIS ALPI, ALPL, ALPP, ALPP, ALPPL2, ALPPL2, DHFR, FPGS, GCH1, GGH, SPR 9 ALPI(2), ALPL(2), ALPP(2), ALPPL2(2), DHFR(1), FPGS(2) 2450112 11 9 11 4 4 0 4 2 1 0 0.17 0.41 251 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 15 FUCA1(1), GLB1(1), HEXA(1), LCT(8), MAN2B1(4), MAN2B2(2), MAN2C1(2), MANBA(1), NEU1(1), NEU2(4), NEU4(4) 8067047 29 21 28 9 14 1 5 4 5 0 0.17 0.41 252 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 21 CHUK(4), IKBKB(2), IL1R1(2), IRAK1(2), MAP3K1(5), MAP3K14(2), MAP3K7(2), NFKB1(1), NFKBIA(2), RIPK1(1), TLR4(1), TNFAIP3(1), TNFRSF1A(2), TNFRSF1B(2) 9716920 29 22 28 14 4 5 6 10 4 0 0.17 0.42 253 EPHA4PATHWAY Eph Kinases and ephrins support platelet aggregation ACTA1, EPHA4, EPHB1, FYN, ITGA1, ITGB1, L1CAM, LYN, RAP1B, SELP 10 ACTA1(1), EPHA4(3), EPHB1(10), ITGA1(1), L1CAM(7), LYN(1), RAP1B(2), SELP(2) 6284921 27 17 26 8 11 5 6 3 2 0 0.17 0.42 254 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(2), JAK1(3), JAK2(4), JAK3(4), PIAS3(4), PTPRU(3), SRC(2), STAT3(2) 6157097 26 19 23 4 12 4 3 5 2 0 0.18 0.43 255 HSA00930_CAPROLACTAM_DEGRADATION Genes involved in caprolactam degradation AKR1A1, ASAHL, ECHS1, EHHADH, HADH, HADHA, HSD17B10, HSD17B4, NTAN1, SIRT1, SIRT2, SIRT5, SIRT7, VNN2, VNN3 13 AKR1A1(1), ECHS1(1), EHHADH(2), HADHA(1), HSD17B10(1), HSD17B4(1), NTAN1(1), SIRT1(2), SIRT2(2), VNN2(1) 4653069 13 11 13 1 2 2 1 2 6 0 0.18 0.43 256 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(7), CDC25B(1), CHEK1(5), MYT1(7) 5572706 20 13 20 0 6 3 2 4 5 0 0.18 0.44 257 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 138 ACTA1(1), ACTA2(2), ADCY1(8), ADCY2(3), ADCY3(3), ADCY4(2), ADCY5(3), ADCY6(2), ADCY7(3), ADCY8(4), ADCY9(5), ATF2(1), ATF4(1), ATP2A2(2), ATP2A3(4), CACNB3(1), CALCA(3), CALM1(1), CAMK2B(1), CAMK2D(1), CAMK2G(4), CNN2(1), CORIN(5), CREB3(1), CRHR1(2), DGKZ(5), FOS(1), GABPA(1), GJA1(1), GNAQ(1), GNB1(1), GNB2(1), GNB3(1), GNB4(2), GNG2(1), GNGT1(1), GRK6(1), GSTO1(3), GUCA2B(1), GUCY1A3(5), IGFBP1(1), IGFBP3(1), IGFBP4(1), IL6(2), ITPR1(7), ITPR2(11), ITPR3(11), MIB1(2), MYL2(2), MYLK2(1), NFKB1(1), NOS1(9), NOS3(5), OXTR(2), PDE4B(1), PDE4D(3), PLCB3(5), PLCD1(1), PLCG1(3), PLCG2(11), PRKAR2A(1), PRKAR2B(1), PRKCA(3), PRKCD(5), PRKCE(1), PRKCH(2), PRKCQ(1), PRKCZ(2), PRKD1(3), RAMP3(2), RGS1(1), RGS14(1), RGS2(1), RGS3(2), RGS4(2), RGS5(1), RGS6(1), RGS7(2), RGS9(2), RYR1(14), RYR2(36), RYR3(17), SLC8A1(2), SP1(6), TNXB(6), USP5(5), YWHAB(1) 67503813 291 119 285 92 127 35 54 44 31 0 0.18 0.44 258 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(2), ACACA(8), ACADM(2), ACADSB(1), ALDH1A1(4), ALDH1A2(3), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH6A1(2), ALDH9A1(1), ECHS1(1), EHHADH(2), HADHA(1), LDHA(2), LDHC(1), MLYCD(1), MUT(2), PCCA(1), PCCB(2), SDS(4), SUCLA2(1), SUCLG1(2) 13418593 50 29 50 11 12 13 10 6 9 0 0.19 0.45 259 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 25 BLVRA(1), BLVRB(1), CP(4), CPOX(1), EPRS(2), FECH(3), GUSB(3), HCCS(3), HMBS(1), HMOX1(2), PPOX(2), UGT1A1(1), UGT1A10(1), UGT1A3(1), UGT1A5(2), UGT1A6(2), UGT1A9(1), UGT2B4(5), UROD(1), UROS(1) 10330169 38 24 38 16 10 4 6 12 6 0 0.19 0.45 260 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 74 ARAF(1), BRAF(6), CACNA1A(4), CRHR1(2), GNA11(2), GNA12(2), GNAI2(1), GNAO1(1), GNAQ(1), GNAS(3), GRIA1(4), GRIA3(5), GRID2(1), GRM1(1), GRM5(1), GUCY1A2(1), GUCY1A3(5), GUCY2C(2), GUCY2D(2), GUCY2F(1), IGF1R(2), ITPR1(7), ITPR2(11), ITPR3(11), KRAS(1), LYN(1), MAP2K1(1), MAP2K2(1), MAPK1(3), MAPK3(2), NOS1(9), NOS3(5), NPR1(6), NPR2(1), NRAS(1), PLA2G12A(3), PLA2G2A(5), PLA2G2F(2), PLA2G3(2), PLA2G4A(4), PLA2G5(1), PLA2G6(3), PLCB1(3), PLCB2(5), PLCB3(5), PLCB4(3), PPP2CA(1), PPP2R1A(1), PPP2R1B(3), PPP2R2A(1), PPP2R2B(1), PPP2R2C(1), PRKCA(3), PRKCG(1), PRKG2(5), RYR1(14) 43885422 175 84 161 64 67 22 32 30 22 2 0.19 0.45 261 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 HSD11B1(2), NR3C1(1), RETN(1), RXRA(3) 2319283 7 8 8 4 1 2 0 1 3 0 0.19 0.45 262 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 98 ADCY1(8), ADCY2(3), ADCY3(3), ADCY4(2), ADCY5(3), ADCY6(2), ADCY7(3), ADCY8(4), ADCY9(5), CALM1(1), CAMK2B(1), CAMK2D(1), CAMK2G(4), CREB3(1), CREB3L1(1), CREB3L3(3), CREB3L4(1), CREBBP(8), DVL2(2), EDNRB(1), EP300(5), FZD1(1), FZD10(4), FZD2(1), FZD3(4), FZD4(3), FZD5(2), FZD6(2), FZD7(1), FZD8(1), FZD9(6), GNAI2(1), GNAO1(1), GNAQ(1), GNAS(3), GSK3B(1), KIT(3), KITLG(2), KRAS(1), LEF1(1), MAP2K1(1), MAP2K2(1), MAPK1(3), MAPK3(2), MITF(2), NRAS(1), PLCB1(3), PLCB2(5), PLCB3(5), PLCB4(3), PRKACG(1), PRKCA(3), PRKCG(1), PRKX(2), TCF7(3), TCF7L2(3), TYR(5), TYRP1(2), WNT10A(1), WNT11(1), WNT16(1), WNT2(5), WNT2B(1), WNT3(3), WNT3A(1), WNT4(3), WNT5A(1), WNT8A(1), WNT8B(3), WNT9A(3), WNT9B(4) 42357653 175 82 171 50 59 21 39 31 23 2 0.20 0.46 263 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 CCNA1(1), CCNE1(1), CCNE2(1), CDKN1B(3), CDKN2A(3), E2F2(3) 3378480 12 11 12 8 3 3 1 1 4 0 0.20 0.46 264 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 31 CD14(2), CHUK(4), ELK1(1), FOS(1), IKBKB(2), IRAK1(2), LY96(1), MAP2K3(1), MAP3K1(5), MAP3K14(2), MAP3K7(2), MAPK14(1), NFKB1(1), NFKBIA(2), PPARA(1), TLR10(1), TLR2(4), TLR4(1), TLR6(6), TLR7(5), TLR9(2) 14541644 47 32 46 25 9 13 8 12 5 0 0.20 0.47 265 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 44 ABCA1(4), ABCA10(2), ABCA12(2), ABCA13(5), ABCA2(3), ABCA3(3), ABCA4(6), ABCA5(4), ABCA6(2), ABCA7(3), ABCA8(1), ABCA9(4), ABCB1(4), ABCB10(2), ABCB11(2), ABCB4(8), ABCB5(7), ABCB6(4), ABCB7(1), ABCB8(4), ABCB9(2), ABCC1(3), ABCC10(2), ABCC11(3), ABCC12(1), ABCC2(3), ABCC3(5), ABCC4(4), ABCC5(7), ABCC6(5), ABCC8(6), ABCC9(12), ABCD1(4), ABCD2(4), ABCD3(2), ABCG1(2), ABCG2(2), ABCG4(6), ABCG5(3), ABCG8(3), CFTR(7), TAP1(4), TAP2(2) 46607696 163 77 162 58 57 18 38 23 24 3 0.20 0.47 266 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 GPX1(2), GSR(1), GSS(1), NFKB1(1), NOX1(2), XDH(8) 4061497 15 11 14 5 2 3 7 1 2 0 0.20 0.47 267 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 23 ALDOA(1), ALDOB(1), ALDOC(3), FBP1(2), FBP2(4), GOT1(1), MDH2(1), ME1(4), ME3(3), PGK2(3), PKLR(4), RPE(1), TKT(2), TKTL1(2), TKTL2(2) 7845277 34 21 34 8 11 5 7 8 3 0 0.20 0.47 268 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 CHUK(4), IKBKAP(4), IKBKB(2), MAP3K1(5), MAP3K14(2), NFKB1(1), NFKBIA(2), RIPK1(1), TNFAIP3(1), TNFRSF1B(2), TRAF1(1), TRAF2(2), TRAF3(3) 9003646 30 21 29 12 6 3 6 11 4 0 0.21 0.48 269 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 17 GUSB(3), RPE(1), UCHL1(1), UGT1A1(1), UGT1A10(1), UGT1A3(1), UGT1A5(2), UGT1A6(2), UGT1A9(1), UGT2B4(5) 6320515 18 16 18 11 4 5 3 3 3 0 0.21 0.48 270 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(7), CD44(4), FCGR3A(1), IL6R(2), TGFB1(1), TGFB2(1), TNFRSF1A(2), TNFRSF1B(2), TNFRSF8(3), TNFSF8(1) 5271297 24 14 24 7 6 4 6 3 5 0 0.21 0.48 271 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(7), C9orf95(1), CD38(2), ENPP3(1), NADK(3), NADSYN1(4), NMNAT2(1), NNMT(1), NT5C1B(3), NT5C2(2), QPRT(3) 8700021 28 21 25 8 10 2 5 9 2 0 0.21 0.48 272 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 31 CHUK(4), IFNB1(1), IKBKB(2), IL1R1(2), IL1RAP(2), IL1RN(1), IL6(2), IRAK1(2), IRAK2(3), IRAK3(2), MAP2K3(1), MAP3K1(5), MAP3K14(2), MAP3K7(2), MAPK14(1), NFKB1(1), NFKBIA(2), TGFB1(1), TGFB2(1) 11783783 37 26 36 16 5 5 5 13 9 0 0.22 0.50 273 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 23 ARSA(1), ARSB(2), ARSD(1), ARSE(1), ASAH1(1), GAL3ST1(2), GALC(2), GBA(1), GLA(1), GLB1(1), LCT(8), NEU1(1), NEU2(4), NEU4(4), PPAP2C(1), SPTLC1(2), SPTLC2(1), UGCG(1) 9552915 35 23 34 15 12 5 4 4 9 1 0.22 0.50 274 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(8), COL4A3(3), COL4A4(4), COL4A5(5), COL4A6(5), SLC23A1(1), SLC23A2(3), SLC2A1(4), SLC2A3(2) 10143840 39 26 37 13 15 10 4 4 6 0 0.23 0.52 275 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 42 APH1A(3), CREBBP(8), CTBP1(3), CTBP2(4), DLL3(1), DTX1(1), DTX3L(1), DVL2(2), EP300(5), HDAC1(1), HDAC2(3), HES1(1), JAG1(3), JAG2(5), LFNG(1), MAML1(3), MAML2(2), MAML3(1), MFNG(2), NCOR2(5), NOTCH1(4), NOTCH2(6), NOTCH3(7), NOTCH4(5), NUMB(1), NUMBL(2), PSEN2(1), RBPJ(1), RBPJL(4), SNW1(1) 25862211 87 52 84 29 27 12 20 15 12 1 0.23 0.52 276 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(4), IFNG(1), IL12B(1), IL2(1) 1206627 7 4 7 0 1 2 0 2 2 0 0.23 0.52 277 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(3), ELK1(1), FOS(1), IL6(2), IL6R(2), JAK1(3), JAK2(4), JAK3(4), MAP2K1(1), MAPK3(2), PTPN11(6), SOS1(1), SRF(2), STAT3(2) 9560632 34 23 32 6 11 5 6 8 4 0 0.23 0.52 278 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), IL4R(6), JAK1(3), JAK2(4), TYK2(3) 4182675 17 12 16 5 10 2 3 1 1 0 0.23 0.52 279 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), IL4R(6), JAK1(3), JAK2(4), TYK2(3) 4182675 17 12 16 5 10 2 3 1 1 0 0.23 0.52 280 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 AKR1B10(2), ALOX15(2), ALOX5(1), CYP2C18(1), CYP2C8(2), CYP2C9(2), CYP2E1(4), CYP3A4(3), CYP3A43(2), CYP3A7(3), PLA2G12A(3), PLA2G2A(5), PLA2G2F(2), PLA2G3(2), PLA2G4A(4), PLA2G5(1), PLA2G6(3), RDH13(1) 9624747 43 22 39 13 15 2 13 8 4 1 0.24 0.52 281 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 137 ADCY1(8), ADCY2(3), ADCY3(3), ADCY4(2), ADCY5(3), ADCY6(2), ADCY7(3), ADCY8(4), ADCY9(5), ADRA1D(1), ADRB1(1), ADRB2(1), ATP1A4(1), ATP2A2(2), ATP2A3(4), ATP2B1(2), ATP2B2(4), ATP2B3(8), CACNA1A(4), CACNA1B(7), CACNA1C(5), CACNA1D(9), CACNA1E(9), CACNA1S(12), CACNB3(1), CALM1(1), CAMK1(2), CAMK2B(1), CAMK2D(1), CAMK2G(4), CAMK4(1), CASQ2(1), CHRM2(4), CHRM3(3), GJA1(1), GJB1(4), GJB3(2), GJB5(2), GJB6(1), GNA11(2), GNAI2(1), GNAO1(1), GNAQ(1), GNB1(1), GNB2(1), GNB3(1), GNB4(2), GNG2(1), GNGT1(1), GRK6(1), ITPR1(7), ITPR2(11), ITPR3(11), KCNB1(3), KCNJ3(2), KCNJ5(3), MIB1(2), NME7(3), PLCB3(5), PRKAR2A(1), PRKAR2B(1), PRKCA(3), PRKCD(5), PRKCE(1), PRKCG(1), PRKCH(2), PRKCQ(1), PRKCZ(2), PRKD1(3), RGS1(1), RGS14(1), RGS2(1), RGS3(2), RGS4(2), RGS5(1), RGS6(1), RGS7(2), RGS9(2), RYR1(14), RYR2(36), RYR3(17), SLC8A1(2), SLC8A3(2), USP5(5), YWHAB(1) 73557180 302 124 298 109 136 38 50 50 28 0 0.24 0.52 282 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 ASAH1(1), BRAF(6), CREB3(1), CREB5(1), MAPK1(3), SNX13(1), SRC(2), TERF2IP(3) 4440672 18 11 15 2 2 3 3 9 1 0 0.24 0.52 283 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(4), MBTPS1(3), SCAP(5), SREBF1(2), SREBF2(3) 4554029 18 12 18 6 7 2 4 0 5 0 0.25 0.54 284 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 45 ABP1(9), AGXT2(2), AKR1B10(2), ALAS1(2), ALAS2(1), AMT(2), AOC2(2), AOC3(2), BHMT(3), CBS(1), CHKA(1), CHKB(1), CTH(1), DAO(3), DLD(1), DMGDH(3), GAMT(1), GATM(2), GCAT(1), GLDC(2), MAOB(1), PHGDH(1), PIPOX(2), PISD(3), PSPH(2), RDH13(1), SARDH(6), SARS2(2), SDS(4), SHMT2(1), TARS(2), TARS2(1) 17182900 68 38 64 15 23 14 17 7 7 0 0.25 0.55 285 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(3), PTPRU(3), STAT1(1), STAT2(5), TYK2(3) 5024612 16 14 16 4 7 1 5 1 2 0 0.26 0.56 286 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 16 B3GNT1(2), B3GNT2(3), B3GNT7(3), B4GALT2(1), B4GALT4(1), CHST1(2), CHST2(3), CHST6(1), FUT8(1), ST3GAL1(2), ST3GAL3(1) 4837895 20 14 20 5 6 6 2 5 1 0 0.26 0.56 287 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(12), CALM1(1), CAPN2(1), CAPNS1(1), EP300(5), HDAC1(1), HDAC2(3), MEF2D(1), NFATC1(3), NFATC2(1), PPP3CB(1), PRKCA(3), SYT1(1) 9559706 34 22 34 10 9 3 8 9 4 1 0.26 0.57 288 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(2), ACPT(3), ALPI(2), ALPL(2), ALPP(2), ALPPL2(2), CYP19A1(3), CYP1A1(1), CYP2A13(2), CYP2A6(1), CYP2B6(2), CYP2C18(1), CYP2C8(2), CYP2C9(2), CYP2D6(3), CYP2E1(4), CYP3A4(3), CYP3A7(3), CYP4B1(3), CYP4F8(1), CYP51A1(1), PON1(4) 11601263 49 29 49 17 21 2 14 11 1 0 0.27 0.57 289 NUCLEOTIDE_GPCRS ADORA1, ADORA2A, ADORA2B, ADORA3, GPR23, LTB4R, P2RY1, P2RY2, P2RY5, P2RY6 8 ADORA1(2), ADORA2B(1), ADORA3(1), P2RY1(1), P2RY2(2), P2RY6(2) 2363953 9 8 9 1 3 0 2 2 2 0 0.27 0.58 290 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 ADH1A(4), ADH1B(3), ADH1C(3), ADH6(2), ADH7(1), AKR1A1(1), ALDH1A1(4), ALDH1A2(3), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH3B1(2), ALDH3B2(1), ALDH9A1(1), ALDOA(1), ALDOB(1), ALDOC(3), BPGM(1), DLAT(1), DLD(1), ENO2(1), ENO3(2), FBP1(2), FBP2(4), G6PC(2), GAPDH(1), GCK(2), GPI(4), HK2(3), HK3(4), LDHA(2), LDHC(1), PDHA1(1), PDHA2(3), PDHB(1), PFKM(3), PFKP(6), PGM3(2), PKLR(4) 19416741 88 44 88 15 42 14 13 13 6 0 0.27 0.58 291 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 ADH1A(4), ADH1B(3), ADH1C(3), ADH6(2), ADH7(1), AKR1A1(1), ALDH1A1(4), ALDH1A2(3), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH3B1(2), ALDH3B2(1), ALDH9A1(1), ALDOA(1), ALDOB(1), ALDOC(3), BPGM(1), DLAT(1), DLD(1), ENO2(1), ENO3(2), FBP1(2), FBP2(4), G6PC(2), GAPDH(1), GCK(2), GPI(4), HK2(3), HK3(4), LDHA(2), LDHC(1), PDHA1(1), PDHA2(3), PDHB(1), PFKM(3), PFKP(6), PGM3(2), PKLR(4) 19416741 88 44 88 15 42 14 13 13 6 0 0.27 0.58 292 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 C1QB(1), C1R(1), C1S(1), C2(2), C3(8), C5(1), C6(3), C7(6), C8A(3), C9(1) 6877628 27 17 26 20 9 3 7 5 2 1 0.27 0.58 293 HSA00627_1,4_DICHLOROBENZENE_DEGRADATION Genes involved in 1,4-dichlorobenzene degradation CMBL 1 CMBL(1) 207423 1 1 1 0 1 0 0 0 0 0 0.27 0.58 294 HSA00232_CAFFEINE_METABOLISM Genes involved in caffeine metabolism CYP1A2, CYP2A13, CYP2A6, CYP2A7, NAT1, NAT2, XDH 7 CYP2A13(2), CYP2A6(1), NAT2(1), XDH(8) 3252534 12 10 12 4 3 2 4 1 2 0 0.27 0.58 295 COMPLEMENT_ACTIVATION_CLASSICAL C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C8B, C9, DAF, MASP1 13 C1QB(1), C1R(1), C1S(1), C2(2), C3(8), C5(1), C6(3), C7(6), C8A(3), C8B(5), C9(1), MASP1(2) 8218368 34 20 33 21 10 5 9 7 2 1 0.28 0.58 296 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 37 CALM1(1), CAMK1(2), ELK1(1), FPR1(1), GNA15(4), GNB1(1), GNGT1(1), MAP2K1(1), MAP2K2(1), MAP2K3(1), MAP3K1(5), MAPK1(3), MAPK14(1), MAPK3(2), NCF1(2), NFATC1(3), NFATC2(1), NFATC3(1), NFATC4(2), NFKB1(1), NFKBIA(2), PAK1(2), PIK3C2G(9), PLCB1(3), PPP3CB(1), SYT1(1) 15238833 53 30 53 19 10 7 11 15 9 1 0.28 0.58 297 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 21 ALDOA(1), ALDOB(1), ALDOC(3), FBP1(2), FBP2(4), GOT1(1), MDH2(1), ME1(4), ME2(2), ME3(3), PKLR(4), RPE(1), TKT(2) 6979042 29 18 29 6 10 3 6 8 2 0 0.28 0.58 298 HSA00785_LIPOIC_ACID_METABOLISM Genes involved in lipoic acid metabolism LIAS, LIPT1, LOC387787 2 LIAS(1), LIPT1(1) 620625 2 2 2 0 0 0 1 1 0 0 0.28 0.58 299 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 37 ACACA(8), ALDH1A1(4), ALDH1A2(3), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH9A1(1), DLAT(1), DLD(1), GRHPR(1), LDHA(2), LDHC(1), LDHD(1), MDH2(1), ME1(4), ME2(2), ME3(3), PC(3), PCK1(4), PDHA1(1), PDHA2(3), PDHB(1), PKLR(4) 14781438 56 32 56 14 17 10 12 10 7 0 0.28 0.58 300 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(1), CDKN1A(1), CHEK1(5), NEK1(2) 2788786 9 8 9 1 1 1 2 3 2 0 0.29 0.60 301 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 CHUK(4), IKBKAP(4), IKBKB(2), MAP3K1(5), MAP3K14(2), NFKB1(1), NFKBIA(2), TNFAIP3(1), TRAF3(3) 7318170 24 16 23 9 3 3 4 10 4 0 0.29 0.60 302 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 CALM1(1), CAMK1(2), CAMK2B(1), CAMK2D(1), CAMK2G(4), CAMK4(1), CAMKK1(3), CAMKK2(1), SYT1(1) 4626443 15 13 15 6 3 1 2 6 3 0 0.30 0.60 303 SA_DIACYLGLYCEROL_SIGNALING DAG (diacylglycerol) signaling activity ESR1, ESR2, ITPKA, PDE1A, PDE1B, PLCB1, PLCB2, PRL, TRH, VIP 10 ESR1(3), ESR2(1), PDE1A(1), PLCB1(3), PLCB2(5), PRL(3), TRH(1), VIP(1) 4434609 18 11 18 5 10 3 2 1 1 1 0.30 0.60 304 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 29 AKR1C4(2), ARSB(2), ARSD(1), ARSE(1), CYP11B2(4), HSD11B1(2), HSD17B3(1), HSD17B8(1), HSD3B2(2), STS(2), SULT1E1(1), SULT2A1(1), UGT1A1(1), UGT1A10(1), UGT1A3(1), UGT1A5(2), UGT1A6(2), UGT1A9(1), UGT2B4(5) 10343168 33 23 33 22 10 6 7 6 4 0 0.30 0.61 305 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(8), EP300(5), NCOA3(4), PRKACG(1), PRKAR2A(1), PRKAR2B(1), RARA(5), RXRA(3) 8142271 29 19 27 7 6 4 7 8 3 1 0.31 0.62 306 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(8), GNA12(2), PRKACG(1), PRKAG1(2), PRKAR2A(1), PRKAR2B(1) 4103160 15 11 15 5 4 1 3 5 2 0 0.31 0.62 307 N_GLYCAN_DEGRADATION AGA, FLJ21865, FUCA1, FUCA2, GLB1, HEXA, HEXB, LCT, MAN2C1, MANBA, NEU1, NEU2, NEU3, NEU4 13 FUCA1(1), GLB1(1), HEXA(1), LCT(8), MAN2C1(2), MANBA(1), NEU1(1), NEU2(4), NEU4(4) 6545653 23 15 22 7 11 1 3 4 4 0 0.31 0.62 308 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 18 CALM1(1), CDKN1A(1), GNAQ(1), MARCKS(1), NFATC1(3), NFATC2(1), NFATC3(1), NFATC4(2), PLCG1(3), PPP3CB(1), PRKCA(3), SP1(6), SP3(1), SYT1(1) 8245499 26 19 26 11 4 4 4 8 6 0 0.31 0.62 309 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 ATP5O(1), ATP6AP1(2), ATP6V0A1(3), ATP6V0A4(5), ATP6V0D1(3), ATP6V1A(3), ATP6V1B1(1), ATP6V1B2(1), ATP6V1C1(2), ATP6V1C2(2), ATP6V1G1(2), ATP6V1G2(1), ATP6V1H(1) 6141389 27 16 27 8 9 6 8 1 3 0 0.31 0.62 310 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 ATP5O(1), ATP6AP1(2), ATP6V0A1(3), ATP6V0A4(5), ATP6V0D1(3), ATP6V1A(3), ATP6V1B1(1), ATP6V1B2(1), ATP6V1C1(2), ATP6V1C2(2), ATP6V1G1(2), ATP6V1G2(1), ATP6V1H(1) 6141389 27 16 27 8 9 6 8 1 3 0 0.31 0.62 311 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 ATP5O(1), ATP6AP1(2), ATP6V0A1(3), ATP6V0A4(5), ATP6V0D1(3), ATP6V1A(3), ATP6V1B1(1), ATP6V1B2(1), ATP6V1C1(2), ATP6V1C2(2), ATP6V1G1(2), ATP6V1G2(1), ATP6V1H(1) 6141389 27 16 27 8 9 6 8 1 3 0 0.31 0.62 312 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 FOS(1), FOSL2(1), IFNAR2(1), IFNB1(1), NFKB1(1), TNFRSF11A(3), TNFSF11(4) 4476253 12 11 12 7 4 3 2 0 3 0 0.31 0.62 313 HSA00830_RETINOL_METABOLISM Genes involved in retinol metabolism ALDH1A1, ALDH1A2, BCMO1, RDH5 4 ALDH1A1(4), ALDH1A2(3), BCMO1(2), RDH5(1) 1582419 10 5 10 1 3 5 1 0 1 0 0.31 0.62 314 UBIQUINONE_BIOSYNTHESIS NDUFA1, NDUFA10, NDUFA11, NDUFA4, NDUFA5, NDUFA8, NDUFB2, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFS1, NDUFS2, NDUFV1, NDUFV2 14 NDUFA10(2), NDUFA4(2), NDUFA8(1), NDUFB7(1), NDUFS2(1), NDUFV1(2), NDUFV2(2) 2695597 11 8 12 1 2 3 2 2 2 0 0.32 0.62 315 LIMONENE_AND_PINENE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, ECHS1, EHHADH, HADHA, SDS 12 ALDH1A1(4), ALDH1A2(3), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH9A1(1), ECHS1(1), EHHADH(2), HADHA(1), SDS(4) 4899111 23 13 23 5 5 8 4 3 3 0 0.32 0.62 316 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(2), HDAC9(5), MEF2A(1), MEF2C(1), MEF2D(1), MYOD1(2) 3035540 12 8 12 4 1 4 4 1 2 0 0.32 0.62 317 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(8), EP300(5), ESR1(3), MAPK1(3), MAPK3(2), PELP1(2), SRC(2) 5861877 25 14 25 4 6 5 8 4 1 1 0.32 0.62 318 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(3), JAK2(4), JAK3(4), PIAS1(2), PIAS3(4), PTPRU(3), SOAT1(2) 5522242 22 15 19 4 12 1 4 4 1 0 0.32 0.62 319 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 23 NRF1(2), TAX1BP3(1), UBE2A(1), UBE2I(1), UBE2J1(1), UBE2J2(1), UBE2L3(1), UBE2M(3), UBE3A(4) 4137499 15 11 16 1 3 2 5 1 3 1 0.33 0.63 320 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(4), APOE(1), CETP(2), HMGCR(1), LCAT(1), LDLR(4), LIPC(1), LRP1(15), SCARB1(1), SOAT1(2) 10040960 32 21 29 9 5 5 12 5 4 1 0.33 0.63 321 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(4), ADH1B(3), ADH1C(3), ADH6(2), ADH7(1), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH9A1(1) 5388913 21 14 21 5 11 1 5 4 0 0 0.34 0.65 322 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(3), HLA-DRA(1), HLA-DRB1(2), IFNB1(1), IFNG(1), IL12B(1), IL2(1), IL4(1), IL6(2), IL7(1), TGFB1(1), TGFB2(1) 5198747 16 12 14 5 2 3 1 6 4 0 0.34 0.65 323 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), ACADM(2), ACADS(4), ACADSB(1), ACADVL(3), ACOX1(2), ACOX3(1), ACSL3(3), ACSL4(2), ACSL5(2), ACSL6(4), ADH1A(4), ADH1B(3), ADH1C(3), ADH6(2), ADH7(1), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH9A1(1), CPT1A(1), CPT1C(2), CPT2(1), CYP4A11(3), CYP4A22(4), ECHS1(1), EHHADH(2), HADHA(1), HSD17B10(1), HSD17B4(1) 19720139 63 40 62 16 23 4 14 12 10 0 0.34 0.66 324 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 ACTA1(1), ADCY1(8), GNAS(3), GNB1(1), GNGT1(1), MAPK1(3), MAPK3(2), MYT1(7), PRKACG(1), PRKAR2A(1), PRKAR2B(1), SRC(2) 7939238 31 19 31 7 14 3 5 6 3 0 0.35 0.66 325 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(1), ALDOB(1), ALDOC(3), FBP1(2), FBP2(4), G6PD(2), GPI(4), PFKM(3), PFKP(6), PGLS(2), PGM3(2), PRPS1L1(1), PRPS2(2), RPE(1), TAL1(1), TALDO1(1), TKT(2) 8108679 38 20 38 7 16 7 3 8 4 0 0.35 0.67 326 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 55 BMP5(3), BMP6(3), BTRC(1), CSNK1G1(2), CSNK1G2(1), DHH(1), FBXW11(2), GLI1(4), GLI2(8), GLI3(3), GSK3B(1), HHIP(4), LRP2(28), PRKACG(1), PRKX(2), PTCH1(6), PTCH2(2), SHH(2), SMO(2), STK36(2), SUFU(2), WNT10A(1), WNT11(1), WNT16(1), WNT2(5), WNT2B(1), WNT3(3), WNT3A(1), WNT4(3), WNT5A(1), WNT8A(1), WNT8B(3), WNT9A(3), WNT9B(4), ZIC2(1) 23802830 109 53 108 44 42 21 21 12 13 0 0.36 0.68 327 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 31 ABAT(2), ADC(2), ALDH4A1(1), ALDH5A1(2), CAD(6), CPS1(6), EARS2(2), EPRS(2), GAD1(4), GAD2(3), GCLC(1), GFPT1(5), GFPT2(2), GLS(3), GLUD2(4), GLUL(1), GMPS(1), GOT1(1), GSR(1), GSS(1), NADSYN1(4), NAGK(2), QARS(3) 15751750 59 32 59 13 14 9 15 17 3 1 0.36 0.68 328 PHENYLALANINE_TYROSINE_AND_TRYPTOPHAN_BIOSYNTHESIS ENO1, ENO2, ENO3, FARS2, FARSLB, GOT1, GOT2, PAH, TAT, YARS 9 ENO2(1), ENO3(2), GOT1(1), PAH(1), TAT(3), YARS(2) 3374325 10 9 10 4 4 2 2 2 0 0 0.36 0.68 329 HSA00471_D_GLUTAMINE_AND_D_GLUTAMATE_METABOLISM Genes involved in D-glutamine and D-glutamate metabolism GLS, GLS2, GLUD1, GLUD2 4 GLS(3), GLUD2(4) 1683449 7 5 7 2 3 0 3 0 1 0 0.36 0.68 330 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 67 ADCY1(8), ADCY8(4), ARAF(1), ATF4(1), BRAF(6), CACNA1C(5), CALM1(1), CAMK2B(1), CAMK2D(1), CAMK2G(4), CAMK4(1), CREBBP(8), EP300(5), GNAQ(1), GRIA1(4), GRIN1(3), GRIN2A(13), GRIN2B(4), GRIN2C(2), GRIN2D(2), GRM1(1), GRM5(1), ITPR1(7), ITPR2(11), ITPR3(11), KRAS(1), MAP2K1(1), MAP2K2(1), MAPK1(3), MAPK3(2), NRAS(1), PLCB1(3), PLCB2(5), PLCB3(5), PLCB4(3), PPP1CB(1), PPP1CC(1), PPP1R12A(2), PPP3CB(1), PPP3R1(1), PPP3R2(1), PRKACG(1), PRKCA(3), PRKCG(1), PRKX(2), RAP1B(2), RAPGEF3(1), RPS6KA2(2), RPS6KA3(5) 39543158 155 72 149 55 52 24 34 29 14 2 0.37 0.69 331 HSA00300_LYSINE_BIOSYNTHESIS Genes involved in lysine biosynthesis AADAT, AASDHPPT, AASS, KARS 4 AASS(3), KARS(4) 1930467 7 5 7 2 0 1 1 4 1 0 0.37 0.69 332 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(2), AGT(3), AGTR1(2), AGTR2(1), COL4A1(4), COL4A2(8), COL4A3(3), COL4A4(4), COL4A5(5), COL4A6(5), REN(2) 10340714 39 23 37 11 13 11 6 5 4 0 0.37 0.69 333 HSA00680_METHANE_METABOLISM Genes involved in methane metabolism ADH5, CAT, EPX, LPO, MPO, MTHFR, PRDX6, SHMT1, SHMT2, TPO 10 EPX(6), LPO(1), MPO(3), MTHFR(3), SHMT2(1), TPO(4) 4632196 18 13 18 9 12 0 2 1 3 0 0.38 0.69 334 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), CXCR3(2), ETV5(2), IFNG(1), IL12B(1), IL12RB1(4), IL12RB2(4), IL18R1(1), JAK2(4), MAPK14(1), STAT4(1), TYK2(3) 7214838 26 17 25 11 11 1 7 2 5 0 0.38 0.69 335 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(8), GNAS(3), GNB1(1), GNGT1(1) 2556429 13 10 13 4 7 1 3 1 1 0 0.38 0.69 336 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(2), PLCG1(3), PRKCA(3), PTK2B(1) 2728774 9 7 9 6 2 1 3 2 1 0 0.38 0.70 337 EICOSANOID_SYNTHESIS ALOX12, ALOX15, ALOX15B, ALOX5, ALOX5AP, DPEP1, GGT1, IPLA2(GAMMA), LTA4H, LTC4S, PLA2G2A, PLA2G6, PTGDS, PTGES, PTGIS, PTGS1, PTGS2, TBXAS1 17 ALOX15(2), ALOX15B(1), ALOX5(1), DPEP1(3), GGT1(2), LTA4H(1), PLA2G2A(5), PLA2G6(3), PTGIS(1), PTGS1(2), TBXAS1(3) 5851365 24 15 20 7 8 4 6 2 4 0 0.38 0.70 338 O_GLYCAN_BIOSYNTHESIS GALNT1, GALNT10, GALNT2, GALNT3, GALNT4, GALNT6, GALNT7, GALNT8, GALNT9, GCNT1, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, WBSCR17 14 GALNT1(3), GALNT10(3), GALNT2(4), GALNT6(3), GALNT7(1), GALNT8(3), GALNT9(3), ST3GAL1(2), WBSCR17(7) 5757903 29 15 29 14 15 4 6 1 3 0 0.39 0.70 339 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 CCR3(2), GNAQ(1), GNAS(3), GNB1(1), GNGT1(1), LIMK1(1), MAP2K1(1), MAPK1(3), MAPK3(2), MYL2(2), NOX1(2), PIK3C2G(9), PLCB1(3), PPP1R12B(6), PRKCA(3), PTK2(2), ROCK2(4) 10057245 46 20 46 10 12 7 12 11 3 1 0.39 0.70 340 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 ATP5O(1), ATP6AP1(2), ATP6V0A1(3), ATP6V0A4(5), ATP6V0D1(3), ATP6V1A(3), ATP6V1B1(1), ATP6V1B2(1), ATP6V1C1(2), ATP6V1C2(2), ATP6V1G1(2), ATP6V1G2(1), ATP6V1H(1) 6464244 27 16 27 8 9 6 8 1 3 0 0.39 0.70 341 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 10 ALDOA(1), CTSD(1), ESR1(3), GREB1(2), MTA1(4), MTA3(2), PDZK1(1), TUBA8(4) 4036321 18 10 18 7 7 2 5 1 3 0 0.39 0.71 342 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 CD28(1), CD3E(1), CD3G(1), IFNG(1), IL2(1), IL2RA(3), IL4(1), TGFB1(1), TGFB2(1), TGFBR1(1), TGFBR2(5), TGFBR3(2), TOB1(2), TOB2(1) 4320259 22 10 22 3 5 3 4 3 7 0 0.39 0.71 343 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 30 C1GALT1C1(3), GALNT1(3), GALNT10(3), GALNT11(1), GALNT12(1), GALNT13(1), GALNT14(2), GALNT2(4), GALNT5(1), GALNT6(3), GALNT7(1), GALNT8(3), GALNT9(3), GALNTL1(2), GALNTL2(2), GALNTL4(1), GALNTL5(3), GCNT3(2), GCNT4(1), OGT(3), ST3GAL1(2), ST6GALNAC1(2), WBSCR17(7) 12995770 54 29 54 22 27 5 9 3 10 0 0.39 0.71 344 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 DFFA(1), DFFB(3), GZMB(3), TOP2A(1), TOP2B(1) 3551959 9 8 9 2 2 0 2 3 2 0 0.40 0.72 345 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 CPS1(6), GLS(3), GOT1(1) 3019519 10 7 10 2 2 2 4 1 1 0 0.40 0.72 346 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), ME1(4), PC(3), PDHA1(1), SLC25A11(3) 3635305 13 9 13 5 3 1 4 4 1 0 0.40 0.72 347 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 36 ARSA(1), ARSD(1), ARSE(1), ASAH1(1), B4GALT6(1), CERK(1), ENPP7(3), GAL3ST1(2), GALC(2), GBA(1), GLA(1), GLB1(1), LCT(8), NEU1(1), NEU2(4), NEU4(4), PPAP2C(1), SGMS1(1), SGMS2(1), SMPD3(1), SPHK1(1), SPHK2(2), SPTLC1(2), SPTLC2(1), UGCG(1), UGT8(2) 13885751 46 30 47 18 16 8 6 5 10 1 0.41 0.72 348 IFNGPATHWAY IFN gamma signaling pathway IFNG, IFNGR1, IFNGR2, JAK1, JAK2, STAT1 6 IFNG(1), IFNGR1(1), IFNGR2(1), JAK1(3), JAK2(4), STAT1(1) 3343293 11 8 10 0 6 0 1 2 2 0 0.41 0.73 349 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 91 ACTB(1), BCL2(3), CABIN1(12), CALM1(1), CAMK2B(1), CAMK4(1), CD3E(1), CD3G(1), CDKN1A(1), CNR1(2), CREBBP(8), CSNK2A1(3), EGR2(3), EGR3(4), EP300(5), FCER1A(3), FCGR3A(1), FOS(1), GATA3(2), GATA4(2), GRLF1(4), GSK3B(1), IFNB1(1), IFNG(1), IL2(1), IL2RA(3), IL4(1), IL6(2), ITK(3), KPNA5(1), MAP2K7(1), MAPK14(1), MAPK9(2), MEF2A(1), MEF2D(1), MYF5(1), NFAT5(3), NFATC1(3), NFATC2(1), NFATC3(1), NFATC4(2), NFKB2(1), NFKBIB(1), NFKBIE(1), NUP214(3), P2RX7(2), PAK1(2), PPP3CB(1), PPP3R1(1), PTPRC(4), SLA(1), SP1(6), SP3(1), TGFB1(1), TRAF2(2), TRPV6(7), VAV1(6), VAV2(3), VAV3(2), XPO5(1) 35624234 137 62 137 39 36 21 33 23 23 1 0.42 0.74 350 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 26 ALDOA(1), ALDOB(1), ALDOC(3), DERA(2), FBP1(2), FBP2(4), G6PD(2), GPI(4), PFKM(3), PFKP(6), PGLS(2), PGM3(2), PRPS1L1(1), PRPS2(2), RPE(1), TALDO1(1), TKT(2), TKTL1(2), TKTL2(2) 9580655 43 22 43 7 18 6 6 8 5 0 0.42 0.74 351 HEME_BIOSYNTHESIS ALAD, ALAS1, ALAS2, CPOX, FECH, HMBS, PPOX, UROD, UROS 9 ALAS1(2), ALAS2(1), CPOX(1), FECH(3), HMBS(1), PPOX(2), UROD(1), UROS(1) 3096938 12 8 12 1 2 1 3 3 3 0 0.42 0.74 352 ACETYLCHOLINE_SYNTHESIS ACHE, CHAT, CHKA, PCYT1A, PDHA1, PDHA2, PEMT, SLC18A3 8 CHAT(3), CHKA(1), PCYT1A(1), PDHA1(1), PDHA2(3) 2740861 9 8 9 4 5 0 0 1 3 0 0.42 0.74 353 BIOSYNTHESIS_OF_STEROIDS DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, IDI1, LSS, MVD, MVK, NQO1, NQO2, PMVK, SC5DL, SQLE, VKORC1 14 DHCR7(4), FDPS(2), HMGCR(1), LSS(1), MVD(1), MVK(1), NQO2(1), PMVK(1), SC5DL(2), SQLE(1) 4352042 15 10 14 1 6 0 3 3 3 0 0.43 0.74 354 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(5), AMY2B(1), ASCC3(4), ATP13A2(8), DDX18(1), DDX23(3), DDX4(1), DDX41(1), DDX47(2), DDX54(1), DDX56(2), DHX58(2), ENPP3(1), EP400(15), ERCC2(1), ERCC3(2), G6PC(2), GAA(3), GANC(1), GBA(1), GBE1(1), GCK(2), GPI(4), GUSB(3), GYS2(3), HK2(3), HK3(4), IFIH1(2), MGAM(7), MOV10L1(2), PGM3(2), PYGB(4), PYGL(1), PYGM(2), RAD54B(3), RAD54L(2), RUVBL2(4), SETX(4), SI(3), SKIV2L2(1), SMARCA2(5), SMARCA5(2), TREH(2), UGP2(1), UGT1A1(1), UGT1A10(1), UGT1A3(1), UGT1A5(2), UGT1A6(2), UGT1A9(1), UGT2A1(5), UGT2A3(3), UGT2B10(1), UGT2B11(3), UGT2B17(1), UGT2B28(5), UGT2B4(5), UGT2B7(3), UXS1(1) 48283018 159 79 156 56 56 23 34 28 18 0 0.43 0.74 355 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 42 ACACA(8), ACACB(9), ACOT12(1), ACSS2(2), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH9A1(1), DLAT(1), DLD(1), GRHPR(1), LDHA(2), LDHAL6A(2), LDHAL6B(1), LDHC(1), LDHD(1), MDH2(1), ME1(4), ME2(2), ME3(3), PC(3), PCK1(4), PCK2(1), PDHA1(1), PDHA2(3), PDHB(1), PKLR(4) 18815701 65 37 65 20 22 6 16 13 8 0 0.43 0.74 356 HSA00400_PHENYLALANINE_TYROSINE_AND_TRYPTOPHAN_BIOSYNTHESIS Genes involved in phenylalanine, tyrosine and tryptophan biosynthesis FARS2, FARSA, FARSB, GOT1, GOT2, PAH, TAT, YARS, YARS2 9 FARSA(1), FARSB(1), GOT1(1), PAH(1), TAT(3), YARS(2), YARS2(2) 3538569 11 9 11 2 2 4 3 2 0 0 0.43 0.74 357 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 53 AANAT(1), ABP1(9), ACMSD(1), ALDH1A1(4), ALDH1A2(3), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH9A1(1), AOC2(2), AOC3(2), AOX1(7), CYP19A1(3), CYP1A1(1), CYP2A13(2), CYP2A6(1), CYP2B6(2), CYP2C18(1), CYP2C8(2), CYP2C9(2), CYP2D6(3), CYP2E1(4), CYP3A4(3), CYP3A7(3), CYP4B1(3), CYP4F8(1), CYP51A1(1), DDC(1), ECHS1(1), EHHADH(2), HAAO(1), HADHA(1), KYNU(3), MAOB(1), SDS(4), TDO2(2), TPH1(3) 21968333 88 44 86 22 36 13 20 14 5 0 0.43 0.75 358 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), BIRC2(1), BIRC3(1), DFFA(1), DFFB(3), GZMB(3), PRF1(3), SCAP(5), SREBF1(2), SREBF2(3) 7117067 23 16 23 9 8 1 4 4 6 0 0.44 0.75 359 HSA00430_TAURINE_AND_HYPOTAURINE_METABOLISM Genes involved in taurine and hypotaurine metabolism BAAT, CDO1, CSAD, GAD1, GAD2, GGT1, GGTL3, GGTL4 6 BAAT(1), CSAD(2), GAD1(4), GAD2(3), GGT1(2) 2278836 12 6 12 2 4 3 2 3 0 0 0.44 0.76 360 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(2), ACP6(2), ACPT(3), ENPP3(1), LHPP(1), MTMR1(2), MTMR2(3), RFK(1), TYR(5) 6011045 20 12 20 5 4 4 4 6 2 0 0.44 0.76 361 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 24 ABAT(2), ALDH4A1(1), ALDH5A1(2), CAD(6), CPS1(6), EPRS(2), GAD1(4), GAD2(3), GCLC(1), GFPT1(5), GLS(3), GLUL(1), GMPS(1), GOT1(1), GSS(1), NADSYN1(4), QARS(3) 13204749 46 26 46 9 10 9 11 13 3 0 0.45 0.76 362 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 39 AGL(5), AMY2B(1), ENPP3(1), G6PC(2), GAA(3), GBE1(1), GCK(2), GPI(4), GUSB(3), GYS2(3), HK2(3), HK3(4), MGAM(7), PGM3(2), PYGB(4), PYGL(1), PYGM(2), SI(3), UCHL1(1), UGT1A1(1), UGT1A10(1), UGT1A3(1), UGT1A5(2), UGT1A6(2), UGT1A9(1), UGT2B4(5), UXS1(1) 21856473 66 42 64 30 30 8 12 9 7 0 0.45 0.76 363 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 27 ABP1(9), ALDH1A3(1), ALDH3A1(3), ALDH3B1(2), ALDH3B2(1), AOC2(2), AOC3(2), DDC(1), EPX(6), ESCO1(2), GOT1(1), HPD(1), LPO(1), MAOB(1), MPO(3), MYST3(4), MYST4(4), PNPLA3(1), SH3GLB1(2), TAT(3), TPO(4) 13787304 54 32 55 11 25 7 5 11 6 0 0.45 0.76 364 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 ACTG2(2), ACTR3(2), AKT1(1), ANGPTL2(2), CFL2(1), FLNA(14), FLNC(6), FSCN3(2), LIMK1(1), MYH2(13), MYLK(7), MYLK2(1), PAK1(2), PAK3(2), PAK6(1), PAK7(3), RHO(1), ROCK1(3), ROCK2(4), RPS4X(1), VASP(2), WASF1(1) 18440072 72 39 72 23 29 8 16 9 10 0 0.46 0.77 365 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 12 CDK5R1(1), EGR1(2), MAP2K1(1), MAP2K2(1), MAPK1(3), MAPK3(2), NGFR(1) 3196853 11 8 11 2 4 1 2 3 1 0 0.46 0.77 366 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 C1QB(1), C1R(1), C1S(1), C2(2), C3(8), C5(1), C6(3), C7(6), C8A(3), C9(1), MASP1(2), MBL2(1) 8383457 30 18 29 23 9 3 8 7 2 1 0.46 0.77 367 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 25 APC(7), ASAH1(1), CERK(1), CREB3(1), CREB5(1), DAG1(2), EPHB2(6), FOS(1), GNAQ(1), ITPKB(2), MAP2K7(1), MAPK1(3), MAPK8IP1(3), MAPK8IP2(3), MAPK8IP3(5), MAPK9(2) 11048405 40 24 40 11 12 4 10 9 5 0 0.46 0.77 368 BETAOXIDATIONPATHWAY Beta-Oxidation of Fatty Acids ACADL, ACADM, ACADS, ACAT1, ECHS1, HADHA 6 ACADM(2), ACADS(4), ECHS1(1), HADHA(1) 2142674 8 6 9 2 3 1 2 1 1 0 0.46 0.77 369 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 11 ALAS1(2), ALAS2(1), CPO(3), FECH(3), GATA1(1), HMBS(1), UROD(1), UROS(1) 3207720 13 7 13 2 2 3 2 4 2 0 0.46 0.77 370 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 21 BCL2(3), MAP2K1(1), MAP3K1(5), MAPK1(3), MAPK3(2), NFKB1(1), NSMAF(3), RIPK1(1), TNFRSF1A(2), TRAF2(2) 8274482 23 18 23 7 5 4 4 5 5 0 0.47 0.78 371 MITOCHONDRIAL_FATTY_ACID_BETAOXIDATION ACADL, ACADM, ACADS, ACADVL, ACSL1, ACSL3, ACSL4, CPT1A, CPT2, DCI, EHHADH, HADHA, HADHSC, MGC5139, PECR, SCP2, SLC25A20 15 ACADM(2), ACADS(4), ACADVL(3), ACSL3(3), ACSL4(2), CPT1A(1), CPT2(1), EHHADH(2), HADHA(1), PECR(1) 6771058 20 14 21 4 6 3 4 5 2 0 0.48 0.79 372 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 ANXA2(1), ANXA4(1), ANXA5(1), CYP11A1(1), EDNRA(1), EDNRB(1), HPGD(1), HSD11B1(2), PLA2G4A(4), PRL(3), PTGDR(1), PTGER2(2), PTGER4(2), PTGFR(2), PTGIR(1), PTGIS(1), PTGS1(2), SCGB1A1(1), TBXAS1(3) 8177226 31 16 31 9 9 6 3 8 4 1 0.48 0.79 373 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 ACTG2(2), ADCY3(3), ADCY9(5), AK1(1), ARF4(1), ARL4D(1), ATP6V0A1(3), ATP6V0A2(1), ATP6V0A4(5), ATP6V0D1(3), ATP6V0D2(1), ATP6V1A(3), ATP6V1C1(2), ATP6V1C2(2), ATP6V1G1(2), ATP6V1G2(1), ATP6V1H(1), GNAS(3), PLCG1(3), PLCG2(11), PRKCA(3), SEC61A1(1), TRIM23(1) 14879216 59 32 59 22 24 11 12 5 7 0 0.48 0.79 374 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), BCL2(3), BID(4), CASP8AP2(3), CES1(2) 4143460 13 9 10 0 2 1 3 5 2 0 0.49 0.80 375 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(8), ADRB2(1), CFTR(7), GNAS(3), PRKACG(1), PRKAR2A(1), PRKAR2B(1) 5000185 22 13 22 6 11 3 4 2 2 0 0.49 0.80 376 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(2), ARHGDIB(4), CASP1(4), GZMB(3), PRF1(3) 5217895 17 11 17 7 3 4 2 4 4 0 0.49 0.80 377 TERPENOID_BIOSYNTHESIS FDFT1, FDPS, FDPS, LOC402397, IDI1, SQLE 4 FDPS(2), SQLE(1) 1248932 3 3 3 0 1 0 0 2 0 0 0.49 0.81 378 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 6 ASAH1(1), DAG1(2), GNAQ(1), ITPKB(2) 2334197 6 6 6 1 2 0 0 2 2 0 0.50 0.81 379 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 30 ABP1(9), ACY1(1), ADC(2), AGMAT(1), ALDH18A1(1), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH9A1(1), AMD1(1), AOC2(2), AOC3(2), ARG2(2), CPS1(6), GATM(2), MAOB(1), ODC1(1), OTC(2), SAT1(1), SAT2(1) 11918551 43 25 43 9 13 10 8 12 0 0 0.51 0.82 380 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 63 ACSS2(2), ADH1A(4), ADH1B(3), ADH1C(3), ADH6(2), ADH7(1), AKR1A1(1), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH3B1(2), ALDH3B2(1), ALDH9A1(1), ALDOA(1), ALDOB(1), ALDOC(3), BPGM(1), DLAT(1), DLD(1), ENO2(1), ENO3(2), FBP1(2), FBP2(4), G6PC(2), GALM(1), GAPDH(1), GAPDHS(2), GCK(2), GPI(4), HK2(3), HK3(4), LDHA(2), LDHAL6A(2), LDHAL6B(1), LDHC(1), PDHA1(1), PDHA2(3), PDHB(1), PFKM(3), PFKP(6), PGK2(3), PGM3(2), PKLR(4) 22858971 92 46 92 21 41 12 15 16 8 0 0.51 0.83 381 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 AACS(2), AADAC(1), ABAT(2), ACADS(4), ACSM1(3), AKR1B10(2), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH5A1(2), ALDH9A1(1), DDHD1(1), ECHS1(1), EHHADH(2), GAD1(4), GAD2(3), HADHA(1), HMGCL(1), HMGCS1(1), HMGCS2(3), HSD17B10(1), HSD17B4(1), L2HGDH(1), OXCT1(1), PDHA1(1), PDHA2(3), PDHB(1), PLA1A(1), RDH13(1) 16399088 52 32 53 20 18 7 10 9 8 0 0.52 0.83 382 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), IFNG(1), IL12B(1), IL16(4), IL2(1), IL4(1), IL6(2) 3964825 11 8 11 5 2 1 2 4 2 0 0.52 0.83 383 VALINE_LEUCINE_AND_ISOLEUCINE_BIOSYNTHESIS BCAT1, IARS, LARS, LARS2, PDHA1, PDHA2, PDHB 7 BCAT1(1), IARS(4), LARS(3), LARS2(1), PDHA1(1), PDHA2(3), PDHB(1) 4061066 14 9 14 4 5 4 1 0 4 0 0.52 0.84 384 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(8), CPT1A(1), LEPR(1), PRKAA2(1), PRKAG1(2), PRKAG2(5) 5919449 18 12 18 3 8 1 5 1 3 0 0.53 0.85 385 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 CYP27B1(3), CYP51A1(1), DHCR24(3), DHCR7(4), FDPS(2), GGCX(1), HMGCR(1), HSD17B7(1), IDI2(1), LSS(1), MVD(1), MVK(1), PMVK(1), SC5DL(2), SQLE(1), TM7SF2(2) 7681268 26 16 25 7 8 2 7 3 6 0 0.53 0.85 386 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 CALM1(1), CCL2(2), FOS(1), GNAQ(1), MAPK14(1), PLCG1(3), PRKCA(3), PTK2B(1), SYT1(1) 5281234 14 11 14 9 3 2 2 6 1 0 0.53 0.85 387 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 A4GALT(4), B3GALNT1(1), B3GALT5(2), FUT1(1), FUT9(1), GBGT1(2), GLA(1), HEXA(1), ST3GAL1(2) 4233734 15 11 16 9 5 1 4 2 3 0 0.54 0.85 388 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 32 AKR1B10(2), B4GALT2(1), G6PC(2), GAA(3), GALE(2), GALK1(3), GALK2(5), GALT(1), GANC(1), GCK(2), GLA(1), GLB1(1), HK2(3), HK3(4), LCT(8), MGAM(7), PFKM(3), PFKP(6), PGM3(2), RDH13(1), UGP2(1) 15097310 59 32 55 14 30 5 11 8 5 0 0.54 0.85 389 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(3), IL22RA1(1), JAK1(3), JAK2(4), JAK3(4), STAT1(1), STAT3(2), STAT5A(2), STAT5B(2), TYK2(3) 7302229 26 16 24 6 12 2 6 5 1 0 0.54 0.86 390 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(2), ACACA(8), ACACB(9), ACADM(2), ACSS2(2), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH6A1(2), ALDH9A1(1), ECHS1(1), EHHADH(2), HADHA(1), LDHA(2), LDHAL6A(2), LDHAL6B(1), LDHC(1), MLYCD(1), MUT(2), PCCA(1), PCCB(2), SUCLA2(1), SUCLG1(2) 16123336 52 29 52 13 16 7 13 8 8 0 0.55 0.86 391 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 15 CHUK(4), MAP3K14(2), MAPK14(1), NFKB1(1), TNFRSF13B(2), TNFSF13B(2), TRAF2(2), TRAF3(3), TRAF5(1) 5745691 18 12 17 6 4 0 4 7 3 0 0.55 0.86 392 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(2), CHIA(2), CHIT1(1), CMAS(1), CTBS(3), GFPT1(5), GFPT2(2), GNE(3), GNPDA1(1), HEXA(1), HK2(3), HK3(4), LHPP(1), MTMR1(2), MTMR2(3), NAGK(2), NPL(3), PGM3(2), UAP1(1) 11395607 42 23 39 9 12 3 12 8 6 1 0.55 0.87 393 STREPTOMYCIN_BIOSYNTHESIS GCK, HK1, HK2, HK3, IMPA1, PGM1, PGM3, TGDS 8 GCK(2), HK2(3), HK3(4), IMPA1(1), PGM3(2), TGDS(1) 4066968 13 10 12 1 7 1 2 3 0 0 0.55 0.87 394 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 18 ATF2(1), CHUK(4), IFNG(1), IKBKB(2), IL2(1), IL4(1), MAP3K1(5), MAP3K5(1), MAPK14(1), NFKB1(1), NFKBIA(2), TNFSF9(3), TRAF2(2) 7816794 25 15 24 13 8 2 3 7 5 0 0.56 0.87 395 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 13 ACAA1(1), ACOX1(2), ACOX3(1), ELOVL2(2), ELOVL5(1), FADS1(1), FADS2(1), FASN(7), HADHA(1), PECR(1), SCD(2) 5319808 20 12 20 3 6 3 4 4 3 0 0.56 0.88 396 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(5), CR2(6), HLA-DRA(1), HLA-DRB1(2), ITGAL(4), ITGB2(5), PTPRC(4) 5799042 27 11 26 13 6 6 7 1 7 0 0.58 0.89 397 1_2_DICHLOROETHANE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A1(4), ALDH1A2(3), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH9A1(1) 3235255 15 8 15 3 5 5 3 2 0 0 0.58 0.89 398 ASCORBATE_AND_ALDARATE_METABOLISM ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A1(4), ALDH1A2(3), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH9A1(1) 3235255 15 8 15 3 5 5 3 2 0 0 0.58 0.89 399 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(8), GNAS(3), GNB1(1), GNGT1(1), PPP2CA(1), PRKAA2(1), PRKACG(1), PRKAG1(2), PRKAG2(5), PRKAR2A(1), PRKAR2B(1) 5958974 25 15 25 6 12 1 6 4 2 0 0.58 0.89 400 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 ALG3(2), ALG5(1), B4GALT2(1), DDOST(2), DPAGT1(1), FUT8(1), MAN1A1(3), MGAT1(1), MGAT2(2), MGAT3(3), MGAT4A(2), RPN1(1), ST6GAL1(4) 7750835 24 15 24 5 6 5 3 5 5 0 0.58 0.89 401 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 BLVRA(1), BLVRB(1), HMOX1(2), IL10RA(1), IL6(2), JAK1(3), STAT1(1), STAT3(2), STAT5A(2) 4931464 15 10 15 4 4 2 2 3 4 0 0.58 0.89 402 NUCLEOTIDE_METABOLISM ADSL, ADSS, DHFR, HPRT1, IMPDH1, MTHFD2, NME2, OAZ1, POLA, POLB, POLD1, POLG, PRPS2, RRM1, SAT, SRM 14 DHFR(1), IMPDH1(2), OAZ1(1), POLD1(3), POLG(4), PRPS2(2), RRM1(2) 4959256 15 10 14 6 4 2 3 3 3 0 0.58 0.89 403 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 24 ATF2(1), BCR(1), BLNK(2), ELK1(1), FOS(1), LYN(1), MAP2K1(1), MAP3K1(5), MAPK1(3), MAPK3(2), MAPK8IP3(5), PAPPA(6), RPS6KA3(5), SOS1(1), SYK(2), VAV1(6), VAV2(3), VAV3(2) 12633746 48 26 48 14 18 9 9 8 4 0 0.59 0.90 404 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 43 ALDOA(1), ALDOB(1), ALDOC(3), DLAT(1), DLD(1), ENO2(1), ENO3(2), FBP1(2), FBP2(4), G6PC(2), GAPDH(1), GAPDHS(2), GCK(2), GOT1(1), GPI(4), HK2(3), HK3(4), LDHA(2), LDHAL6B(1), LDHC(1), MDH2(1), PC(3), PCK1(4), PDHA1(1), PDHA2(3), PDHB(1), PFKM(3), PFKP(6), PGK2(3), PKLR(4) 16619362 68 32 67 20 26 11 11 13 7 0 0.59 0.90 405 HSA00031_INOSITOL_METABOLISM Genes involved in inositol metabolism ALDH6A1, TPI1 2 ALDH6A1(2) 653274 2 2 2 0 0 1 1 0 0 0 0.60 0.91 406 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 CALM1(1), CAMK1(2), CAMK2B(1), CAMK2D(1), CAMK2G(4), CAMK4(1), ESRRA(2), HDAC5(4), MEF2A(1), MEF2C(1), MEF2D(1), PPARA(1), PPP3CB(1), SLC2A4(3), SYT1(1) 8008658 25 16 25 7 4 4 6 7 4 0 0.60 0.91 407 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 58 ATP12A(5), ATP5O(1), ATP6AP1(2), ATP6V0A1(3), ATP6V0A4(5), ATP6V0D1(3), ATP6V1A(3), ATP6V1B1(1), ATP6V1B2(1), ATP6V1C1(2), ATP6V1C2(2), ATP6V1G1(2), ATP6V1G2(1), ATP6V1H(1), ATP7B(3), COX10(1), COX8A(1), NDUFA10(2), NDUFA4(2), NDUFA8(1), NDUFB7(1), NDUFS2(1), NDUFV1(2), NDUFV2(2), PPA2(1), UQCRC1(3) 14093507 52 28 53 15 14 11 13 7 7 0 0.60 0.92 408 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(8), CALM1(1), ELK1(1), FOS(1), GNAQ(1), GNAS(3), GNB1(1), GNGT1(1), MAP2K1(1), MAPK3(2), NFATC1(3), NFATC2(1), NFATC3(1), NFATC4(2), PLCG1(3), PPP3CB(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PRKCA(3), RPS6KA3(5), SYT1(1) 13613042 43 27 43 15 12 6 8 12 5 0 0.61 0.92 409 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), GTF2B(2), GTF2E1(1), GTF2F1(1), HDAC3(1), NCOA1(3), NCOA2(1), NCOA3(4), NCOR2(5), POLR2A(2), RARA(5), RXRA(3), TBP(2) 9687615 32 19 30 8 8 2 9 6 7 0 0.61 0.92 410 NUCLEOTIDE_SUGARS_METABOLISM GALE, GALT, TGDS, UGDH, UXS1 5 GALE(2), GALT(1), TGDS(1), UXS1(1) 1560555 5 3 5 0 2 2 0 1 0 0 0.61 0.92 411 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 CCL5(1), CCR3(2), HLA-DRA(1), HLA-DRB1(2) 1233437 6 3 6 0 0 3 0 2 1 0 0.62 0.92 412 RIBOFLAVIN_METABOLISM ACP1, ACP2, ACP5, ACPP, ACPT, ENPP1, ENPP3, FLAD1, RFK, TYR 10 ACP5(2), ACPT(3), ENPP3(1), RFK(1), TYR(5) 3874593 12 7 12 4 2 2 2 5 1 0 0.63 0.93 413 BOTULINPATHWAY Blockade of Neurotransmitter Relase by Botulinum Toxin CHRM1, CHRNA1, SNAP25, STX1A, VAMP2 5 SNAP25(2), VAMP2(1) 1301392 3 3 3 1 2 0 0 0 1 0 0.63 0.93 414 SULFUR_METABOLISM BPNT1, PAPSS1, PAPSS2, SULT1A2, SULT1A3, SULT1A3, SULT1A4, SULT1E1, SULT2A1, SUOX 7 BPNT1(1), PAPSS2(1), SULT1E1(1), SULT2A1(1), SUOX(4) 2470997 8 5 8 5 2 1 1 3 1 0 0.63 0.93 415 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 10 ANPEP(3), CKM(1), EIF4E(2), FBL(1), LDHA(2), LDHC(1), MAPK14(1), NCL(3) 3536753 14 7 14 3 4 1 1 5 3 0 0.63 0.93 416 HSA00902_MONOTERPENOID_BIOSYNTHESIS Genes involved in monoterpenoid biosynthesis CYP2C19, CYP2C9 2 CYP2C9(2) 827895 2 2 2 2 1 0 1 0 0 0 0.63 0.93 417 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 CYP2E1(4), NR1I3(2), PTGS1(2) 2149083 8 5 8 5 3 0 3 1 1 0 0.63 0.93 418 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 87 ACVR1(3), ACVR1C(2), ACVR2A(5), ACVR2B(1), ACVRL1(2), AMHR2(3), BMP5(3), BMP6(3), BMPR1A(2), BMPR1B(1), BMPR2(2), CDKN2B(1), COMP(1), CREBBP(8), CUL1(5), DCN(2), EP300(5), FST(2), GDF5(2), GDF6(1), GDF7(1), ID1(1), IFNG(1), INHBA(3), INHBB(2), INHBE(1), LEFTY1(5), LEFTY2(2), LTBP1(1), MAPK1(3), MAPK3(2), PPP2CA(1), PPP2R1A(1), PPP2R1B(3), PPP2R2A(1), PPP2R2B(1), PPP2R2C(1), RBL1(3), RBL2(1), RHOA(1), ROCK1(3), ROCK2(4), RPS6KB1(1), SMAD3(1), SMAD4(1), SMAD7(1), SMAD9(1), SMURF1(6), SP1(6), TGFB1(1), TGFB2(1), TGFBR1(1), TGFBR2(5), THBS1(3), THBS2(5), THBS3(1), THBS4(2), ZFYVE16(2), ZFYVE9(2) 39416944 136 63 133 36 32 27 31 27 18 1 0.63 0.93 419 METHANE_METABOLISM ADH5, ATP6V0C, SHMT1, CAT, EPX, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, SHMT1, SHMT2, TPO 13 EPX(6), LPO(1), MPO(3), PRDX2(2), SHMT2(1), TPO(4) 4676705 17 11 17 9 11 0 2 1 3 0 0.64 0.94 420 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), ADH1A(4), ADH1B(3), ADH1C(3), ADH6(2), ADH7(1), AKR1C4(2), ALDH1A1(4), ALDH1A2(3), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH9A1(1), BAAT(1), CEL(3), CYP27A1(1), SOAT2(2) 9397592 38 19 38 9 16 10 8 4 0 0 0.64 0.94 421 BENZOATE_DEGRADATION_VIA_COA_LIGATION ACAT1, ACAT2, ACYP1, ACYP2, ECHS1, EHHADH, GCDH, HADHA, SDHB, SDS 10 ECHS1(1), EHHADH(2), HADHA(1), SDS(4) 3135228 8 6 8 4 0 3 1 1 3 0 0.65 0.94 422 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(4), CARM1(1), CREBBP(8), EP300(5), ERCC3(2), ESR1(3), GRIP1(6), GTF2E1(1), GTF2F1(1), HDAC1(1), HDAC2(3), HDAC3(1), HDAC4(1), HDAC5(4), HDAC6(3), MEF2C(1), NCOR2(5), NRIP1(3), PELP1(2), POLR2A(2), TBP(2) 18281204 59 34 59 14 19 7 18 6 8 1 0.65 0.95 423 CREMPATHWAY The transcription factor CREM activates a post-meiotic transcriptional cascade culminating in spermatogenesis. ADCY1, CREM, FHL5, FSHB, FSHR, GNAS, XPO1 7 ADCY1(8), FSHR(1), GNAS(3), XPO1(2) 3767123 14 10 14 3 8 1 3 1 1 0 0.65 0.95 424 LYSINE_BIOSYNTHESIS AADAT, AASDH, AASDHPPT, AASS, KARS 5 AASDH(2), AASS(3), KARS(4) 2839594 9 5 9 3 0 2 1 4 2 0 0.65 0.95 425 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 43 CBL(1), CD28(1), DAG1(2), EPHB2(6), FBXW7(2), GRAP2(1), ITK(3), ITPKB(2), MAPK1(3), NFAT5(3), NFKB1(1), NFKB2(1), NFKBIA(2), NFKBIB(1), NFKBIE(1), NFKBIL1(1), NFKBIL2(6), PAK1(2), PAK3(2), PAK6(1), PAK7(3), PLCG1(3), PTPRC(4), RASGRP1(1), RASGRP2(2), RASGRP3(2), RASGRP4(3), SOS1(1), SOS2(4), VAV1(6), ZAP70(5) 21669826 76 39 76 28 25 11 13 15 12 0 0.66 0.95 426 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 21 APAF1(1), ARHGDIB(4), BIRC2(1), BIRC3(1), CASP1(4), CASP2(1), CASP4(1), CASP6(1), DFFA(1), DFFB(3), GZMB(3), LMNB1(1), LMNB2(3), PRF1(3) 7723788 28 16 28 7 4 5 5 8 6 0 0.67 0.96 427 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(2), FOS(1), MAPK14(1), THBS1(3) 2982491 7 6 7 4 1 2 0 3 1 0 0.67 0.96 428 HSA00780_BIOTIN_METABOLISM Genes involved in biotin metabolism BTD, HLCS, SPCS1, SPCS3 4 BTD(2), HLCS(2) 1249454 4 3 4 2 1 1 0 0 2 0 0.67 0.96 429 FATTY_ACID_BIOSYNTHESIS_PATH_2 ACAA1, ACAA2, ACAT1, ACAT2, ECHS1, EHHADH, HADHA, HADHB, SDS 9 ACAA1(1), ECHS1(1), EHHADH(2), HADHA(1), SDS(4) 3366834 9 6 9 3 1 3 1 1 3 0 0.67 0.96 430 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), ACADM(2), ACADS(4), ACADSB(1), ALDH1A1(4), ALDH1A2(3), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH6A1(2), ALDH9A1(1), AOX1(7), BCAT1(1), BCKDHA(2), BCKDHB(1), ECHS1(1), EHHADH(2), HADHA(1), HIBADH(1), HMGCL(1), MCCC1(1), MCCC2(1), MUT(2), OXCT1(1), PCCA(1), PCCB(2), SDS(4) 14547809 54 27 53 15 17 12 11 7 7 0 0.67 0.96 431 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(7), CDH1(3), CREBBP(8), EP300(5), MAP2K1(1), MAP3K7(2), MAPK3(2), SKIL(2), TGFB1(1), TGFB2(1), TGFBR1(1), TGFBR2(5) 10432659 38 18 38 9 9 6 11 6 5 1 0.67 0.96 432 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), BCL2(3), BID(4), BIRC2(1), BIRC3(1), CASP6(1), DFFA(1), DFFB(3), DIABLO(1) 5449727 16 12 13 2 3 0 5 7 1 0 0.67 0.96 433 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(4), MMP2(1), MMP9(2), RECK(1), TIMP3(2) 3004129 10 7 10 1 5 1 2 1 1 0 0.68 0.96 434 HSA00900_TERPENOID_BIOSYNTHESIS Genes involved in terpenoid biosynthesis FDFT1, FDPS, GGPS1, IDI1, IDI2, SQLE 6 FDPS(2), IDI2(1), SQLE(1) 1690221 4 3 4 0 1 0 0 2 1 0 0.68 0.96 435 STEROID_BIOSYNTHESIS CYP17A1, F13B, HSD17B1, HSD17B2, HSD17B3, HSD17B4, HSD17B7, HSD3B1, HSD3B2 9 CYP17A1(1), F13B(2), HSD17B3(1), HSD17B4(1), HSD17B7(1), HSD3B2(2) 3278617 8 6 8 6 2 0 4 0 2 0 0.68 0.96 436 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 21 AARS(3), ABAT(2), AGXT2(2), ASNS(1), CAD(6), GAD1(4), GAD2(3), GOT1(1), NARS(1), PC(3) 10342147 26 19 26 13 5 5 7 6 3 0 0.68 0.96 437 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 34 GOSR2(2), SNAP23(1), SNAP25(2), SNAP29(1), STX11(1), STX19(1), STX2(1), STX3(1), STX4(1), STX5(2), STX7(1), STX8(1), TSNARE1(2), USE1(1), VAMP2(1), VAMP5(1) 6371131 20 12 20 7 6 3 1 5 5 0 0.69 0.97 438 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_NEOLACTOSERIES ABO, B3GNT1, FUT1, FUT2, FUT9, GCNT2, ST8SIA1 7 ABO(2), B3GNT1(2), FUT1(1), FUT9(1), GCNT2(1) 2428650 7 5 7 3 3 1 1 1 1 0 0.69 0.97 439 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 60 A4GALT(4), ABO(2), B3GALNT1(1), B3GALT2(1), B3GALT5(2), B3GNT1(2), B3GNT2(3), B3GNT3(1), B3GNT4(2), B3GNT5(1), B4GALNT1(4), B4GALT2(1), B4GALT4(1), B4GALT6(1), FUT1(1), FUT5(2), FUT6(2), FUT7(5), FUT9(1), GBGT1(2), GCNT2(1), PIGA(1), PIGG(3), PIGH(1), PIGK(3), PIGM(1), PIGO(6), PIGQ(3), PIGS(1), PIGT(1), PIGV(2), ST3GAL1(2), ST3GAL3(1), ST3GAL6(2), ST6GALNAC3(4), ST6GALNAC5(2), ST6GALNAC6(1), UGCG(1) 19100973 75 37 72 19 22 8 26 14 5 0 0.69 0.97 440 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), LCMT1(1), PCYT1A(1), PCYT1B(2), PRMT6(5), PRMT7(2), PRMT8(1) 5565883 13 11 9 5 3 0 8 1 1 0 0.70 0.98 441 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 15 ACTA1(1), APAF1(1), BCL2(3), DAXX(4), MAPKAPK2(1), MAPKAPK3(1) 4559228 11 9 11 4 2 1 4 2 2 0 0.70 0.98 442 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 28 CALM1(1), GNAQ(1), MAP2K1(1), MAP2K2(1), MAP2K3(1), MAP3K1(5), MAPK1(3), MAPK14(1), MAPK3(2), PAK1(2), PLCG1(3), PRKCA(3), PTK2B(1), SOS1(1), SRC(2), SYT1(1) 11397828 29 20 29 13 6 5 4 10 4 0 0.71 0.98 443 CHOLESTEROL_BIOSYNTHESIS C10orf110, CYP51A1, DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, HMGCS1, IDI1, LSS, MVD, MVK, NSDHL, PMVK, SC4MOL, SC5DL, SQLE 15 CYP51A1(1), DHCR7(4), FDPS(2), HMGCR(1), HMGCS1(1), LSS(1), MVD(1), MVK(1), PMVK(1), SC5DL(2), SQLE(1) 5222852 16 9 15 3 5 0 5 3 3 0 0.71 0.98 444 HSA00521_STREPTOMYCIN_BIOSYNTHESIS Genes involved in streptomycin biosynthesis GCK, HK1, HK2, HK3, IMPA1, IMPA2, ISYNA1, PGM1, PGM3, TGDS 10 GCK(2), HK2(3), HK3(4), IMPA1(1), PGM3(2), TGDS(1) 4578927 13 10 12 2 7 1 2 3 0 0 0.71 0.98 445 HSA03060_PROTEIN_EXPORT Genes involved in protein export OXA1L, SEC61A2, SRP19, SRP54, SRP68, SRP72, SRP9, SRPR 8 OXA1L(1), SRP54(1), SRPR(4) 3024644 6 5 6 2 2 0 2 0 2 0 0.72 0.99 446 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 19 EXT2(5), EXTL1(1), EXTL2(2), EXTL3(4), HS2ST1(2), HS3ST1(1), HS3ST3A1(3), HS3ST5(2), HS6ST2(3), HS6ST3(3), NDST1(2), NDST2(2), NDST3(2), NDST4(5) 8299249 37 17 37 7 10 5 10 5 7 0 0.72 0.99 447 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 30 GTF2B(2), GTF2E1(1), GTF2E2(1), GTF2F1(1), GTF2H4(1), GTF2IRD1(2), TAF1(4), TAF1L(14), TAF2(2), TAF4(2), TAF4B(1), TAF5(2), TAF6(3), TAF6L(2), TAF7(2), TAF7L(2), TAF9(1), TBPL2(2) 14193225 45 22 43 14 13 4 14 6 8 0 0.72 0.99 448 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(1), IARS(4), IARS2(1), LARS(3), LARS2(1), PDHA1(1), PDHA2(3), PDHB(1), VARS(3), VARS2(5) 7433431 23 14 23 7 7 4 3 4 5 0 0.73 0.99 449 CHONDROITIN B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 8 B4GALT7(1), HS3ST1(1), HS3ST3A1(3), XYLT1(3), XYLT2(1) 2558268 9 7 9 1 5 1 2 1 0 0 0.73 0.99 450 HEPARAN_SULFATE_BIOSYNTHESIS B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 8 B4GALT7(1), HS3ST1(1), HS3ST3A1(3), XYLT1(3), XYLT2(1) 2558268 9 7 9 1 5 1 2 1 0 0 0.73 0.99 451 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 67 FAU(1), MRPS7(1), RPL10L(1), RPL11(1), RPL14(1), RPL18A(2), RPL22L1(1), RPL3(1), RPL31(1), RPL32(1), RPL35A(1), RPL36A(1), RPL36AL(1), RPL39(1), RPL8(1), RPS10(2), RPS12(1), RPS2(1), RPS25(1), RPS28(1), RPS3(1), RPS3A(2), RPS4Y1(1), RPS5(2), RPSA(1) 8850132 29 18 28 11 9 4 6 4 6 0 0.73 0.99 452 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(2), BTK(1), CALM1(1), ELK1(1), FOS(1), LYN(1), MAP2K1(1), MAP3K1(5), MAPK14(1), MAPK3(2), NFATC1(3), NFATC2(1), NFATC3(1), NFATC4(2), PLCG1(3), PPP3CB(1), PRKCA(3), SOS1(1), SYK(2), SYT1(1), VAV1(6) 15272232 40 26 40 23 9 7 8 11 5 0 0.73 0.99 453 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), ABCG2(2), BCHE(3), CES1(2), CES2(1), CYP3A4(3), UGT1A1(1), UGT1A10(1), UGT1A3(1), UGT1A5(2), UGT1A6(2), UGT1A9(1) 9335101 25 17 25 16 7 5 4 4 5 0 0.73 0.99 454 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(1), ASPH(2), EP300(5), EPO(1), HIF1A(1), LDHA(2), NOS3(5), VHL(1) 6659170 18 11 18 9 4 0 5 6 2 1 0.73 0.99 455 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 22 CHUK(4), CREBBP(8), EP300(5), IKBKB(2), MAP2K3(1), MAP3K14(2), MAP3K7(2), MAPK14(1), NFKB1(1), NFKBIA(2), NR3C1(1), TGFBR1(1), TGFBR2(5), TLR2(4) 11876729 39 20 38 13 6 7 10 9 6 1 0.73 0.99 456 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(2), ASNS(1), CA1(1), CA12(2), CA3(1), CA5A(3), CA5B(1), CA6(1), CA7(2), CA8(2), CPS1(6), CTH(1), GLS(3), GLUD2(4), GLUL(1), HAL(2) 8479240 33 16 33 7 14 4 7 4 4 0 0.73 0.99 457 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 24 ATM(7), BMPR1B(1), CCND2(1), CDKN1B(3), EGR1(2), ESR2(1), FSHR(1), LHCGR(1), MSH5(3), NCOR1(5), NR5A1(1), NRIP1(3), PGR(4), PTGER2(2), VDR(2), ZP2(2) 14056328 39 23 39 12 11 5 12 4 6 1 0.74 0.99 458 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 57 APC(7), AXIN1(2), CCND2(1), DVL2(2), FZD1(1), FZD10(4), FZD2(1), FZD3(4), FZD5(2), FZD6(2), FZD7(1), FZD8(1), FZD9(6), GSK3B(1), LDLR(4), MAPK9(2), PLAU(2), PRKCA(3), PRKCD(5), PRKCE(1), PRKCG(1), PRKCH(2), PRKCI(1), PRKCQ(1), PRKCZ(2), PRKD1(3), RHOA(1), TCF7(3), WNT10A(1), WNT11(1), WNT16(1), WNT2(5), WNT2B(1), WNT3(3), WNT4(3), WNT5A(1) 23140736 82 43 79 26 27 7 18 14 16 0 0.74 0.99 459 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 15 CHUK(4), CREBBP(8), EP300(5), HDAC3(1), IKBKB(2), NFKB1(1), NFKBIA(2), RIPK1(1), TNFRSF1A(2), TNFRSF1B(2) 9036928 28 15 27 12 4 4 9 6 4 1 0.74 0.99 460 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(2), ACO2(1), AFMID(3), GRHPR(1), HAO1(1), HAO2(2), HYI(2), MDH2(1), MTHFD1L(1) 5436982 14 11 14 7 7 1 4 2 0 0 0.74 0.99 461 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 29 BRAF(6), CREB3(1), CREB5(1), DUSP4(3), DUSP9(1), EEF2K(2), EIF4E(2), MAP2K1(1), MAP2K2(1), MAPK1(3), MAPK3(2), MKNK1(1), NFKB1(1), RPS6KA2(2), RPS6KA3(5), SOS1(1), SOS2(4), TRAF3(3) 11863709 40 21 36 10 11 4 7 15 3 0 0.74 0.99 462 HSA00520_NUCLEOTIDE_SUGARS_METABOLISM Genes involved in nucleotide sugars metabolism GALE, GALT, TGDS, UGDH, UGP2, UXS1 6 GALE(2), GALT(1), TGDS(1), UGP2(1), UXS1(1) 1991565 6 3 6 0 2 2 1 1 0 0 0.75 1.00 463 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(1), ACTB(1), ARHGEF2(6), ARPC5L(1), CD14(2), CDH1(3), CTTN(1), EZR(3), HCLS1(5), KRT18(3), LY96(1), NCL(3), OCLN(1), PRKCA(3), RHOA(1), ROCK1(3), ROCK2(4), TLR4(1), TLR5(4), TUBA1A(2), TUBA1C(1), TUBA3C(3), TUBA4A(1), TUBA8(4), TUBB1(1), TUBB2A(1), TUBB2C(1), TUBB3(1), TUBB4(2), TUBB4Q(4), TUBB8(1) 20832705 69 38 65 27 21 9 14 19 6 0 0.75 1.00 464 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(1), ACTB(1), ARHGEF2(6), ARPC5L(1), CD14(2), CDH1(3), CTTN(1), EZR(3), HCLS1(5), KRT18(3), LY96(1), NCL(3), OCLN(1), PRKCA(3), RHOA(1), ROCK1(3), ROCK2(4), TLR4(1), TLR5(4), TUBA1A(2), TUBA1C(1), TUBA3C(3), TUBA4A(1), TUBA8(4), TUBB1(1), TUBB2A(1), TUBB2C(1), TUBB3(1), TUBB4(2), TUBB4Q(4), TUBB8(1) 20832705 69 38 65 27 21 9 14 19 6 0 0.75 1.00 465 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), ABP1(9), AOC2(2), AOC3(2), CES1(2), DDHD1(1), ESCO1(2), MYST3(4), MYST4(4), PLA1A(1), PNPLA3(1), SH3GLB1(2) 10220356 31 19 31 6 11 5 5 6 4 0 0.76 1.00 466 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(2), ASNS(1), CA1(1), CA12(2), CA3(1), CA5A(3), CA5B(1), CA6(1), CA7(2), CA8(2), CPS1(6), CTH(1), GLS(3), GLUL(1), HAL(2) 7581930 29 14 29 6 12 4 5 4 4 0 0.76 1.00 467 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(8), ADRB2(1), GNAS(3), PLCE1(7), PRKACG(1), PRKAR2A(1), PRKAR2B(1) 5703176 22 12 22 3 9 3 4 3 3 0 0.76 1.00 468 SMALL_LIGAND_GPCRS C9orf47, CNR1, CNR2, DNMT1, EDG1, EDG2, EDG5, EDG6, MTNR1A, MTNR1B, PTAFR, PTGDR, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, TBXA2R 13 CNR1(2), CNR2(3), DNMT1(5), PTAFR(2), PTGDR(1), PTGER2(2), PTGER4(2), PTGFR(2), PTGIR(1) 4337739 20 9 20 8 6 2 1 8 3 0 0.76 1.00 469 HSA00791_ATRAZINE_DEGRADATION Genes involved in atrazine degradation ADAR, APOBEC1, APOBEC2, APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3F, APOBEC3G, APOBEC4 9 ADAR(1), APOBEC1(2), APOBEC3B(1), APOBEC3F(2), APOBEC3G(1) 2977124 7 5 7 2 3 1 2 0 1 0 0.76 1.00 470 HSA00053_ASCORBATE_AND_ALDARATE_METABOLISM Genes involved in ascorbate and aldarate metabolism ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, MIOX, UGDH 9 ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH9A1(1), MIOX(1) 3423771 9 7 9 3 4 1 2 2 0 0 0.76 1.00 471 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 SLPI(1) 661770 1 1 1 1 1 0 0 0 0 0 0.76 1.00 472 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 22 BTK(1), DLG4(2), EPHB2(6), F2(1), F2RL3(1), MAP2K5(1), MAPK1(3), MAPK7(3), PLD2(1), PTK2(2), RASAL1(3), SRC(2), TEC(5), VAV1(6) 10846676 37 21 37 12 12 8 9 6 2 0 0.77 1.00 473 HYPERTROPHY_MODEL ADAM10, ANKRD1, ATF3, CYR61, DUSP14, EIF4E, EIF4EBP1, GDF8, HBEGF, IFNG, IFRD1, IL18, IL1A, IL1R1, JUND, MYOG, NR4A3, TCF8, VEGF, WDR1 17 ADAM10(2), DUSP14(1), EIF4E(2), IFNG(1), IL1R1(2), NR4A3(1), WDR1(2) 4340112 11 7 11 6 1 2 0 5 3 0 0.77 1.00 474 GLOBOSIDE_METABOLISM A4GALT, FUT1, FUT2, FUT9, GBGT1, GLA, HEXA, HEXB, NAGA, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, ST8SIA1 13 A4GALT(4), FUT1(1), FUT9(1), GBGT1(2), GLA(1), HEXA(1), ST3GAL1(2) 3976029 12 9 13 9 5 1 2 1 3 0 0.77 1.00 475 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 29 ATG12(1), ATG5(1), GABARAPL1(1), IFNA13(1), IFNA14(1), IFNA17(1), IFNA21(1), IFNA5(1), IFNA7(2), IFNG(1), PIK3C3(1), PIK3R4(2), PRKAA2(1), ULK1(1), ULK2(6), ULK3(1) 8181741 23 13 23 5 4 2 7 5 5 0 0.77 1.00 476 HSA00730_THIAMINE_METABOLISM Genes involved in thiamine metabolism LHPP, MTMR1, MTMR2, MTMR6, NFS1, PHPT1, THTPA, TPK1 8 LHPP(1), MTMR1(2), MTMR2(3), THTPA(1) 2569519 7 4 7 1 2 1 2 1 1 0 0.78 1.00 477 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 39 ATF2(1), DAXX(4), DDIT3(1), ELK1(1), HMGN1(1), MAP3K1(5), MAP3K5(1), MAP3K7(2), MAP3K9(2), MAPK14(1), MAPKAPK2(1), MAX(2), MEF2A(1), MEF2C(1), MEF2D(1), MKNK1(1), PLA2G4A(4), RIPK1(1), STAT1(1), TGFB1(1), TGFB2(1), TGFBR1(1), TRAF2(2) 14709253 37 23 37 8 10 6 5 10 5 1 0.78 1.00 478 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 ECHS1(1), HADHA(1), HSD17B10(1), HSD17B4(1), MECR(2) 3446007 6 5 6 1 1 1 0 2 2 0 0.78 1.00 479 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 21 ACAD8(1), ADH1A(4), ADH1B(3), ADH1C(3), ADH6(2), ADH7(1), DHRS7(1), ESCO1(2), MYST3(4), MYST4(4), PNPLA3(1), SH3GLB1(2) 9862884 28 17 28 6 10 3 6 5 4 0 0.78 1.00 480 GLYOXYLATE_AND_DICARBOXYLATE_METABOLISM ACO1, ACO2, CS, GRHPR, HAO1, HAO2, HYI, MDH1, MDH2, MTHFD1, MTHFD1L, MTHFD2 12 ACO1(2), ACO2(1), GRHPR(1), HAO1(1), HAO2(2), HYI(2), MDH2(1), MTHFD1L(1) 5187062 11 10 11 7 5 1 4 1 0 0 0.78 1.00 481 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 42 CDC7(2), CDT1(1), DIAPH2(3), MCM10(1), MCM2(3), MCM3(3), MCM4(3), MCM5(1), MCM6(1), MCM7(2), NACA(7), PCNA(1), POLA2(3), POLD1(3), POLD4(1), POLE(4), POLE2(2), PRIM1(1), RFC1(3), RFC2(1), RFC3(1), RFC4(2), RFC5(1), RPA4(2), UBA52(1), UBB(1), UBC(1) 20051853 55 32 52 22 15 3 15 5 17 0 0.79 1.00 482 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(1), CDKN1A(1), EPO(1), EPOR(1), GRIN1(3), HIF1A(1), JAK2(4), NFKB1(1), NFKBIA(2) 4989920 15 9 13 3 6 2 3 3 1 0 0.79 1.00 483 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), ACADM(2), ACOX1(2), ACOX3(1), ACSL3(3), ACSL4(2), ACSL5(2), ACSL6(4), APOA2(1), APOA5(1), AQP7(2), CD36(2), CPT1A(1), CPT1C(2), CPT2(1), CYP27A1(1), CYP4A11(3), CYP4A22(4), CYP8B1(2), EHHADH(2), FADS2(1), GK(1), GK2(2), HMGCS2(3), ILK(2), ME1(4), NR1H3(1), OLR1(3), PCK1(4), PCK2(1), PLTP(1), PPARA(1), RXRA(3), RXRB(1), RXRG(1), SCD(2), SLC27A1(3), SLC27A2(7), SLC27A4(2), SLC27A6(4), SORBS1(2), UBC(1), UCP1(1) 25986066 90 44 88 31 25 12 15 21 17 0 0.79 1.00 484 HSA00550_PEPTIDOGLYCAN_BIOSYNTHESIS Genes involved in peptidoglycan biosynthesis GLUL, PGLYRP2 2 GLUL(1) 738713 1 1 1 0 1 0 0 0 0 0 0.79 1.00 485 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(2), ARHGEF1(2), GNA12(2), GNAQ(1), GNB1(1), GNGT1(1), MYL2(2), MYLK(7), PLCB1(3), PPP1R12B(6), PRKCA(3), ROCK1(3) 8359857 33 14 33 9 10 3 10 6 3 1 0.80 1.00 486 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 57 AANAT(1), ABP1(9), ACMSD(1), AFMID(3), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH9A1(1), AOC2(2), AOC3(2), AOX1(7), CARM1(1), CYP1A1(1), CYP1B1(4), DDC(1), ECHS1(1), EHHADH(2), HAAO(1), HADHA(1), HSD17B10(1), HSD17B4(1), INMT(1), KYNU(3), LCMT1(1), MAOB(1), NFX1(3), OGDH(1), OGDHL(5), PRMT6(5), PRMT7(2), PRMT8(1), TDO2(2), TPH1(3) 24107439 75 42 69 25 33 8 17 12 5 0 0.80 1.00 487 SA_FAS_SIGNALING The TNF-type receptor Fas induces apoptosis on ligand binding. BCL2, CASP3, CASP8, CFL1, CFLAR, P11, PDE6D, TNFRSF6, TNFSF6 6 BCL2(3), PDE6D(1) 1564927 4 3 4 1 0 1 2 0 1 0 0.80 1.00 488 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 33 AARS(3), AARS2(3), ABAT(2), ACY3(1), ADSSL1(1), AGXT2(2), ASNS(1), CAD(6), DLAT(1), DLD(1), GAD1(4), GAD2(3), GOT1(1), NARS(1), NARS2(1), PC(3), PDHA1(1), PDHA2(3), PDHB(1) 15040466 39 25 39 20 12 8 8 6 5 0 0.80 1.00 489 HSA00660_C5_BRANCHED_DIBASIC_ACID_METABOLISM Genes involved in C5-branched dibasic acid metabolism ILVBL, SUCLA2 2 SUCLA2(1) 851992 1 1 1 2 0 1 0 0 0 0 0.80 1.00 490 GLYCOSAMINOGLYCAN_DEGRADATION ARSB, GALNS, GLB1, GNS, GUSB, HEXA, HEXB, IDS, IDUA, LCT, NAGLU 11 ARSB(2), GALNS(1), GLB1(1), GUSB(3), HEXA(1), LCT(8), NAGLU(1) 5692197 17 10 17 7 7 0 3 3 4 0 0.80 1.00 491 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(5), CAPNS1(1), CDK5R1(1), GSK3B(1), MAPT(1), PPP2CA(1) 3492849 12 6 12 2 5 1 3 3 0 0 0.80 1.00 492 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 24 CASP2(1), CHUK(4), CRADD(1), IKBKB(2), MAP2K3(1), MAP3K1(5), MAP3K14(2), MAP4K2(1), MAPK14(1), NFKB1(1), NFKBIA(2), RIPK1(1), TNFRSF1A(2), TRAF2(2) 9608353 26 17 26 16 6 3 5 7 5 0 0.80 1.00 493 DNA_POLYMERASE POLA, POLB, POLD1, POLD2, POLE, POLG, POLL, POLQ, POLS 7 POLD1(3), POLE(4), POLG(4), POLL(2), POLQ(7) 6680545 20 11 19 10 4 4 5 3 3 1 0.80 1.00 494 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 21 F2(1), F2RL3(1), GNB1(1), GNGT1(1), ITGA1(1), MAP2K1(1), MAPK1(3), MAPK3(2), PLA2G4A(4), PLCB1(3), PRKCA(3), PTGS1(2), PTK2(2), SRC(2), SYK(2), TBXAS1(3) 9811189 32 16 32 8 11 5 5 7 2 2 0.81 1.00 495 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 14 CSF2RB(4), FOS(1), JAK2(4), MAP2K1(1), MAPK3(2), PTPN6(4), SOS1(1), STAT5A(2), STAT5B(2) 6718112 21 12 20 4 11 1 5 3 1 0 0.82 1.00 496 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(3), POLA2(3), POLD1(3), POLD4(1), POLE(4), POLE2(2), POLE3(2), POLG(4), POLH(2), POLI(2), POLK(1), POLL(2), POLM(1), POLQ(7), PRIM1(1), PRIM2(5), REV1(1), REV3L(6), RFC5(1) 16489008 51 24 46 17 11 7 15 7 10 1 0.82 1.00 497 PANTOTHENATE_AND_COA_BIOSYNTHESIS BCAT1, COASY, DPYD, DPYS, ENPP1, ENPP3, PANK1, PANK2, PANK3, PANK4, PPCS, UPB1 12 BCAT1(1), DPYD(2), DPYS(2), ENPP3(1), PANK3(1), PANK4(2), PPCS(1), UPB1(1) 5466314 11 8 11 6 2 2 2 3 2 0 0.82 1.00 498 CYSTEINE_METABOLISM CARS, CTH, GOT1, GOT2, LDHA, LDHB, LDHC, MPST 8 CTH(1), GOT1(1), LDHA(2), LDHC(1), MPST(1) 2737319 6 4 6 1 1 1 2 1 1 0 0.82 1.00 499 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 21 APC(7), AXIN1(2), BTRC(1), CREBBP(8), CSNK2A1(3), CTBP1(3), FZD1(1), GSK3B(1), HDAC1(1), MAP3K7(2), PPP2CA(1), TLE1(6), WIF1(2) 11291036 38 19 38 10 11 4 8 9 6 0 0.82 1.00 500 NOTCHPATHWAY Proteolysis and Signaling Pathway of Notch ADAM17, DLL1, FURIN, NOTCH1, PSEN1, RBPSUH 5 FURIN(1), NOTCH1(4) 3187804 5 5 3 2 0 0 0 5 0 0 0.82 1.00 501 HSA00643_STYRENE_DEGRADATION Genes involved in styrene degradation FAH, GSTZ1, HGD 2 FAH(1) 530101 1 1 1 1 0 1 0 0 0 0 0.83 1.00 502 HSA05050_DENTATORUBROPALLIDOLUYSIAN_ATROPHY Genes involved in dentatorubropallidoluysian atrophy (DRPLA) ATN1, BAIAP2, CASP1, CASP3, CASP7, CASP8, GAPDH, INS, INSR, ITCH, MAGI1, MAGI2, RERE, WWP1, WWP2 15 ATN1(2), CASP1(4), GAPDH(1), INSR(5), ITCH(1), MAGI1(2), MAGI2(4), RERE(5), WWP2(2) 9532109 26 17 26 13 9 6 2 6 3 0 0.83 1.00 503 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 10 BAG4(1), BIRC3(1), RIPK1(1), TNFRSF1A(2), TNFRSF1B(2), TRAF2(2) 3357368 9 6 9 6 3 2 2 2 0 0 0.83 1.00 504 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(3), SNCAIP(2), UBE2E2(2), UBE2L3(1) 2567484 8 4 8 2 2 0 2 2 2 0 0.83 1.00 505 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(2), ACAA1(1), ACADM(2), ACADS(4), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH6A1(2), ALDH9A1(1), AOX1(7), BCAT1(1), BCKDHA(2), BCKDHB(1), DBT(1), DLD(1), ECHS1(1), EHHADH(2), HADHA(1), HIBADH(1), HMGCL(1), HMGCS1(1), HMGCS2(3), HSD17B10(1), HSD17B4(1), MCCC1(1), MCCC2(1), MUT(2), OXCT1(1), PCCA(1), PCCB(2) 17450125 52 28 51 14 20 7 10 7 8 0 0.83 1.00 506 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 16 GATA3(2), IL4(1), MAP2K3(1), MAPK14(1), NFATC1(3), NFATC2(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1) 4513284 12 8 12 9 2 0 1 5 4 0 0.83 1.00 507 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(3), DYRK1B(1), GLI2(8), GLI3(3), GSK3B(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1), SHH(2), SMO(2), SUFU(2) 6443477 25 12 24 16 6 8 4 5 2 0 0.84 1.00 508 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 69 ACACB(9), ACSL3(3), ACSL4(2), ACSL5(2), ACSL6(4), AKT1(1), AKT2(1), AKT3(1), CAMKK1(3), CAMKK2(1), CD36(2), CHUK(4), CPT1A(1), CPT1C(2), CPT2(1), G6PC(2), IKBKB(2), IRS1(4), IRS4(3), JAK1(3), JAK2(4), JAK3(4), LEPR(1), MAPK9(2), NFKB1(1), NFKB2(1), NFKBIA(2), NFKBIB(1), NFKBIE(1), PCK1(4), PCK2(1), PPARA(1), PPARGC1A(2), PRKAA2(1), PRKAG1(2), PRKAG2(5), PRKAG3(3), PRKCQ(1), PTPN11(6), RXRA(3), RXRB(1), RXRG(1), SLC2A1(4), SLC2A4(3), STAT3(2), TNFRSF1A(2), TNFRSF1B(2), TRAF2(2), TYK2(3) 32767225 117 54 113 39 42 14 23 19 19 0 0.84 1.00 509 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 ALDH4A1(1), GLS(3), OAT(1), PRODH(1) 2059879 6 3 6 1 2 0 1 1 2 0 0.84 1.00 510 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(3), CBS(1), CTH(1), DNMT1(5), DNMT3A(3), DNMT3B(3), MARS(1), MAT1A(2), MTAP(1), MTFMT(1), MTR(2), TAT(3) 8300658 28 16 28 9 11 9 2 3 3 0 0.84 1.00 511 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 19 CAMK2B(1), CAMK2D(1), CAMK2G(4), DAG1(2), ITPKB(2), ITPR1(7), ITPR2(11), ITPR3(11), NFAT5(3), PDE6A(4), PDE6B(7), PDE6C(1), PDE6D(1), SLC6A13(2) 14093721 57 26 57 15 20 9 11 9 8 0 0.84 1.00 512 SYNTHESIS_AND_DEGRADATION_OF_KETONE_BODIES ACAT1, ACAT2, BDH, HMGCL, OXCT1 4 HMGCL(1), OXCT1(1) 1377947 2 2 2 0 0 0 1 1 0 0 0.85 1.00 513 AMINOSUGARS_METABOLISM CMAS, CYB5R3, GCK, GFPT1, GNE, GNPDA1, GNPDA2, HEXA, HEXB, HK1, HK2, HK3, PGM3, RENBP, UAP1 15 CMAS(1), GCK(2), GFPT1(5), GNE(3), GNPDA1(1), HEXA(1), HK2(3), HK3(4), PGM3(2), UAP1(1) 6734770 23 12 22 3 10 2 4 4 3 0 0.85 1.00 514 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 27 BAG4(1), BIRC2(1), BIRC3(1), MAP3K3(4), MAP3K7(2), NFKB1(1), NFKB2(1), NFKBIA(2), NFKBIB(1), NFKBIE(1), NFKBIL1(1), NFKBIL2(6), RALBP1(3), RIPK1(1), TNFAIP3(1), TNFRSF1A(2), TNFRSF1B(2), TRAF2(2) 10653196 33 17 33 16 10 5 5 8 5 0 0.85 1.00 515 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 93 ANK2(8), CDR1(2), DGKI(3), FAU(1), PIGK(3), RPL10(1), RPL11(1), RPL14(1), RPL15(1), RPL18A(2), RPL3(1), RPL31(1), RPL32(1), RPL35A(1), RPL39(1), RPL5(2), RPL8(1), RPLP0(2), RPS10(2), RPS12(1), RPS2(1), RPS25(1), RPS28(1), RPS3(1), RPS3A(2), RPS4X(1), RPS4Y1(1), RPS5(2), RPS6KA2(2), RPS6KA3(5), RPS6KB1(1), RPSA(1), TBC1D10C(2), TSPAN9(1), UBA52(1), UBB(1), UBC(1) 20833415 61 34 60 25 20 10 14 5 12 0 0.86 1.00 516 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 90 AKT1(1), AKT3(1), CAPN1(5), CAPN10(2), CAPN11(1), CAPN2(1), CAPN3(2), CAPN5(1), CAPN6(5), CAPNS1(1), CAV1(1), CAV3(1), DOCK1(9), GIT2(2), ILK(2), ITGA10(3), ITGA11(2), ITGA2(4), ITGA2B(2), ITGA3(2), ITGA4(7), ITGA5(1), ITGA6(2), ITGA7(3), ITGA8(7), ITGA9(1), ITGAD(7), ITGAE(3), ITGAL(4), ITGAM(8), ITGAV(1), ITGAX(7), ITGB2(5), ITGB3(1), ITGB4(5), ITGB5(2), ITGB6(5), ITGB7(2), ITGB8(3), MAP2K1(1), MAP2K2(1), MAP2K3(1), MAPK6(1), MAPK7(3), MYLK2(1), PAK1(2), PAK3(2), PAK6(1), PIK3R2(5), PTK2(2), PXN(1), RAP1B(2), RHO(1), ROCK1(3), ROCK2(4), SEPP1(1), SHC3(1), SORBS1(2), SOS1(1), SRC(2), TLN1(6), TNS1(5), VASP(2), VAV2(3), VAV3(2), VCL(2), ZYX(2) 52505328 182 77 181 71 69 23 38 27 25 0 0.86 1.00 517 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(3), ASH2L(1), CARM1(1), CTCFL(3), EED(2), EHMT1(3), EHMT2(2), EZH1(2), EZH2(2), FBXO11(3), HCFC1(3), HSF4(1), JMJD4(2), KDM6A(2), MEN1(2), MLL(3), MLL2(7), MLL3(12), MLL4(7), MLL5(3), NSD1(7), OGT(3), PPP1CB(1), PPP1CC(1), PRDM2(2), PRDM7(1), PRDM9(8), PRMT6(5), PRMT7(2), PRMT8(1), RBBP5(3), SETD1A(1), SETD2(9), SETD7(2), SETD8(1), SETDB2(3), SMYD3(1), SUV39H2(3), SUV420H1(1), SUV420H2(3), SUZ12(1), WHSC1(4), WHSC1L1(7) 46933904 134 64 129 39 27 21 38 23 25 0 0.86 1.00 518 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 34 AKT1(1), AKT2(1), AKT3(1), ARHGEF11(3), BCL2(3), DLG4(2), LPA(6), MAP3K1(5), MAP3K5(1), NFKB1(1), NFKB2(1), NFKBIA(2), NFKBIB(1), NFKBIE(1), NFKBIL1(1), NFKBIL2(6), PHKA2(4), PIK3CB(2), PLD2(1), PTK2(2), ROCK1(3), ROCK2(4), SRF(2) 19326712 54 30 54 20 16 11 10 7 10 0 0.86 1.00 519 KERATAN_SULFATE_BIOSYNTHESIS B3GNT1, B4GALT1, B4GALT2, B4GALT3, B4GALT5, FUT8, SIAT4A, SIAT4B, SIAT6, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4 10 B3GNT1(2), B4GALT2(1), FUT8(1), ST3GAL1(2), ST3GAL3(1) 3137179 7 5 7 1 2 2 2 0 1 0 0.87 1.00 520 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 ALDOA(1), ALDOB(1), ALDOC(3), FBP1(2), FBP2(4), FPGT(1), GCK(2), GMDS(1), GMPPA(1), HK2(3), HK3(4), MPI(1), PFKFB1(2), PFKFB3(1), PFKFB4(2), PFKM(3), PFKP(6), PMM1(1) 9558665 39 18 38 5 17 5 7 9 1 0 0.87 1.00 521 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(3), ELK1(1), EPO(1), EPOR(1), FOS(1), JAK2(4), MAP2K1(1), MAPK3(2), PLCG1(3), PTPN6(4), SOS1(1), STAT5A(2), STAT5B(2) 8596885 26 15 25 7 13 2 6 3 2 0 0.87 1.00 522 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 GPD2(1), UQCRC1(3) 2672895 4 4 4 4 0 2 0 1 1 0 0.87 1.00 523 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 37 EEF1A2(2), EEF1D(4), EEF2(4), EEF2K(2), EIF2AK1(2), EIF2AK2(1), EIF2AK3(1), EIF2B2(2), EIF2B3(1), EIF2B4(1), EIF2S2(1), EIF2S3(3), EIF4A1(4), EIF4E(2), EIF4G1(2), EIF4G3(1), EIF5A(1), EIF5B(3), ETF1(1), GSPT2(1), KIAA0664(4), PABPC3(2) 17275881 45 23 44 13 10 5 7 17 6 0 0.87 1.00 524 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 111 ATP12A(5), ATP4A(5), ATP5B(2), ATP5C1(1), ATP5G2(1), ATP5H(1), ATP5I(1), ATP5O(1), ATP6AP1(2), ATP6V0A1(3), ATP6V0A2(1), ATP6V0A4(5), ATP6V0D1(3), ATP6V0D2(1), ATP6V1A(3), ATP6V1B1(1), ATP6V1B2(1), ATP6V1C1(2), ATP6V1C2(2), ATP6V1G1(2), ATP6V1G2(1), ATP6V1H(1), COX10(1), COX15(1), COX7B2(1), COX8A(1), CYC1(1), LHPP(1), NDUFA10(2), NDUFA3(1), NDUFA4(2), NDUFA4L2(1), NDUFA8(1), NDUFB1(1), NDUFB7(1), NDUFS2(1), NDUFS4(1), NDUFS7(1), NDUFV1(2), NDUFV2(2), PPA1(1), PPA2(1), TCIRG1(2), UQCRC1(3), UQCRC2(1), UQCRQ(2) 22312708 77 37 78 25 23 16 20 10 8 0 0.88 1.00 525 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 37 AGT(3), AGTR2(1), CALM1(1), CAMK2B(1), CAMK2D(1), CAMK2G(4), F2(1), GNA11(2), GNB1(1), GNGT1(1), JAK2(4), MAP2K1(1), MAP2K2(1), MAPK1(3), MAPK14(1), MAPK3(2), MAPT(1), MYLK(7), PLCG1(3), PRKCA(3), PTK2B(1), SOS1(1), STAT1(1), STAT3(2), STAT5A(2), SYT1(1) 16725683 50 29 49 20 15 6 11 14 4 0 0.88 1.00 526 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 16 ALDH1L1(3), AMT(2), ATIC(1), DHFR(1), FTCD(3), GART(3), MTFMT(1), MTHFD1L(1), MTHFR(3), MTR(2), SHMT2(1) 7607519 21 12 21 9 5 4 5 3 4 0 0.88 1.00 527 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(8), EP300(5), NCOA1(3), NCOA2(1), RXRA(3) 7314514 20 11 21 5 3 4 7 2 3 1 0.88 1.00 528 HSA00920_SULFUR_METABOLISM Genes involved in sulfur metabolism BPNT1, CHST11, CHST12, CHST13, PAPSS1, PAPSS2, SULT1A1, SULT1A2, SULT1A3, SULT1A4, SULT1E1, SULT2A1, SULT2B1, SUOX 12 BPNT1(1), CHST11(1), CHST12(1), CHST13(1), PAPSS2(1), SULT1E1(1), SULT2A1(1), SUOX(4) 3705994 11 6 11 5 4 1 2 3 1 0 0.88 1.00 529 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_LACTOSERIES ABO, FUT1, FUT2, FUT3, FUT5, FUT6, SIAT6, ST3GAL3 7 ABO(2), FUT1(1), FUT5(2), FUT6(2), ST3GAL3(1) 1913974 8 3 8 5 5 1 1 1 0 0 0.89 1.00 530 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 39 ANAPC1(4), ANAPC10(2), ANAPC11(1), ANAPC2(1), ANAPC4(2), ANAPC5(2), BTRC(1), CDC20(2), CDC23(1), CDC27(3), CUL1(5), CUL2(4), CUL3(1), FBXW11(2), FBXW7(2), ITCH(1), SMURF1(6), TCEB2(1), UBE2E2(2), VHL(1), WWP2(2) 16014634 46 23 47 10 11 4 9 12 10 0 0.89 1.00 531 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), NFKBIA(2), PLCB1(3), PRKCA(3) 3347164 10 4 10 5 2 1 2 3 1 1 0.89 1.00 532 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 ADRB1(1), AKT1(1), APC(7), ASAH1(1), CAV3(1), DAG1(2), DLG4(2), EPHB2(6), GNAQ(1), ITPR1(7), ITPR2(11), ITPR3(11), KCNJ3(2), KCNJ5(3), MAPK1(3), RHO(1), RYR1(14) 18204668 74 32 74 23 30 13 13 13 5 0 0.90 1.00 533 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 PSMA1(1), PSMA3(2), PSMA5(1), PSMB1(1), PSMB4(1), PSMC3(1), PSMD14(1), RPN1(1), UBE2A(1), UBE3A(4) 5186159 14 6 14 3 1 2 3 5 2 1 0.91 1.00 534 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 32 APAF1(1), BCL2(3), BID(4), BIRC2(1), BIRC3(1), CASP6(1), CHUK(4), DFFA(1), DFFB(3), GAS2(1), MAP3K14(2), NFKB1(1), NFKBIA(2), RIPK1(1), SPTAN1(6), TNFRSF10A(2), TNFRSF25(1), TNFSF10(5), TRAF2(2) 13385023 42 22 39 13 8 1 14 15 4 0 0.91 1.00 535 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 RANBP1(1), RANBP2(1), RANGAP1(1) 3294692 3 3 3 2 1 0 1 1 0 0 0.91 1.00 536 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), CLOCK(1), CRY1(3), CRY2(2), PER1(3) 3359241 10 5 10 4 2 1 3 1 3 0 0.91 1.00 537 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(3), ALG10B(4), ALG12(1), ALG3(2), ALG5(1), ALG8(1), ALG9(1), B4GALT2(1), DDOST(2), DOLPP1(1), DPAGT1(1), FUT8(1), MAN1A1(3), MAN1A2(1), MAN1C1(1), MAN2A1(2), MGAT1(1), MGAT2(2), MGAT3(3), MGAT4A(2), MGAT5B(4), RFT1(1), RPN1(1), ST6GAL1(4) 16795454 44 24 44 15 13 7 8 10 6 0 0.91 1.00 538 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 11 APC(7), AXIN1(2), BTRC(1), FZD1(1), GSK3B(1), NOTCH1(4) 7699463 16 11 14 8 3 0 4 8 1 0 0.91 1.00 539 FOSBPATHWAY FOSB gene expression and drug abuse CDK5, FOSB, GRIA2, JUND, PPP1R1B 5 FOSB(2) 1481400 2 2 2 4 2 0 0 0 0 0 0.92 1.00 540 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 17 CARM1(1), DHRS7(1), LCMT1(1), PRMT6(5), PRMT7(2), PRMT8(1) 5679684 11 9 7 7 3 0 7 1 0 0 0.92 1.00 541 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 85 AICDA(3), CAD(6), CANT1(2), CTPS(3), DCK(1), DCTD(1), DHODH(2), DPYD(2), DPYS(2), ENTPD1(1), ENTPD3(1), ITPA(1), NME7(3), NT5C1B(3), NT5C2(2), NUDT2(1), PNPT1(1), POLA1(3), POLA2(3), POLD1(3), POLD4(1), POLE(4), POLE2(2), POLE3(2), POLR1A(3), POLR1B(1), POLR1C(1), POLR2A(2), POLR2B(4), POLR2D(1), POLR3A(3), POLR3B(4), POLR3G(2), POLR3GL(1), PRIM1(1), PRIM2(5), RFC5(1), RRM1(2), TK2(1), TXNRD1(1), TXNRD2(3), UPB1(1), UPP1(2), UPP2(1), ZNRD1(1) 32471747 94 48 90 37 28 12 26 11 17 0 0.92 1.00 542 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 LCT(8), MPI(1), PYGL(1), PYGM(2), TREH(2) 5368237 14 8 14 9 8 1 2 2 1 0 0.92 1.00 543 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), BMPR1A(2), BMPR1B(1), BMPR2(2) 2548853 6 3 6 1 0 2 1 3 0 0 0.92 1.00 544 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), EIF2AK4(2), EIF2S2(1), EIF2S3(3), GSK3B(1) 4666550 8 5 8 2 1 1 1 2 3 0 0.92 1.00 545 HSA00363_BISPHENOL_A_DEGRADATION Genes involved in bisphenol A degradation AKR1B10, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, HSD3B7, PON1, PON2, PON3, RDH11, RDH12, RDH13, RDH14 13 AKR1B10(2), DHRS7(1), PON1(4), PON3(2), RDH13(1) 3385089 10 5 10 3 4 1 3 2 0 0 0.92 1.00 546 HSA00601_GLYCOSPHINGOLIPID_BIOSYNTHESIS_LACTOSERIES Genes involved in glycosphingolipid biosynthesis - lactoseries ABO, B3GALT1, B3GALT2, B3GALT5, B3GNT5, FUT1, FUT2, FUT3, ST3GAL3, ST3GAL4 10 ABO(2), B3GALT2(1), B3GALT5(2), B3GNT5(1), FUT1(1), ST3GAL3(1) 2868757 8 4 8 6 4 1 2 1 0 0 0.92 1.00 547 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), ACAD8(1), ADH1A(4), ADH1B(3), ADH1C(3), ADH6(2), ADH7(1), AKR1B10(2), AKR1C4(2), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH9A1(1), BAAT(1), CEL(3), CYP27A1(1), RDH13(1), SOAT1(2), SOAT2(2) 12781541 37 20 37 9 17 7 8 5 0 0 0.93 1.00 548 SRCRPTPPATHWAY Activation of Src by Protein-tyrosine phosphatase alpha CCNB1, CDC2, CDC25A, CDC25B, CDC25C, CSK, GRB2, PRKCA, PRKCB1, PTPRA, SRC 9 CDC25B(1), PRKCA(3), PTPRA(4), SRC(2) 3687886 10 5 10 2 4 1 2 1 2 0 0.93 1.00 549 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 108 A4GNT(1), ALG1(3), ALG10B(4), ALG12(1), ALG3(2), ALG8(1), ALG9(1), B3GNT1(2), B3GNT2(3), B3GNT7(3), B4GALT2(1), B4GALT4(1), B4GALT7(1), C1GALT1C1(3), CHST1(2), CHST11(1), CHST12(1), CHST13(1), CHST14(1), CHST2(3), CHST3(1), CHST6(1), CHST7(2), CHSY1(1), DDOST(2), DPAGT1(1), EXT2(5), EXTL1(1), EXTL2(2), EXTL3(4), FUT8(1), GALNT1(3), GALNT10(3), GALNT11(1), GALNT12(1), GALNT13(1), GALNT14(2), GALNT2(4), GALNT5(1), GALNT6(3), GALNT7(1), GALNT8(3), GALNT9(3), GALNTL1(2), GALNTL2(2), GALNTL4(1), GALNTL5(3), GCNT3(2), GCNT4(1), HS2ST1(2), HS3ST1(1), HS3ST3A1(3), HS3ST5(2), HS6ST2(3), HS6ST3(3), MAN1A1(3), MAN1A2(1), MAN1C1(1), MAN2A1(2), MGAT1(1), MGAT2(2), MGAT3(3), MGAT4A(2), MGAT5B(4), NDST1(2), NDST2(2), NDST3(2), NDST4(5), OGT(3), RPN1(1), ST3GAL1(2), ST3GAL3(1), ST6GAL1(4), ST6GALNAC1(2), UST(2), WBSCR17(7), XYLT1(3), XYLT2(1) 43749781 164 66 164 50 60 23 32 24 25 0 0.93 1.00 550 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 16 B3GAT1(1), B3GAT2(1), B4GALT7(1), CHST11(1), CHST12(1), CHST13(1), CHST14(1), CHST3(1), CHST7(2), CHSY1(1), UST(2), XYLT1(3), XYLT2(1) 5485838 17 10 17 6 7 1 5 1 3 0 0.93 1.00 551 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 B4GALNT1(4), GLB1(1), HEXA(1), LCT(8), ST3GAL1(2), ST6GALNAC3(4), ST6GALNAC5(2), ST6GALNAC6(1) 6634452 23 11 23 9 13 1 4 3 2 0 0.93 1.00 552 HSA00625_TETRACHLOROETHENE_DEGRADATION Genes involved in tetrachloroethene degradation AKR1B10, EPHX2, HSD3B7, RDH11, RDH12, RDH13, RDH14 7 AKR1B10(2), EPHX2(2), RDH13(1) 1922363 5 3 5 0 4 0 1 0 0 0 0.93 1.00 553 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 FOS(1), MAP2K1(1), MAPK1(3), MAPK3(2), NFKB1(1), NFKBIA(2), PLCB1(3), PRKCA(3) 6221687 16 8 16 9 3 3 3 4 2 1 0.93 1.00 554 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 84 ATF2(1), BRAF(6), CHUK(4), DAXX(4), ELK1(1), FOS(1), IKBKB(2), MAP2K1(1), MAP2K2(1), MAP2K3(1), MAP2K5(1), MAP2K7(1), MAP3K1(5), MAP3K10(3), MAP3K12(5), MAP3K13(2), MAP3K14(2), MAP3K2(1), MAP3K3(4), MAP3K4(2), MAP3K5(1), MAP3K6(5), MAP3K7(2), MAP3K9(2), MAP4K1(1), MAP4K2(1), MAP4K3(1), MAP4K4(5), MAPK1(3), MAPK13(1), MAPK14(1), MAPK3(2), MAPK6(1), MAPK7(3), MAPK9(2), MAPKAPK2(1), MAPKAPK3(1), MAX(2), MEF2A(1), MEF2C(1), MEF2D(1), MKNK1(1), NFKB1(1), NFKBIA(2), PAK1(2), RIPK1(1), RPS6KA2(2), RPS6KA3(5), RPS6KB1(1), SP1(6), STAT1(1), TGFB1(1), TGFB2(1), TGFBR1(1), TRAF2(2) 37712148 113 54 109 39 32 13 15 31 22 0 0.93 1.00 555 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 23 GPAA1(2), GPLD1(2), PGAP1(3), PIGA(1), PIGG(3), PIGH(1), PIGK(3), PIGM(1), PIGO(6), PIGQ(3), PIGS(1), PIGT(1), PIGV(2) 9471806 29 14 29 4 8 4 10 4 2 1 0.93 1.00 556 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 GNAQ(1), GNB1(1), GNGT1(1), HTR2C(2), PLCB1(3) 2874536 8 3 8 7 2 1 1 3 0 1 0.94 1.00 557 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 22 AKT1(1), AP2A1(2), AP2M1(4), BTK(1), EEA1(2), GRASP(2), GSK3B(1), LYN(1), PFKM(3), PFKP(6), PLCG1(3), PRKCE(1), PRKCZ(2), RPS6KB1(1), VAV2(3) 9711807 33 15 33 11 9 8 4 5 7 0 0.94 1.00 558 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(3), ELK1(1), FOS(1), IL2(1), IL2RA(3), IL2RB(1), JAK1(3), JAK3(4), MAP2K1(1), MAPK3(2), SOS1(1), STAT5A(2), STAT5B(2), SYK(2) 9381702 27 14 26 12 9 2 7 6 3 0 0.94 1.00 559 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 FOS(1), MAPK3(2), OPRK1(1), POLR2A(2), PRKACG(1), PRKAR2A(1), PRKAR2B(1) 5009356 9 7 9 3 4 1 1 2 1 0 0.94 1.00 560 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 39 ARNTL(1), CBX3(1), CLDN5(2), CLOCK(1), CRY1(3), CRY2(2), DAZAP2(1), EIF4G2(2), GFRA1(1), GSTM3(1), GSTP1(1), HERPUD1(1), KLF9(1), NCKAP1(2), NCOA4(3), PER1(3), PER2(2), PPP1R3C(1), PURA(1), SF3A3(2), TOB1(2), TUBB3(1), UCP3(2), UGP2(1), ZFR(1) 14458089 39 20 38 11 10 2 12 8 7 0 0.94 1.00 561 PROTEASOME PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1, PSMB10, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMB8, PSMB9 17 PSMA1(1), PSMA3(2), PSMA5(1), PSMB1(1), PSMB4(1), PSMB8(1) 3478665 7 4 7 1 1 1 1 3 1 0 0.95 1.00 562 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 GNAS(3), GNB1(1), GNGT1(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PRKCA(3) 3641689 11 5 11 8 4 0 3 4 0 0 0.95 1.00 563 METHIONINEPATHWAY Catabolic Pathways for Methionine, Isoleucine, Threonine and Valine BCKDHB, BCKDK, CBS, CTH, MUT 5 BCKDHB(1), BCKDK(1), CBS(1), CTH(1), MUT(2) 1933650 6 2 6 4 4 0 1 0 1 0 0.95 1.00 564 INOSITOL_METABOLISM ALDH6A1, ALDOA, ALDOB, ALDOC, TPI1 5 ALDH6A1(2), ALDOA(1), ALDOB(1), ALDOC(3) 1572725 7 2 7 1 3 2 1 1 0 0 0.95 1.00 565 HSA00460_CYANOAMINO_ACID_METABOLISM Genes involved in cyanoamino acid metabolism ASRGL1, GBA, GBA3, GGT1, GGTL3, GGTL4, SHMT1, SHMT2 6 GBA(1), GGT1(2), SHMT2(1) 2166090 4 3 4 1 2 0 1 0 1 0 0.95 1.00 566 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(7), AXIN1(2), CREBBP(8), EP300(5), FZD1(1), GSK3B(1), HDAC1(1), LDB1(1), LEF1(1), TRRAP(8) 12947179 35 20 35 17 10 4 13 4 3 1 0.95 1.00 567 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 PTK2B(1), SOS1(1), SRC(2) 3530468 4 4 4 4 1 1 1 1 0 0 0.95 1.00 568 SELENOAMINO_ACID_METABOLISM AHCY, CBS, CTH, GGT1, MARS, MARS2, MAT1A, MAT2B, PAPSS1, PAPSS2, SCLY, SEPHS1 12 AHCY(1), CBS(1), CTH(1), GGT1(2), MARS(1), MAT1A(2), PAPSS2(1), SCLY(1), SEPHS1(1) 4922070 11 7 11 7 5 2 2 2 0 0 0.95 1.00 569 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(1), DPYD(2), DPYS(2), ENPP3(1), PANK3(1), PANK4(2), PPCS(1), UPB1(1) 6826923 11 8 11 7 2 2 2 3 2 0 0.95 1.00 570 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 26 ADRBK1(2), AKT1(1), AKT2(1), AKT3(1), DAG1(2), GNAQ(1), ITPKB(2), ITPR1(7), ITPR2(11), ITPR3(11), NFKB1(1), NFKB2(1), NFKBIA(2), NFKBIB(1), NFKBIE(1), NFKBIL1(1), NFKBIL2(6), PHKA2(4), PIK3CB(2), PLD2(1), VN1R1(1) 17422545 60 26 60 15 18 11 9 10 12 0 0.95 1.00 571 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 CSF1R(3), FOS(1), HDAC2(3), HDAC5(4), NCOR2(5), RBL1(3), RBL2(1), SIN3A(2), SIN3B(6) 10170982 28 14 28 7 9 4 8 3 4 0 0.96 1.00 572 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 HMGCL(1), HMGCS1(1), HMGCS2(3), OXCT1(1) 2926677 6 4 6 3 2 0 2 1 1 0 0.96 1.00 573 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 ACTA1(1), ACTR3(2), ARPC1B(1), ARPC2(1), ARPC4(1), NCKAP1(2), NTRK1(4), WASF1(1), WASF2(1) 6163897 14 8 14 7 3 2 2 4 3 0 0.96 1.00 574 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 25 ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH9A1(1), CYP2C9(2), DHRS7(1), ECHS1(1), EHHADH(2), ESCO1(2), HADHA(1), MYST3(4), MYST4(4), PNPLA3(1), SH3GLB1(2), YOD1(2) 12265492 30 18 30 10 7 5 6 6 6 0 0.96 1.00 575 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 11 FOS(1), MAPK1(3), MAPK14(1), NFE2L2(1), PRKCA(3) 3445740 9 4 9 4 2 2 1 4 0 0 0.96 1.00 576 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(2), LCMT1(1), MARS(1), MAT1A(2), PAPSS2(1), PRMT6(5), PRMT7(2), PRMT8(1), SCLY(1), SEPHS1(1) 9855100 21 15 17 12 8 2 8 3 0 0 0.96 1.00 577 ONE_CARBON_POOL_BY_FOLATE ALDH1L1, AMT, ATIC, ATP6V0C, SHMT1, DHFR, GART, MTHFD1, MTHFD1L, MTHFD2, MTHFR, MTHFS, MTR, SHMT1, SHMT2, TYMS 15 ALDH1L1(3), AMT(2), ATIC(1), DHFR(1), GART(3), MTHFD1L(1), MTHFR(3), MTR(2), SHMT2(1) 7282297 17 10 17 9 4 4 5 1 3 0 0.96 1.00 578 RNA_POLYMERASE POLR1B, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLRMT 14 POLR1B(1), POLR2A(2), POLR2B(4), POLR2D(1), POLRMT(1) 5295093 9 7 9 4 4 0 3 1 1 0 0.96 1.00 579 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 40 AKR1B10(2), ALDOA(1), ALDOB(1), ALDOC(3), FBP1(2), FBP2(4), FPGT(1), FUK(1), GMDS(1), GMPPA(1), HK2(3), HK3(4), LHPP(1), MPI(1), MTMR1(2), MTMR2(3), PFKFB1(2), PFKFB2(1), PFKFB3(1), PFKFB4(2), PFKM(3), PFKP(6), PGM2(2), PMM1(1), RDH13(1) 14689970 50 23 49 6 21 6 10 10 3 0 0.96 1.00 580 HSA04710_CIRCADIAN_RHYTHM Genes involved in circadian rhythm ARNTL, BHLHB2, BHLHB3, CLOCK, CRY1, CRY2, CSNK1D, CSNK1E, NPAS2, NR1D1, PER1, PER2, PER3 11 ARNTL(1), CLOCK(1), CRY1(3), CRY2(2), NPAS2(1), NR1D1(3), PER1(3), PER2(2), PER3(1) 6718626 17 10 16 8 5 2 3 4 3 0 0.97 1.00 581 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 109 ADCY1(8), ADCY2(3), ADCY3(3), ADCY4(2), ADCY5(3), ADCY6(2), ADCY7(3), ADCY8(4), AK1(1), ALLC(3), AMPD1(7), AMPD3(4), APRT(3), ATIC(1), ATP5B(2), ATP5C1(1), ATP5G2(1), ATP5H(1), ATP5I(1), CANT1(2), DCK(1), ENPP3(1), ENTPD1(1), GART(3), GMPS(1), GUCY1A2(1), GUCY1A3(5), GUCY2C(2), GUCY2D(2), GUCY2F(1), IMPDH1(2), IMPDH2(1), ITPA(1), NPR1(6), NPR2(1), NUDT2(1), PAPSS2(1), PDE1A(1), PDE4B(1), PDE4C(1), PDE4D(3), PDE5A(2), PDE6B(7), PDE6C(1), PDE7B(1), PDE8A(3), PDE9A(2), PFAS(5), PKLR(4), POLD1(3), POLE(4), POLG(4), POLL(2), POLQ(7), POLR1B(1), POLR2A(2), POLR2B(4), POLR2D(1), POLRMT(1), PRPS1L1(1), PRPS2(2), PRUNE(1), RRM1(2) 51133096 152 70 143 55 59 14 32 24 22 1 0.97 1.00 582 METHIONINE_METABOLISM AHCY, BHMT, CBS, CTH, DNMT1, DNMT2, DNMT3A, DNMT3B, MARS, MARS2, MAT1A, MAT2B, MTR 12 AHCY(1), BHMT(3), CBS(1), CTH(1), DNMT1(5), DNMT3A(3), DNMT3B(3), MARS(1), MAT1A(2), MTR(2) 7027617 22 11 22 9 9 6 2 3 2 0 0.97 1.00 583 HSA00642_ETHYLBENZENE_DEGRADATION Genes involved in ethylbenzene degradation ARD1A, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ESCO1, ESCO2, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1 11 DHRS7(1), ESCO1(2), MYST3(4), MYST4(4), PNPLA3(1), SH3GLB1(2) 6448451 14 8 14 4 2 2 3 3 4 0 0.97 1.00 584 CYANOAMINO_ACID_METABOLISM ATP6V0C, SHMT1, GBA3, GGT1, SHMT1, SHMT2 5 GGT1(2), SHMT2(1) 1612285 3 2 3 0 2 0 1 0 0 0 0.97 1.00 585 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 23 DHRS7(1), ECHS1(1), EHHADH(2), ESCO1(2), FN3K(1), HADHA(1), ITGB1BP3(2), MYST3(4), MYST4(4), PNPLA3(1), SH3GLB1(2), YOD1(2) 10227781 23 13 23 7 4 5 3 5 6 0 0.97 1.00 586 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 47 APAF1(1), BCL2(3), BCL2A1(1), CASP1(4), CASP2(1), CASP4(1), CASP6(1), CRADD(1), DAXX(4), DFFA(1), DFFB(3), NFKB1(1), NFKBIA(2), NGFR(1), NR3C1(1), NTRK1(4), PTPN13(4), RIPK1(1), TNFRSF1A(2), TNFRSF1B(2), TRAF1(1), TRAF2(2), TRAF3(3) 17487405 45 25 45 16 10 7 12 11 5 0 0.97 1.00 587 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 9 ALDOB(1), GPI(4), PKLR(4) 3384490 9 4 9 2 5 0 1 1 2 0 0.98 1.00 588 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 142 ADCY1(8), ADCY2(3), ADCY3(3), ADCY4(2), ADCY5(3), ADCY6(2), ADCY7(3), ADCY8(4), ADCY9(5), ADSSL1(1), AK1(1), AK7(2), ALLC(3), AMPD1(7), AMPD3(4), APRT(3), ATIC(1), CANT1(2), DCK(1), ENPP3(1), ENTPD1(1), ENTPD3(1), GART(3), GMPR(1), GMPR2(1), GMPS(1), GUCY1A2(1), GUCY1A3(5), GUCY2C(2), GUCY2D(2), GUCY2F(1), IMPDH1(2), IMPDH2(1), ITPA(1), NME7(3), NPR1(6), NPR2(1), NT5C1B(3), NT5C2(2), NUDT2(1), PAPSS2(1), PDE11A(2), PDE1A(1), PDE1C(4), PDE2A(3), PDE3B(4), PDE4B(1), PDE4C(1), PDE4D(3), PDE5A(2), PDE6D(1), PDE7A(2), PDE7B(1), PDE8A(3), PDE8B(3), PDE9A(2), PFAS(5), PKLR(4), PNPT1(1), POLA1(3), POLA2(3), POLD1(3), POLD4(1), POLE(4), POLE2(2), POLE3(2), POLR1A(3), POLR1B(1), POLR1C(1), POLR2A(2), POLR2B(4), POLR2D(1), POLR3A(3), POLR3B(4), POLR3G(2), POLR3GL(1), PRIM1(1), PRIM2(5), PRPS1L1(1), PRPS2(2), PRUNE(1), RFC5(1), RRM1(2), XDH(8), ZNRD1(1) 65586450 204 83 193 70 71 28 43 27 35 0 0.98 1.00 589 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 ACTA1(1), ACTR3(2), ARPC1B(1), ARPC2(1), ARPC4(1), WASF1(1) 3282209 7 3 7 1 1 1 1 1 3 0 0.98 1.00 590 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 41 ALPI(2), ALPL(2), ALPP(2), ALPPL2(2), ASCC3(4), ATP13A2(8), DDX18(1), DDX23(3), DDX4(1), DDX41(1), DDX47(2), DDX54(1), DDX56(2), DHFR(1), DHX58(2), EP400(15), ERCC2(1), ERCC3(2), FPGS(2), IFIH1(2), MOV10L1(2), RAD54B(3), RAD54L(2), RUVBL2(4), SETX(4), SKIV2L2(1), SMARCA2(5), SMARCA5(2) 24991247 79 37 79 26 25 13 18 14 9 0 0.98 1.00 591 GANGLIOSIDE_BIOSYNTHESIS B3GALT4, GALGT, SIAT4A, SIAT4B, SIAT7B, SIAT7D, SIAT9, ST3GAL1, ST3GAL2, ST3GAL4, ST3GAL5, ST6GALNAC2, ST6GALNAC4, ST8SIA1 8 ST3GAL1(2) 2219692 2 2 2 1 1 0 1 0 0 0 0.98 1.00 592 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 31 ACVR1(3), APC(7), ATF2(1), AXIN1(2), BMP10(2), BMP5(3), BMPR1A(2), BMPR2(2), FZD1(1), GATA4(2), GSK3B(1), MAP3K7(2), MEF2C(1), MYL2(2), RFC1(3), TGFB1(1), TGFB2(1), TGFBR1(1), TGFBR2(5), TGFBR3(2) 14155219 44 18 44 13 9 6 13 10 6 0 0.98 1.00 593 AKAPCENTROSOMEPATHWAY Protein Kinase A at the Centrosome AKAP9, ARHA, CDC2, MAP2, PCNT1, PCNT2, PPP1CA, PPP2CA, PRKACB, PRKACG, PRKAG1, PRKAR2A, PRKAR2B, PRKCE, PRKCL1 10 AKAP9(4), MAP2(3), PPP2CA(1), PRKACG(1), PRKAG1(2), PRKAR2A(1), PRKAR2B(1), PRKCE(1) 7405607 14 8 14 9 2 5 2 3 2 0 0.98 1.00 594 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 54 CAD(6), CANT1(2), CTPS(3), DCK(1), DCTD(1), DHODH(2), DPYD(2), DPYS(2), ENTPD1(1), ITPA(1), NUDT2(1), POLD1(3), POLE(4), POLG(4), POLL(2), POLQ(7), POLR1B(1), POLR2A(2), POLR2B(4), POLR2D(1), POLRMT(1), RRM1(2), TK2(1), TXNRD1(1), UPB1(1), UPP1(2) 22781723 58 30 57 26 15 9 19 7 7 1 0.98 1.00 595 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 35 CCNH(2), ERCC3(2), GTF2B(2), GTF2E1(1), GTF2E2(1), GTF2H4(1), ILK(2), POLR1A(3), POLR1B(1), POLR2A(2), POLR2B(4), POLR3B(4), POLR3D(1), TAF5(2), TAF6(3), TAF7(2), TAF9(1), TBP(2) 14056316 36 17 35 6 7 5 13 5 6 0 0.98 1.00 596 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 35 AKT1(1), CREB3(1), CREB5(1), DUSP10(1), EEF2K(2), EIF4E(2), ELK1(1), IL1R1(2), MAP2K3(1), MAP3K10(3), MAP3K4(2), MAP3K5(1), MAP3K7(2), MAPK1(3), MAPK13(1), MAPK14(1), MAPKAPK2(1), MKNK1(1), NFKB1(1), SRF(2) 13300265 30 18 30 9 10 4 1 11 4 0 0.98 1.00 597 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 ACTR3(2), ARHGAP1(1), ARHGAP4(1), ARHGAP5(2), ARHGAP6(1), ARHGEF1(2), ARHGEF11(3), ARHGEF5(1), ARPC1B(1), ARPC2(1), ARPC4(1), DIAPH1(2), GSN(2), LIMK1(1), MYL2(2), MYLK(7), OPHN1(1), PIP5K1B(2), PPP1R12B(6), ROCK1(3), SRC(2), TLN1(6), VCL(2) 18138147 52 23 52 15 21 7 8 6 10 0 0.99 1.00 598 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 AARS(3), AARS2(3), CARS2(3), EARS2(2), EPRS(2), FARSA(1), FARSB(1), HARS(3), HARS2(1), IARS(4), IARS2(1), KARS(4), LARS(3), LARS2(1), MARS(1), MTFMT(1), NARS(1), NARS2(1), PARS2(2), QARS(3), RARS2(1), SARS2(2), TARS(2), TARS2(1), VARS(3), VARS2(5), YARS(2), YARS2(2) 21945440 59 29 58 22 16 9 13 13 8 0 0.99 1.00 599 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(3), POLR1B(1), POLR1C(1), POLR2A(2), POLR2B(4), POLR2D(1), POLR3A(3), POLR3B(4), POLR3G(2), POLR3GL(1), ZNRD1(1) 9520788 23 12 23 3 8 4 5 3 3 0 0.99 1.00 600 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 CCNH(2), CDC25B(1), SHH(2), XPO1(2) 3517835 7 3 7 0 0 2 3 2 0 0 0.99 1.00 601 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(1), DLAT(1), DLD(1), DLST(2), IDH2(2), IDH3G(2), MDH2(1), OGDH(1), PC(3), PDHA1(1), PDHA2(3), PDHB(1), PDK3(1), PDK4(2), PDP2(1), SUCLA2(1), SUCLG1(2) 11406070 26 14 26 17 7 6 7 4 2 0 0.99 1.00 602 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(1), NRG2(1), NRG3(1), PRKCA(3) 3608656 6 3 6 4 3 0 1 1 1 0 0.99 1.00 603 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 13 ACTN1(1), ACTN3(1), CTNNA1(1), CTNNA2(2), PECAM1(2), PTK2(2), PXN(1), SRC(2), VCL(2) 7930015 14 9 14 6 5 2 3 2 2 0 0.99 1.00 604 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 PSMA1(1), PSMA3(2), PSMA5(1), PSMB1(1), PSMB4(1), PSMC2(1), PSMC3(1), PSMD11(1), PSMD12(3) 6453136 12 5 12 3 1 1 2 4 4 0 0.99 1.00 605 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 35 ACTA1(1), ACTN1(1), ACTN3(1), BCR(1), CAPN1(5), CAPNS1(1), CAV1(1), ITGA1(1), MAP2K1(1), MAP2K2(1), MAPK1(3), MAPK3(2), PPP1R12B(6), PTK2(2), PXN(1), ROCK1(3), SOS1(1), SRC(2), TLN1(6), VCL(2), ZYX(2) 18381154 44 22 44 14 16 6 6 11 5 0 0.99 1.00 606 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 ACTA1(1), ACTN1(1), ACTN3(1), CAPN1(5), CAPNS1(1), ITGA1(1), ITGB3(1), PTK2(2), PXN(1), SPTAN1(6), SRC(2), TLN1(6) 11191079 28 13 28 10 13 2 4 7 2 0 1.00 1.00 607 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 ARFGAP1(1), ARFGAP3(1), ARFGEF2(2), COPA(2), GBF1(5), GPLD1(2), KDELR1(1), KDELR2(1) 6465040 15 6 15 6 5 2 3 4 0 1 1.00 1.00 608 HSA00130_UBIQUINONE_BIOSYNTHESIS Genes involved in ubiquinone biosynthesis COQ2, COQ3, COQ5, COQ6, COQ7, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA12, NDUFA13, NDUFB11 8 COQ6(1) 1626459 1 1 1 0 0 0 0 1 0 0 1.00 1.00 609 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 CDK5R1(1), DRD1(2), DRD2(1), GRM1(1), PLCB1(3), PPP2CA(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1) 6247312 12 5 12 11 4 2 1 3 1 1 1.00 1.00 610 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 AARS(3), EPRS(2), HARS(3), IARS(4), KARS(4), LARS(3), LARS2(1), MARS(1), NARS(1), QARS(3), TARS(2), YARS(2) 13075913 29 14 29 11 8 6 5 5 5 0 1.00 1.00 611 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(2), AASS(3), ALDH1A1(4), ALDH1A2(3), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH9A1(1), DLST(2), ECHS1(1), EHHADH(2), EHMT1(3), EHMT2(2), HADHA(1), PLOD1(2), PLOD3(1), SDS(4), SHMT2(1), TMLHE(1) 14665322 40 17 40 9 7 12 9 6 6 0 1.00 1.00 612 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(1), IDH2(2), OGDH(1), SUCLA2(1) 3806392 5 3 5 9 2 1 2 0 0 0 1.00 1.00 613 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 ACTA1(1), RAB11A(1) 1723510 2 1 2 0 1 0 0 1 0 0 1.00 1.00 614 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(8), ADCY2(3), ADCY3(3), ADCY4(2), ADCY5(3), ADCY6(2), ADCY7(3), ADCY8(4), ADCY9(5), AKAP10(4), AKAP11(3), AKAP12(1), AKAP3(2), AKAP4(2), AKAP5(2), AKAP6(5), AKAP7(1), AKAP8(3), AKAP9(4), ARHGEF1(2), CALM1(1), GNA11(2), GNA12(2), GNA15(4), GNAI2(1), GNAL(1), GNAO1(1), GNAQ(1), GNB1(1), GNB2(1), GNB3(1), GNGT1(1), GNGT2(1), ITPR1(7), KCNJ3(2), KRAS(1), NRAS(1), PDE1A(1), PDE1C(4), PDE4B(1), PDE4C(1), PDE4D(3), PDE7A(2), PDE7B(1), PDE8A(3), PDE8B(3), PLCB3(5), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PRKCA(3), PRKCD(5), PRKCE(1), PRKCG(1), PRKCH(2), PRKCI(1), PRKCQ(1), PRKCZ(2), PRKD1(3), PRKD3(6), RHOA(1), SLC9A1(3), USP5(5) 46657373 152 58 151 47 51 24 33 24 20 0 1.00 1.00 615 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 AASS(3), AKR1B10(2), ALDH1A3(1), ALDH2(2), ALDH3A1(3), ALDH3A2(1), ALDH9A1(1), DLST(2), ECHS1(1), EHHADH(2), EHMT1(3), EHMT2(2), HADHA(1), HSD17B10(1), HSD17B4(1), NSD1(7), OGDH(1), OGDHL(5), PIPOX(2), PLOD1(2), PLOD3(1), RDH13(1), SETD1A(1), SETD7(2), SHMT2(1), SUV39H2(3), TMLHE(1) 23173273 53 23 53 14 17 8 14 8 6 0 1.00 1.00 616 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 91 CLK2(2), CLK4(2), COL2A1(2), CPSF1(4), CPSF3(1), CSTF1(1), CSTF2(2), CSTF2T(1), CSTF3(1), DDIT3(1), DHX15(1), DHX16(4), DHX38(4), DHX8(4), DHX9(2), DICER1(4), FUS(1), GIPC1(2), NCBP2(1), NONO(3), NUDT21(2), NXF1(1), PABPN1(2), PHF5A(1), POLR2A(2), PRPF3(1), PRPF4(1), PRPF4B(1), PRPF8(9), PSKH1(1), PTBP1(2), PTBP2(1), RBM17(1), RNGTT(1), SF3A1(2), SF3A3(2), SF3B1(2), SF3B2(2), SNRPB(1), SNRPB2(1), SNRPD1(1), SRPK1(2), SRPK2(3), SRRM1(2), SUPT5H(2), TXNL4A(1), U2AF2(2), XRN2(2) 41964994 94 40 97 19 28 9 22 14 21 0 1.00 1.00