rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p q 1 HSA04510_FOCAL_ADHESION Genes involved in focal adhesion ACTB, ACTG1, ACTN1, ACTN2, ACTN3, ACTN4, AKT1, AKT2, AKT3, ARHGAP5, BAD, BCAR1, BCL2, BIRC2, BIRC3, BIRC4, BRAF, CAPN2, CAV1, CAV2, CAV3, CCND1, CCND2, CCND3, CDC42, CHAD, COL11A1, COL11A2, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A2, COL4A4, COL4A6, COL5A1, COL5A2, COL5A3, COL6A1, COL6A2, COL6A3, COL6A6, COMP, CRK, CRKL, CTNNB1, DIAPH1, DOCK1, EGF, EGFR, ELK1, ERBB2, FARP2, FIGF, FLNA, FLNB, FLNC, FLT1, FN1, FYN, GRB2, GRLF1, GSK3B, HGF, HRAS, IBSP, IGF1, IGF1R, ILK, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAV, ITGB1, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, JUN, KDR, LAMA1, LAMA2, LAMA3, LAMA4, LAMA5, LAMB1, LAMB2, LAMB3, LAMB4, LAMC1, LAMC2, LAMC3, LOC653852, MAP2K1, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MET, MLCK, MRCL3, MRLC2, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLK, MYLK2, MYLPF, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PARVA, PARVB, PARVG, PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, PDGFRB, PDPK1, PGF, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIP5K1C, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PRKCA, PRKCB1, PRKCG, PTEN, PTK2, PXN, RAC1, RAC2, RAC3, RAF1, RAP1A, RAP1B, RAPGEF1, RELN, RHOA, ROCK1, ROCK2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SPP1, SRC, THBS1, THBS2, THBS3, THBS4, TLN1, TLN2, TNC, TNN, TNR, TNXB, VASP, VAV1, VAV2, VAV3, VCL, VEGFA, VEGFB, VEGFC, VTN, VWF, ZYX 190 ACTN2(2), AKT1(2), AKT2(2), ARHGAP5(1), BCAR1(2), BIRC2(2), BIRC3(1), BRAF(3), CCND2(1), CHAD(1), COL11A1(2), COL1A2(6), COL2A1(3), COL4A1(1), COL4A4(2), COL4A6(2), COL5A1(2), COL5A2(1), COL5A3(2), COL6A3(5), COL6A6(5), DIAPH1(1), DOCK1(1), EGF(1), EGFR(4), ERBB2(3), FARP2(2), FIGF(2), FLNA(2), FLNB(1), FLNC(3), FLT1(2), FN1(2), FYN(1), GRLF1(2), GSK3B(1), HGF(1), HRAS(2), ILK(1), ITGA1(1), ITGA11(2), ITGA3(2), ITGA6(2), ITGA8(1), ITGA9(2), ITGB1(2), ITGB5(3), ITGB6(2), ITGB7(1), JUN(1), KDR(2), LAMA1(3), LAMA2(5), LAMA3(1), LAMA4(3), LAMA5(4), LAMB1(3), LAMB2(1), LAMB4(4), LAMC2(3), LAMC3(3), MAPK10(1), MAPK9(1), MET(1), MYL7(1), MYL9(1), MYLK(2), PAK1(1), PAK4(2), PAK6(1), PAK7(1), PARVG(1), PDGFD(1), PDGFRA(3), PGF(1), PIK3CB(1), PIK3CD(1), PIK3CG(4), PIK3R1(2), PIP5K1C(1), PRKCG(2), PTK2(1), RELN(3), ROCK1(2), SOS1(4), SOS2(2), THBS1(4), THBS2(1), THBS3(1), THBS4(1), TLN1(3), TLN2(4), TNC(2), TNN(2), TNR(3), TNXB(1), VAV1(1), VAV3(1), VCL(1), VEGFA(1), VTN(1), VWF(5) 179589537 204 138 204 88 23 56 87 10 28 0 6.00e-15 3.69e-12 2 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 129 ACTN2(2), AKT1(2), AKT2(2), ASH1L(2), CDK4(1), CLDN10(2), CLDN16(1), CLDN2(2), CLDN4(1), CSNK2A2(1), CTNNA1(2), CTNNA2(4), CTNNA3(3), EPB41(1), EPB41L2(2), EPB41L3(2), EXOC4(2), F11R(1), HCLS1(1), HRAS(2), INADL(2), LLGL1(1), LLGL2(1), MAGI1(2), MAGI2(1), MAGI3(1), MLLT4(1), MPDZ(3), MRAS(1), MYH1(4), MYH10(2), MYH11(5), MYH13(2), MYH14(2), MYH2(5), MYH3(3), MYH4(2), MYH6(3), MYH7(2), MYH7B(2), MYH8(1), MYH9(2), MYL7(1), MYL9(1), PARD3(1), PARD6B(1), PPM1J(1), PPP2CA(2), PPP2R1A(1), PPP2R2B(1), PPP2R3A(2), PPP2R4(1), PRKCD(2), PRKCG(2), PRKCH(2), PRKCI(1), PRKCQ(2), PRKCZ(1), SPTAN1(1), TJP1(1), TJP2(1), ZAK(1) 95102609 110 91 110 56 7 38 36 6 23 0 9.26e-12 1.93e-09 3 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(1), ACTN2(2), APC(5), APC2(3), ARHGEF7(1), ARPC2(1), ARPC3(1), BCAR1(2), BDKRB1(1), BRAF(3), CHRM2(1), CHRM5(2), CSK(1), CYFIP1(2), CYFIP2(1), DIAPH1(1), DIAPH2(1), DIAPH3(1), DOCK1(1), EGF(1), EGFR(4), F2(2), FGD1(3), FGF20(1), FGF6(1), FGFR1(1), FGFR2(2), FGFR3(1), FGFR4(1), FN1(2), GIT1(2), GNA13(1), GNG12(1), GRLF1(2), HRAS(2), IQGAP1(1), IQGAP2(1), IQGAP3(3), ITGA1(1), ITGA11(2), ITGA3(2), ITGA6(2), ITGA8(1), ITGA9(2), ITGAE(2), ITGAL(2), ITGAX(1), ITGB1(2), ITGB5(3), ITGB6(2), ITGB7(1), LIMK2(1), MRAS(1), MSN(2), MYH10(2), MYH14(2), MYH9(2), MYL7(1), MYL9(1), MYLK(2), NCKAP1(1), NCKAP1L(1), PAK1(1), PAK4(2), PAK6(1), PAK7(1), PDGFRA(3), PIK3CB(1), PIK3CD(1), PIK3CG(4), PIK3R1(2), PIP4K2A(2), PIP5K1C(1), PPP1R12B(1), PTK2(1), ROCK1(2), SLC9A1(1), SOS1(4), SOS2(2), SSH2(2), SSH3(1), TIAM1(2), TIAM2(2), VAV1(1), VAV3(1), VCL(1), WASL(2) 136629755 144 108 144 60 13 36 67 3 25 0 9.40e-12 1.93e-09 4 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 167 ADCY2(1), ADCY7(1), ADCY8(4), ADCY9(2), ADORA2A(1), ADRB2(1), ATP2A1(2), ATP2A2(2), ATP2B3(1), ATP2B4(1), AVPR1A(2), BDKRB1(1), CACNA1A(1), CACNA1C(5), CACNA1D(4), CACNA1E(1), CACNA1F(3), CACNA1H(3), CACNA1I(3), CACNA1S(1), CALM2(1), CAMK2G(2), CCKAR(2), CCKBR(1), CD38(1), CHRM2(1), CHRM5(2), CHRNA7(1), DRD1(1), EGFR(4), ERBB2(3), ERBB3(3), ERBB4(3), GNAL(1), GNAS(1), GRIN1(1), GRIN2A(3), GRM1(1), GRM5(1), HTR2A(1), HTR2C(1), HTR5A(1), HTR6(1), HTR7(1), ITPKA(1), ITPKB(1), ITPR1(1), ITPR2(4), ITPR3(1), MYLK(2), NOS1(5), NOS3(1), NTSR1(1), P2RX1(1), PDE1B(2), PDE1C(1), PDGFRA(3), PHKA1(1), PHKB(2), PHKG1(1), PLCB1(1), PLCB2(1), PLCB4(3), PLCD1(1), PLCD4(2), PLCE1(1), PLCG1(1), PLCG2(1), PPP3CC(1), PRKACA(1), PRKACB(1), PRKCG(2), PTAFR(1), PTGFR(1), PTK2B(2), RYR1(3), RYR2(3), RYR3(3), SLC25A4(1), SLC8A1(1), SLC8A3(1), SPHK2(1), TACR1(1), TACR2(1), TACR3(2), TRPC1(1), VDAC3(1) 134793666 145 121 145 59 14 44 59 5 23 0 5.01e-11 7.72e-09 5 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 ACTN2(2), ACVR1B(3), ACVR1C(2), CDH1(2), CREBBP(3), CSNK2A2(1), CTNNA1(2), CTNNA2(4), CTNNA3(3), CTNND1(3), EGFR(4), EP300(3), ERBB2(3), FARP2(2), FER(2), FGFR1(1), FYN(1), INSR(4), IQGAP1(1), LMO7(3), MAP3K7(1), MET(1), MLLT4(1), PARD3(1), PTPRB(2), PTPRF(3), PTPRJ(4), PTPRM(1), PVRL3(2), SMAD2(1), SMAD4(4), SNAI1(1), SNAI2(1), SORBS1(1), SSX2IP(1), TCF7(2), TGFBR2(2), TJP1(1), VCL(1), WASL(2) 58917089 82 69 81 29 7 26 30 6 13 0 2.20e-09 2.71e-07 6 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 108 ACTN2(2), ARHGAP5(1), BCAR1(2), CDH5(1), CLDN10(2), CLDN16(1), CLDN2(2), CLDN4(1), CTNNA1(2), CTNNA2(4), CTNNA3(3), CTNND1(3), F11R(1), GRLF1(2), ITGAL(2), ITGB1(2), ITK(2), MLLT4(1), MSN(2), MYL7(1), MYL9(1), NCF1(1), NOX1(1), NOX3(2), PIK3CB(1), PIK3CD(1), PIK3CG(4), PIK3R1(2), PLCG1(1), PLCG2(1), PRKCG(2), PTK2(1), PTK2B(2), PTPN11(1), RAPGEF3(2), RAPGEF4(1), RASSF5(1), ROCK1(2), VAV1(1), VAV3(1), VCAM1(1), VCL(1) 60319616 68 54 68 26 8 14 28 2 16 0 4.70e-08 4.82e-06 7 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(2), CD44(2), CHAD(1), COL11A1(2), COL1A2(6), COL2A1(3), COL4A1(1), COL4A4(2), COL4A6(2), COL5A1(2), COL5A2(1), COL5A3(2), COL6A3(5), COL6A6(5), FN1(2), FNDC1(2), GP1BA(1), HSPG2(1), ITGA1(1), ITGA11(2), ITGA3(2), ITGA6(2), ITGA8(1), ITGA9(2), ITGB1(2), ITGB5(3), ITGB6(2), ITGB7(1), LAMA1(3), LAMA2(5), LAMA3(1), LAMA4(3), LAMA5(4), LAMB1(3), LAMB2(1), LAMB4(4), LAMC2(3), LAMC3(3), RELN(3), SV2C(2), THBS1(4), THBS2(1), THBS3(1), THBS4(1), TNC(2), TNN(2), TNR(3), TNXB(1), VTN(1), VWF(5) 109979156 116 94 116 53 17 30 42 8 19 0 9.10e-08 7.92e-06 8 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 235 ADCYAP1R1(1), ADORA2A(1), ADRB2(1), AVPR1A(2), BDKRB1(1), C3AR1(1), CALCR(1), CCKAR(2), CCKBR(1), CHRM2(1), CHRM5(2), CNR2(1), CRHR2(1), DRD1(1), DRD5(1), F2(2), GABBR1(1), GABRA3(2), GABRA4(2), GABRA5(1), GABRA6(1), GABRB1(1), GABRB3(1), GABRE(3), GABRG2(2), GABRQ(3), GABRR1(2), GABRR2(2), GH2(1), GHR(1), GIPR(1), GLP2R(1), GLRA1(1), GPR35(1), GPR50(1), GPR63(1), GPR83(1), GRIA1(5), GRIA2(1), GRIA4(3), GRID2(5), GRIK1(1), GRIK2(1), GRIK3(1), GRIK5(1), GRIN1(1), GRIN2A(3), GRIN2B(4), GRIN3B(2), GRM1(1), GRM2(2), GRM3(1), GRM4(1), GRM5(1), GRM7(1), GRM8(1), GZMA(1), HRH4(1), HTR1A(1), HTR2A(1), HTR2C(1), HTR5A(1), HTR6(1), HTR7(1), LEPR(1), LTB4R(1), MAS1(1), MC3R(1), MCHR2(3), NMBR(1), NPFFR2(1), NPY1R(1), NTSR1(1), OPRD1(1), OPRM1(1), P2RX1(1), P2RY10(2), P2RY13(1), P2RY2(1), PARD3(1), PRLR(1), PTAFR(1), PTGDR(1), PTGER2(1), PTGFR(1), SSTR1(2), SSTR4(1), TAAR2(1), TACR1(1), TACR2(1), TACR3(2), THRA(1), TSHR(1) 107023493 128 104 128 41 12 34 59 5 18 0 1.03e-07 7.92e-06 9 HSA04012_ERBB_SIGNALING_PATHWAY Genes involved in ErbB signaling pathway ABL1, ABL2, AKT1, AKT2, AKT3, ARAF, AREG, BAD, BRAF, BTC, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CBL, CBLB, CBLC, CDKN1A, CDKN1B, CRK, CRKL, EGF, EGFR, EIF4EBP1, ELK1, ERBB2, ERBB3, ERBB4, EREG, FRAP1, GAB1, GRB2, GSK3B, HBEGF, HRAS, JUN, KRAS, MAP2K1, MAP2K2, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MYC, NCK1, NCK2, NRAS, NRG1, NRG2, NRG3, NRG4, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PLCG2, PRKCA, PRKCB1, PRKCG, PTK2, RAF1, RPS6KB1, RPS6KB2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SRC, STAT5A, STAT5B, TGFA 84 ABL2(2), AKT1(2), AKT2(2), BRAF(3), BTC(1), CAMK2G(2), CBL(1), CBLB(1), CDKN1A(1), EGF(1), EGFR(4), ERBB2(3), ERBB3(3), ERBB4(3), GAB1(1), GSK3B(1), HRAS(2), JUN(1), MAP2K7(1), MAPK10(1), MAPK9(1), NRG1(3), NRG2(1), NRG3(2), PAK1(1), PAK4(2), PAK6(1), PAK7(1), PIK3CB(1), PIK3CD(1), PIK3CG(4), PIK3R1(2), PLCG1(1), PLCG2(1), PRKCG(2), PTK2(1), RPS6KB1(2), SOS1(4), SOS2(2), STAT5B(1) 49422728 70 59 70 29 8 20 30 1 11 0 4.33e-06 0.00030 10 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 16 ABCB1(3), AKT1(2), ATM(8), CDKN1A(1), CPB2(1), HIF1A(1), IGFBP3(1), NFKBIB(1) 9340461 18 17 18 8 2 4 6 0 6 0 8.35e-06 0.00051 11 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(1), CD22(2), CD274(1), CD34(1), CD4(1), CDH1(2), CDH2(1), CDH3(2), CDH4(4), CDH5(1), CLDN10(2), CLDN16(1), CLDN2(2), CLDN4(1), CNTN1(3), CNTNAP1(3), CNTNAP2(3), F11R(1), GLG1(2), HLA-B(1), HLA-C(1), HLA-DMB(1), HLA-DQB1(2), HLA-DRA(1), HLA-DRB1(3), HLA-E(1), HLA-F(1), ITGA6(2), ITGA8(1), ITGA9(2), ITGAL(2), ITGB1(2), ITGB7(1), L1CAM(1), MPZL1(1), NCAM2(2), NEGR1(2), NEO1(1), NFASC(3), NRXN1(5), NRXN2(1), NRXN3(2), PTPRC(4), PTPRF(3), PTPRM(1), PVRL3(2), SELE(3), SELP(1), SELPLG(3), VCAM1(1), VCAN(2) 71331516 94 78 94 36 14 25 35 9 11 0 9.22e-06 0.00052 12 HSA00950_ALKALOID_BIOSYNTHESIS_I Genes involved in alkaloid biosynthesis I DDC, GOT1, GOT2, TAT, TYR 5 DDC(2), GOT1(2), GOT2(3), TYR(2) 2303193 9 9 9 0 1 2 2 1 3 0 0.000012 0.00061 13 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(4), AGMAT(2), ALDH1A2(1), ALDH1B1(2), ALDH3A2(1), ALDH4A1(1), AOC2(1), ARG1(1), CPS1(5), DAO(1), GATM(2), GOT1(2), GOT2(3), MAOA(1), MAOB(1), NOS1(5), NOS3(1), P4HA1(2), P4HA2(1), SMS(1) 21376576 38 35 38 10 3 9 16 3 7 0 0.000015 0.00071 14 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 32 ABP1(4), ADH1B(1), ADHFE1(1), ALDH3B1(1), ALDH3B2(1), AOC2(1), AOX1(5), DBH(2), DCT(1), DDC(2), GOT1(2), GOT2(3), MAOA(1), MAOB(1), TH(1), TPO(1), TYR(2) 15283136 30 27 30 6 4 4 10 6 6 0 0.000023 0.0010 15 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 12 CREBBP(3), DAXX(2), HRAS(2), PAX3(1), PML(2), RARA(2), RB1(3), SIRT1(1), SP100(1), TNFRSF1A(1) 8835809 18 18 18 10 1 6 8 1 2 0 0.000033 0.0014 16 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 81 ACVR1(1), ACVR1B(3), AKT1(2), AURKB(1), BMPR2(2), BUB1(1), CDKL2(1), CDS2(1), CLK2(1), CLK4(1), CSNK2A2(1), DGKB(1), DGKH(1), DGKQ(1), DGKZ(1), INPP4A(1), INPP4B(2), INPP5A(1), ITPKA(1), ITPKB(1), MAP3K10(1), NEK3(2), OCRL(2), PAK4(2), PIK3C2G(1), PIK3CB(1), PIK3CG(4), PLCB1(1), PLCB2(1), PLCB4(3), PLCD1(1), PLCG1(1), PLCG2(1), PRKACA(1), PRKACB(1), PRKCD(2), PRKCG(2), PRKCH(2), PRKCQ(2), PRKCZ(1), PRKD1(3), PRKG1(1), RPS6KA1(1), RPS6KA2(1), RPS6KA3(1), RPS6KB1(2) 55054327 66 58 66 18 7 18 23 2 16 0 0.000035 0.0014 17 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 43 AKT1(2), AKT2(2), BRAF(3), FIGF(2), HIF1A(1), PGF(1), PIK3CB(1), PIK3CD(1), PIK3CG(4), PIK3R1(2), RHEB(1), RICTOR(2), RPS6KA1(1), RPS6KA2(1), RPS6KA3(1), RPS6KA6(3), RPS6KB1(2), TSC1(2), TSC2(2), ULK3(2), VEGFA(1) 24574629 37 34 37 11 5 8 13 2 9 0 0.000037 0.0014 18 CYSTEINE_METABOLISM CARS, CTH, GOT1, GOT2, LDHA, LDHB, LDHC, MPST 8 CARS(2), GOT1(2), GOT2(3), LDHB(1), LDHC(1), MPST(1) 3269686 10 10 10 1 1 2 3 0 4 0 0.000046 0.0016 19 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 245 ACVR1B(3), ACVR1C(2), AKT1(2), AKT2(2), ATF4(1), BRAF(3), CACNA1A(1), CACNA1C(5), CACNA1D(4), CACNA1E(1), CACNA1F(3), CACNA1H(3), CACNA1I(3), CACNA1S(1), CACNA2D1(1), CACNB1(1), CACNG3(1), CACNG5(1), DAXX(2), DUSP10(1), DUSP3(1), DUSP8(1), ECSIT(2), EGF(1), EGFR(4), ELK4(2), FGF20(1), FGF6(1), FGFR1(1), FGFR2(2), FGFR3(1), FGFR4(1), FLNA(2), FLNB(1), FLNC(3), GNG12(1), HRAS(2), IL1R2(1), JUN(1), MAP2K3(2), MAP2K7(1), MAP3K1(1), MAP3K10(1), MAP3K12(2), MAP3K3(1), MAP3K4(3), MAP3K5(1), MAP3K6(1), MAP3K7(1), MAP4K1(1), MAP4K2(1), MAP4K3(1), MAP4K4(2), MAPK10(1), MAPK8IP1(1), MAPK8IP3(1), MAPK9(1), MAPKAPK5(1), MAPT(1), MAX(2), MKNK2(2), MRAS(1), NFATC2(1), NTRK2(1), PAK1(1), PDGFRA(3), PLA2G12A(1), PLA2G6(2), PPM1A(1), PPP3CC(1), PPP5C(2), PRKACA(1), PRKACB(1), PRKCG(2), PTPN7(1), RAPGEF2(5), RASGRF1(1), RASGRF2(1), RASGRP2(2), RASGRP4(2), RPS6KA1(1), RPS6KA2(1), RPS6KA3(1), RPS6KA6(3), SOS1(4), SOS2(2), STK3(1), TAOK2(2), TAOK3(1), TGFB2(1), TGFB3(1), TGFBR2(2), TNFRSF1A(1), TRAF6(1), ZAK(1) 139797090 152 112 152 56 21 39 61 7 24 0 0.000072 0.0023 20 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 ADCY8(4), ATF4(1), BRAF(3), CACNA1C(5), CALM2(1), CAMK2G(2), CREBBP(3), EP300(3), GRIA1(5), GRIA2(1), GRIN1(1), GRIN2A(3), GRIN2B(4), GRM1(1), GRM5(1), HRAS(2), ITPR1(1), ITPR2(4), ITPR3(1), PLCB1(1), PLCB2(1), PLCB4(3), PPP3CC(1), PRKACA(1), PRKACB(1), PRKCG(2), RAPGEF3(2), RPS6KA1(1), RPS6KA2(1), RPS6KA3(1), RPS6KA6(3) 50350448 64 58 64 26 4 22 23 2 13 0 0.000077 0.0024 21 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 ADCY2(1), ADCY5(3), ADCY7(1), ADCY8(4), ADCY9(2), ATF4(1), CACNA1C(5), CACNA1D(4), CACNA1F(3), CACNA1S(1), CALM2(1), CAMK2G(2), EGFR(4), GNAS(1), GNRH2(1), HRAS(2), ITPR1(1), ITPR2(4), ITPR3(1), JUN(1), MAP2K3(2), MAP2K7(1), MAP3K1(1), MAP3K3(1), MAP3K4(3), MAPK10(1), MAPK9(1), PLA2G12A(1), PLA2G6(2), PLCB1(1), PLCB2(1), PLCB4(3), PLD1(1), PLD2(1), PRKACA(1), PRKACB(1), PRKCD(2), PTK2B(2), SOS1(4), SOS2(2) 63917816 75 65 75 23 5 21 35 1 13 0 0.000082 0.0024 22 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 108 ANAPC1(3), ANAPC4(1), ATM(8), ATR(4), BUB1(1), CCNA1(2), CCNB2(2), CCNB3(2), CCND2(1), CDC14A(2), CDC25A(1), CDC27(1), CDC6(1), CDK2(1), CDK4(1), CDKN1A(1), CDKN2A(1), CDKN2C(1), CHEK2(1), CREBBP(3), CUL1(2), EP300(3), ESPL1(3), GSK3B(1), MAD2L1(1), MCM2(3), MCM6(2), MCM7(1), ORC1L(1), ORC4L(1), ORC5L(1), PCNA(1), PLK1(1), PRKDC(2), RB1(3), RBL2(1), SMAD2(1), SMAD4(4), SMC1A(1), SMC1B(1), TGFB2(1), TGFB3(1), WEE1(1), YWHAE(1) 67040487 76 61 76 45 5 22 28 4 17 0 0.00011 0.0032 23 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 45 INPP4A(1), INPP4B(2), INPP5A(1), INPP5B(1), ITPKA(1), ITPKB(1), MIOX(1), OCRL(2), PI4KA(2), PI4KB(2), PIK3C3(3), PIK3CB(1), PIK3CD(1), PIK3CG(4), PIP4K2A(2), PIP5K1C(1), PLCB1(1), PLCB2(1), PLCB4(3), PLCD1(1), PLCD4(2), PLCE1(1), PLCG1(1), PLCG2(1), PTPMT1(1), SYNJ1(4) 35045927 42 37 42 16 2 13 13 1 11 2 0.00013 0.0035 24 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 53 ASH1L(2), ASH2L(1), DOT1L(2), EHMT2(2), EZH1(1), EZH2(2), FBXO11(2), HCFC1(1), HSF4(1), KDM6A(3), MLL(1), MLL2(6), MLL3(9), MLL4(2), MLL5(4), NSD1(2), OGT(3), PRDM9(2), PRMT1(1), PRMT5(1), PRMT6(1), PRMT7(2), PRMT8(1), RBBP5(2), SETD1A(1), SETDB1(1), SETMAR(1), SUV420H1(1), SUZ12(2), WHSC1(1), WHSC1L1(4) 56389423 65 58 65 30 7 15 25 1 17 0 0.00017 0.0042 25 HSA00460_CYANOAMINO_ACID_METABOLISM Genes involved in cyanoamino acid metabolism ASRGL1, GBA, GBA3, GGT1, GGTL3, GGTL4, SHMT1, SHMT2 6 GBA(2), GBA3(1), GGT1(2), SHMT1(1), SHMT2(2) 2824354 8 8 8 2 0 1 4 1 2 0 0.00017 0.0042 26 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(4), ACY1(1), AGMAT(2), ALDH18A1(1), ALDH1B1(2), ALDH3A2(1), AOC2(1), ARG1(1), ASS1(1), CPS1(5), GATM(2), MAOA(1), MAOB(1), SAT1(1), SAT2(1), SMS(1) 14578957 26 26 26 8 1 6 14 3 2 0 0.00018 0.0042 27 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(1), FUCA2(1), GBA(2), GLB1(3), GNS(1), GUSB(2), HEXA(1), HGSNAT(1), HPSE(1), HPSE2(3), HYAL1(1), HYAL2(1), IDS(2), IDUA(1), LCT(1), MAN2B2(2), MAN2C1(4), NAGLU(1), SPAM1(2) 16850879 31 27 31 6 3 10 10 3 5 0 0.00019 0.0044 28 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 BRAF(3), DAXX(2), HRAS(2), JUN(1), MAP2K3(2), MAP2K7(1), MAP3K1(1), MAP3K10(1), MAP3K11(1), MAP3K12(2), MAP3K3(1), MAP3K4(3), MAP3K5(1), MAP3K6(1), MAP3K7(1), MAP4K1(1), MAP4K2(1), MAP4K3(1), MAP4K4(2), MAP4K5(3), MAPK10(1), MAPK4(1), MAPK9(1), MAPKAPK5(1), MAX(2), MEF2A(1), MKNK2(2), PAK1(1), RELA(1), RIPK1(1), RPS6KA1(1), RPS6KA2(1), RPS6KA3(1), RPS6KB1(2), STAT1(3), TGFB2(1), TGFB3(1), TRADD(1) 47551987 54 47 54 14 7 13 20 0 14 0 0.00021 0.0046 29 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 56 ABP1(4), ADH1B(1), ADH5(1), ADHFE1(1), ALDH3B1(1), ALDH3B2(1), AOC2(1), AOX1(5), DBH(2), DCT(1), DDC(2), GOT1(2), GOT2(3), LCMT2(1), MAOA(1), MAOB(1), MYST3(4), PNPLA3(1), PRMT5(1), PRMT6(1), PRMT7(2), PRMT8(1), TH(1), TPO(1), TYR(2), TYRP1(1) 28874502 43 37 43 9 6 7 17 6 7 0 0.00024 0.0050 30 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 CARS(2), CARS2(1), GOT1(2), GOT2(3), LDHAL6B(1), LDHB(1), LDHC(1), MPST(1), SULT4A1(1) 6120236 13 13 13 1 1 2 4 0 6 0 0.00025 0.0050 31 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(4), ALDH3B1(1), ALDH3B2(1), AOC2(1), DDC(2), GOT1(2), GOT2(3), MAOA(1), MAOB(1), MPO(3), PRDX1(1), PRDX5(1), TPO(1) 10813926 22 19 22 2 2 5 8 4 3 0 0.00026 0.0050 32 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(5), APC2(3), AXIN1(1), CACYBP(1), CAMK2G(2), CCND2(1), CHD8(1), CREBBP(3), CSNK2A2(1), CUL1(2), CXXC4(1), DKK2(1), EP300(3), FBXW11(1), FZD1(2), FZD10(1), FZD4(1), FZD5(1), GSK3B(1), JUN(1), LRP5(1), LRP6(1), MAP3K7(1), MAPK10(1), MAPK9(1), NFAT5(1), NFATC2(1), NFATC3(2), NKD1(1), PLCB1(1), PLCB2(1), PLCB4(3), PORCN(1), PPP2CA(2), PPP2R1A(1), PPP2R2B(1), PPP3CC(1), PRICKLE1(1), PRKACA(1), PRKACB(1), PRKCG(2), ROCK1(2), SFRP1(2), SFRP4(1), SMAD2(1), SMAD4(4), TBL1X(1), TBL1XR1(2), TBL1Y(1), TCF7(2), VANGL1(1), VANGL2(1), WNT3A(1), WNT5B(1), WNT7B(1), WNT9A(1) 77939546 81 70 79 48 1 30 31 0 19 0 0.00027 0.0050 33 G1PATHWAY CDK4/6-cyclin D and CDK2-cyclin E phosphorylate Rb, which allows the transcription of genes needed for the G1/S cell cycle transition. ABL1, ATM, ATR, CCNA1, CCND1, CCNE1, CDC2, CDC25A, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, DHFR, E2F1, GSK3B, HDAC1, MADH3, MADH4, RB1, SKP2, TFDP1, TGFB1, TGFB2, TGFB3, TP53 24 ATM(8), ATR(4), CCNA1(2), CDC25A(1), CDK2(1), CDK4(1), CDKN1A(1), CDKN2A(1), GSK3B(1), RB1(3), TGFB2(1), TGFB3(1) 14306967 25 22 25 19 1 10 8 0 6 0 0.00027 0.0050 34 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), ARG1(1), ASS1(1), CPS1(5), DAO(1), EPRS(1), GATM(2), GOT1(2), GOT2(3), LAP3(2), NOS1(5), NOS3(1), P4HA1(2), P4HA2(1), PARS2(1) 17335384 29 27 29 10 2 8 13 0 6 0 0.00028 0.0050 35 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 BRAF(3), CACNA1A(1), GNA13(1), GNAO1(1), GNAS(1), GNAZ(1), GRIA1(5), GRIA2(1), GRID2(5), GRM1(1), GRM5(1), GUCY1A2(1), GUCY1A3(2), GUCY2C(2), GUCY2F(1), HRAS(2), ITPR1(1), ITPR2(4), ITPR3(1), NOS1(5), NOS3(1), NPR1(3), NPR2(1), PLA2G12A(1), PLA2G6(2), PLCB1(1), PLCB2(1), PLCB4(3), PPP2CA(2), PPP2R1A(1), PPP2R2B(1), PRKCG(2), PRKG1(1), PRKG2(1), RYR1(3) 54982218 64 58 64 34 4 23 25 2 10 0 0.00029 0.0050 36 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 BMP2(1), BMP4(1), BMP6(1), BMP7(1), BMP8B(1), CSNK1G1(1), CSNK1G2(1), FBXW11(1), GLI2(3), GLI3(2), GSK3B(1), HHIP(2), LRP2(7), PRKACA(1), PRKACB(1), PTCH1(2), PTCH2(1), SMO(2), STK36(1), WNT3A(1), WNT5B(1), WNT7B(1), WNT9A(1) 29022754 35 35 35 14 0 12 18 2 3 0 0.00030 0.0052 37 HSA00401_NOVOBIOCIN_BIOSYNTHESIS Genes involved in novobiocin biosynthesis GOT1, GOT2, TAT 3 GOT1(2), GOT2(3) 1287858 5 5 5 0 1 1 1 0 2 0 0.00041 0.0068 38 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(1), GLB1(3), GNS(1), GUSB(2), HEXA(1), HGSNAT(1), HPSE(1), HPSE2(3), HYAL1(1), HYAL2(1), IDS(2), IDUA(1), LCT(1), NAGLU(1), SPAM1(2) 10147121 22 20 22 3 3 7 5 3 4 0 0.00042 0.0068 39 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 IFNAR1(1), IFNB1(1), JAK1(2), PTPRU(2), STAT1(3), STAT2(1), TYK2(2) 6164882 12 12 12 3 1 5 2 1 3 0 0.00051 0.0080 40 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 25 ATM(8), BMPR1B(1), CCND2(1), CDK4(1), EGR1(1), GJA4(1), MLH1(1), NCOR1(2), NRIP1(4), PGR(1), PRLR(1), PTGER2(1), SMPD1(1), VDR(1) 16906629 25 24 25 7 0 7 11 2 5 0 0.00052 0.0080 41 CYANOAMINO_ACID_METABOLISM ATP6V0C, SHMT1, GBA3, GGT1, SHMT1, SHMT2 5 GBA3(1), GGT1(2), SHMT1(1), SHMT2(2) 2108602 6 6 6 0 0 0 3 1 2 0 0.00061 0.0092 42 UREACYCLEPATHWAY Ammonia released from amino acid deamination is used to produce carbamoyl phosphate, which is used to convert ornithine to citrulline, from which urea is eventually formed. ARG1, ASL, ASS, CPS1, GLS, GLUD1, GOT1 6 ARG1(1), CPS1(5), GLS(1), GOT1(2) 3745761 9 9 9 0 0 3 3 0 3 0 0.00081 0.012 43 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 89 ACVR1(1), ACVR1B(3), ACVR1C(2), ACVR2A(1), AMHR2(2), BMP2(1), BMP4(1), BMP6(1), BMP7(1), BMP8B(1), BMPR1B(1), BMPR2(2), CHRD(1), CREBBP(3), CUL1(2), DCN(2), EP300(3), INHBE(1), LTBP1(1), PPP2CA(2), PPP2R1A(1), PPP2R2B(1), RBL2(1), ROCK1(2), RPS6KB1(2), SMAD2(1), SMAD4(4), SMAD9(2), SMURF2(2), TGFB2(1), TGFB3(1), TGFBR2(2), THBS1(4), THBS2(1), THBS3(1), THBS4(1), ZFYVE16(2), ZFYVE9(3) 48527294 64 55 64 17 8 19 22 3 12 0 0.00084 0.012 44 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 78 AIFM1(2), AKT1(2), AKT2(2), ATM(8), BIRC2(2), BIRC3(1), CAPN1(1), CASP10(2), CASP7(1), CASP8(1), CSF2RB(1), IL3(1), IRAK1(2), IRAK3(1), PIK3CB(1), PIK3CD(1), PIK3CG(4), PIK3R1(2), PPP3CC(1), PRKACA(1), PRKACB(1), RELA(1), RIPK1(1), TNFRSF10A(1), TNFRSF1A(1), TNFSF10(1), TRADD(1) 39323993 44 42 44 16 7 9 20 0 8 0 0.00092 0.013 45 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 IFNAR1(1), IFNB1(1), JAK1(2), STAT1(3), STAT2(1), TYK2(2) 5284693 10 10 10 3 0 4 2 1 3 0 0.00099 0.014 46 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), FBP1(1), GOT1(2), GOT2(3), GPT2(1), MDH1(1), ME1(1), ME2(1), ME3(1), PGK1(3) 8643968 15 15 15 3 2 4 4 2 3 0 0.0011 0.015 47 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 92 CABIN1(3), CALM2(1), CDKN1A(1), CREBBP(3), EGR2(1), EGR3(1), EP300(3), GATA4(1), GRLF1(2), GSK3A(2), GSK3B(1), HRAS(2), IFNB1(1), IL3(1), ITK(2), JUNB(2), MAP2K7(1), MAPK9(1), MEF2A(1), NFAT5(1), NFATC2(1), NFATC3(2), NFKBIB(1), NPPB(1), NUP214(1), OPRD1(1), PAK1(1), PPP3CC(1), PTPRC(4), RELA(1), TRPV6(1), VAV1(1), VAV3(1), XPO5(1) 44261565 49 47 49 19 6 16 20 1 6 0 0.0011 0.015 48 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 144 AKT1(2), AKT2(2), CBL(1), CBLB(1), CCND2(1), CREBBP(3), CSF2RB(1), CSF3R(1), EP300(3), GH2(1), GHR(1), IFNA21(1), IFNA5(1), IFNA7(1), IFNA8(1), IFNAR1(1), IFNB1(1), IFNGR1(1), IFNGR2(1), IL12RB1(1), IL12RB2(1), IL19(1), IL21(1), IL21R(1), IL22RA1(1), IL23A(1), IL2RB(1), IL3(1), IL4R(1), IL6R(1), IL6ST(2), IRF9(1), JAK1(2), JAK2(2), JAK3(1), LEPR(1), LIFR(1), PIAS1(2), PIK3CB(1), PIK3CD(1), PIK3CG(4), PIK3R1(2), PRLR(1), PTPN11(1), SOS1(4), SOS2(2), SPRED1(2), SPRY2(1), STAM(1), STAT1(3), STAT2(1), STAT4(2), STAT5B(1), STAT6(2), TPO(1), TYK2(2) 68439881 80 66 80 29 10 31 29 2 8 0 0.0012 0.015 49 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(2), CR2(2), HLA-DRA(1), HLA-DRB1(3), ITGAL(2), PTPRC(4) 7337450 14 13 14 5 2 2 5 1 4 0 0.0013 0.016 50 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 11 ATM(8), CDC25A(1), CDK2(1), CDK4(1), RB1(3), WEE1(1) 8341934 15 13 15 14 0 4 6 0 5 0 0.0013 0.016 51 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), FBP1(1), GOT1(2), GOT2(3), GPT2(1), MDH1(1), ME1(1), ME3(1), PGK1(3), TKTL2(2) 9676635 16 16 16 4 2 4 5 2 3 0 0.0014 0.017 52 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 71 CALM2(1), CDS2(1), DGKB(1), DGKH(1), DGKQ(1), DGKZ(1), INPP4A(1), INPP4B(2), INPP5A(1), INPP5B(1), ITPKA(1), ITPKB(1), ITPR1(1), ITPR2(4), ITPR3(1), OCRL(2), PI4KA(2), PI4KB(2), PIK3C2G(1), PIK3C3(3), PIK3CB(1), PIK3CD(1), PIK3CG(4), PIK3R1(2), PIP4K2A(2), PIP5K1C(1), PLCB1(1), PLCB2(1), PLCB4(3), PLCD1(1), PLCD4(2), PLCE1(1), PLCG1(1), PLCG2(1), PRKCG(2), PTPMT1(1), SYNJ1(4) 60678171 58 52 58 24 5 17 21 1 12 2 0.0018 0.021 53 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 CD4(1), FYN(1), HLA-DRA(1), HLA-DRB1(3), PTPRC(4), ZAP70(1) 4341535 11 10 11 5 1 4 3 1 2 0 0.0018 0.021 54 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 31 AKT1(2), AKT2(2), CD19(1), CDKN2A(1), GAB1(1), ITPR1(1), ITPR2(4), ITPR3(1), PDK1(1), PHF11(1), PLCG2(1), PPP1R13B(1), PREX1(3), PTPRC(4), RPS6KA1(1), RPS6KA2(1), RPS6KA3(1), RPS6KB1(2), SAG(1), SYK(1), TEC(1), VAV1(1) 25909146 33 32 33 9 3 9 11 2 8 0 0.0018 0.021 55 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 62 ATM(8), ATR(4), BAI1(1), CASP8(1), CCNB2(2), CCNB3(2), CCND2(1), CDK2(1), CDK4(1), CDKN1A(1), CDKN2A(1), CHEK2(1), IGFBP3(1), LRDD(1), RFWD2(3), RRM2(1), SERPINB5(2), THBS1(4), TP53I3(3), TSC2(2) 30552910 41 37 41 20 3 11 17 2 8 0 0.0018 0.021 56 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(4), ALDH3B1(1), ALDH3B2(1), AOC2(1), DDC(2), GOT1(2), GOT2(3), MAOA(1), MAOB(1), MPO(3), MYST3(4), PNPLA3(1), TPO(1) 16770427 25 22 25 4 2 7 9 4 3 0 0.0022 0.023 57 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(1), EGFR(4), ERBB3(3), NRG1(3) 5030470 11 11 11 2 2 3 4 0 2 0 0.0022 0.023 58 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(3), BDKRB1(1), C1QA(1), C1QC(1), C1S(1), C3(4), C3AR1(1), C4BPA(1), C5(4), C6(2), C7(2), C8A(1), C9(1), CD55(1), CFB(1), CFH(2), CPB2(1), CR1(2), CR2(2), F12(1), F13A1(1), F2(2), F5(3), F8(1), FGA(1), MASP2(1), PLAT(2), PLAU(3), PLG(1), PROC(2), SERPINA1(1), SERPIND1(1), SERPINF2(1), SERPING1(2), TFPI(1), VWF(5) 44176232 61 51 61 20 2 22 28 1 8 0 0.0022 0.024 59 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 139 ADCY2(1), ADCY5(3), ADCY7(1), ADCY8(4), ADCY9(2), ADRB2(1), ANXA6(2), ATP1A4(2), ATP2A2(2), ATP2B3(1), CACNA1A(1), CACNA1C(5), CACNA1D(4), CACNA1E(1), CACNA1S(1), CACNB1(1), CALM2(1), CALR(1), CAMK1(1), CAMK2G(2), CASQ1(1), CASQ2(1), CHRM2(1), CHRM5(2), GJA4(1), GJB6(1), GNAO1(1), GNAZ(1), GNB1(2), GNG12(1), GNG3(1), GRK6(1), ITPR1(1), ITPR2(4), ITPR3(1), KCNJ3(3), KCNJ5(1), MYCBP(1), PKIA(1), PRKACA(1), PRKACB(1), PRKCD(2), PRKCG(2), PRKCH(2), PRKCQ(2), PRKCZ(1), PRKD1(3), RGS17(1), RGS18(1), RGS2(1), RGS3(3), RGS9(1), RYR1(3), RYR2(3), RYR3(3), SLC8A1(1), SLC8A3(1) 94915598 95 79 95 33 8 31 35 2 19 0 0.0023 0.024 60 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 15 ATM(8), CDK2(1), CDK4(1), CDKN1A(1), PCNA(1), RB1(3) 8595584 15 13 15 12 0 4 6 0 5 0 0.0023 0.024 61 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 110 ADCY2(1), ADCY5(3), ADCY7(1), ADCY8(4), ADSL(1), AK2(1), AK5(1), ALLC(1), AMPD3(1), ATP5A1(1), ATP5G2(1), ENPP3(2), GART(1), GDA(1), GUCY1A2(1), GUCY1A3(2), GUCY2C(2), GUCY2F(1), IMPDH1(1), IMPDH2(2), NPR1(3), NPR2(1), PAPSS2(1), PDE4A(2), PDE4C(4), PDE5A(1), PDE6C(2), PDE8A(1), PFAS(1), POLD1(2), POLE(1), POLL(1), POLQ(3), POLR2A(4), POLR2B(1), POLR2I(1), POLRMT(1), PRPS1L1(1), PRPS2(1), PRUNE(1), RRM2(1) 63445862 63 55 63 11 11 15 20 3 14 0 0.0024 0.024 62 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), ADCY2(1), ADCY5(3), ADCY7(1), ADCY8(4), ADCY9(2), ATF4(1), ATF5(1), ATP2A2(2), CALM2(1), CAMK2G(2), CNN2(1), DGKZ(1), GABPA(1), GBA2(3), GNB1(2), GNG12(1), GNG3(1), GRK6(1), GUCA2A(1), GUCY1A3(2), IGFBP3(1), ITPR1(1), ITPR2(4), ITPR3(1), JUN(1), NOS1(5), NOS3(1), PKIA(1), PLCD1(1), PLCG1(1), PLCG2(1), PRKACA(1), PRKACB(1), PRKCD(2), PRKCH(2), PRKCQ(2), PRKCZ(1), PRKD1(3), RAMP1(1), RAMP3(1), RGS17(1), RGS18(1), RGS2(1), RGS3(3), RGS9(1), RLN1(1), RYR1(3), RYR2(3), RYR3(3), SLC8A1(1), TNXB(1) 85419334 84 72 84 28 10 22 40 1 11 0 0.0025 0.025 63 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 DPM2(1), EGFR(4), GNAS(1), GNB1(2), HRAS(2), ITGB1(2), KLK2(1), MKNK2(2), PDGFRA(3), PPP2CA(2), RPS6KA1(1), SOS1(4) 16247220 25 24 25 8 3 8 11 0 3 0 0.0027 0.026 64 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 128 ACACA(3), AKT1(2), AKT2(2), BRAF(3), CALM2(1), CBL(1), CBLB(1), FBP1(1), GSK3B(1), GYS1(2), GYS2(1), HRAS(2), INSR(4), IRS1(1), LIPE(2), MAPK10(1), MAPK9(1), MKNK2(2), PCK1(2), PDE3A(2), PDE3B(1), PFKM(2), PHKA1(1), PHKB(2), PHKG1(1), PIK3CB(1), PIK3CD(1), PIK3CG(4), PIK3R1(2), PPARGC1A(3), PPP1R3A(1), PPP1R3D(1), PRKACA(1), PRKACB(1), PRKAG1(2), PRKAG2(1), PRKCI(1), PRKCZ(1), PTPRF(3), RHEB(1), RPS6KB1(2), SORBS1(1), SOS1(4), SOS2(2), TSC1(2), TSC2(2) 76189507 79 68 79 30 9 26 31 3 10 0 0.0027 0.026 65 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 136 CHAD(1), COL11A1(2), COL17A1(1), COL1A2(6), COL2A1(3), COL4A1(1), COL4A4(2), COL4A6(2), COL5A1(2), COL5A2(1), COL5A3(2), COL6A3(5), COL6A6(5), DSC2(1), DSC3(1), DSG1(2), DSG2(1), DSG3(1), DSG4(1), FN1(2), GJA4(1), GJA8(1), GJB6(1), GJC2(1), GJD2(1), GJD4(1), ITGA6(2), KRT12(1), KRT13(1), KRT15(2), KRT16(1), KRT18(1), KRT2(1), KRT28(1), KRT31(1), KRT33A(1), KRT35(1), KRT36(2), KRT4(2), KRT6B(1), KRT72(1), KRT73(1), KRT74(1), KRT75(2), KRT78(1), KRT79(2), KRT82(1), KRT84(1), KRT85(2), KRT86(1), LAMA1(3), LAMA2(5), LAMA3(1), LAMA4(3), LAMA5(4), LAMB1(3), LAMB2(1), LAMB4(4), LAMC2(3), LAMC3(3), LMNB1(1), RELN(3), THBS1(4), THBS2(1), THBS3(1), THBS4(1), TNC(2), TNN(2), TNR(3), TNXB(1), VTN(1), VWF(5) 119620779 134 95 134 55 18 32 52 8 24 0 0.0029 0.028 66 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 12 APC(5), AXIN1(1), DLL1(1), FZD1(2), GSK3B(1), NOTCH1(6) 9575567 16 16 16 10 1 3 9 0 3 0 0.0030 0.028 67 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 81 ATM(8), BUB1(1), CCNA1(2), CCNB2(2), CCNB3(2), CCND2(1), CDAN1(1), CDC14A(2), CDC25A(1), CDC6(1), CDH1(2), CDK2(1), CDK4(1), CDKN1A(1), CDKN2A(1), CHEK2(1), DTX4(1), EP300(3), ESPL1(3), GSK3B(1), HDAC4(1), MAD2L1(1), MCM2(3), MCM6(2), MCM7(1), ORC1L(1), ORC4L(1), ORC5L(1), PCNA(1), PLK1(1), PRKDC(2), PTPRA(1), RB1(3), SMAD4(4), TBC1D8(1), WEE1(1) 54741221 61 52 61 39 4 16 25 3 13 0 0.0031 0.028 68 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 58 APC(5), AXIN1(1), CCND2(1), FZD1(2), FZD10(1), FZD5(1), GSK3B(1), JUN(1), MAPK10(1), MAPK9(1), PAFAH1B1(1), PLAU(3), PRKCD(2), PRKCG(2), PRKCH(2), PRKCI(1), PRKCQ(2), PRKCZ(1), PRKD1(3), SFRP4(1), TCF7(2), WNT5B(1), WNT7B(1) 28540264 37 34 36 22 2 14 15 0 6 0 0.0031 0.028 69 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(4), C5(4), C6(2), C7(2), C8A(1), C9(1) 6324134 14 13 14 0 0 3 9 1 1 0 0.0034 0.030 70 ALKALOID_BIOSYNTHESIS_II ABP1, AOC2, AOC3, CES1, ESD 5 ABP1(4), AOC2(1), CES1(3) 2863414 8 8 8 1 1 2 2 3 0 0 0.0034 0.030 71 METHANE_METABOLISM ADH5, ATP6V0C, SHMT1, CAT, EPX, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, SHMT1, SHMT2, TPO 13 ADH5(1), CAT(2), MPO(3), PRDX1(1), PRDX5(1), SHMT1(1), SHMT2(2), TPO(1) 5834910 12 12 12 0 1 2 8 0 1 0 0.0034 0.030 72 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 30 AKT1(2), AKT2(2), ANKRD6(1), APC(5), AXIN1(1), DACT1(2), DKK2(1), FSTL1(1), GSK3A(2), GSK3B(1), LRP1(5), MVP(1), NKD1(1), PTPRA(1), SFRP1(2) 19769296 28 26 27 13 2 7 12 1 6 0 0.0037 0.032 73 NFATPATHWAY Cardiac hypertrophy is induced by NF-ATc4 and GATA4, which are stimulated through calcineurin activated by CaMK. ACTA1, AGT, AKT1, CALM1, CALM2, CALM3, CALR, CAMK1, CAMK1G, CAMK4, CREBBP, CSNK1A1, CTF1, DTR, EDN1, ELSPBP1, F2, FGF2, FKBP1A, GATA4, GSK3B, HAND1, HAND2, HRAS, IGF1, LIF, MAP2K1, MAPK1, MAPK14, MAPK3, MAPK8, MEF2C, MYH2, NFATC1, NFATC2, NFATC3, NFATC4, NKX2-5, NPPA, PIK3CA, PIK3R1, PPP3CA, PPP3CB, PPP3CC, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RAF1, RPS6KB1, SYT1 50 ACTA1(1), AKT1(2), CALM2(1), CALR(1), CAMK1(1), CREBBP(3), ELSPBP1(1), F2(2), GATA4(1), GSK3B(1), HRAS(2), MYH2(5), NFATC2(1), NFATC3(2), PIK3R1(2), PPP3CC(1), PRKACB(1), RPS6KB1(2) 23452436 30 30 30 12 4 7 12 0 7 0 0.0041 0.035 74 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 92 ADCY2(1), ADCY5(3), ADCY7(1), ADCY8(4), ADCY9(2), DRD1(1), EGF(1), EGFR(4), GJD2(1), GNAS(1), GRM1(1), GRM5(1), GUCY1A2(1), GUCY1A3(2), GUCY2C(2), GUCY2F(1), HRAS(2), HTR2A(1), HTR2C(1), ITPR1(1), ITPR2(4), ITPR3(1), NPR1(3), NPR2(1), PDGFD(1), PDGFRA(3), PLCB1(1), PLCB2(1), PLCB4(3), PRKACA(1), PRKACB(1), PRKCG(2), PRKG1(1), PRKG2(1), SOS1(4), SOS2(2), TJP1(1), TUBA3C(1), TUBA3D(1), TUBA4A(1), TUBAL3(1), TUBB1(1) 65019970 68 60 68 29 8 22 25 1 12 0 0.0051 0.042 75 INOSITOL_PHOSPHATE_METABOLISM IMPA1, INPP1, INPP4A, INPP4B, INPP5A, INPPL1, ITPKA, ITPKB, MIOX, OCRL, PIK3C2A, PIK3C2B, PIK3C2G, PIK3CA, PIK3CB, PIK3CG, PIK4CA, PIK4CA, LOC220686, PIP5K2B, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCG1, PLCG2 22 INPP4A(1), INPP4B(2), INPP5A(1), ITPKA(1), ITPKB(1), MIOX(1), OCRL(2), PIK3C2G(1), PIK3CB(1), PIK3CG(4), PLCB1(1), PLCB2(1), PLCB4(3), PLCD1(1), PLCG1(1), PLCG2(1) 21141005 23 22 23 8 1 7 7 0 8 0 0.0051 0.042 76 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 24 AKT1(2), AKT2(2), GSK3A(2), GSK3B(1), IL4R(1), IRS1(1), JAK1(2), JAK3(1), MAP4K1(1), PDK1(1), PIK3CD(1), PIK3R1(2), PPP1R13B(1), SOS1(4), SOS2(2), STAT6(2) 16275620 26 24 26 5 6 5 11 1 3 0 0.0054 0.044 77 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(5), CDH1(2), CREBBP(3), EP300(3), MAP3K7(1), SKIL(1), TGFB2(1), TGFB3(1), TGFBR2(2) 12682942 19 19 19 13 3 4 8 0 4 0 0.0055 0.044 78 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(2), APC(5), AXIN1(1), FZD1(2), GSK3B(1), IRAK1(2), LBP(2), PIK3R1(2), PPP2CA(2), RELA(1), TLR4(1) 13551385 21 21 21 13 3 5 10 0 3 0 0.0056 0.044 79 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), DLAT(2), FBP1(1), GAPDHS(2), GOT1(2), GOT2(3), GPI(1), HK1(3), LDHAL6B(1), LDHB(1), LDHC(1), MDH1(1), PCK1(2), PDHX(1), PFKM(2), PGAM1(1), PGK1(3) 20479664 28 25 28 6 1 7 9 4 7 0 0.0057 0.044 80 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 162 ADORA2A(1), ADRB2(1), AVPR1A(2), BDKRB1(1), C3AR1(1), CCKAR(2), CCKBR(1), CHML(1), CHRM2(1), CHRM5(2), CMKLR1(1), CNR2(1), DRD1(1), DRD5(1), GPR17(1), GPR173(2), GPR174(3), GPR35(1), GPR50(1), GPR63(1), GPR83(1), HTR1A(1), HTR2A(1), HTR2C(1), HTR5A(1), HTR6(1), HTR7(1), LTB4R(1), MAS1(1), MC3R(1), NMBR(1), NPY1R(1), NTSR1(1), OPN1SW(1), OPRD1(1), OPRM1(1), OR12D3(1), OR1F1(1), OR5V1(1), OR7A5(1), OR8B8(1), P2RY10(2), P2RY13(1), P2RY2(1), PTAFR(1), PTGDR(1), PTGER2(1), PTGFR(1), SSTR1(2), SSTR4(1) 57449655 58 54 58 16 4 16 30 1 7 0 0.0059 0.045 81 BBCELLPATHWAY Fas ligand expression by T cells induces apoptosis in Fas-expressing, inactive B cells. CD28, CD4, HLA-DRA, HLA-DRB1, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 4 CD4(1), HLA-DRA(1), HLA-DRB1(3) 1043406 5 4 5 3 0 2 1 1 1 0 0.0060 0.045 82 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(1), EEF1D(1), EIF2AK1(3), EIF2AK2(2), EIF2AK3(1), EIF2B1(2), EIF2B2(1), EIF2S2(1), EIF4A2(1), EIF4E(1), EIF4G1(2), EIF4G3(1), EIF5(2), EIF5A(1), ETF1(3), KIAA0664(2), PABPC1(1), PABPC3(3), SLC35A4(2) 21641122 31 29 31 12 6 9 9 2 5 0 0.0061 0.045 83 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 19 AKT1(2), EIF4A2(1), EIF4E(1), EIF4G1(2), EIF4G2(2), EIF4G3(1), PIK3R1(2), PPP2CA(2), RPS6KB1(2), TSC1(2), TSC2(2) 11905892 19 19 19 4 3 7 3 2 4 0 0.0062 0.046 84 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 C1QA(1), C1S(1), C3(4), C5(4), C6(2), C7(2), C8A(1), C9(1) 8609056 16 15 16 1 0 3 11 1 1 0 0.0067 0.049 85 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(4), C5(4), C6(2), C7(2), ITGAL(2), ITGB1(2), SELP(1), SELPLG(3), VCAM1(1) 12196641 21 20 21 3 1 3 13 2 2 0 0.0069 0.050 86 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 35 ANPEP(3), G6PD(1), GGT1(2), GPX3(3), GSS(1), IDH1(1), IDH2(1), OPLAH(1), TXNDC12(1) 10517621 14 14 14 5 1 4 6 0 3 0 0.0070 0.050 87 HSA04660_T_CELL_RECEPTOR_SIGNALING_PATHWAY Genes involved in T cell receptor signaling pathway AKT1, AKT2, AKT3, BCL10, CARD11, CBL, CBLB, CBLC, CD247, CD28, CD3D, CD3E, CD3G, CD4, CD40LG, CD8A, CD8B, CDC42, CDK4, CHP, CHUK, CSF2, CTLA4, FOS, FYN, GRAP2, GRB2, HRAS, ICOS, IFNG, IKBKB, IKBKG, IL10, IL2, IL4, IL5, ITK, JUN, KRAS, LAT, LCK, LCP2, MALT1, MAP3K14, MAP3K8, NCK1, NCK2, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NRAS, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDCD1, PDK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKCQ, PTPN6, PTPRC, RASGRP1, RHOA, SOS1, SOS2, TEC, TNF, VAV1, VAV2, VAV3, ZAP70 91 AKT1(2), AKT2(2), CARD11(3), CBL(1), CBLB(1), CD4(1), CDK4(1), FYN(1), HRAS(2), ITK(2), JUN(1), MALT1(1), NFAT5(1), NFATC2(1), NFATC3(2), NFKBIB(1), PAK1(1), PAK4(2), PAK6(1), PAK7(1), PDK1(1), PIK3CB(1), PIK3CD(1), PIK3CG(4), PIK3R1(2), PLCG1(1), PPP3CC(1), PRKCQ(2), PTPRC(4), SOS1(4), SOS2(2), TEC(1), VAV1(1), VAV3(1), ZAP70(1) 48557885 55 49 55 19 6 21 22 1 5 0 0.0077 0.055 88 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(1), CALR(1), CD4(1), CD74(1), CIITA(1), CTSB(2), CTSL1(1), HLA-B(1), HLA-C(1), HLA-DMB(1), HLA-DQB1(2), HLA-DRA(1), HLA-DRB1(3), HLA-E(1), HLA-F(1), HSP90AA1(3), HSP90AB1(1), HSPA5(2), IFNA21(1), IFNA5(1), IFNA7(1), IFNA8(1), KLRC1(1), TAP1(1), TAP2(1) 21291644 32 29 32 12 5 12 8 3 4 0 0.0083 0.058 89 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 DAXX(2), HRAS(2), HSPB2(1), MAP3K1(1), MAP3K5(1), MAP3K7(1), MAPKAPK5(1), MAX(2), MEF2A(1), RIPK1(1), STAT1(3), TGFB2(1), TGFB3(1), TRADD(1) 18158506 19 19 19 2 3 7 3 0 6 0 0.0084 0.058 90 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 21 AKT1(2), CDK2(1), CDK4(1), CDKN1A(1), HRAS(2), PAK1(1), PIK3R1(2), RB1(3), RELA(1) 8940515 14 14 14 10 2 5 5 0 2 0 0.0084 0.058 91 IFNGPATHWAY IFN gamma signaling pathway IFNG, IFNGR1, IFNGR2, JAK1, JAK2, STAT1 6 IFNGR1(1), IFNGR2(1), JAK1(2), JAK2(2), STAT1(3) 4048587 9 8 9 1 0 5 2 0 2 0 0.0085 0.058 92 HSA00680_METHANE_METABOLISM Genes involved in methane metabolism ADH5, CAT, EPX, LPO, MPO, MTHFR, PRDX6, SHMT1, SHMT2, TPO 10 ADH5(1), CAT(2), MPO(3), MTHFR(1), SHMT1(1), SHMT2(2), TPO(1) 5734934 11 11 11 0 1 2 7 0 1 0 0.0086 0.058 93 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 CDK2(1), CUL1(2), FBXW7(3), RB1(3) 4196502 9 8 9 8 0 2 4 0 3 0 0.0090 0.059 94 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 ADCY2(1), ADCY5(3), ADCY7(1), ADCY8(4), ADCY9(2), AKAP10(1), AKAP11(1), AKAP7(1), AKAP9(4), CALM2(1), CHMP1B(1), GNA13(1), GNAL(1), GNAO1(1), GNAZ(1), GNB1(2), GNG12(1), GNG3(1), HRAS(2), IL18BP(1), ITPR1(1), KCNJ3(3), PDE1B(2), PDE1C(1), PDE4A(2), PDE4C(4), PDE8A(1), PPP3CC(1), PRKACA(1), PRKACB(1), PRKCD(2), PRKCG(2), PRKCH(2), PRKCI(1), PRKCQ(2), PRKCZ(1), PRKD1(3), PRKD3(2), SLC9A1(1) 57930118 64 56 64 25 8 18 25 2 11 0 0.0090 0.059 95 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 61 AKT1(2), AKT2(2), CARD11(3), CD19(1), CD22(2), CR2(2), GSK3B(1), HRAS(2), JUN(1), LILRB3(3), MALT1(1), NFAT5(1), NFATC2(1), NFATC3(2), NFKBIB(1), PIK3CB(1), PIK3CD(1), PIK3CG(4), PIK3R1(2), PLCG2(1), PPP3CC(1), SYK(1), VAV1(1), VAV3(1) 35308829 38 36 38 14 4 14 13 0 7 0 0.0095 0.061 96 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 CD4(1), CREBBP(3), CSK(1), GNAS(1), GNB1(2), HLA-DRA(1), HLA-DRB1(3), PRKACB(1), PTPRC(4), ZAP70(1) 11034545 18 16 18 7 1 6 8 1 2 0 0.010 0.064 97 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 CD4(1), CREBBP(3), CSK(1), GNAS(1), GNB1(2), HLA-DRA(1), HLA-DRB1(3), PRKACB(1), PTPRC(4), ZAP70(1) 11034545 18 16 18 7 1 6 8 1 2 0 0.010 0.064 98 PLK3PATHWAY Active Plk3 phosphorylates CDC25c, blocking the G2/M transition, and phosphorylates p53 to induce apoptosis. ATM, ATR, CDC25C, CHEK1, CHEK2, CNK, TP53, YWHAH 6 ATM(8), ATR(4), CHEK2(1) 7423126 13 12 13 12 0 4 4 1 4 0 0.010 0.064 99 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 13 ARPC2(1), ARPC3(1), PAK1(1), PDGFRA(3), PIK3R1(2), WASL(2) 5528940 10 10 10 7 2 1 5 0 2 0 0.010 0.064 100 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(2), CDK2(1), CUL1(2), RB1(3) 4308009 8 8 8 6 0 3 2 0 3 0 0.010 0.064 101 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 ACSL1(1), ACSL3(1), ACSL5(1), ACSL6(2), AKT1(2), AKT2(2), CAMKK1(1), CAMKK2(2), IRS1(1), JAK1(2), JAK2(2), JAK3(1), LEPR(1), MAPK10(1), MAPK9(1), NFKBIB(1), NPY(1), PCK1(2), POMC(1), PPARGC1A(3), PRKAG1(2), PRKAG2(1), PRKCQ(2), PTPN11(1), RELA(1), RXRB(1), RXRG(2), TNFRSF1A(1), TRADD(1), TYK2(2) 39820344 43 41 43 17 4 14 18 2 5 0 0.011 0.068 102 G1_TO_S_CELL_CYCLE_REACTOME ATM, CCNA1, CCNB1, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCNG2, CCNH, CDC25A, CDC45L, CDK2, CDK4, CDK7, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CREB3, CREB3L1, CREB3L3, CREB3L4, CREBL1, CREBL1, TNXB, E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, FLJ14001, GADD45A, GBA2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, MNAT1, MYC, MYT1, NACA, NACA, FKSG17, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, POLA2, POLE, POLE2, PRIM1, PRIM2A, RB1, RBL1, RPA1, RPA2, RPA3, TFDP1, TFDP2, TP53, WEE1 63 ATM(8), CCNA1(2), CCND2(1), CDC25A(1), CDK2(1), CDK4(1), CDKN1A(1), CDKN2A(1), CDKN2C(1), GBA2(3), MCM2(3), MCM6(2), MCM7(1), MNAT1(1), NACA(2), ORC1L(1), ORC4L(1), ORC5L(1), PCNA(1), POLE(1), POLE2(1), RB1(3), RPA3(1), TFDP2(3), TNXB(1), WEE1(1) 36318895 44 39 44 26 4 13 18 1 8 0 0.011 0.069 103 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(3), ACO1(3), ACSS1(2), ACSS2(2), IDH1(1), IDH2(1), MDH1(1) 6525575 13 12 13 7 1 2 8 0 2 0 0.012 0.073 104 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 27 BRAF(3), EGFR(4), ERBB2(3), ERBB4(3), ETV6(1), NOTCH1(6), NOTCH2(2), NOTCH3(2), PIWIL2(1), SOS1(4), SOS2(2), SPIRE1(1), SPIRE2(1) 23130667 33 31 33 16 2 10 15 1 5 0 0.013 0.074 105 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), ACTN2(2), DMD(6), MYBPC1(1), MYBPC2(1), MYBPC3(2), MYH3(3), MYH6(3), MYH7(2), MYH8(1), MYL1(1), MYL9(1), MYOM1(3), NEB(7), TMOD1(1), TNNT1(1), TNNT2(1), TNNT3(1), TTN(39) 69036756 77 64 77 24 15 27 25 1 9 0 0.013 0.077 106 FOLATE_BIOSYNTHESIS ALPI, ALPL, ALPP, ALPP, ALPPL2, ALPPL2, DHFR, FPGS, GCH1, GGH, SPR 9 ALPI(1), ALPL(2), ALPP(2), ALPPL2(1), FPGS(2) 3096940 8 7 8 3 0 1 5 1 1 0 0.014 0.078 107 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), EIF4E(1), LDHB(1), LDHC(1), NCL(3) 4342884 9 9 9 3 2 2 2 1 2 0 0.014 0.078 108 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 HRAS(2), JAK1(2), JUN(1), MAP3K1(1), PDGFRA(3), PIK3R1(2), PLCG1(1), SOS1(4), STAT1(3) 16015802 19 19 19 12 3 5 6 0 5 0 0.014 0.078 109 HSA00750_VITAMIN_B6_METABOLISM Genes involved in vitamin B6 metabolism AOX1, PDXK, PDXP, PNPO, PSAT1 5 AOX1(5), PDXP(1) 2380775 6 6 6 0 1 1 2 1 1 0 0.014 0.078 110 HSA00400_PHENYLALANINE_TYROSINE_AND_TRYPTOPHAN_BIOSYNTHESIS Genes involved in phenylalanine, tyrosine and tryptophan biosynthesis FARS2, FARSA, FARSB, GOT1, GOT2, PAH, TAT, YARS, YARS2 9 GOT1(2), GOT2(3), PAH(1), YARS2(1) 4268604 7 7 7 0 1 2 2 0 2 0 0.015 0.083 111 STILBENE_COUMARINE_AND_LIGNIN_BIOSYNTHESIS EPX, GBA3, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TPO, TYR 10 GBA3(1), MPO(3), PRDX1(1), PRDX5(1), TPO(1), TYR(2) 4776007 9 9 9 0 0 2 5 1 1 0 0.016 0.091 112 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 ADCY2(1), ADCY5(3), ADCY7(1), ADCY8(4), ADCY9(2), ADSL(1), AK2(1), AK5(1), ALLC(1), AMPD3(1), ENPP3(2), GART(1), GDA(1), GUCY1A2(1), GUCY1A3(2), GUCY2C(2), GUCY2F(1), IMPDH1(1), IMPDH2(2), NPR1(3), NPR2(1), NT5C1B(1), NT5C3(1), NUDT9(1), PAPSS2(1), PDE11A(2), PDE1C(1), PDE2A(2), PDE3B(1), PDE4A(2), PDE4C(4), PDE5A(1), PDE8A(1), PFAS(1), POLD1(2), POLD3(1), POLE(1), POLE2(1), POLR1A(1), POLR1C(1), POLR2A(4), POLR2B(1), POLR2I(1), POLR3A(1), POLR3B(5), POLR3G(1), POLR3H(1), PRIM2(1), PRPS1L1(1), PRPS2(1), PRUNE(1), RRM2(1), XDH(2) 81223845 80 68 78 16 10 22 28 3 17 0 0.017 0.091 113 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 42 AKT1(2), AKT2(2), ARHGAP1(1), ARHGEF11(1), ITPR1(1), ITPR2(4), ITPR3(1), MYLK(2), PAK1(1), PAK4(2), PAK6(1), PAK7(1), PDK1(1), PIK3CD(1), PIK3CG(4), PIK3R1(2), PPP1R13B(1), RACGAP1(1), ROCK1(2), SAG(1), WASL(2) 33341830 34 34 34 9 3 8 17 2 4 0 0.017 0.091 114 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 HLA-DRA(1), HLA-DRB1(3), IL3(1) 1328354 5 4 5 2 1 1 1 1 1 0 0.017 0.091 115 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(1), F2(2), FGA(1), PLAT(2), PLAU(3), PLG(1) 6608056 11 11 11 6 1 4 2 0 4 0 0.017 0.092 116 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 14 AKT1(2), EGFR(4), POLR2A(4), PPP2CA(2), RB1(3), TERT(1), TNKS(1), XRCC5(1) 13405837 18 17 18 9 2 8 5 0 3 0 0.017 0.092 117 EICOSANOID_SYNTHESIS ALOX12, ALOX15, ALOX15B, ALOX5, ALOX5AP, DPEP1, GGT1, IPLA2(GAMMA), LTA4H, LTC4S, PLA2G2A, PLA2G6, PTGDS, PTGES, PTGIS, PTGS1, PTGS2, TBXAS1 17 ALOX15B(2), ALOX5(1), GGT1(2), LTA4H(1), PLA2G6(2), PTGDS(1), PTGS2(2) 7375888 11 11 11 2 0 5 3 0 3 0 0.018 0.093 118 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 98 AKT1(2), AKT2(2), CASP8(1), CXCL11(1), IFNA21(1), IFNA5(1), IFNA7(1), IFNA8(1), IFNAR1(1), IFNB1(1), IRAK1(2), JUN(1), LBP(2), MAP2K3(2), MAP2K7(1), MAP3K7(1), MAPK10(1), MAPK9(1), PIK3CB(1), PIK3CD(1), PIK3CG(4), PIK3R1(2), RELA(1), RIPK1(1), STAT1(3), TICAM1(2), TICAM2(1), TLR1(1), TLR4(1), TLR6(1), TLR7(1), TLR8(2), TRAF3(1), TRAF6(1) 42608813 47 42 47 14 7 16 16 0 8 0 0.018 0.093 119 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 HBXIP(1), HRAS(2), PTK2B(2), SOS1(4) 4312977 9 9 9 0 1 3 4 0 1 0 0.018 0.093 120 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 ADCY8(4), CACNA1A(1), GNAS(1), GNB1(2), GNG3(1), GRM4(1), ITPR3(1), PLCB2(1), PRKACA(1), PRKACB(1), SCNN1A(2), SCNN1G(1), TAS1R2(3), TAS2R3(1), TAS2R38(1), TAS2R46(2), TAS2R50(1), TAS2R60(1), TAS2R8(1), TAS2R9(1), TRPM5(2) 27822259 30 29 30 11 3 10 12 0 5 0 0.019 0.097 121 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 C1QA(1), C1S(1), C3(4), C5(4), C6(2), C7(2), C8A(1), C9(1), MASP2(1) 10519915 17 16 17 3 0 4 11 1 1 0 0.019 0.097 122 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 73 AKT1(2), AKT2(2), FYN(1), GAB2(1), HRAS(2), IL3(1), MAP2K3(2), MAP2K7(1), MAPK10(1), MAPK9(1), PDK1(1), PIK3CB(1), PIK3CD(1), PIK3CG(4), PIK3R1(2), PLA2G12A(1), PLA2G6(2), PLCG1(1), PLCG2(1), PRKCD(2), SOS1(4), SOS2(2), SYK(1), VAV1(1), VAV3(1) 34173804 39 34 39 14 6 8 19 1 5 0 0.019 0.097 123 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 ACTN2(2), BCAR1(2), CSK(1), CTNNA1(2), CTNNA2(4), PTK2(1), VCL(1) 9824853 13 12 13 5 3 4 2 1 3 0 0.020 0.099 124 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 DAXX(2), EGF(1), EGFR(4), HRAS(2), JUN(1), MAP2K3(2), MAP2K7(1), MAP3K1(1), MAP3K5(1), PPP2CA(2), PRKCD(2), PRKCG(2), PRKCH(2), PRKCQ(2), RELA(1), RIPK1(1), TNFRSF1A(1) 24032454 28 26 28 12 5 8 9 0 6 0 0.020 0.10 125 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 11 AKT1(2), DPM2(1), HRAS(2), KLK2(1), PIK3R1(2), PLCG1(1), SOS1(4) 6591762 13 12 13 4 3 5 5 0 0 0 0.021 0.10 126 GLUTATHIONE_METABOLISM ANPEP, G6PD, GCLC, GCLM, GGT1, GPX1, GPX2, GPX3, GPX4, GPX5, GSS, GSTA1, GSTA2, GSTA3, GSTA4, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, IDH1, IDH2, MGST1, MGST2, MGST3, PGD 29 ANPEP(3), G6PD(1), GGT1(2), GPX3(3), GSS(1), IDH1(1), IDH2(1) 8825515 12 12 12 6 1 3 6 0 2 0 0.024 0.12 127 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(2), BIRC3(1), CASP8(1), RIPK1(1), TNFRSF1A(1), TRADD(1) 3973275 7 7 6 2 0 2 4 0 1 0 0.024 0.12 128 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 IFNGR1(1), JAK1(2), JAK2(2), PTPRU(2), STAT1(3) 5666393 10 9 10 1 1 6 1 0 2 0 0.025 0.12 129 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 23 ARNT(1), EIF1(1), EIF2B1(2), EIF2B2(1), EIF2S2(1), FLT1(2), FLT4(3), HIF1A(1), HRAS(2), KDR(2), NOS3(1), PIK3R1(2), PLCG1(1), PTK2(1) 15167831 21 21 21 11 5 6 8 1 1 0 0.026 0.12 130 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 16 IFNGR1(1), IFNGR2(1), JAK2(2), RB1(3), RELA(1), TNFRSF1A(1), WT1(3) 8445249 12 12 12 10 0 5 6 0 1 0 0.026 0.12 131 COMPLEMENT_ACTIVATION_CLASSICAL C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C8B, C9, DAF, MASP1 13 C1QA(1), C1S(1), C3(4), C5(4), C6(2), C7(2), C8A(1), C9(1) 10221977 16 15 16 1 0 3 11 1 1 0 0.027 0.12 132 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 60 AKT1(2), AKT2(2), CDK2(1), CDKN2A(1), CREB5(1), ERBB4(3), GAB1(1), GSK3A(2), GSK3B(1), IRS1(1), MET(1), PAK1(1), PAK4(2), PAK6(1), PAK7(1), PARD3(1), PDK1(1), PIK3CD(1), PPP1R13B(1), PREX1(3), PTK2(1), RPS6KA1(1), RPS6KA2(1), RPS6KA3(1), RPS6KB1(2), SOS1(4), SOS2(2), TSC1(2), TSC2(2), YWHAE(1) 35288464 45 41 45 13 4 13 20 3 5 0 0.027 0.12 133 NICOTINATE_AND_NICOTINAMIDE_METABOLISM AOX1, CD38, ENPP1, ENPP3, NADSYN1, NMNAT1, NMNAT2, NNMT, NNT, NP, NT5C, NT5E, NT5M, QPRT 13 AOX1(5), CD38(1), ENPP3(2), NNT(4) 7197618 12 12 12 0 2 3 3 2 2 0 0.027 0.12 134 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 ALOX5(1), CBR1(1), CYP4F2(1), GGT1(2), LTA4H(1), MPO(3), PLA2G6(2), PRDX1(1), PRDX5(1), PTGDS(1), PTGS2(2), TPO(1) 13668371 17 17 17 3 0 6 8 0 3 0 0.027 0.12 135 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 31 AKT1(2), AKT2(2), CDKN2A(1), GSK3A(2), GSK3B(1), IARS(1), PDK1(1), PPP1R13B(1), RPS6KA1(1), RPS6KA2(1), RPS6KA3(1), RPS6KB1(2), SOS1(4), SOS2(2), TEC(1), YWHAE(1) 16213115 24 22 24 7 3 6 10 1 4 0 0.027 0.12 136 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 25 AKT1(2), AKT2(2), IARS(1), IL4R(1), JAK1(2), JAK2(2), JAK3(1), PPP1R13B(1), RPS6KB1(2), SERPINA4(1), SOS1(4), SOS2(2), STAT6(2), TYK2(2) 17109693 25 21 25 4 3 6 10 1 5 0 0.028 0.12 137 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(4), AGXT(1), AGXT2(1), AKR1B10(2), ALAS2(1), AOC2(1), CHDH(2), DAO(1), DMGDH(1), GATM(2), MAOA(1), MAOB(1), PHGDH(1), RDH13(1), SARDH(1), SARS(2), SHMT1(1), SHMT2(2), TARS(1), TARS2(2) 21206867 29 26 29 6 3 9 11 3 3 0 0.028 0.12 138 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 B3GNT6(1), C1GALT1C1(1), GALNT1(1), GALNT11(1), GALNT2(1), GALNT5(3), GALNT7(3), GALNTL2(1), GALNTL4(1), GCNT1(2), OGT(3), WBSCR17(1) 15859519 19 19 19 9 3 6 5 0 5 0 0.028 0.12 139 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 6 MAX(2), WT1(3) 2976575 5 5 5 2 0 2 2 0 1 0 0.028 0.13 140 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(3), ABCA12(4), ABCA13(5), ABCA2(1), ABCA4(2), ABCA5(3), ABCA6(1), ABCA7(4), ABCA8(2), ABCA9(2), ABCB1(3), ABCB11(2), ABCB4(1), ABCC1(1), ABCC10(1), ABCC11(1), ABCC12(2), ABCC3(3), ABCC4(3), ABCC5(1), ABCC6(1), ABCC8(1), ABCC9(3), ABCD2(1), ABCD3(1), ABCD4(3), ABCG1(1), ABCG4(2), ABCG5(1), CFTR(3), TAP1(1), TAP2(1) 57591290 68 56 68 29 4 25 29 4 6 0 0.029 0.13 141 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(2), B3GALT4(1), FAU(1), IL6ST(2), PIGK(1), RPL15(1), RPL19(1), RPL22(1), RPL27(1), RPL30(1), RPL31(1), RPL34(1), RPL4(1), RPL5(1), RPL7(1), RPLP0(1), RPS13(1), RPS26(1), RPS29(1), RPS3A(1), RPS6KA1(1), RPS6KA2(1), RPS6KA3(1), RPS6KA6(3), RPS6KB1(2), SLC36A2(1), TSPAN9(1) 25573777 32 29 32 7 3 10 13 1 5 0 0.030 0.13 142 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(2), CALM2(1), CHRNA1(1), FLT1(2), FLT4(3), KDR(2), NOS3(1), PDE2A(2), PDE3A(2), PDE3B(1), PRKACB(1), PRKG1(1), PRKG2(1), RYR2(3) 20010945 24 24 24 8 6 6 8 1 3 0 0.030 0.13 143 PHENYLALANINE_TYROSINE_AND_TRYPTOPHAN_BIOSYNTHESIS ENO1, ENO2, ENO3, FARS2, FARSLB, GOT1, GOT2, PAH, TAT, YARS 9 GOT1(2), GOT2(3), PAH(1) 4059837 6 6 6 0 1 1 2 0 2 0 0.031 0.13 144 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(2), CCND2(1), CDC25A(1), CDK2(1), CDK4(1), CDKN1A(1), CDKN2A(1), CDKN2C(1), RB1(3) 7818193 12 11 12 9 0 6 4 0 2 0 0.032 0.14 145 SA_TRKA_RECEPTOR The TrkA receptor binds nerve growth factor to activate MAP kinase pathways and promote cell growth. AKT1, AKT2, AKT3, ARHA, CDKN1A, ELK1, GRB2, HRAS, MAP2K1, MAP2K2, NGFB, NGFR, NTRK1, PIK3CA, PIK3CD, SHC1, SOS1 14 AKT1(2), AKT2(2), CDKN1A(1), HRAS(2), PIK3CD(1), SOS1(4) 6897589 12 12 12 0 1 5 6 0 0 0 0.033 0.14 146 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 ALOX15B(2), ALOX5(1), CBR1(1), CYP2B6(1), CYP2C18(1), CYP2C19(1), CYP2C8(1), CYP2J2(1), CYP4A11(2), CYP4A22(1), CYP4F2(1), DHRS4(1), EPHX2(1), GGT1(2), GPX3(3), LTA4H(1), PLA2G12A(1), PLA2G6(2), PTGDS(1), PTGS2(2) 19256833 27 24 27 7 3 6 13 1 4 0 0.033 0.14 147 ST_ADRENERGIC Adrenergic receptors respond to epinephrine and norepinephrine signaling. AKT1, APC, AR, ASAH1, BF, BRAF, CAMP, CCL13, CCL15, CCL16, DAG1, EGFR, GAS, GNA11, GNA15, GNAI1, GNAQ, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, KCNJ3, KCNJ5, KCNJ9, MAPK1, MAPK10, MAPK14, PHKA2, PIK3CA, PIK3CD, PIK3R1, PITX2, PTX1, PTX3, RAF1, SRC 33 AKT1(2), APC(5), AR(1), BRAF(3), EGFR(4), ITPKA(1), ITPKB(1), ITPR1(1), ITPR2(4), ITPR3(1), KCNJ3(3), KCNJ5(1), MAPK10(1), PIK3CD(1), PIK3R1(2) 25416835 31 28 31 18 4 10 10 1 6 0 0.035 0.15 148 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(2), IL4R(1), IRS1(1), JAK1(2), JAK3(1), RPS6KB1(2), STAT6(2) 7150692 11 10 11 2 2 2 3 0 4 0 0.035 0.15 149 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(2), AKT2(2), BRAF(3), EGFR(4), EPHB2(1), ITPKA(1), ITPKB(1), ITPR1(1), ITPR2(4), ITPR3(1), KCNJ3(3), KCNJ5(1), PIK3CB(1), PLCB1(1), PLCB2(1), PLCB4(3), SOS1(4), SOS2(2) 29039649 36 33 36 14 2 14 14 1 5 0 0.036 0.15 150 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(4), AGXT(1), AGXT2(1), ALAS2(1), AOC2(1), CHDH(2), DAO(1), DMGDH(1), GATM(2), MAOA(1), MAOB(1), PLCB2(1), PLCG1(1), PLCG2(1), SARDH(1), SARS(2), SHMT1(1), SHMT2(2), TARS(1) 20779099 26 25 26 6 1 8 11 3 3 0 0.036 0.15 151 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 44 CBL(1), CSK(1), EPHB2(1), FBXW7(3), ITK(2), ITPKA(1), ITPKB(1), NFAT5(1), NFKBIB(1), NFKBIL2(1), PAK1(1), PAK4(2), PAK6(1), PAK7(1), PLCG1(1), PTPRC(4), RASGRP2(2), RASGRP4(2), SOS1(4), SOS2(2), VAV1(1), ZAP70(1) 27286173 35 32 35 11 4 12 16 0 3 0 0.036 0.15 152 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 14 AKT1(2), AKT2(2), ILK(1), PDK1(1), PIK3CD(1), PTK2B(2), RBL2(1), SOS1(4) 8490913 14 14 14 1 1 5 6 1 1 0 0.037 0.15 153 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 48 CREBBP(3), EP300(3), HSD17B4(1), JUN(1), ME1(1), NCOA1(1), NCOR1(2), NCOR2(3), NR1H3(1), NRIP1(4), PIK3R1(2), PRKACB(1), PTGS2(2), RB1(3), RELA(1), STAT5B(1) 29325386 30 29 30 18 2 8 16 0 4 0 0.038 0.15 154 GLYCOSAMINOGLYCAN_DEGRADATION ARSB, GALNS, GLB1, GNS, GUSB, HEXA, HEXB, IDS, IDUA, LCT, NAGLU 11 ARSB(1), GLB1(3), GNS(1), GUSB(2), HEXA(1), IDS(2), IDUA(1), LCT(1), NAGLU(1) 7108167 13 11 13 3 1 4 4 1 3 0 0.038 0.15 155 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 BAG4(2), CASP2(1), CASP8(1), JUN(1), LMNB1(1), MADD(2), MAP3K1(1), MAP3K7(1), PAK1(1), PRKDC(2), RB1(3), RIPK1(1), SPTAN1(1), TNFRSF1A(1), TRADD(1) 19552017 20 20 19 13 0 6 9 0 5 0 0.038 0.15 156 NOTCHPATHWAY Proteolysis and Signaling Pathway of Notch ADAM17, DLL1, FURIN, NOTCH1, PSEN1, RBPSUH 5 DLL1(1), NOTCH1(6) 3935694 7 7 7 2 1 1 4 0 1 0 0.039 0.15 157 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 25 EGF(1), EGFR(4), HRAS(2), JAK1(2), JUN(1), MAP3K1(1), PIK3R1(2), PLCG1(1), SOS1(4), STAT1(3) 17304203 21 21 21 9 4 7 6 0 4 0 0.039 0.15 158 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 37 GTF2E2(2), GTF2H1(2), GTF2H2(2), ILK(1), MNAT1(1), POLR1A(1), POLR2A(4), POLR2B(1), POLR2I(1), POLR3B(5), POLR3H(1), TAF13(1), TAF5(3) 17252534 25 24 23 11 2 12 8 0 3 0 0.039 0.15 159 MRPPATHWAY Cancer cells resistant to numerous drugs are called multidrug-resistant (MDR) and express ATP-binding cassette transporter proteins that pump the drugs out of cells. ABCB1, ABCB11, ABCB4, ABCC1, ABCC3, GSTP1 6 ABCB1(3), ABCB11(2), ABCB4(1), ABCC1(1), ABCC3(3) 7150579 10 10 10 0 0 6 2 1 1 0 0.040 0.15 160 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(4), ALDH1A2(1), ALDH1B1(2), ALDH3A2(1), ALDH3B1(1), ALDH3B2(1), AOC2(1), DDC(2), HARS(1), MAOA(1), MAOB(1), PRPS2(1) 12024157 17 16 17 3 2 2 8 4 1 0 0.041 0.16 161 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 21 AKT1(2), HRAS(2), JAK2(2), JUN(1), MAP3K1(1), PIK3R1(2), SOS1(4), STAT1(3), STAT5B(1) 12435432 18 18 18 5 3 7 7 0 1 0 0.042 0.16 162 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 19 AKT1(2), ATM(8), CASP7(1), PTK2(1), STAT1(3), TLN1(3) 13196032 18 17 18 11 1 6 8 0 3 0 0.042 0.16 163 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 ACADS(2), ALDH1A2(1), ALDH1B1(2), ALDH3A2(1), AOX1(5), BCAT1(1), ECHS1(1), HADHA(1), HADHB(2), IVD(1), MCCC2(3), MCEE(1), OXCT1(1), PCCA(1), PCCB(1) 17749922 24 24 24 7 6 6 8 1 3 0 0.043 0.16 164 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(8), CDC25A(1), WEE1(1) 6831521 10 9 10 9 0 2 5 0 3 0 0.043 0.16 165 G2PATHWAY Activated Cdc2-cyclin B kinase regulates the G2/M transition; DNA damage stimulates the DNA-PK/ATM/ATR kinases, which inactivate Cdc2. ATM, ATR, BRCA1, CCNB1, CDC2, CDC25A, CDC25B, CDC25C, CDC34, CDKN1A, CDKN2D, CHEK1, CHEK2, EP300, GADD45A, MDM2, MYT1, PLK, PRKDC, RPS6KA1, TP53, WEE1, YWHAH, YWHAQ 21 ATM(8), ATR(4), BRCA1(1), CDC25A(1), CDKN1A(1), CHEK2(1), EP300(3), PRKDC(2), RPS6KA1(1), WEE1(1) 20858560 23 22 23 18 0 8 8 1 6 0 0.043 0.16 166 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(5), CD38(1), ENPP3(2), NNT(4), NT5C1B(1), NT5C3(1), NUDT12(1) 10657174 15 15 15 3 2 4 5 2 2 0 0.044 0.16 167 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 14 AKT1(2), BCAR1(2), ILK(1), ITGB1(2), PIK3R1(2), PTK2(1), SOS1(4) 7901277 14 13 14 4 4 3 6 0 1 0 0.045 0.16 168 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 13 JUN(1), KEAP1(2), NFE2L2(4) 4243937 7 7 7 5 0 1 4 1 1 0 0.045 0.16 169 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 32 AKT1(2), CBL(1), HRAS(2), IL2RB(1), IRS1(1), JAK1(2), JAK3(1), PIK3R1(2), RPS6KB1(2), SOS1(4), STAT5B(1), SYK(1) 16383799 20 20 20 8 4 5 6 0 5 0 0.048 0.17 170 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 CALM2(1), CAMK2G(2), F2(2), FYN(1), GNB1(2), HRAS(2), JAK2(2), MAPT(1), MYLK(2), PLCG1(1), PTK2B(2), SOS1(4), STAT1(3) 20609579 25 25 25 7 1 7 13 2 2 0 0.049 0.18 171 ASBCELLPATHWAY B cells require interaction with helper T cells to produce antigen-specific immunoglobulins as a key element of the human immune response. CD28, CD4, CD80, HLA-DRA, HLA-DRB1, IL10, IL2, IL4, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 8 CD4(1), HLA-DRA(1), HLA-DRB1(3) 1828206 5 4 5 3 0 2 1 1 1 0 0.050 0.18 172 HSA00940_PHENYLPROPANOID_BIOSYNTHESIS Genes involved in phenylpropanoid biosynthesis EPX, GBA, GBA3, LPO, MPO, PRDX6, TPO 7 GBA(2), GBA3(1), MPO(3), TPO(1) 4168251 7 7 7 2 0 3 3 1 0 0 0.050 0.18 173 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 76 AKT1(2), AKT2(2), ARHGEF7(1), BCAR1(2), BRAF(3), CDKN2A(1), CSE1L(1), DOCK1(1), EPHB2(1), FYN(1), GRB7(1), GRLF1(2), ILK(1), ITGA1(1), ITGA11(2), ITGA3(2), ITGA6(2), ITGA8(1), ITGA9(2), MAP2K7(1), MAP3K11(1), MAPK10(1), MAPK8IP1(1), MAPK8IP3(1), MAPK9(1), MRAS(1), MYLK(2), PAK1(1), PAK4(2), PAK6(1), PAK7(1), PIK3CB(1), PLCG1(1), PLCG2(1), PTK2(1), ROCK1(2), SOS1(4), SOS2(2), TLN1(3), TLN2(4) 58648293 62 50 62 27 5 18 30 2 7 0 0.052 0.19 174 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@ 16 HLA-DRA(1), HLA-DRB1(3), ITK(2), PIK3R1(2), PTPN11(1) 5064595 9 7 9 6 2 2 2 1 2 0 0.054 0.19 175 SIG_BCR_SIGNALING_PATHWAY Members of the BCR signaling pathway AKT1, AKT2, AKT3, BAD, BCL2, BCR, BLNK, BTK, CD19, CD22, CD81, CR2, CSK, DAG1, FLOT1, FLOT2, GRB2, GSK3A, GSK3B, INPP5D, ITPR1, ITPR2, ITPR3, LYN, MAP4K1, MAPK1, MAPK3, NFATC1, NFATC2, NR0B2, PDK1, PIK3CA, PIK3CD, PIK3R1, PLCG2, PPP1R13B, PPP3CA, PPP3CB, PPP3CC, PTPRC, RAF1, SHC1, SOS1, SOS2, SYK, VAV1 45 AKT1(2), AKT2(2), CD19(1), CD22(2), CR2(2), CSK(1), GSK3A(2), GSK3B(1), ITPR1(1), ITPR2(4), ITPR3(1), MAP4K1(1), NFATC2(1), PDK1(1), PIK3CD(1), PIK3R1(2), PLCG2(1), PPP1R13B(1), PPP3CC(1), PTPRC(4), SOS1(4), SOS2(2), SYK(1), VAV1(1) 35031548 40 37 40 8 6 11 15 1 7 0 0.057 0.20 176 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 32 ACVR1(1), APC(5), AXIN1(1), BMP2(1), BMP4(1), BMP7(1), BMPR2(2), CHRD(1), FZD1(2), GATA4(1), GSK3B(1), MAP3K7(1), NPPB(1), RFC1(1), TGFB2(1), TGFB3(1), TGFBR2(2) 17503505 24 21 24 11 6 5 8 0 5 0 0.057 0.20 177 LYSINE_BIOSYNTHESIS AADAT, AASDH, AASDHPPT, AASS, KARS 5 AASDH(2), AASDHPPT(1), AASS(1), KARS(1) 3427954 5 5 5 1 0 2 0 0 3 0 0.058 0.20 178 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 21 HRAS(2), IL6R(1), IL6ST(2), JAK1(2), JAK2(2), JAK3(1), JUN(1), PTPN11(1), SOS1(4) 11734328 16 15 16 5 3 4 6 0 3 0 0.062 0.21 179 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(2), BIRC2(2), BIRC3(1), CASP8(1), JUN(1), MAP3K3(1), MAP3K7(1), NFKBIB(1), NFKBIL2(1), NR2C2(1), RALBP1(1), RIPK1(1), TNFRSF1A(1), TRADD(1) 12878207 16 16 15 8 2 5 6 0 3 0 0.064 0.22 180 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 20 AKT1(2), EIF4A2(1), EIF4E(1), EIF4G1(2), EIF4G2(2), EIF4G3(1), GHR(1), IRS1(1), PABPC1(1), PIK3R1(2), RPS6KB1(2) 12208852 16 16 16 11 3 6 3 1 3 0 0.064 0.22 181 HSA00785_LIPOIC_ACID_METABOLISM Genes involved in lipoic acid metabolism LIAS, LIPT1, LOC387787 2 LIAS(2) 748503 2 2 2 1 0 1 1 0 0 0 0.064 0.22 182 LONGEVITYPATHWAY Caloric restriction in animals often increases lifespan, which may occur via decreased IGF receptor expression and consequent expression of stress-resistance proteins. AKT1, CAT, FOXO3A, GH1, GHR, HRAS, IGF1, IGF1R, PIK3CA, PIK3R1, SHC1, SOD1, SOD2, SOD3 12 AKT1(2), CAT(2), GHR(1), HRAS(2), PIK3R1(2) 5391393 9 9 9 3 2 3 4 0 0 0 0.067 0.23 183 P27PATHWAY p27 blocks the G1/S transition by inhibiting the checkpoint kinase cdk2/cyclin E and is inhibited by cdk2-mediated ubiquitination. CCNE1, CDK2, CDKN1B, CKS1B, CUL1, E2F1, NEDD8, RB1, RBX1, SKP1A, SKP2, TFDP1, UBE2M 12 CDK2(1), CUL1(2), RB1(3) 4269289 6 6 6 5 0 2 1 0 3 0 0.067 0.23 184 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 17 DPM2(1), HRAS(2), JUN(1), KLK2(1), PIK3R1(2), PLCG1(1), SOS1(4) 8207442 12 12 12 3 3 4 5 0 0 0 0.068 0.23 185 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 33 GTF2A1(1), GTF2E2(2), GTF2H1(2), GTF2H2(2), GTF2I(1), TAF1(2), TAF13(1), TAF1L(2), TAF4B(2), TAF5(3), TAF5L(1), TAF7L(2) 17607334 21 21 21 5 1 7 11 1 1 0 0.068 0.23 186 UBIQUINONE_BIOSYNTHESIS NDUFA1, NDUFA10, NDUFA11, NDUFA4, NDUFA5, NDUFA8, NDUFB2, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFS1, NDUFS2, NDUFV1, NDUFV2 15 NDUFA10(1), NDUFB6(1), NDUFS1(2), NDUFS2(1), NDUFV2(1) 3436193 6 6 6 2 1 2 3 0 0 0 0.070 0.23 187 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 40 ARNTL(1), CLOCK(1), EIF4G2(2), ETV6(1), HERPUD1(1), HSPA8(4), MYF6(1), NCKAP1(1), NCOA4(2), PER1(2), PER2(1), PSMA4(1), UGP2(1), ZFR(3) 17955631 22 21 22 7 1 7 9 1 4 0 0.070 0.23 188 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(1), EGFR(4), MAP3K1(1), NCOR2(3), RARA(2), THRA(1) 8436214 12 12 12 0 1 4 4 0 3 0 0.072 0.24 189 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 IL22RA1(1), JAK1(2), JAK2(2), JAK3(1), STAT1(3), STAT5B(1), TYK2(2) 9052577 12 11 12 6 1 4 4 1 2 0 0.075 0.25 190 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(2), ITGAL(2), ITGB1(2), SELE(3) 6346170 9 9 9 4 1 2 5 0 1 0 0.079 0.26 191 ATMPATHWAY The tumor-suppressing protein kinase ATM responds to radiation-induced DNA damage by blocking cell-cycle progression and activating DNA repair. ABL1, ATM, BRCA1, CDKN1A, CHEK1, CHEK2, GADD45A, JUN, MAPK8, MDM2, MRE11A, NBS1, NFKB1, NFKBIA, RAD50, RAD51, RBBP8, RELA, TP53, TP73 18 ATM(8), BRCA1(1), CDKN1A(1), CHEK2(1), JUN(1), RAD50(4), RELA(1) 14075699 17 16 17 14 0 3 9 1 4 0 0.084 0.27 192 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 BIRC2(2), BIRC3(1), CASP10(2), CASP7(1), CASP8(1), SCAP(1), SREBF2(3) 8808028 11 11 11 3 4 1 4 0 2 0 0.086 0.28 193 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(1), AR(1), ESRRA(1), NR1H2(2), NR1H3(1), NR1I2(1), NR2C2(1), NR2F2(1), NR5A2(2), PGR(1), RARA(2), RARB(1), RORA(1), RORC(1), RXRB(1), RXRG(2), THRA(1), VDR(1) 20251673 22 21 21 8 3 7 5 2 5 0 0.086 0.28 194 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), GAA(2), GALE(1), GALK1(1), GALK2(1), GLB1(3), HK1(3), LALBA(1), LCT(1), MGAM(2), PFKM(2), RDH13(1), UGP2(1) 18848844 21 20 21 3 1 6 7 2 5 0 0.088 0.28 195 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 14 APC(5), AXIN1(1), CREBBP(3), EP300(3), FZD1(2), GSK3B(1), TRRAP(2) 15946260 17 17 17 15 0 3 11 0 3 0 0.089 0.28 196 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 124 BRAF(3), FYN(1), HLA-B(1), HLA-C(1), HLA-E(1), HRAS(2), IFNA21(1), IFNA5(1), IFNA7(1), IFNA8(1), IFNAR1(1), IFNB1(1), IFNGR1(1), IFNGR2(1), ITGAL(2), KLRC1(1), MICB(1), NFAT5(1), NFATC2(1), NFATC3(2), PAK1(1), PIK3CB(1), PIK3CD(1), PIK3CG(4), PIK3R1(2), PLCG1(1), PLCG2(1), PPP3CC(1), PRKCG(2), PTK2B(2), PTPN11(1), SH3BP2(1), SOS1(4), SOS2(2), SYK(1), TNFRSF10A(1), TNFSF10(1), ULBP2(1), ULBP3(1), VAV1(1), VAV3(1), ZAP70(1) 53963207 57 49 57 27 6 21 21 0 9 0 0.090 0.28 197 TSP1PATHWAY Thrombospondin-1 (TSP-1) inhibits angiogenesis by inducing caspase-dependent apoptosis in microvascular endothelial cells. CASP3, CD36, FOS, FYN, JUN, MAPK14, THBS1 7 FYN(1), JUN(1), THBS1(4) 3591166 6 6 6 2 0 1 4 1 0 0 0.090 0.28 198 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(1), EGF(1), EGFR(4), MET(1), PDGFRA(3) 9609009 11 11 11 8 2 3 3 0 3 0 0.091 0.28 199 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), ARG1(1), CPS1(5), GATM(2), SMS(1) 8493042 11 11 11 5 0 4 5 0 2 0 0.097 0.30 200 HSA00625_TETRACHLOROETHENE_DEGRADATION Genes involved in tetrachloroethene degradation AKR1B10, EPHX2, HSD3B7, RDH11, RDH12, RDH13, RDH14 7 AKR1B10(2), EPHX2(1), RDH13(1) 2364724 4 4 4 0 1 0 2 0 1 0 0.097 0.30 201 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 CD4(1), ITGAL(2), PTPRC(4) 5512508 7 7 7 3 1 2 3 0 1 0 0.099 0.30 202 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 16 ADRB2(1), AKT1(2), CALM2(1), GNAS(1), GNB1(2), NOS3(1), PIK3R1(2), RELA(1) 7543169 11 11 11 5 2 4 5 0 0 0 0.10 0.31 203 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 68 AKT1(2), AKT2(2), HRAS(2), KDR(2), NFAT5(1), NFATC2(1), NFATC3(2), NOS3(1), PIK3CB(1), PIK3CD(1), PIK3CG(4), PIK3R1(2), PLA2G12A(1), PLA2G6(2), PLCG1(1), PLCG2(1), PPP3CC(1), PRKCG(2), PTGS2(2), PTK2(1), SPHK2(1), VEGFA(1) 33934406 34 31 34 18 3 11 14 0 6 0 0.10 0.31 204 GPCRDB_CLASS_C_METABOTROPIC_GLUTAMATE_PHEROMONE CASR, GABBR1, GPCR5A, GPR51, GPRC5A, GPRC5B, GPRC5C, GPRC5D, GRM1, GRM2, GRM3, GRM4, GRM5, GRM7, GRM8 13 CASR(1), GABBR1(1), GPRC5A(1), GPRC5C(1), GRM1(1), GRM2(2), GRM3(1), GRM4(1), GRM5(1), GRM7(1), GRM8(1) 9761324 12 12 12 2 3 3 5 0 1 0 0.10 0.31 205 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 15 CREBBP(3), EP300(3), FYN(1), JAK1(2), JAK3(1), PIK3R1(2), PTK2B(2), STAT5B(1) 12764009 15 14 15 10 3 2 6 0 4 0 0.10 0.31 206 HSA03020_RNA_POLYMERASE Genes involved in RNA polymerase POLR1A, POLR1B, POLR1C, POLR1D, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLR3A, POLR3B, POLR3G, POLR3GL, POLR3H, POLR3K, ZNRD1 23 POLR1A(1), POLR1C(1), POLR2A(4), POLR2B(1), POLR2I(1), POLR3A(1), POLR3B(5), POLR3G(1), POLR3H(1) 11422889 16 15 14 2 1 8 4 0 3 0 0.10 0.31 207 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 21 ARFIP2(1), CHN1(2), MAP3K1(1), MYLK(2), PAK1(1), PDGFRA(3), PIK3R1(2), PLD1(1), PPP1R12B(1), RALBP1(1), RPS6KB1(2), TRIO(1), VAV1(1) 16145719 19 18 19 8 5 2 5 1 6 0 0.10 0.31 208 RNA_POLYMERASE POLR1B, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLRMT 14 POLR2A(4), POLR2B(1), POLR2I(1), POLRMT(1) 6443467 7 6 7 2 0 1 3 0 3 0 0.10 0.31 209 HSA00300_LYSINE_BIOSYNTHESIS Genes involved in lysine biosynthesis AADAT, AASDHPPT, AASS, KARS 4 AASDHPPT(1), AASS(1), KARS(1) 2333393 3 3 3 1 0 1 0 0 2 0 0.11 0.31 210 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 HRAS(2), IL2RB(1), JAK1(2), JAK3(1), JUN(1), SOS1(4), STAT5B(1), SYK(1) 11540060 13 13 13 3 2 3 5 0 3 0 0.11 0.31 211 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 22 APC(5), AXIN1(1), CREBBP(3), FZD1(2), GSK3B(1), MAP3K7(1), PPP2CA(2) 14204951 15 15 15 12 0 3 8 0 4 0 0.11 0.31 212 O_GLYCAN_BIOSYNTHESIS GALNT1, GALNT10, GALNT2, GALNT3, GALNT4, GALNT6, GALNT7, GALNT8, GALNT9, GCNT1, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, WBSCR17 14 GALNT1(1), GALNT2(1), GALNT7(3), GCNT1(2), WBSCR17(1) 7055661 8 8 8 3 1 2 2 0 3 0 0.11 0.31 213 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 43 CREBBP(3), DLL1(1), DLL4(1), DTX3(2), DTX3L(1), DTX4(1), EP300(3), JAG1(1), MAML1(2), MAML2(1), MAML3(1), NCOR2(3), NCSTN(1), NOTCH1(6), NOTCH2(2), NOTCH3(2), NUMB(2), PSEN2(1), RBPJL(1) 32576394 35 31 35 17 4 6 16 1 6 2 0.11 0.31 214 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(3), ACO1(3), CLYBL(1), CS(1), IDH1(1), IDH2(1), MDH1(1), OGDH(2), OGDHL(1), PCK1(2), SDHA(1), SDHD(1), SUCLG1(2), SUCLG2(1) 14727273 21 18 21 9 1 9 8 0 3 0 0.11 0.31 215 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 41 AKT1(2), BRAF(3), CREB5(1), CREBBP(3), EGR1(1), EGR2(1), EGR3(1), FRS2(2), JUN(1), MAP1B(1), MAP2K7(1), MAPK10(1), MAPK8IP1(1), MAPK8IP3(1), MAPK9(1), PIK3C2G(1), PIK3CD(1), PIK3R1(2), PTPN11(1), RPS6KA3(1), TH(1) 24031774 28 26 28 14 4 6 13 1 4 0 0.11 0.31 216 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 BAG4(2), BIRC2(2), BIRC3(1), CASP2(1), CASP7(1), CASP8(1), DAXX(2), LMNB1(1), MAP2K7(1), MAP3K1(1), MAP3K5(1), PRKCD(2), PRKDC(2), PSEN2(1), PTK2(1), RB1(3), RELA(1), RIPK1(1), SPTAN1(1), TNFRSF1A(1), TRADD(1) 34282887 28 27 27 17 4 8 11 0 5 0 0.11 0.32 217 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 ALDH4A1(1), CPS1(5), EPRS(1), GAD1(1), GFPT1(1), GLS(1), GLS2(1), GOT1(2), GOT2(3), GPT2(1), GSS(1) 16220031 18 17 18 6 2 8 5 0 3 0 0.11 0.32 218 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(2), BCAR1(2), CAPN1(1), CAPN10(1), CAPN11(1), CAPN3(1), CAPN7(1), CAPN9(1), CSK(1), DOCK1(1), FYN(1), ILK(1), ITGA11(2), ITGA3(2), ITGA6(2), ITGA8(1), ITGA9(2), ITGAE(2), ITGAL(2), ITGAX(1), ITGB1(2), ITGB5(3), ITGB6(2), ITGB7(1), MAP2K3(2), MAPK10(1), MAPK4(1), PAK1(1), PAK4(2), PAK6(1), PTK2(1), ROCK1(2), SDCCAG8(1), SORBS1(1), SOS1(4), TLN1(3), TNS1(3), VAV3(1), VCL(1) 66784386 61 56 61 18 4 18 32 0 7 0 0.11 0.32 219 BLOOD_CLOTTING_CASCADE F10, F11, F12, F13B, F2, F5, F7, F8, F8A1, F9, FGA, FGB, FGG, LPA, PLG, PLAT, PLAU, PLG, SERPINB2, SERPINE1, SERPINF2, VWF 20 F12(1), F2(2), F5(3), F8(1), FGA(1), PLAT(2), PLAU(3), PLG(1), SERPINF2(1), VWF(5) 17065317 20 19 20 11 0 8 8 0 4 0 0.11 0.32 220 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 46 AKT1(2), AKT2(2), BRD4(4), CBL(1), CDKN2A(1), GSK3A(2), GSK3B(1), IRS1(1), LNPEP(2), PARD3(1), PDK1(1), PIK3CD(1), PIK3R1(2), RPS6KA1(1), RPS6KA2(1), RPS6KA3(1), RPS6KB1(2), SORBS1(1), SOS1(4), SOS2(2), YWHAE(1) 26693235 34 30 34 12 6 12 10 1 5 0 0.11 0.32 221 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(1), GLI2(3), GLI3(2), GSK3B(1), PRKACB(1), SMO(2) 7807771 10 10 10 3 0 3 6 1 0 0 0.11 0.32 222 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(1), EGFR(4), HRAS(2), PTPRB(2), SOS1(4), SPRY2(1) 12052154 15 15 15 5 2 6 4 1 2 0 0.12 0.32 223 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 ACACA(3), ACSS1(2), ACSS2(2), ALDH1B1(2), ALDH3A2(1), ECHS1(1), HADHA(1), LDHAL6B(1), LDHB(1), LDHC(1), MCEE(1), MLYCD(1), PCCA(1), PCCB(1), SUCLG1(2), SUCLG2(1) 19481375 22 22 22 10 2 7 7 1 5 0 0.12 0.32 224 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 CREBBP(3), EP300(3), RELA(1), RIPK1(1), TNFRSF1A(1), TRADD(1), TRAF6(1) 10891870 11 11 11 6 0 1 7 0 3 0 0.12 0.32 225 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 20 ATM(8), ATR(4), BRCA1(1), BRCA2(2), CHEK2(1), FANCE(3), FANCF(1), FANCG(1), RAD50(4) 21307487 25 23 25 15 0 8 11 1 5 0 0.12 0.32 226 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 CALM2(1), GRIN1(1), GRIN2A(3), GRIN2B(4), NOS1(5), PPP3CC(1), PRKACB(1) 12465844 16 16 16 7 1 5 9 0 1 0 0.12 0.32 227 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 IL4R(1), JAK1(2), JAK2(2), TYK2(2) 5132519 7 6 7 3 0 2 2 1 2 0 0.12 0.32 228 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 IL4R(1), JAK1(2), JAK2(2), TYK2(2) 5132519 7 6 7 3 0 2 2 1 2 0 0.12 0.32 229 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(5), CREB5(1), EPHB2(1), ITPKA(1), ITPKB(1), JUN(1), MAP2K7(1), MAPK10(1), MAPK8IP1(1), MAPK8IP3(1), MAPK9(1) 13528521 15 15 15 13 1 5 6 0 3 0 0.13 0.34 230 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 GABRA3(2), GABRA4(2), GABRA5(1), GABRA6(1) 3887372 6 6 6 2 2 1 2 1 0 0 0.13 0.34 231 ST_DICTYOSTELIUM_DISCOIDEUM_CAMP_CHEMOTAXIS_PATHWAY The fungus Dictyostelium discoideum is a model system for cytoskeletal organization during chemotaxis. ACTR2, ACTR3, AKT1, ANGPTL2, BF, DAG1, DGKA, ETFA, GCA, ITGA9, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, MAP2K1, MAPK1, MAPK3, NR1I3, PAK1, PDE3A, PDE3B, PI3, PIK3C2G, PIK3CA, PIK3CD, PIK3R1, PLDN, PSME1, RIPK3, RPS4X, SGCB, VASP 31 AKT1(2), GCA(1), ITGA9(2), ITPKA(1), ITPKB(1), ITPR1(1), ITPR2(4), ITPR3(1), PAK1(1), PDE3A(2), PDE3B(1), PIK3C2G(1), PIK3CD(1), PIK3R1(2), RIPK3(1) 23300574 22 21 22 7 3 6 9 1 3 0 0.13 0.34 232 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(3), CS(1), IDH1(1), IDH2(1), MDH1(1), PCK1(2), SDHA(1), SUCLG1(2), SUCLG2(1) 10188980 13 13 13 7 0 6 4 0 3 0 0.13 0.34 233 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), LUM(1) 1784260 3 3 3 0 0 1 1 0 1 0 0.13 0.34 234 N_GLYCAN_DEGRADATION AGA, FLJ21865, FUCA1, FUCA2, GLB1, HEXA, HEXB, LCT, MAN2C1, MANBA, NEU1, NEU2, NEU3, NEU4 13 FUCA2(1), GLB1(3), HEXA(1), LCT(1), MAN2C1(4) 7953557 10 9 10 3 0 4 4 1 1 0 0.13 0.34 235 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 CD4(1), HLA-DRA(1), HLA-DRB1(3) 2492016 5 4 5 4 0 2 1 1 1 0 0.13 0.34 236 HSA00310_LYSINE_DEGRADATION Genes involved in lysine degradation AADAT, AASDHPPT, AASS, ACAT1, ACAT2, AKR1B10, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, BBOX1, DLST, DOT1L, ECHS1, EHHADH, EHMT1, EHMT2, GCDH, HADH, HADHA, HSD17B10, HSD17B4, HSD3B7, NSD1, OGDH, OGDHL, PIPOX, PLOD1, PLOD2, PLOD3, RDH11, RDH12, RDH13, RDH14, SETD1A, SETD7, SETDB1, SHMT1, SHMT2, SPCS1, SPCS3, SUV39H1, SUV39H2, TMLHE 47 AASDHPPT(1), AASS(1), AKR1B10(2), ALDH1B1(2), ALDH3A2(1), BBOX1(1), DOT1L(2), ECHS1(1), EHMT2(2), HADH(1), HADHA(1), HSD17B4(1), NSD1(2), OGDH(2), OGDHL(1), PLOD2(1), PLOD3(1), RDH13(1), SETD1A(1), SETDB1(1), SHMT1(1), SHMT2(2) 28031433 29 29 29 6 2 7 14 1 5 0 0.13 0.34 237 ST_MYOCYTE_AD_PATHWAY Cardiac myocytes have a variety of adrenergic receptors that induce subtype-specific signaling effects. ADRB1, AKT1, APC, ASAH1, BF, CAMP, CAV3, DAG1, DLG4, EPHB2, GAS, GNAI1, GNAQ, HTATIP, ITPR1, ITPR2, ITPR3, KCNJ3, KCNJ5, KCNJ9, MAPK1, PITX2, PLB, PTX1, PTX3, RAC1, RHO, RYR1 23 AKT1(2), APC(5), EPHB2(1), ITPR1(1), ITPR2(4), ITPR3(1), KCNJ3(3), KCNJ5(1), RYR1(3) 22957004 21 21 21 16 0 7 9 1 4 0 0.13 0.35 238 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), ALG10(1), ALG10B(1), ALG13(1), ALG3(1), ALG8(1), B3GNT6(1), B3GNT7(1), B4GALT4(2), C1GALT1C1(1), CHST1(1), DPAGT1(1), EXT1(1), EXTL3(1), FUT11(1), GALNT1(1), GALNT11(1), GALNT2(1), GALNT5(3), GALNT7(3), GALNTL2(1), GALNTL4(1), GCNT1(2), HS6ST3(1), MAN1A2(1), MAN2A1(1), MGAT3(1), MGAT4A(1), MGAT5(1), NDST4(1), OGT(3), RPN1(2), RPN2(1), ST3GAL3(1), STT3B(1), WBSCR17(1), XYLT1(1), XYLT2(1) 53571744 47 43 47 19 4 14 17 1 11 0 0.13 0.35 239 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(4), AOC2(1), CES1(3), CES7(1), MYST3(4), PNPLA3(1) 12415482 15 14 15 4 1 4 7 3 0 0 0.14 0.35 240 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 GPI(1), HK1(3), PGAM1(1), PGK1(3) 4267803 8 6 8 2 0 2 5 1 0 0 0.14 0.35 241 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(4), ALDH1B1(2), ALDH3A2(1), ALDH3B1(1), ALDH3B2(1), AOC2(1), DDC(2), HARS(1), HARS2(1), LCMT2(1), MAOA(1), MAOB(1), PRMT5(1), PRMT6(1), PRMT7(2), PRMT8(1), PRPS2(1), UROC1(1) 19387189 24 20 24 4 2 3 13 4 2 0 0.14 0.35 242 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 19 B2M(1), ITGB1(2), KLRC1(1), PAK1(1), PIK3R1(2), PTK2B(2), SYK(1), VAV1(1) 8117877 11 11 11 4 3 2 3 0 3 0 0.14 0.35 243 HSA00430_TAURINE_AND_HYPOTAURINE_METABOLISM Genes involved in taurine and hypotaurine metabolism BAAT, CDO1, CSAD, GAD1, GAD2, GGT1, GGTL3, GGTL4 6 GAD1(1), GGT1(2) 2829117 3 3 3 1 0 0 2 0 1 0 0.14 0.36 244 HSA00530_AMINOSUGARS_METABOLISM Genes involved in aminosugars metabolism AMDHD2, CHIA, CHIT1, CMAS, CTBS, CYB5R1, CYB5R3, GFPT1, GFPT2, GNE, GNPDA1, GNPDA2, GNPNAT1, HEXA, HEXB, HK1, HK2, HK3, LHPP, MTMR1, MTMR2, MTMR6, NAGK, NANS, NPL, PGM3, PHPT1, RENBP, UAP1 29 AMDHD2(1), CHIA(1), CHIT1(1), CTBS(1), CYB5R1(2), GFPT1(1), GNPDA1(1), HEXA(1), HK1(3), MTMR1(2), MTMR2(1), NANS(1), RENBP(2) 14081415 18 17 18 2 1 5 10 1 1 0 0.14 0.36 245 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(1), ALPL(2), ALPP(2), ALPPL2(1), ASCC3(2), ATP13A2(4), DDX18(2), DDX50(2), DDX56(1), DHX58(1), EP400(1), FPGS(2), IFIH1(2), RAD54L(1), SKIV2L2(1), SMARCA2(4), SMARCA5(2) 30961716 31 28 31 12 0 9 16 1 5 0 0.14 0.36 246 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 ITGAL(2), PTPRC(4) 5218168 6 6 6 2 1 1 3 0 1 0 0.14 0.36 247 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 CASP1(1), CASP7(1), CASP8(1), INSR(4), MAGI1(2), MAGI2(1), RERE(2), WWP2(1) 11513864 13 13 13 4 1 5 4 1 2 0 0.14 0.36 248 NUCLEOTIDE_GPCRS ADORA1, ADORA2A, ADORA2B, ADORA3, GPR23, LTB4R, P2RY1, P2RY2, P2RY5, P2RY6 8 ADORA2A(1), LTB4R(1), P2RY2(1) 2696735 3 3 3 2 0 0 2 0 1 0 0.14 0.36 249 GHPATHWAY Growth hormone receptors dimerize on ligand binding and activate the JAK2 protein kinase. GH1, GHR, GRB2, HRAS, INS, INSR, IRS1, JAK2, MAP2K1, MAPK1, MAPK3, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, PTPN6, RAF1, RPS6KA1, SHC1, SLC2A4, SOCS1, SOS1, SRF, STAT5A, STAT5B, TCF1 23 GHR(1), HRAS(2), INSR(4), IRS1(1), JAK2(2), PIK3R1(2), PLCG1(1), RPS6KA1(1), SOS1(4), STAT5B(1) 14992951 19 18 19 7 3 6 9 1 0 0 0.14 0.36 250 HCMVPATHWAY Cytomegalovirus activates MAP kinase pathways in the host cell, inducing transcription of viral genes. AKT1, CREB1, MAP2K1, MAP2K2, MAP2K3, MAP2K6, MAP3K1, MAPK1, MAPK14, MAPK3, NFKB1, PIK3CA, PIK3R1, RB1, RELA, SP1 15 AKT1(2), MAP2K3(2), MAP3K1(1), PIK3R1(2), RB1(3), RELA(1) 8605934 11 10 11 9 3 3 3 0 2 0 0.15 0.36 251 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 64 ACSS1(2), ACSS2(2), ADH1B(1), ADH5(1), ADHFE1(1), ALDH1B1(2), ALDH3A2(1), ALDH3B1(1), ALDH3B2(1), ALDOA(1), DLAT(2), FBP1(1), GAPDHS(2), GPI(1), HK1(3), LDHAL6B(1), LDHB(1), LDHC(1), PFKM(2), PGAM1(1), PGK1(3) 28165196 31 28 31 7 3 4 13 4 7 0 0.15 0.36 252 NEUROTRANSMITTERSPATHWAY Biosynthesis of neurotransmitters DBH, GAD1, HDC, PNMT, TH, TPH1 6 DBH(2), GAD1(1), TH(1) 2859292 4 4 4 1 0 0 3 1 0 0 0.15 0.36 253 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 6 AKT1(2), PIK3R1(2), PLCB1(1), PLCG1(1), VAV1(1) 5281141 7 7 7 5 2 1 3 0 1 0 0.15 0.36 254 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 PSMA3(1), PSMA4(1), PSMA6(1), RPN1(2), RPN2(1), UBE2A(1) 6432172 7 7 7 3 1 0 3 2 1 0 0.15 0.36 255 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 14 ARF1(1), CDK2(1), CDK4(1), CDKN1A(1), CDKN2A(1) 3503720 5 5 5 2 0 3 1 0 1 0 0.15 0.36 256 SMALL_LIGAND_GPCRS C9orf47, CNR1, CNR2, DNMT1, EDG1, EDG2, EDG5, EDG6, MTNR1A, MTNR1B, PTAFR, PTGDR, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, TBXA2R 13 CNR2(1), DNMT1(2), PTAFR(1), PTGDR(1), PTGER2(1), PTGFR(1) 5361002 7 7 7 1 0 3 3 0 1 0 0.15 0.36 257 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(2), ITGAL(2), SELE(3) 5605345 7 7 7 4 0 2 4 0 1 0 0.15 0.36 258 APOPTOSIS_GENMAPP APAF1, BAK1, BCL2L7P1, BAX, BCL2, BCL2L1, BID, BIRC2, BIRC3, BIRC4, CASP2, CASP3, CASP6, CASP7, CASP8, CASP9, CYCS, FADD, FAS, FASLG, GZMB, IKBKG, JUN, MAP2K4, MAP3K1, MAP3K14, MAPK10, MCL1, MDM2, MYC, NFKB1, NFKBIA, PARP1, PRF1, RELA, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TNFSF10, TP53, TRADD, TRAF1, TRAF2 40 BIRC2(2), BIRC3(1), CASP2(1), CASP7(1), CASP8(1), JUN(1), MAP3K1(1), MAPK10(1), PARP1(2), RELA(1), RIPK1(1), TNFRSF1A(1), TNFSF10(1), TRADD(1) 17824438 16 16 16 5 3 2 6 1 4 0 0.16 0.37 259 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 14 AKT1(2), HRAS(2), IRS1(1), PIK3R1(2), SOS1(4) 8053385 11 11 11 5 3 3 5 0 0 0 0.16 0.38 260 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(1), HRAS(2), IL3(1), JAK2(2), SOS1(4), STAT5B(1) 8336733 11 11 11 1 2 4 5 0 0 0 0.16 0.38 261 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 ADSL(1), AGXT(1), AGXT2(1), ASNS(1), DARS(1), GAD1(1), GOT1(2), GOT2(3), GPT2(1) 12801712 12 12 12 4 1 3 4 0 4 0 0.16 0.38 262 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 BCAR1(2), CALM2(1), HRAS(2), JUN(1), MAP2K3(2), MAP3K1(1), PAK1(1), PLCG1(1), PTK2B(2), SOS1(4) 13925154 17 16 17 7 2 3 9 0 3 0 0.16 0.38 263 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 99 ADCY2(1), ADCY5(3), ADCY7(1), ADCY8(4), ADCY9(2), CALM2(1), CAMK2G(2), CREBBP(3), DCT(1), EP300(3), FZD1(2), FZD10(1), FZD4(1), FZD5(1), GNAO1(1), GNAS(1), GSK3B(1), HRAS(2), KITLG(1), MITF(1), PLCB1(1), PLCB2(1), PLCB4(3), POMC(1), PRKACA(1), PRKACB(1), PRKCG(2), TCF7(2), TYR(2), TYRP1(1), WNT3A(1), WNT5B(1), WNT7B(1), WNT9A(1) 52988976 52 48 51 33 1 17 28 0 6 0 0.16 0.38 264 HSA00730_THIAMINE_METABOLISM Genes involved in thiamine metabolism LHPP, MTMR1, MTMR2, MTMR6, NFS1, PHPT1, THTPA, TPK1 8 MTMR1(2), MTMR2(1), THTPA(1), TPK1(1) 3141313 5 5 5 1 0 3 2 0 0 0 0.16 0.38 265 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 17 AKT1(2), EIF2S2(1), EIF4E(1), GSK3B(1), PIK3R1(2), PPP2CA(2), RPS6KB1(2) 8212940 11 11 11 4 4 2 2 0 3 0 0.16 0.38 266 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 35 AKT1(2), FLNA(2), FLNC(3), FSCN1(2), MYH2(5), MYLK(2), PAK1(1), PAK4(2), PAK6(1), PAK7(1), ROCK1(2), WASL(2) 23076020 25 23 25 5 1 8 12 1 3 0 0.16 0.38 267 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 CREBBP(3), EP300(3), NCOA3(3), PRKACB(1), RARA(2) 10035320 12 12 12 4 0 4 7 0 1 0 0.16 0.38 268 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(2), ITGAL(2), ITGB1(2), SELE(3), SELP(1) 8328406 10 10 10 5 1 2 6 0 1 0 0.16 0.38 269 BETAOXIDATIONPATHWAY Beta-Oxidation of Fatty Acids ACADL, ACADM, ACADS, ACAT1, ECHS1, HADHA 6 ACADS(2), ECHS1(1), HADHA(1) 2649293 4 4 4 3 0 1 3 0 0 0 0.16 0.38 270 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 29 CD4(1), HLA-DRA(1), HLA-DRB1(3), IFNB1(1), IL3(1), TGFB2(1), TGFB3(1) 6360873 9 8 9 5 2 3 2 1 1 0 0.17 0.38 271 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 ABP1(4), ALDH1B1(2), ALDH3A2(1), AOC2(1), AOX1(5), CAT(2), CYP1A1(1), DDC(2), ECHS1(1), HADH(1), HADHA(1), HSD17B4(1), LCMT2(1), MAOA(1), MAOB(1), OGDH(2), OGDHL(1), PRMT5(1), PRMT6(1), PRMT7(2), PRMT8(1), TPH2(2) 29445365 35 30 35 8 4 9 15 5 2 0 0.17 0.38 272 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 CS(1), IDH2(1), MDH1(1), OGDH(2), SDHA(1) 4644957 6 6 6 1 0 2 3 0 1 0 0.17 0.38 273 HSA00970_AMINOACYL_TRNA_BIOSYNTHESIS Genes involved in aminoacyl-tRNA biosynthesis AARS, AARS2, CARS, CARS2, DARS, DARS2, EARS2, EPRS, FARS2, FARSA, FARSB, GARS, HARS, HARS2, IARS, IARS2, KARS, LARS, LARS2, MARS, MARS2, MTFMT, NARS, NARS2, PARS2, QARS, RARS, RARS2, SARS, SARS2, TARS, TARS2, VARS, VARS2, WARS, WARS2, YARS, YARS2 38 AARS2(1), CARS(2), CARS2(1), DARS(1), EPRS(1), HARS(1), HARS2(1), IARS(1), IARS2(2), KARS(1), MARS(1), NARS2(1), PARS2(1), SARS(2), TARS(1), TARS2(2), VARS2(4), YARS2(1) 25902714 25 25 25 8 4 6 10 0 5 0 0.17 0.38 274 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 GAA(2), GALE(1), GALK1(1), GALK2(1), GLB1(3), HK1(3), LALBA(1), LCT(1), MGAM(2), PFKM(2) 15995501 17 16 17 3 0 5 6 2 4 0 0.17 0.38 275 INSULINPATHWAY Insulin regulates glucose levels via Ras-mediated transcriptional activation. CSNK2A1, ELK1, FOS, GRB2, HRAS, INS, INSR, IRS1, JUN, MAP2K1, MAPK3, MAPK8, PIK3CA, PIK3R1, PTPN11, RAF1, RASA1, SHC1, SLC2A4, SOS1, SRF 20 HRAS(2), INSR(4), IRS1(1), JUN(1), PIK3R1(2), PTPN11(1), SOS1(4) 11274767 15 14 15 6 3 4 7 1 0 0 0.17 0.39 276 REDUCTIVE_CARBOXYLATE_CYCLE_CO2_FIXATION ACO1, ACO2, FH, IDH1, IDH2, MDH1, MDH2, SDHB, SUCLA2 9 ACO1(3), IDH1(1), IDH2(1), MDH1(1) 4389294 6 6 6 3 0 2 3 0 1 0 0.17 0.39 277 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 CALM2(1), CAMK1(1), CAMK2G(2), CAMKK1(1), CAMKK2(2) 5731873 7 7 7 1 0 1 4 1 1 0 0.18 0.39 278 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 ACADS(2), ALDH1B1(2), ALDH3A2(1), AOX1(5), BCAT1(1), ECHS1(1), HADH(1), HADHA(1), HADHB(2), HSD17B4(1), IVD(1), MCCC2(3), MCEE(1), OXCT1(1), PCCA(1), PCCB(1) 21299672 25 24 25 7 5 8 8 1 3 0 0.18 0.39 279 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 21 HRAS(2), JAK2(2), JUN(1), PIK3R1(2), PLCG1(1), SOS1(4), STAT1(3), STAT5B(1) 13661813 16 16 16 7 3 6 7 0 0 0 0.18 0.39 280 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 13 AKT1(2), GHR(1), PIK3R1(2), PPP2CA(2), RELA(1) 5883504 8 8 8 2 2 3 2 0 1 0 0.18 0.39 281 HSA00130_UBIQUINONE_BIOSYNTHESIS Genes involved in ubiquinone biosynthesis COQ2, COQ3, COQ5, COQ6, COQ7, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA12, NDUFA13, NDUFB11 7 COQ5(2), COQ6(1) 1910582 3 3 3 0 0 0 2 1 0 0 0.18 0.39 282 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 GNB1(2), HTR2C(1), PLCB1(1), TUB(1) 3496315 5 5 5 0 0 2 2 0 1 0 0.18 0.39 283 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 DPM2(1), EGR1(1), HRAS(2), KLK2(1) 3984279 5 5 5 1 0 3 1 1 0 0 0.18 0.39 284 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 15 CD4(1), IL12RB1(1), IL12RB2(1), JAK2(2), STAT4(2), TYK2(2) 7207181 9 9 9 4 1 4 2 1 1 0 0.18 0.39 285 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 DAO(1) 354468 1 1 1 0 0 1 0 0 0 0 0.18 0.39 286 CREMPATHWAY The transcription factor CREM activates a post-meiotic transcriptional cascade culminating in spermatogenesis. ADCY1, CREM, FHL5, FSHB, FSHR, GNAS, XPO1 7 CREM(1), FHL5(2), GNAS(1), XPO1(2) 4562040 6 6 6 1 0 3 2 1 0 0 0.18 0.39 287 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 BCL2A1(2), CASP1(1), CASP10(2), CASP2(1), CASP4(1), CASP7(1), CASP8(1), DAXX(2), PTPN13(1), RIPK1(1), SFRS2IP(1), TFG(1), TNFRSF1A(1), TRADD(1), TRAF3(1), TRAF6(1) 21618286 19 19 19 3 3 2 10 0 4 0 0.19 0.40 288 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(2), ARF1(1), EEA1(1), GSK3A(2), GSK3B(1), PFKM(2), PLCG1(1), PRKCZ(1), RAB5A(1), RPS6KB1(2) 12465674 14 14 14 3 2 4 5 0 3 0 0.19 0.40 289 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), AASDHPPT(1), AASS(1), ALDH1A2(1), ALDH1B1(2), ALDH3A2(1), BBOX1(1), DOT1L(2), ECHS1(1), EHMT2(2), HADHA(1), PLOD2(1), PLOD3(1), SHMT1(1), SHMT2(2) 17622460 20 19 20 2 1 5 9 1 4 0 0.19 0.40 290 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 CASP10(2), CASP7(1), CASP8(1), DAXX(2), JUN(1), LMNB1(1), MAP3K1(1), MAP3K7(1), PAK1(1), PRKDC(2), PTPN13(1), RB1(3), RIPK2(1), SPTAN1(1) 21115404 19 19 19 12 3 3 8 0 5 0 0.19 0.40 291 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(2), CREB5(1), DUSP10(1), EIF4E(1), MAP2K3(2), MAP3K10(1), MAP3K4(3), MAP3K5(1), MAP3K7(1), MAPKAPK5(1), MKNK2(2), NR2C2(1), TRAF6(1) 16402798 18 16 18 4 3 4 8 0 3 0 0.19 0.40 292 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(2), JAK2(2), JAK3(1), TYK2(2) 5821323 7 6 7 5 1 1 2 1 2 0 0.19 0.40 293 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 HLA-DRA(1), HLA-DRB1(3), IFNGR1(1), IFNGR2(1), IL12RB1(1), IL12RB2(1), IL4R(1) 6138997 9 8 9 3 1 4 2 1 1 0 0.19 0.40 294 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 FUCA2(1), GLB1(3), HEXA(1), LCT(1), MAN2B2(2), MAN2C1(4) 9810644 12 10 12 3 0 5 5 1 1 0 0.19 0.40 295 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), RAB1A(1), RAB5A(1), RAB9A(1) 2127794 4 4 4 1 2 0 2 0 0 0 0.20 0.41 296 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), HADH(1), HADHA(1), HADHB(2), HSD17B4(1), MECR(1) 4127532 7 6 7 1 2 3 2 0 0 0 0.20 0.41 297 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 12 AKT1(2), MUSK(1), PIK3R1(2), PTK2(1), PTK2B(2), TERT(1) 7114233 9 9 9 5 2 3 3 0 1 0 0.20 0.41 298 PROSTAGLANDIN_SYNTHESIS_REGULATION ANXA1, ANXA2, ANXA3, ANXA4, ANXA5, ANXA6, ANXA8, CYP11A1, EDN1, EDNRA, EDNRB, HPGD, HSD11B1, HSD11B2, PLA2G4A, PRL, PTGDR, PTGDS, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, PTGIS, PTGS1, PTGS2, S100A6, SCGB1A1, TBXAS1 27 ANXA3(1), ANXA4(1), ANXA6(2), CYP11A1(1), HPGD(1), PTGDR(1), PTGDS(1), PTGER2(1), PTGFR(1), PTGS2(2) 10086362 12 12 12 4 0 6 3 0 3 0 0.20 0.41 299 BIOGENIC_AMINE_SYNTHESIS AANAT, ACHE, CHAT, COMT, DBH, DDC, DXYS155E, GAD1, GAD2, HDC, MAOA, PAH, PNMT, SLC18A3, TH, TPH1 15 DBH(2), DDC(2), GAD1(1), MAOA(1), PAH(1), TH(1) 7000508 8 8 8 4 1 1 4 2 0 0 0.20 0.41 300 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 HMOX1(1), JAK1(2), STAT1(3) 5907858 6 6 6 4 0 4 0 0 2 0 0.20 0.41 301 PAR1PATHWAY Activated extracellular thrombin cleaves and activates the G-protein coupled receptors PAR1 and PAR4, which activate platelets. ADCY1, ARHA, ARHGEF1, F2, F2R, F2RL3, GNA12, GNA13, GNAI1, GNAQ, GNB1, GNGT1, MAP3K7, PIK3CA, PIK3R1, PLCB1, PPP1R12B, PRKCA, PRKCB1, PTK2B, ROCK1 18 F2(2), GNA13(1), GNB1(2), MAP3K7(1), PIK3R1(2), PLCB1(1), PPP1R12B(1), PTK2B(2), ROCK1(2) 11595143 14 14 14 4 3 4 3 0 4 0 0.20 0.41 302 HSA00930_CAPROLACTAM_DEGRADATION Genes involved in caprolactam degradation AKR1A1, ASAHL, ECHS1, EHHADH, HADH, HADHA, HSD17B10, HSD17B4, NTAN1, SIRT1, SIRT2, SIRT5, SIRT7, VNN2, VNN3 13 ECHS1(1), HADH(1), HADHA(1), HSD17B4(1), SIRT1(1), SIRT5(1) 5762755 6 6 6 0 0 4 1 0 1 0 0.20 0.41 303 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 ABP1(4), ALDH1B1(2), ALDH3A2(1), AOC2(1), DPYS(1), ECHS1(1), GAD1(1), HADHA(1), MLYCD(1), SMS(1) 13188242 14 14 14 6 0 1 9 3 1 0 0.20 0.42 304 DREAMPATHWAY The transcription factor DREAM blocks expression of the prodynorphin gene, which encodes the ligand of an opioid receptor that blocks pain signaling. CREB1, CREM, CSEN, FOS, JUN, MAPK3, OPRK1, POLR2A, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B 13 CREM(1), JUN(1), POLR2A(4), PRKACB(1) 6231588 7 6 7 0 0 2 4 0 1 0 0.21 0.42 305 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), ACTN2(2), BCAR1(2), CAPN1(1), CSK(1), FYN(1), HRAS(2), ITGA1(1), ITGB1(2), JUN(1), PPP1R12B(1), PTK2(1), ROCK1(2), SOS1(4), TLN1(3), VCL(1) 23124901 26 23 26 9 4 8 11 0 3 0 0.21 0.42 306 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 12 ALAS2(1), CPO(1), FECH(1), HBB(2) 4040289 5 5 5 2 2 1 0 0 2 0 0.22 0.44 307 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 GNAS(1), GNB1(2), PPP2CA(2), PRKACB(1), PRKAG1(2), PRKAG2(1) 7378253 9 9 9 1 1 3 4 0 1 0 0.22 0.44 308 GLYOXYLATE_AND_DICARBOXYLATE_METABOLISM ACO1, ACO2, CS, GRHPR, HAO1, HAO2, HYI, MDH1, MDH2, MTHFD1, MTHFD1L, MTHFD2 12 ACO1(3), CS(1), MDH1(1), MTHFD1(2), MTHFD1L(1) 6313760 8 8 8 2 1 2 5 0 0 0 0.22 0.44 309 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 ARSD(1), ARSE(1), B4GALT6(1), ENPP7(3), GAL3ST1(1), GBA(2), GLB1(3), LCT(1), PPAP2C(1), SGPP2(1), SMPD1(1), SPHK2(1), UGT8(2) 16946269 19 18 18 11 1 9 5 1 3 0 0.22 0.44 310 IONPATHWAY Activated phospholipase C hydrolyzes the lipid PIP3 into second messengers DAG, which activates protein kinase C, and IP3, which induces calcium influx into the cytoplasm. P2RY2, PLCG1, PRKCA, PRKCB1, PTK2B 4 P2RY2(1), PLCG1(1), PTK2B(2) 3302272 4 4 4 2 0 1 2 0 1 0 0.22 0.44 311 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 AKT1(2), GNB1(2), PDGFRA(3), PIK3R1(2), PLCB1(1), PTK2(1), SMPD1(1) 12310556 12 12 12 14 2 2 5 0 3 0 0.22 0.44 312 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 25 AKT1(2), CAMK2G(2), GNAS(1), HRAS(2), PIK3R1(2), PRKACB(1), RPS6KA1(1), SOS1(4) 13092283 15 15 15 7 3 4 8 0 0 0 0.23 0.45 313 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(2), CDK2(1), CDK4(1), CDKN2A(1) 4271198 5 5 5 3 0 2 2 0 1 0 0.23 0.45 314 HSA00740_RIBOFLAVIN_METABOLISM Genes involved in riboflavin metabolism ACP1, ACP2, ACP5, ACP6, ACPP, ACPT, ENPP1, ENPP3, FLAD1, LHPP, MTMR1, MTMR2, MTMR6, PHPT1, RFK, TYR 16 ACP5(1), ENPP3(2), FLAD1(1), MTMR1(2), MTMR2(1), TYR(2) 7398735 9 9 9 0 1 1 5 1 1 0 0.23 0.45 315 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 GTF2A1(1), NCOA1(1), NCOA2(1), NCOA3(3), NCOR2(3), POLR2A(4), RARA(2) 12323664 15 12 15 8 1 4 9 0 1 0 0.23 0.45 316 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 ABP1(4), ALDH1A2(1), ALDH1B1(2), ALDH3A2(1), AOC2(1), DPYS(1), ECHS1(1), GAD1(1), HADHA(1), MLYCD(1), SMS(1) 14198337 15 15 15 7 1 1 9 3 1 0 0.23 0.45 317 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 ABP1(4), ALDH1A2(1), ALDH1B1(2), ALDH3A2(1), AOC2(1), AOX1(5), CAT(2), CYP19A1(1), CYP1A1(1), CYP2B6(1), CYP2C18(1), CYP2C19(1), CYP2C8(1), CYP2F1(1), CYP2J2(1), CYP4B1(1), DDC(2), ECHS1(1), HADHA(1), MAOA(1), MAOB(1) 26774162 31 27 31 8 5 4 14 7 1 0 0.23 0.45 318 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 247 ACVR1(1), ACVR1B(3), ACVR2A(1), AMHR2(2), BMP2(1), BMP7(1), BMPR1B(1), BMPR2(2), CCL2(1), CSF1R(1), CSF2RB(1), CSF3R(1), CXCL11(1), EDA(1), EGF(1), EGFR(4), FLT1(2), FLT3(1), FLT4(3), GH2(1), GHR(1), HGF(1), IFNA21(1), IFNA5(1), IFNA7(1), IFNA8(1), IFNAR1(1), IFNB1(1), IFNGR1(1), IFNGR2(1), IL12RB1(1), IL12RB2(1), IL17RB(1), IL19(1), IL1R2(1), IL21(1), IL21R(1), IL22RA1(1), IL23A(1), IL25(1), IL2RB(1), IL3(1), IL4R(1), IL6R(1), IL6ST(2), INHBE(1), KDR(2), KITLG(1), LEPR(1), LIFR(1), MET(1), PDGFRA(3), PF4(1), PLEKHO2(1), PRLR(1), TGFB2(1), TGFB3(1), TGFBR2(2), TNFRSF10A(1), TNFRSF11B(1), TNFRSF1A(1), TNFRSF4(1), TNFRSF9(1), TNFSF10(1), TNFSF9(1), TPO(1), VEGFA(1), XCL1(1) 85021508 83 73 83 32 15 28 30 2 8 0 0.23 0.45 319 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(1), EGF(1), EGFR(4), HRAS(2), ITGA1(1), ITGB1(2), MYLK(2), PRKACB(1), PTK2(1), TLN1(3) 16353942 19 18 19 5 3 4 9 1 2 0 0.23 0.45 320 SA_BONE_MORPHOGENETIC Bone morphogenetic protein binds to its receptor to induce ectopic bone formation and promote development of the viscera. BMP1, BMPR1A, BMPR1B, BMPR2, MADH1, MADH4, MADH6 4 BMP1(1), BMPR1B(1), BMPR2(2) 3044412 4 4 4 0 1 1 0 0 2 0 0.24 0.45 321 RIBOFLAVIN_METABOLISM ACP1, ACP2, ACP5, ACPP, ACPT, ENPP1, ENPP3, FLAD1, RFK, TYR 10 ACP5(1), ENPP3(2), FLAD1(1), TYR(2) 4791318 6 6 6 0 1 0 3 1 1 0 0.24 0.46 322 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), FBP1(1), G6PD(1), GPI(1), PFKM(2), PRPS1L1(1), PRPS2(1), TALDO1(3) 9949466 11 11 11 6 1 2 6 1 1 0 0.24 0.47 323 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 GGT1(2), LCMT2(1), MARS(1), PAPSS2(1), PRMT5(1), PRMT6(1), PRMT7(2), PRMT8(1), SEPHS2(1) 12156958 11 11 11 4 1 3 4 1 2 0 0.25 0.47 324 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(3), CS(1), MDH1(1), ME1(1) 4534099 6 6 6 3 0 1 5 0 0 0 0.25 0.47 325 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 ADRB2(1), CFTR(3), GNAS(1), PRKACB(1) 6212768 6 6 6 3 0 2 3 0 1 0 0.25 0.47 326 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(1), AKT1(2), AKT2(2), ITPKA(1), ITPKB(1), ITPR1(1), ITPR2(4), ITPR3(1), NFKBIB(1), NFKBIL2(1), PDK1(1), PIK3CB(1), PLD1(1), PLD2(1), PLD3(1) 21894326 20 20 20 4 1 7 8 1 3 0 0.25 0.47 327 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), FBP1(1), G6PD(1), GPI(1), PFKM(2), PRPS1L1(1), PRPS2(1), TALDO1(3), TKTL2(2) 11846628 13 13 13 7 2 2 7 1 1 0 0.25 0.47 328 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 16 AKT1(2), HRAS(2), MEF2A(1), PIK3R1(2), PLCG1(1), RPS6KA1(1) 8518621 9 9 9 3 2 2 4 0 1 0 0.25 0.47 329 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(3), NRG2(1), NRG3(2) 4419237 6 6 6 5 0 2 2 1 1 0 0.25 0.47 330 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 CALM2(1), EGFR(4), HRAS(2), JUN(1), MAP3K1(1), MEF2A(1), PAK1(1), PTK2(1), PTK2B(2), SOS1(4) 16739717 18 18 18 8 2 5 8 0 3 0 0.25 0.47 331 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(2), JAK2(2), JAK3(1), PIAS1(2), PTPRU(2) 6880358 9 7 9 2 2 3 2 0 2 0 0.25 0.47 332 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(1), CREBBP(3), EP300(3), GTF2A1(1), HDAC4(1), NCOR2(3), NRIP1(4), POLR2A(4) 23237069 20 18 20 16 0 5 12 0 3 0 0.25 0.47 333 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 ARHGAP5(1), CASP1(1), CASP10(2), CASP8(1), JUN(1) 6305637 6 6 6 0 1 0 3 0 2 0 0.25 0.47 334 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 21 ARHGAP5(1), DIAPH1(1), FYN(1), HRAS(2), ITGA1(1), ITGB1(2), MYLK(2), PIK3R1(2), PTK2(1), ROCK1(2), TLN1(3) 17559471 18 18 18 8 3 5 8 1 1 0 0.26 0.47 335 HSA00232_CAFFEINE_METABOLISM Genes involved in caffeine metabolism CYP1A2, CYP2A13, CYP2A6, CYP2A7, NAT1, NAT2, XDH 7 NAT1(1), NAT2(2), XDH(2) 3923609 5 5 5 2 2 0 3 0 0 0 0.26 0.48 336 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(1), MST1(2), MST1R(1) 2938899 4 4 4 0 0 1 3 0 0 0 0.26 0.48 337 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 ACACA(3), ALDH1A2(1), ALDH1B1(2), ALDH3A2(1), ECHS1(1), HADHA(1), LDHB(1), LDHC(1), MCEE(1), MLYCD(1), PCCA(1), PCCB(1), SUCLG1(2), SUCLG2(1) 16259033 18 18 18 8 2 7 5 1 3 0 0.26 0.48 338 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(3), CS(1), MDH1(1), MTHFD1(2), MTHFD1L(1) 6623274 8 8 8 2 1 2 5 0 0 0 0.26 0.48 339 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 GABRA3(2), GABRA4(2), GABRA5(1), GABRA6(1), GPHN(1) 5923064 7 7 7 1 2 1 3 1 0 0 0.27 0.48 340 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 GNAS(1), GNB1(2), PRKACA(1) 3105255 4 4 4 1 0 2 2 0 0 0 0.27 0.48 341 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 29 AKT1(2), CABIN1(3), CALM2(1), CAMK1(1), INSR(4), MEF2A(1), NFATC2(1), PIK3R1(2), PPP3CC(1) 15721590 16 16 16 5 2 5 4 2 3 0 0.27 0.48 342 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), IFNA21(1), IFNA5(1), IFNA7(1), IFNA8(1), PIK3C3(3), PIK3R4(3), ULK3(2) 10173933 13 12 13 3 2 7 3 0 1 0 0.27 0.48 343 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(1), COL4A3(1), COL4A4(2), COL4A5(4), COL4A6(2), SLC23A1(1), SLC23A2(1), SLC2A3(2) 12745592 14 14 14 6 1 6 5 2 0 0 0.27 0.48 344 GANGLIOSIDE_BIOSYNTHESIS B3GALT4, GALGT, SIAT4A, SIAT4B, SIAT7B, SIAT7D, SIAT9, ST3GAL1, ST3GAL2, ST3GAL4, ST3GAL5, ST6GALNAC2, ST6GALNAC4, ST8SIA1 8 B3GALT4(1), ST6GALNAC2(2), ST8SIA1(1) 2764393 4 4 4 1 1 2 1 0 0 0 0.27 0.48 345 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 38 AKT1(2), AKT2(2), CD19(1), CSK(1), EPHB2(1), ITPKA(1), ITPKB(1), NFAT5(1), NFKBIB(1), NFKBIL2(1), PIK3CD(1), PIK3R1(2), PLCG2(1), PPP1R13B(1), SERPINA4(1), SOS1(4), SOS2(2), SYK(1), VAV1(1) 24256777 26 25 26 7 4 9 10 0 3 0 0.27 0.49 346 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(1), GNA13(1), GNB1(2), MYLK(2), PLCB1(1), PPP1R12B(1), ROCK1(2) 10219794 10 10 10 2 1 3 3 1 2 0 0.27 0.49 347 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), EIF5(2), GSK3B(1) 5656518 7 7 7 2 1 3 2 0 1 0 0.28 0.49 348 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 ABLIM1(2), ABLIM2(1), DCC(2), DPYSL2(1), EFNB2(1), EPHA1(1), EPHA4(1), EPHA5(1), EPHA8(2), EPHB1(1), EPHB2(1), EPHB4(2), EPHB6(4), FES(2), FYN(1), GSK3B(1), HRAS(2), ITGB1(2), L1CAM(1), LIMK2(1), MET(1), NFAT5(1), NFATC2(1), NFATC3(2), NGEF(1), NTN4(1), PAK1(1), PAK4(2), PAK6(1), PAK7(1), PLXNA2(2), PLXNA3(1), PLXNB1(3), PLXNC1(2), PPP3CC(1), PTK2(1), RGS3(3), RND1(1), ROBO1(2), ROBO2(2), ROBO3(1), ROCK1(2), SEMA3A(1), SEMA3C(1), SEMA3D(3), SEMA3E(1), SEMA4A(1), SEMA4D(1), SEMA4F(1), SEMA4G(1), SEMA6C(1), SEMA6D(1), SLIT1(3), SLIT2(1), SLIT3(3), SRGAP1(1), SRGAP2(1), UNC5A(1), UNC5B(1), UNC5C(1), UNC5D(2) 95824475 89 75 89 41 5 35 37 3 9 0 0.28 0.49 349 EPHA4PATHWAY Eph Kinases and ephrins support platelet aggregation ACTA1, EPHA4, EPHB1, FYN, ITGA1, ITGB1, L1CAM, LYN, RAP1B, SELP 10 ACTA1(1), EPHA4(1), EPHB1(1), FYN(1), ITGA1(1), ITGB1(2), L1CAM(1), SELP(1) 7734869 9 9 9 5 2 0 7 0 0 0 0.28 0.49 350 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 12 ARNT(1), ASPH(2), EP300(3), HIF1A(1), JUN(1), NOS3(1) 7975936 9 9 9 5 1 3 4 0 1 0 0.28 0.49 351 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 JUN(1), MAP3K1(1), MAP3K5(1), MAP4K5(3), RELA(1), TNFRSF9(1), TNFSF9(1) 9737473 9 9 9 2 1 2 4 0 2 0 0.29 0.50 352 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 RB1(3) 3283960 3 3 3 7 0 2 0 0 1 0 0.29 0.50 353 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 CS(1), DLAT(2), IDH2(1), MDH1(1), OGDH(2), PDHX(1), PDK1(1), PDK3(1), PDP2(1), SDHA(1), SDHD(1), SUCLG1(2), SUCLG2(1) 14060874 16 15 16 6 0 8 4 2 2 0 0.29 0.50 354 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 EGF(1), EGFR(4), HRAS(2), JUN(1), PLCG1(1), RELA(1) 10055215 10 10 10 5 1 3 5 0 1 0 0.29 0.50 355 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 15 FLT3(1), IL3(1), KITLG(1), TGFB2(1), TGFB3(1) 4157404 5 5 5 1 2 2 1 0 0 0 0.29 0.50 356 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 CASP8(1), MAP3K1(1), NSMAF(2), RELA(1), RIPK1(1), SMPD1(1), TNFRSF1A(1), TRADD(1) 10095378 9 9 9 5 0 1 5 0 3 0 0.30 0.51 357 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), ARPC2(1), ARPC3(1), WASL(2) 4028140 5 5 5 2 1 1 3 0 0 0 0.30 0.51 358 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 31 MAP2K7(1), MAPK10(1), MAPK8IP1(1), MAPK8IP3(1), MAPK9(1), MAPKAPK5(1), NFKBIB(1), NFKBIL2(1), PIK3CD(1), PIK3R1(2), TRAF3(1), TRAF5(1), TRAF6(1) 14708719 14 14 14 8 4 3 4 0 3 0 0.30 0.51 359 CXCR4PATHWAY CXCR4 is a G-protein coupled receptor that responds to the ligand SDF-1 by activating Ras and PI3 kinase to promote lymphocyte chemotaxis. BCAR1, CRK, CXCL12, CXCR4, GNAI1, GNAQ, GNB1, GNGT1, HRAS, MAP2K1, MAPK1, MAPK3, NFKB1, PIK3C2G, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, PTK2, PTK2B, PXN, RAF1, RELA 22 BCAR1(2), GNB1(2), HRAS(2), PIK3C2G(1), PIK3R1(2), PLCG1(1), PTK2(1), PTK2B(2), RELA(1) 12688537 14 13 14 8 2 2 8 0 2 0 0.30 0.51 360 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 ALDH4A1(1), CPS1(5), EPRS(1), GAD1(1), GFPT1(1), GLS(1), GLS2(1), GOT1(2), GOT2(3), GPT2(1), GSS(1) 19339213 18 17 18 7 2 8 5 0 3 0 0.30 0.51 361 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 37 AKT1(2), DUSP10(1), DUSP8(1), GAB1(1), JUN(1), MAP2K7(1), MAP3K1(1), MAP3K10(1), MAP3K11(1), MAP3K12(2), MAP3K3(1), MAP3K4(3), MAP3K5(1), MAP3K7(1), MAPK10(1), MAPK9(1), NFATC3(2), NR2C2(1), TRAF6(1), ZAK(1) 24143205 25 24 25 5 3 10 6 0 6 0 0.30 0.51 362 NITROGEN_METABOLISM AMT, ASNS, CA1, CA12, CA14, CA2, CA3, CA4, CA5A, CA5B, CA6, CA7, CA8, CA9, CPS1, CTH, GLS, GLS2, GLUD1, GLUL, HAL 21 ASNS(1), CA5B(1), CA9(1), CPS1(5), GLS(1), GLS2(1) 9233145 10 10 10 1 0 6 4 0 0 0 0.30 0.52 363 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 AARS2(1), ADSL(1), AGXT(1), AGXT2(1), ASNS(1), ASS1(1), DARS(1), DLAT(2), GAD1(1), GOT1(2), GOT2(3), GPT2(1), NARS2(1) 18623928 17 15 17 6 2 3 5 1 6 0 0.30 0.52 364 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 BIRC2(2), BIRC3(1), CASP1(1), CASP10(2), CASP2(1), CASP4(1), CASP7(1), CASP8(1), LMNB1(1) 9445671 11 11 11 4 3 3 4 0 1 0 0.31 0.52 365 HSA00550_PEPTIDOGLYCAN_BIOSYNTHESIS Genes involved in peptidoglycan biosynthesis GLUL, PGLYRP2 2 PGLYRP2(1) 886309 1 1 1 0 0 0 1 0 0 0 0.31 0.52 366 HSA00520_NUCLEOTIDE_SUGARS_METABOLISM Genes involved in nucleotide sugars metabolism GALE, GALT, TGDS, UGDH, UGP2, UXS1 6 GALE(1), UGP2(1), UXS1(1) 2499944 3 3 3 1 0 2 0 1 0 0 0.31 0.52 367 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 60 ATP12A(3), ATP6AP1(1), ATP6V0A4(1), ATP6V1B1(1), ATP6V1B2(1), ATP7B(2), COX6A2(1), COX7A2(1), NDUFA10(1), NDUFB6(1), NDUFS1(2), NDUFS2(1), NDUFV2(1), PPA2(2), SDHA(1), SHMT1(1) 18211634 21 20 21 8 7 5 7 0 2 0 0.31 0.52 368 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), ARG1(1), GLS(1) 2682479 3 3 3 1 0 2 0 0 1 0 0.31 0.52 369 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 TGFB2(1), TGFB3(1), TGFBR2(2), TOB2(2) 5263043 6 6 6 2 3 2 0 1 0 0 0.31 0.52 370 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 HRAS(2), JAK2(2), JUN(1), PLCG1(1), SOS1(4), STAT5B(1) 10648180 11 11 11 2 1 3 7 0 0 0 0.31 0.52 371 EXTRINSICPATHWAY The extrinsic prothrombin activation pathway requires the release of thromboplastin from damaged tissues to activate the blood clotting cascade. F10, F2, F2R, F3, F5, F7, FGA, FGB, FGG, PROC, PROS1, SERPINC1, TFPI 13 F2(2), F5(3), FGA(1), PROC(2), TFPI(1) 7922110 9 9 9 3 0 5 3 0 1 0 0.31 0.52 372 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), GRIN1(1), HIF1A(1), JAK2(2), RELA(1) 6289138 7 7 7 0 1 2 4 0 0 0 0.31 0.52 373 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 80 AGL(1), ASCC3(2), ATP13A2(4), DDX18(2), DDX50(2), DDX56(1), DHX58(1), ENPP3(2), EP400(1), GAA(2), GBA(2), GBA3(1), GPI(1), GUSB(2), GYS1(2), GYS2(1), HK1(3), IFIH1(2), MGAM(2), RAD54L(1), SI(3), SKIV2L2(1), SMARCA2(4), SMARCA5(2), UGP2(1), UGT1A1(1), UGT1A7(2), UGT1A8(1), UGT2A1(1), UGT2A3(2), UGT2B11(1), UGT2B15(1), UGT2B28(1), UXS1(1) 60334316 57 47 57 23 4 16 23 5 9 0 0.32 0.52 374 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 18 ABCA1(4), HMGCR(1), LIPC(1), LRP1(5), SCARB1(2) 12763083 13 13 13 5 2 6 2 2 1 0 0.32 0.53 375 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 CAPN1(1), GSK3B(1), MAPT(1), PPP2CA(2) 4631579 5 5 5 0 0 1 1 1 2 0 0.32 0.53 376 HSA00150_ANDROGEN_AND_ESTROGEN_METABOLISM Genes involved in androgen and estrogen metabolism AKR1C4, AKR1D1, ARSD, ARSE, CARM1, CYP11B1, CYP11B2, CYP19A1, HEMK1, HSD11B1, HSD11B2, HSD17B1, HSD17B12, HSD17B2, HSD17B3, HSD17B7, HSD17B8, HSD3B1, HSD3B2, LCMT1, LCMT2, METTL2B, METTL6, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, SRD5A1, SRD5A2, STS, SULT1E1, SULT2A1, SULT2B1, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, WBSCR22 54 ARSD(1), ARSE(1), CYP11B2(1), CYP19A1(1), HSD17B1(1), HSD17B2(1), HSD17B8(1), LCMT2(1), PRMT5(1), PRMT6(1), PRMT7(2), PRMT8(1), STS(1), UGT1A1(1), UGT1A7(2), UGT1A8(1), UGT2A1(1), UGT2A3(2), UGT2B11(1), UGT2B15(1), UGT2B28(1) 23525307 24 24 24 8 2 6 12 2 2 0 0.33 0.53 377 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 BRAF(3), CREB5(1), SNX13(3) 5738631 7 6 7 6 0 3 3 0 1 0 0.33 0.54 378 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 MBTPS1(1), SCAP(1), SREBF2(3) 5716128 5 5 5 2 1 1 2 0 1 0 0.33 0.54 379 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 ARSB(1), ARSD(1), ARSE(1), GAL3ST1(1), GBA(2), GLB1(3), LCT(1), PPAP2C(1), SMPD1(1) 11522198 12 11 12 9 0 5 4 1 2 0 0.33 0.54 380 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 CDC6(1), CDK2(1), DIAPH2(1), MCM2(3), MCM6(2), MCM7(1), NACA(2), ORC1L(1), ORC4L(1), ORC5L(1), PCNA(1), POLD1(2), POLD3(1), POLE(1), POLE2(1), RFC1(1), RFC2(1), RPA3(1), RPA4(1) 24938612 24 24 24 12 5 4 8 0 7 0 0.34 0.55 381 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(1), DPAGT1(1), MGAT3(1), MGAT4A(1), MGAT5(1), RPN1(2), RPN2(1) 9452406 8 8 8 4 0 1 4 1 2 0 0.34 0.55 382 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 IL6R(1), JAK1(2), JAK2(2), JAK3(1), PTPRU(2) 7589078 8 7 8 4 2 2 1 0 3 0 0.35 0.56 383 GAMMA_HEXACHLOROCYCLOHEXANE_DEGRADATION ACP1, ACP2, ACP5, ACPP, ACPT, ALPI, ALPL, ALPP, ALPP, ALPPL2, ALPPL2, CYP19A1, CYP1A1, CYP1A2, CYP2A6, CYP2A6, CYP2A7, CYP2A7P1, CYP2A13, CYP2B6, CYP2C18, CYP2C19, CYP2C19, CYP2C9, CYP2C8, CYP2C9, CYP2D6, CYP2E1, CYP2F1, CYP2J2, CYP3A4, CYP3A5, CYP3A7, CYP4B1, CYP4F8, CYP51A1, PON1 31 ACP5(1), ALPI(1), ALPL(2), ALPP(2), ALPPL2(1), CYP19A1(1), CYP1A1(1), CYP2B6(1), CYP2C18(1), CYP2C19(1), CYP2C8(1), CYP2F1(1), CYP2J2(1), CYP4B1(1) 14358228 16 14 16 6 2 1 10 2 1 0 0.35 0.56 384 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 CHPT1(1), LCMT2(1), PRMT5(1), PRMT6(1), PRMT7(2), PRMT8(1) 6913934 7 7 7 2 1 1 3 0 2 0 0.35 0.57 385 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 67 ACSL1(1), ACSL3(1), ACSL5(1), ACSL6(2), ANGPTL4(1), APOA5(1), AQP7(1), CYP4A11(2), CYP4A22(1), CYP8B1(2), DBI(1), FADS2(1), GK(1), ILK(1), ME1(1), NR1H3(1), PCK1(2), PLTP(1), RXRB(1), RXRG(2), SCP2(2), SLC27A1(2), SLC27A6(1), SORBS1(1), UCP1(1) 31653372 32 29 32 12 5 12 11 0 4 0 0.35 0.57 386 HSA04120_UBIQUITIN_MEDIATED_PROTEOLYSIS Genes involved in ubiquitin mediated proteolysis ANAPC1, ANAPC10, ANAPC11, ANAPC2, ANAPC4, ANAPC5, ANAPC7, BTRC, CDC16, CDC20, CDC23, CDC26, CDC27, CUL1, CUL2, CUL3, FBXW11, FBXW7, FZR1, ITCH, LOC728919, RBX1, SKP1, SKP2, SMURF1, SMURF2, TCEB1, TCEB2, UBA1, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2D4, UBE2E1, UBE2E2, UBE2E3, VHL, WWP1, WWP2 38 ANAPC1(3), ANAPC4(1), CDC27(1), CUL1(2), CUL3(1), FBXW11(1), FBXW7(3), SMURF2(2), TCEB1(1), UBA1(1), UBE2E2(1), WWP2(1) 19786768 18 18 18 7 0 4 10 1 3 0 0.36 0.57 387 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(3), CREB5(1), EIF4E(1), MKNK2(2), RPS6KA1(1), RPS6KA2(1), RPS6KA3(1), SOS1(4), SOS2(2), TRAF3(1) 14641693 17 15 17 7 3 4 8 0 2 0 0.36 0.57 388 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), PPP2CA(2), PRKACB(1), PRKAG1(2) 8972421 9 9 9 3 0 3 4 0 2 0 0.36 0.57 389 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 45 ADH1B(1), ADHFE1(1), ALDH1A2(1), ALDH1B1(2), ALDH3A2(1), CEL(1), DGKB(1), DGKH(1), DGKQ(1), DGKZ(1), GK(1), GLB1(3), LCT(1), LIPC(1), LIPF(1), PNLIP(2), PNLIPRP2(1), PPAP2C(1) 23466314 22 20 22 7 3 2 11 2 4 0 0.36 0.57 390 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(1), CD4(1), IL3(1), KITLG(1) 3117195 4 4 4 2 1 3 0 0 0 0 0.36 0.57 391 HSA00791_ATRAZINE_DEGRADATION Genes involved in atrazine degradation ADAR, APOBEC1, APOBEC2, APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3F, APOBEC3G, APOBEC4 9 ADAR(2), APOBEC4(1) 3607442 3 3 3 3 1 1 0 0 1 0 0.36 0.57 392 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), FBP1(1), FPGT(1), HK1(3), KHK(2), MPI(1), MTMR1(2), MTMR2(1), PFKM(2), PGM2(1), RDH13(1) 18400760 18 17 18 6 1 5 8 2 2 0 0.37 0.57 393 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 BIRC2(2), BIRC3(1), CASP10(2), CASP7(1), CASP8(1), GAS2(1), RELA(1), RIPK1(1), SPTAN1(1), TNFRSF10A(1), TNFSF10(1), TRADD(1) 16548992 14 14 14 3 4 1 6 0 3 0 0.37 0.57 394 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), JUN(1), MAP2K3(2), MAP3K1(1), MAP4K2(1), RELA(1), RIPK1(1), TANK(1), TNFRSF1A(1), TRADD(1) 11885639 11 10 11 4 2 1 6 0 2 0 0.37 0.58 395 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 20 IL12RB1(1), IL12RB2(1), JAK2(2), JUN(1), STAT4(2), TYK2(2) 9126453 9 9 9 4 1 3 3 1 1 0 0.37 0.58 396 FREEPATHWAY Neutrophils release superoxide to induce lysis in invading bacteria; in neighboring endothelial cells, superoxide dismutase scavenges radicals but produces pro-apoptotic peroxides. GPX1, GSR, GSS, IL8, NFKB1, NOX1, RELA, SOD1, TNF, XDH 10 GSS(1), NOX1(1), RELA(1), XDH(2) 4846850 5 5 5 1 0 1 4 0 0 0 0.37 0.58 397 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 17 CALM2(1), CCL2(1), JUN(1), PLCG1(1), PTK2B(2) 6583910 6 6 6 4 0 1 4 0 1 0 0.38 0.59 398 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 POLD1(2), POLD3(1), POLE(1), POLE2(1), POLG2(3), POLH(2), POLI(2), POLL(1), POLM(1), POLQ(3), PRIM2(1), REV3L(4) 20602122 22 20 22 5 4 4 8 1 5 0 0.38 0.59 399 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 DHRS2(1), LCMT2(1), PRMT5(1), PRMT6(1), PRMT7(2), PRMT8(1) 7021984 7 7 7 1 1 2 3 0 1 0 0.39 0.60 400 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 33 ACTA1(1), DOCK1(1), GAB1(1), HGF(1), HRAS(2), ITGA1(1), ITGB1(2), JUN(1), MAP4K1(1), MET(1), PAK1(1), PIK3R1(2), PTK2(1), PTK2B(2), PTPN11(1), SOS1(4) 20788559 23 21 23 16 6 3 13 0 1 0 0.39 0.60 401 HYPERTROPHY_MODEL ADAM10, ANKRD1, ATF3, CYR61, DUSP14, EIF4E, EIF4EBP1, GDF8, HBEGF, IFNG, IFRD1, IL18, IL1A, IL1R1, JUND, MYOG, NR4A3, TCF8, VEGF, WDR1 17 ADAM10(1), ANKRD1(1), EIF4E(1), IFRD1(1), NR4A3(1), WDR1(1) 5400923 6 6 6 1 1 1 3 0 1 0 0.39 0.60 402 EEA1PATHWAY The FYVE-finger proteins EEA1 and HRS are localized to endosome membranes and regulate sorting and ubiquitination in the vesicle transport system. EEA1, EGF, EGFR, HGS, RAB5A, TF, TFRC 7 EEA1(1), EGF(1), EGFR(4), RAB5A(1) 6276884 7 7 7 0 2 3 1 0 1 0 0.39 0.60 403 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 CREBBP(3), GZMA(1), HMGB2(1) 5262970 5 5 5 2 0 0 3 1 1 0 0.40 0.61 404 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), DHRS2(1), RDH13(1) 4130052 4 4 4 0 1 1 1 0 1 0 0.40 0.61 405 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 B3GNT7(1), B4GALT4(2), CHST1(1), ST3GAL3(1) 5736792 5 5 5 2 0 1 1 0 3 0 0.41 0.62 406 STARCH_AND_SUCROSE_METABOLISM AGL, AMY1A, AMY1B, AMY1C, AMY2A, AMY2B, AMY2B, RNPC3, ENPP1, ENPP3, G6PC, GAA, GANAB, GBA3, GBE1, GCK, GPI, GUSB, GYS1, GYS2, HK1, HK2, HK3, MGAM, PGM1, PGM3, PYGB, PYGL, PYGM, SI, UCHL1, UCHL3, UGDH, UGT1A10, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A9, UGT2B15, UGT2B4, UXS1 41 AGL(1), ENPP3(2), GAA(2), GBA3(1), GPI(1), GUSB(2), GYS1(2), GYS2(1), HK1(3), MGAM(2), SI(3), UCHL3(1), UGT1A1(1), UGT1A7(2), UGT1A8(1), UGT2B15(1), UXS1(1) 27566105 27 25 27 11 4 5 8 5 5 0 0.41 0.62 407 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), GREB1(2), HSPB2(1), MTA3(1) 5154148 5 5 5 1 1 0 3 1 0 0 0.41 0.62 408 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 52 CCKBR(1), CELSR1(3), CELSR3(1), CHRM2(1), EMR3(4), GPR116(1), GPR133(3), GPR17(1), GPR84(2), GRM1(1), HRH4(1), LGR6(2), LPHN3(3), NTSR1(1), OR8G2(1), P2RY13(1), PTGFR(1), SMO(2), TSHR(1) 31849963 31 28 31 8 2 9 16 1 3 0 0.41 0.62 409 HSA00620_PYRUVATE_METABOLISM Genes involved in pyruvate metabolism ACACA, ACACB, ACAT1, ACAT2, ACOT12, ACSS1, ACSS2, ACYP1, ACYP2, AKR1B1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, DLAT, DLD, GLO1, GRHPR, HAGH, HAGHL, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, LDHD, MDH1, MDH2, ME1, ME2, ME3, PC, PCK1, PCK2, PDHA1, PDHA2, PDHB, PKLR, PKM2 41 ACACA(3), ACSS1(2), ACSS2(2), ALDH1B1(2), ALDH3A2(1), DLAT(2), HAGH(1), LDHAL6B(1), LDHB(1), LDHC(1), MDH1(1), ME1(1), ME2(1), ME3(1), PCK1(2) 22788407 22 20 22 8 3 3 7 3 6 0 0.42 0.63 410 NUCLEOTIDE_SUGARS_METABOLISM GALE, GALT, TGDS, UGDH, UXS1 5 GALE(1), UXS1(1) 1987535 2 2 2 1 0 1 0 1 0 0 0.42 0.63 411 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 ADH1B(1), ADHFE1(1), ALDH1A2(1), ALDH1B1(2), ALDH3A2(1), ALDH3B1(1), ALDH3B2(1), ALDOA(1), DLAT(2), FBP1(1), GPI(1), HK1(3), LDHB(1), LDHC(1), PFKM(2), PGAM1(1), PGK1(3) 23773969 24 21 24 6 2 4 10 3 5 0 0.42 0.63 412 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 ADH1B(1), ADHFE1(1), ALDH1A2(1), ALDH1B1(2), ALDH3A2(1), ALDH3B1(1), ALDH3B2(1), ALDOA(1), DLAT(2), FBP1(1), GPI(1), HK1(3), LDHB(1), LDHC(1), PFKM(2), PGAM1(1), PGK1(3) 23773969 24 21 24 6 2 4 10 3 5 0 0.42 0.63 413 HSA00053_ASCORBATE_AND_ALDARATE_METABOLISM Genes involved in ascorbate and aldarate metabolism ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, MIOX, UGDH 9 ALDH1B1(2), ALDH3A2(1), MIOX(1) 4166374 4 4 4 0 0 0 3 0 1 0 0.42 0.63 414 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_LACTOSERIES ABO, FUT1, FUT2, FUT3, FUT5, FUT6, SIAT6, ST3GAL3 7 FUT6(1), ST3GAL3(1) 2302256 2 2 2 1 0 0 1 0 1 0 0.42 0.63 415 HSA00902_MONOTERPENOID_BIOSYNTHESIS Genes involved in monoterpenoid biosynthesis CYP2C19, CYP2C9 2 CYP2C19(1) 986886 1 1 1 0 0 0 0 1 0 0 0.43 0.63 416 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 RANBP2(5) 4065861 5 5 5 0 0 3 1 1 0 0 0.43 0.63 417 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), PER1(2) 4198038 4 4 4 2 0 2 1 0 1 0 0.43 0.63 418 FCER1PATHWAY In mast cells, Fc epsilon receptor 1 activates BTK, PKC, and the MAP kinase pathway to promote degranulation and arachnidonic acid release. BTK, CALM1, CALM2, CALM3, ELK1, FCER1A, FCER1G, FOS, GRB2, HRAS, JUN, LYN, MAP2K1, MAP2K4, MAP2K7, MAP3K1, MAPK1, MAPK3, MAPK8, NFATC1, NFATC2, NFATC3, NFATC4, PAK2, PIK3CA, PIK3R1, PLA2G4A, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCB1, RAF1, SHC1, SOS1, SYK, SYT1, VAV1 36 CALM2(1), HRAS(2), JUN(1), MAP2K7(1), MAP3K1(1), NFATC2(1), NFATC3(2), PIK3R1(2), PLCG1(1), PPP3CC(1), SOS1(4), SYK(1), VAV1(1) 19644609 19 19 19 9 4 5 7 0 3 0 0.43 0.64 419 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 JUNB(2), MAP2K3(2), NFATC2(1), PRKACB(1) 5522879 6 5 6 3 1 0 4 0 1 0 0.43 0.64 420 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 ASNS(1), CA5B(1), CA9(1), CPS1(5), GLS(1), GLS2(1) 10330878 10 10 10 1 0 6 4 0 0 0 0.43 0.64 421 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 31 ADRB2(1), CHRM2(1), CHRM5(2), DRD1(1), DRD5(1), HTR1A(1), HTR2A(1), HTR2C(1), HTR5A(1), HTR6(1), HTR7(1) 12206396 12 12 12 3 1 6 3 1 1 0 0.44 0.64 422 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 CDC25A(1), MNAT1(1), XPO1(2) 4251172 4 4 4 1 1 0 2 1 0 0 0.44 0.64 423 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 41 CALM2(1), FYN(1), HRAS(2), JUN(1), MAP3K1(1), NFATC2(1), NFATC3(2), PIK3R1(2), PLCG1(1), PPP3CC(1), PTPN7(1), RELA(1), SOS1(4), VAV1(1), ZAP70(1) 22170112 21 21 21 13 3 7 9 0 2 0 0.44 0.64 424 HSA00040_PENTOSE_AND_GLUCURONATE_INTERCONVERSIONS Genes involved in pentose and glucuronate interconversions AKR1B1, DCXR, GUSB, RPE, UGDH, UGP2, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, XYLB 25 GUSB(2), UGP2(1), UGT1A1(1), UGT1A7(2), UGT1A8(1), UGT2A1(1), UGT2A3(2), UGT2B11(1), UGT2B15(1), UGT2B28(1) 12253964 13 13 13 2 2 4 4 1 2 0 0.44 0.64 425 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(2), GNB1(2), HRAS(2), ITGA1(1), ITGB1(2), PLCB1(1), PTK2(1), SYK(1) 11956135 12 11 12 6 1 1 7 0 3 0 0.44 0.64 426 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(3), LEPR(1), PRKAG1(2), PRKAG2(1) 7140097 7 7 7 0 2 1 2 1 1 0 0.44 0.64 427 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 DAB1(1), FYN(1), LRP8(1), RELN(3), VLDLR(2) 6826972 8 7 8 6 1 4 3 0 0 0 0.44 0.64 428 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 20 AKT1(2), HRAS(2), PIK3R1(2), RALBP1(1), RELA(1) 8358117 8 8 8 3 2 2 3 0 1 0 0.45 0.64 429 PYRUVATE_METABOLISM ACACA, ACAS2, ACAS2L, ACAT1, ACAT2, ACYP1, ACYP2, ADH5, AKR1B1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, CACH_1, DLAT, DLD, GLO1, GRHPR, HAGH, HAGHL, LDHA, LDHB, LDHC, LDHD, MDH1, MDH2, ME1, ME2, ME3, PC, PCK1, PDHA1, PDHA2, PDHB, PKLR, PKM2 36 ACACA(3), ADH5(1), ALDH1A2(1), ALDH1B1(2), ALDH3A2(1), DLAT(2), HAGH(1), LDHB(1), LDHC(1), MDH1(1), ME1(1), ME2(1), ME3(1), PCK1(2) 17986634 19 17 19 6 4 3 5 3 4 0 0.45 0.64 430 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), ACTN2(2), CAPN1(1), ITGA1(1), ITGB1(2), PTK2(1), SPTAN1(1), TLN1(3) 14281837 12 12 12 8 2 2 6 0 2 0 0.45 0.64 431 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 14 CDKN2A(1), PIK3R1(2), POLR1A(1), POLR1C(1), RB1(3) 8251297 8 7 8 10 2 4 1 0 1 0 0.45 0.64 432 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 CALM2(1), CAMK1(1), GNB1(2), HRAS(2), MAP2K3(2), MAP3K1(1), NCF1(1), NFATC2(1), NFATC3(2), PAK1(1), PIK3C2G(1), PLCB1(1), PPP3CC(1), RELA(1) 18855704 18 17 18 5 1 4 9 0 4 0 0.45 0.64 433 ONE_CARBON_POOL_BY_FOLATE ALDH1L1, AMT, ATIC, ATP6V0C, SHMT1, DHFR, GART, MTHFD1, MTHFD1L, MTHFD2, MTHFR, MTHFS, MTR, SHMT1, SHMT2, TYMS 15 GART(1), MTHFD1(2), MTHFD1L(1), MTHFR(1), SHMT1(1), SHMT2(2) 8840957 8 8 8 1 1 1 5 0 1 0 0.45 0.64 434 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 55 ADH1B(1), ADH5(1), ADHFE1(1), AGK(3), ALDH1B1(2), ALDH3A2(1), CEL(1), DGKB(1), DGKH(1), DGKQ(1), DGKZ(1), GK(1), GLB1(3), LCT(1), LIPC(1), LIPF(1), PNLIP(2), PNLIPRP2(1), PNPLA3(1), PPAP2C(1) 28674109 26 23 26 6 4 4 12 2 4 0 0.45 0.64 435 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(1), COL4A3(1), COL4A4(2), COL4A5(4), COL4A6(2), F12(1), F2(2), F5(3), F8(1), FGA(1), PROC(2), SERPING1(2) 22068126 22 21 22 11 1 9 10 1 1 0 0.46 0.64 436 SELENOAMINO_ACID_METABOLISM AHCY, CBS, CTH, GGT1, MARS, MARS2, MAT1A, MAT2B, PAPSS1, PAPSS2, SCLY, SEPHS1 12 GGT1(2), MARS(1), PAPSS2(1) 6052156 4 4 4 3 0 1 1 1 1 0 0.46 0.64 437 LIMONENE_AND_PINENE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, ECHS1, EHHADH, HADHA, SDS 12 ALDH1A2(1), ALDH1B1(2), ALDH3A2(1), ECHS1(1), HADHA(1) 5997941 6 6 6 1 1 1 4 0 0 0 0.46 0.64 438 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(1), ANPEP(3), ENPEP(1), LNPEP(2), MAS1(1), MME(1), REN(1) 10314524 10 10 10 5 4 3 2 0 1 0 0.46 0.64 439 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 IRAK1(2), MAP3K1(1), MAP3K7(1), RELA(1), RIPK1(1), TLR4(1), TNFRSF1A(1), TRADD(1), TRAF6(1) 11860348 10 9 10 6 1 0 5 0 4 0 0.46 0.64 440 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 19 HRAS(2), IRS1(1), JUN(1), PIK3R1(2), PTPN11(1), SOS1(4) 10903059 11 11 11 7 3 2 6 0 0 0 0.46 0.64 441 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 55 CTPS(1), DCTD(1), DPYS(1), POLD1(2), POLE(1), POLL(1), POLQ(3), POLR2A(4), POLR2B(1), POLR2I(1), POLRMT(1), RRM2(1), TK2(1), UNG(2) 28285743 21 20 21 7 3 3 8 1 6 0 0.46 0.65 442 ETCPATHWAY Energy is extracted from carbohydrates via oxidation and transferred to the mitochondrial electron transport chain, which couples ATP synthesis to the reduction of oxygen to water. ATP5A1, CYCS, GPD2, MTCO1, NDUFA1, SDHA, SDHB, SDHC, SDHD, UQCRC1 9 ATP5A1(1), SDHA(1), SDHD(1) 3201878 3 3 3 0 1 1 0 0 1 0 0.47 0.65 443 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), RPL19(1), RPL27(1), RPL30(1), RPL31(1), RPL34(1), RPL7(1), RPS13(1), RPS26(1), RPS29(1), RPS3A(1) 10851359 11 10 11 4 0 5 5 0 1 0 0.47 0.65 444 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 B3GNT3(1), B3GNT5(1), B4GALT4(2), FUT6(1), GCNT2(1), ST3GAL6(1), ST8SIA1(1) 7359256 8 7 8 2 1 3 2 1 1 0 0.47 0.65 445 ANDROGEN_AND_ESTROGEN_METABOLISM AKR1C4, AKR1D1, ARSB, ARSD, ARSE, CYP11B1, CYP11B2, HSD11B1, HSD11B2, HSD17B2, HSD17B3, HSD17B8, HSD3B1, HSD3B2, SRD5A1, SRD5A2, STS, SULT1E1, SULT2A1, UGT1A10, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A9, UGT2B15, UGT2B4 30 ARSB(1), ARSD(1), ARSE(1), CYP11B2(1), HSD17B2(1), HSD17B8(1), STS(1), UGT1A1(1), UGT1A7(2), UGT1A8(1), UGT2B15(1) 12758150 12 12 12 5 1 3 5 1 2 0 0.47 0.65 446 HSA00601_GLYCOSPHINGOLIPID_BIOSYNTHESIS_LACTOSERIES Genes involved in glycosphingolipid biosynthesis - lactoseries ABO, B3GALT1, B3GALT2, B3GALT5, B3GNT5, FUT1, FUT2, FUT3, ST3GAL3, ST3GAL4 10 B3GALT2(1), B3GNT5(1), ST3GAL3(1) 3498397 3 3 3 1 0 0 1 1 1 0 0.48 0.66 447 HSA00604_GLYCOSPHINGOLIPID_BIOSYNTHESIS_GANGLIOSERIES Genes involved in glycosphingolipid biosynthesis - ganglioseries B3GALT4, B4GALNT1, GLB1, HEXA, HEXB, LCT, SLC33A1, ST3GAL1, ST3GAL2, ST3GAL5, ST6GALNAC3, ST6GALNAC4, ST6GALNAC5, ST6GALNAC6, ST8SIA1, ST8SIA5 16 B3GALT4(1), GLB1(3), HEXA(1), LCT(1), SLC33A1(2), ST8SIA1(1) 8074688 9 8 9 6 1 4 2 1 1 0 0.48 0.66 448 CAPROLACTAM_DEGRADATION AKR1A1, ECHS1, EHHADH, HADHA, SDS 5 ECHS1(1), HADHA(1) 2398269 2 2 2 0 0 1 1 0 0 0 0.48 0.66 449 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(1), IARS2(2), VARS2(4) 8400540 8 8 8 3 1 2 4 0 1 0 0.48 0.66 450 BOTULINPATHWAY Blockade of Neurotransmitter Relase by Botulinum Toxin CHRM1, CHRNA1, SNAP25, STX1A, VAMP2 5 CHRNA1(1) 1597225 1 1 1 1 0 0 0 0 1 0 0.49 0.66 451 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), ALOX5(1), CYP2C18(1), CYP2C19(1), CYP2C8(1), CYP2J2(1), PLA2G12A(1), PLA2G6(2), RDH13(1) 11771519 11 11 11 1 3 1 5 1 1 0 0.49 0.66 452 1_2_DICHLOROETHANE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A2(1), ALDH1B1(2), ALDH3A2(1) 3929942 4 4 4 1 1 0 3 0 0 0 0.49 0.66 453 ASCORBATE_AND_ALDARATE_METABOLISM ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A2(1), ALDH1B1(2), ALDH3A2(1) 3929942 4 4 4 1 1 0 3 0 0 0 0.49 0.66 454 SULFUR_METABOLISM BPNT1, PAPSS1, PAPSS2, SULT1A2, SULT1A3, SULT1A3, SULT1A4, SULT1E1, SULT2A1, SUOX 7 PAPSS2(1), SULT1A2(1), SUOX(1) 2978406 3 3 3 2 0 2 0 1 0 0 0.49 0.66 455 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(3), EP300(3), NCOA1(1), NCOA2(1) 9063247 8 8 8 6 1 1 5 0 1 0 0.49 0.67 456 HSA00830_RETINOL_METABOLISM Genes involved in retinol metabolism ALDH1A1, ALDH1A2, BCMO1, RDH5 4 ALDH1A2(1), RDH5(1) 1902186 2 2 2 2 1 0 1 0 0 0 0.49 0.67 457 SA_DIACYLGLYCEROL_SIGNALING DAG (diacylglycerol) signaling activity ESR1, ESR2, ITPKA, PDE1A, PDE1B, PLCB1, PLCB2, PRL, TRH, VIP 10 ITPKA(1), PDE1B(2), PLCB1(1), PLCB2(1) 5458098 5 5 5 2 1 1 1 0 2 0 0.49 0.67 458 FATTY_ACID_BIOSYNTHESIS_PATH_2 ACAA1, ACAA2, ACAT1, ACAT2, ECHS1, EHHADH, HADHA, HADHB, SDS 9 ECHS1(1), HADHA(1), HADHB(2) 4127565 4 4 4 1 2 1 1 0 0 0 0.49 0.67 459 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 ACADS(2), ACSL1(1), ACSL3(1), ACSL5(1), ACSL6(2), ADH1B(1), ADH5(1), ADHFE1(1), ALDH1B1(2), ALDH3A2(1), CYP4A11(2), CYP4A22(1), ECHS1(1), HADH(1), HADHA(1), HADHB(2), HSD17B4(1), PECI(1) 24016108 23 23 23 11 6 4 11 0 2 0 0.50 0.68 460 HSA00642_ETHYLBENZENE_DEGRADATION Genes involved in ethylbenzene degradation ARD1A, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ESCO1, ESCO2, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1 11 DHRS2(1), MYST3(4), PNPLA3(1) 7809532 6 6 6 2 0 3 3 0 0 0 0.51 0.68 461 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 GART(1), MTHFD1(2), MTHFD1L(1), MTHFR(1), SHMT1(1), SHMT2(2) 9294309 8 8 8 1 1 1 5 0 1 0 0.51 0.68 462 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 CUZD1(1), HRAS(2), JUN(1), PLCB1(1), RELA(1) 7475440 6 6 6 3 1 1 3 0 1 0 0.52 0.69 463 PENTOSE_AND_GLUCURONATE_INTERCONVERSIONS AKR1B1, DCXR, GUSB, RPE, RPE, LOC440001, UCHL1, UCHL3, UGDH, UGT1A10, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A9, UGT2B15, UGT2B4 18 GUSB(2), UCHL3(1), UGT1A1(1), UGT1A7(2), UGT1A8(1), UGT2B15(1) 7945896 8 8 8 3 2 2 1 1 2 0 0.52 0.70 464 FEEDERPATHWAY Sugars such as mannose, galactose, and fructose are enzymatically converted to glucose via feeder pathways that lead to glycolysis. HK1, KHK, LCT, MPI, PGM1, PYGL, PYGM, TPI1, TREH 9 HK1(3), KHK(2), LCT(1), MPI(1) 6668597 7 6 7 3 0 3 3 1 0 0 0.52 0.70 465 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 NR1H3(1), NR1H4(1) 2623419 2 2 2 3 0 0 1 1 0 0 0.52 0.70 466 BIOSYNTHESIS_OF_STEROIDS DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, IDI1, LSS, MVD, MVK, NQO1, NQO2, PMVK, SC5DL, SQLE, VKORC1 14 DHCR7(1), FDPS(1), HMGCR(1), PMVK(1), VKORC1(1) 5481897 5 5 5 0 0 2 3 0 0 0 0.53 0.70 467 HSA00471_D_GLUTAMINE_AND_D_GLUTAMATE_METABOLISM Genes involved in D-glutamine and D-glutamate metabolism GLS, GLS2, GLUD1, GLUD2 4 GLS(1), GLS2(1) 2118540 2 2 2 0 0 2 0 0 0 0 0.53 0.70 468 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), FBP1(1), FPGT(1), HK1(3), KHK(2), MPI(1), PFKM(2) 11887077 11 10 11 6 0 4 4 2 1 0 0.53 0.70 469 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(1), GNB1(2), PRKACB(1) 4611498 4 4 4 4 0 1 3 0 0 0 0.54 0.71 470 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(1), CD44(2), IL6R(1), TGFB2(1), TNFRSF1A(1) 6677849 6 6 6 5 2 0 2 0 2 0 0.54 0.71 471 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 CALM2(1), HRAS(2), JUN(1), MAP3K1(1), NFATC2(1), NFATC3(2), PLCG1(1), PPP3CC(1), SOS1(4), SYK(1), VAV1(1) 18528652 16 16 16 10 1 5 7 0 3 0 0.55 0.71 472 HSA00860_PORPHYRIN_AND_CHLOROPHYLL_METABOLISM Genes involved in porphyrin and chlorophyll metabolism ALAD, ALAS1, ALAS2, BLVRA, BLVRB, COX10, COX15, CP, CPOX, EARS2, EPRS, FECH, FTH1, FTMT, GUSB, HCCS, HMBS, HMOX1, HMOX2, MMAB, PPOX, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, UROD, UROS 41 ALAS2(1), COX15(1), CP(1), EPRS(1), FECH(1), FTMT(2), GUSB(2), HMOX1(1), UGT1A1(1), UGT1A7(2), UGT1A8(1), UGT2A1(1), UGT2A3(2), UGT2B11(1), UGT2B15(1), UGT2B28(1) 19666031 20 19 20 5 6 4 5 1 4 0 0.55 0.71 473 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 CALM2(1), GNAS(1), GNB1(2), HRAS(2), JUN(1), NFATC2(1), NFATC3(2), PLCG1(1), PPP3CC(1), PRKACB(1), RPS6KA3(1) 16651595 14 14 14 6 1 5 7 0 1 0 0.55 0.71 474 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), PER1(2), PER2(1), PER3(2) 8363050 7 7 7 2 0 3 2 0 2 0 0.55 0.71 475 DNA_POLYMERASE POLA, POLB, POLD1, POLD2, POLE, POLG, POLL, POLQ, POLS 7 POLD1(2), POLE(1), POLL(1), POLQ(3) 8338612 7 7 7 2 2 1 2 0 2 0 0.55 0.71 476 ACETAMINOPHENPATHWAY Acetaminophen selectively inhibits Cox-3, which is localized to the brain, and yields the toxic metabolite NAPQI when processed by CAR in the liver. CYP1A2, CYP2E1, CYP3A, NR1I3, PTGS1, PTGS2 5 PTGS2(2) 2589307 2 2 2 2 0 1 0 0 1 0 0.55 0.71 477 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(3), EP300(3) 7476649 6 6 6 6 0 1 4 0 1 0 0.55 0.71 478 SYNTHESIS_AND_DEGRADATION_OF_KETONE_BODIES ACAT1, ACAT2, BDH, HMGCL, OXCT1 4 OXCT1(1) 1656909 1 1 1 1 0 0 0 0 1 0 0.56 0.72 479 HSA00900_TERPENOID_BIOSYNTHESIS Genes involved in terpenoid biosynthesis FDFT1, FDPS, GGPS1, IDI1, IDI2, SQLE 6 FDPS(1), IDI2(1) 2173785 2 2 2 0 0 1 1 0 0 0 0.56 0.73 480 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 CDC25A(1), CDKN1A(1), WEE1(1) 3712484 3 3 3 1 0 2 1 0 0 0 0.57 0.73 481 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(1), ALPI(1), ALPL(2), ALPP(2), ALPPL2(1), DHRS2(1) 8505842 8 7 8 4 0 2 5 0 1 0 0.57 0.73 482 PANTOTHENATE_AND_COA_BIOSYNTHESIS BCAT1, COASY, DPYD, DPYS, ENPP1, ENPP3, PANK1, PANK2, PANK3, PANK4, PPCS, UPB1 12 BCAT1(1), COASY(1), DPYS(1), ENPP3(2), PANK2(2) 6682716 7 6 7 1 1 1 4 1 0 0 0.57 0.73 483 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 ADH1B(1), ADH5(1), ADHFE1(1), ALDH1B1(2), ALDH3A2(1) 6580023 6 6 6 2 2 0 3 0 1 0 0.58 0.73 484 IL18PATHWAY Pro-inflammatory IL-18 is activated in macrophages by caspase-1 cleavage and, in conjunction with IL-12, stimulates Th1 cell differentiation. CASP1, IFNG, IL12A, IL12B, IL18, IL2 6 CASP1(1) 1499385 1 1 1 1 0 0 1 0 0 0 0.58 0.73 485 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 ALG10(1), ALG10B(1), ALG13(1), ALG3(1), ALG8(1), DOLPP1(1), DPAGT1(1), MAN1A2(1), MAN2A1(1), MGAT3(1), MGAT4A(1), MGAT5(1), RFT1(1), RPN1(2), RPN2(1), STT3B(1) 20673936 17 16 17 5 0 4 9 1 3 0 0.58 0.74 486 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 EPHB2(1), F2(2), JUN(1), PLD1(1), PLD2(1), PLD3(1), PTK2(1), RASAL1(1), TEC(1), VAV1(1) 13680040 11 11 11 9 0 1 8 0 2 0 0.58 0.74 487 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 66 ATP8A1(1), AVPR1A(2), BDKRB1(1), C3AR1(1), CCKAR(2), CCKBR(1), MC3R(1), NMBR(1), NPY1R(1), NTSR1(1), OPRD1(1), OPRM1(1), SSTR1(2), SSTR4(1), TACR1(1), TACR2(1), TACR3(2), TSHR(1) 24748948 22 21 22 9 2 6 12 0 2 0 0.58 0.74 488 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 FADS2(1), PLA2G12A(1), PLA2G6(2) 5086502 4 4 4 0 0 0 4 0 0 0 0.58 0.74 489 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 DRD1(1), GRM1(1), PLCB1(1), PPP2CA(2), PRKACB(1) 7761224 6 6 6 0 0 1 3 0 2 0 0.59 0.74 490 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 58 CASP10(2), CASP8(1), DAXX(2), DEDD(2), EGFR(4), EPHB2(1), FAIM2(1), MAP2K7(1), MAP3K1(1), MAP3K5(1), MAPK10(1), MAPK8IP1(1), MAPK8IP3(1), MAPK9(1), MET(1), NFAT5(1), NFKBIB(1), NFKBIL2(1), PTPN13(1), RALBP1(1), RIPK1(1), ROCK1(2), SMPD1(1) 35405242 30 28 30 13 6 10 9 0 5 0 0.59 0.74 491 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(1), ITGAL(2) 4112732 3 3 3 1 0 0 2 0 1 0 0.60 0.75 492 MITOCHONDRIAL_FATTY_ACID_BETAOXIDATION ACADL, ACADM, ACADS, ACADVL, ACSL1, ACSL3, ACSL4, CPT1A, CPT2, DCI, EHHADH, HADHA, HADHSC, MGC5139, PECR, SCP2, SLC25A20 15 ACADS(2), ACSL1(1), ACSL3(1), HADHA(1), PECR(1), SCP2(2) 8243036 8 8 8 7 1 3 4 0 0 0 0.60 0.75 493 INOSITOL_METABOLISM ALDH6A1, ALDOA, ALDOB, ALDOC, TPI1 5 ALDOA(1) 1852755 1 1 1 1 0 0 0 1 0 0 0.60 0.75 494 MITRPATHWAY The MyoD/MEF2 transcription factors induce muscle cell differentiation and are repressed by the transcriptional repressor MITR. CAMK1, CAMK1G, HDAC9, MEF2A, MEF2B, MEF2C, MEF2D, MYOD1, YWHAH 9 CAMK1(1), HDAC9(1), MEF2A(1) 4121456 3 3 3 1 1 0 0 0 2 0 0.60 0.75 495 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(1), PRKACB(1), PRKAG1(2) 4969151 4 4 4 1 0 2 2 0 0 0 0.60 0.75 496 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 65 BIRC2(2), BIRC3(1), CASP1(1), CASP10(2), CASP2(1), CASP4(1), CASP7(1), CASP8(1), HELLS(1), JUN(1), MAP3K1(1), MAPK10(1), NFKBIB(1), RELA(1), RIPK1(1), TNFRSF1A(1), TNFSF10(1), TRADD(1), TRAF3(1) 27328869 21 21 21 9 5 4 8 0 4 0 0.61 0.75 497 CYTOKINEPATHWAY Intercellular signaling in the immune system occurs via secretion of cytokines, which promote antigen-dependent B and T cell response. IFNA1, IFNB1, IFNG, IL10, IL12A, IL12B, IL13, IL14, IL15, IL16, IL17, IL18, IL1A, IL2, IL3, IL4, IL5, IL6, IL8, IL9, LTA, TNF 20 IFNB1(1), IL16(2), IL3(1) 4730628 4 4 4 3 1 1 2 0 0 0 0.61 0.75 498 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 IFNAR1(1), IFNB1(1), RELA(1), TRAF6(1) 5365496 4 4 4 2 0 1 2 0 1 0 0.61 0.75 499 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 ADH1B(1), ADH5(1), ADHFE1(1), DHRS2(1), MYST3(4), PNPLA3(1) 11968492 9 9 9 4 2 3 3 0 1 0 0.61 0.75 500 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 ALDH1B1(2), ALDH3A2(1), CYP2C19(1), DHRS2(1), ECHS1(1), HADHA(1), MYST3(4), PNPLA3(1) 14912116 12 11 12 2 0 4 7 1 0 0 0.61 0.76 501 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 ADH1B(1), ADH5(1), ADHFE1(1), AKR1C1(1), ALDH3B1(1), ALDH3B2(1), CYP1A1(1), CYP2B6(1), CYP2C18(1), CYP2C19(1), CYP2C8(1), CYP2F1(1), DHDH(2), UGT1A1(1), UGT1A7(2), UGT1A8(1), UGT2A1(1), UGT2A3(2), UGT2B11(1), UGT2B15(1), UGT2B28(1) 27113692 24 22 24 7 6 3 8 3 4 0 0.62 0.76 502 TERPENOID_BIOSYNTHESIS FDFT1, FDPS, FDPS, LOC402397, IDI1, SQLE 4 FDPS(1) 1645680 1 1 1 0 0 0 1 0 0 0 0.62 0.76 503 NUCLEOTIDE_METABOLISM ADSL, ADSS, DHFR, HPRT1, IMPDH1, MTHFD2, NME2, OAZ1, POLA, POLB, POLD1, POLG, PRPS2, RRM1, SAT, SRM 14 ADSL(1), IMPDH1(1), POLD1(2), PRPS2(1) 6298961 5 5 5 2 1 1 3 0 0 0 0.62 0.76 504 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 HRAS(2), JUN(1), MAP3K1(1), MAPK8IP3(1), RPS6KA1(1), RPS6KA3(1), SOS1(4), SYK(1), VAV1(1), VAV3(1) 15453816 14 13 14 3 2 3 7 0 2 0 0.62 0.76 505 FOSBPATHWAY FOSB gene expression and drug abuse CDK5, FOSB, GRIA2, JUND, PPP1R1B 5 GRIA2(1) 1831849 1 1 1 1 0 1 0 0 0 0 0.62 0.76 506 CHONDROITIN B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 8 XYLT1(1), XYLT2(1) 3182878 2 2 2 1 0 1 1 0 0 0 0.63 0.76 507 HEPARAN_SULFATE_BIOSYNTHESIS B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 8 XYLT1(1), XYLT2(1) 3182878 2 2 2 1 0 1 1 0 0 0 0.63 0.76 508 1_AND_2_METHYLNAPHTHALENE_DEGRADATION ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1 7 ADH1B(1), ADHFE1(1) 2757591 2 2 2 2 1 0 0 0 1 0 0.63 0.76 509 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), GNAS(1), GNB1(2), HRAS(2), PRKACB(1), RPS6KA1(1) 9923836 8 8 8 3 1 2 5 0 0 0 0.63 0.76 510 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 CALM2(1), CAMK2G(2), CLCA4(1), CNGA4(1), GNAL(1), GUCA1B(1), PDE1C(1), PRKACA(1), PRKACB(1), PRKG1(1), PRKG2(1) 15177282 12 12 12 5 2 1 6 2 1 0 0.63 0.76 511 CHOLESTEROL_BIOSYNTHESIS C10orf110, CYP51A1, DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, HMGCS1, IDI1, LSS, MVD, MVK, NSDHL, PMVK, SC4MOL, SC5DL, SQLE 15 DHCR7(1), FDPS(1), HMGCR(1), PMVK(1), SC4MOL(1) 6541540 5 5 5 0 0 1 3 0 1 0 0.63 0.76 512 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 IFNB1(1), IRAK1(2), IRAK3(1), JUN(1), MAP2K3(2), MAP3K1(1), MAP3K7(1), RELA(1), TGFB2(1), TGFB3(1), TRAF6(1) 14495990 13 11 13 2 2 1 7 0 3 0 0.64 0.77 513 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 20 AKT1(2), CSF2RB(1), IL3(1), KITLG(1), PIK3R1(2), PRKACB(1) 9194592 8 8 8 5 3 3 2 0 0 0 0.65 0.78 514 STEROID_BIOSYNTHESIS CYP17A1, F13B, HSD17B1, HSD17B2, HSD17B3, HSD17B4, HSD17B7, HSD3B1, HSD3B2 9 HSD17B1(1), HSD17B2(1), HSD17B4(1) 3943716 3 3 3 2 0 1 1 1 0 0 0.65 0.78 515 AMINOSUGARS_METABOLISM CMAS, CYB5R3, GCK, GFPT1, GNE, GNPDA1, GNPDA2, HEXA, HEXB, HK1, HK2, HK3, PGM3, RENBP, UAP1 15 GFPT1(1), GNPDA1(1), HEXA(1), HK1(3), RENBP(2) 8352039 8 7 8 1 0 4 3 1 0 0 0.65 0.78 516 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(1), CLK4(1), COL2A1(3), CPSF1(2), CPSF2(1), CPSF3(1), CSTF2T(1), CSTF3(3), DHX15(2), DHX8(1), DHX9(1), LSM7(1), METTL3(1), NONO(2), POLR2A(4), PRPF8(6), SF3A2(1), SF3B1(2), SF3B2(2), SFRS12(2), SRPK2(1), SRRM1(1), SUPT5H(2), XRN2(2) 51502543 44 41 44 11 7 15 14 3 5 0 0.66 0.78 517 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 28 CD4(1), IFNGR1(1), IFNGR2(1), IL12RB1(1), IL12RB2(1), IL4R(1), TGFB2(1), TGFB3(1) 9682820 8 8 8 2 2 5 1 0 0 0 0.66 0.78 518 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), IFNB1(1), IL3(1), ITGAX(1), TLR4(1), TLR7(1) 9114542 8 8 8 4 3 1 4 0 0 0 0.66 0.78 519 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@ 6 CD4(1) 1438965 1 1 1 1 0 1 0 0 0 0 0.66 0.78 520 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 CARS(2), DARS(1), EPRS(1), HARS(1), IARS(1), KARS(1), MARS(1), SARS(2), TARS(1) 15693646 11 11 11 7 1 2 6 0 2 0 0.66 0.78 521 ARAPPATHWAY ADP-ribosylation factors (ARFs), members of the Ras superfamily, regulate eukaryotic vesicular trafficking and activate phospholipase D's. ARF1, ARFGAP1, ARFGAP3, ARFGEF2, BIG1, CENTD1, CENTD2, CLTA, CLTB, COP, COPA, DDEF1, DDEF2, GBF1, GPLD1, KDELR1, KDELR2, KDELR3, PSCD1, PSCD2, PSCD3, PSCD4 12 ARF1(1), ARFGEF2(1), CLTA(1), COPA(1), GBF1(2), KDELR2(1) 7965354 7 7 7 2 1 3 2 0 1 0 0.67 0.79 522 PROTEASOME PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1, PSMB10, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMB8, PSMB9 17 PSMA3(1), PSMA4(1), PSMA6(1) 4108699 3 3 3 1 1 0 1 1 0 0 0.67 0.79 523 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 SNAP23(1), STX10(1), STX7(1), STX8(1), TSNARE1(1) 8015575 5 5 5 2 1 1 2 0 1 0 0.67 0.79 524 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 CALM2(1), CAMK1(1), CAMK2G(2), ESRRA(1), MEF2A(1), PPP3CC(1) 10231760 7 7 7 1 0 1 3 0 3 0 0.68 0.80 525 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 CAMK2G(2), ITPKA(1), ITPKB(1), ITPR1(1), ITPR2(4), ITPR3(1), NFAT5(1), PDE6C(2) 17830422 13 13 13 4 0 6 6 0 1 0 0.68 0.80 526 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 COL4A1(1), COL4A3(1), COL4A4(2), COL4A5(4), COL4A6(2), REN(1) 12783227 11 11 11 5 2 4 4 1 0 0 0.68 0.80 527 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 ADH1B(1), ADHFE1(1), ALDH1A2(1), ALDH1B1(2), ALDH3A2(1), CEL(1), HADHB(2), SOAT2(1) 11495128 10 10 10 5 5 0 3 0 2 0 0.68 0.80 528 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 112 ATP12A(3), ATP4A(1), ATP5A1(1), ATP5G2(1), ATP6AP1(1), ATP6V0A4(1), ATP6V0D2(1), ATP6V1B1(1), ATP6V1B2(1), COX15(1), COX6A2(1), COX7A2(1), NDUFA10(1), NDUFB6(1), NDUFS1(2), NDUFS2(1), NDUFS5(1), NDUFV2(1), PPA2(2), SDHA(1), SDHD(1), UQCRC2(1) 27467489 26 24 26 14 7 8 9 0 2 0 0.69 0.80 529 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), DAXX(2), HSPB2(1) 5439787 4 4 4 0 3 0 1 0 0 0 0.69 0.80 530 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(3), CALM2(1), EP300(3), NFATC2(1), PPP3CC(1) 11543941 9 9 9 7 0 3 3 1 2 0 0.69 0.80 531 HSA00650_BUTANOATE_METABOLISM Genes involved in butanoate metabolism AACS, AADAC, ABAT, ACADS, ACAT1, ACAT2, ACSM1, AKR1B10, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH5A1, ALDH7A1, ALDH9A1, BDH1, BDH2, DDHD1, ECHS1, EHHADH, GAD1, GAD2, HADH, HADHA, HMGCL, HMGCS1, HMGCS2, HSD17B10, HSD17B4, HSD3B7, ILVBL, L2HGDH, OXCT1, OXCT2, PDHA1, PDHA2, PDHB, PLA1A, PPME1, PRDX6, RDH11, RDH12, RDH13, RDH14 45 AADAC(1), ACADS(2), AKR1B10(2), ALDH1B1(2), ALDH3A2(1), BDH1(1), ECHS1(1), GAD1(1), HADH(1), HADHA(1), HSD17B4(1), OXCT1(1), RDH13(1) 20122395 16 16 16 7 2 3 9 0 2 0 0.69 0.81 532 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 ACADS(2), ALDH1A2(1), ALDH1B1(2), ALDH3A2(1), ECHS1(1), GAD1(1), HADHA(1), OXCT1(1) 12688083 10 10 10 4 1 1 7 0 1 0 0.70 0.81 533 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(1), CALM2(1), PPP3CC(1), SYNJ1(4) 11127707 7 7 7 6 0 2 3 0 2 0 0.70 0.81 534 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 8 DNAJC3(1), EIF2S2(1), RELA(1) 4593607 3 3 3 0 1 0 2 0 0 0 0.71 0.82 535 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 GNAS(1), GNB1(2), HRAS(2), NOX1(1), PIK3C2G(1), PLCB1(1), PPP1R12B(1), PTK2(1) 12524412 10 10 10 5 1 2 6 0 1 0 0.71 0.82 536 GLUCOCORTICOID_MINERALOCORTICOID_METABOLISM CPN2, CYP11A1, CYP11B2, CYP17A1, HSD11B1, HSD11B2, HSD3B1, HSD3B2 8 CYP11A1(1), CYP11B2(1) 3378168 2 2 2 1 0 1 1 0 0 0 0.71 0.82 537 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 DHRS2(1), ECHS1(1), HADHA(1), MYST3(4), PNPLA3(1) 12436744 8 8 8 2 0 4 4 0 0 0 0.72 0.83 538 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), ARPC2(1), ARPC3(1), NCKAP1(1), WASL(2) 7609349 6 6 6 2 1 2 3 0 0 0 0.72 0.83 539 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 CALM2(1), EGR2(1), EGR3(1), MAP3K1(1), NFATC2(1), PLCG1(1), PPP3CC(1), PRKACB(1), RELA(1) 13247491 9 9 9 1 0 2 5 0 2 0 0.73 0.83 540 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 CREBBP(3), EP300(3), MAP2K3(2), MAP3K7(1), RELA(1), TGFBR2(2) 14552743 12 11 12 4 3 1 6 0 2 0 0.73 0.84 541 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 DHCR7(1), FDPS(1), HMGCR(1), IDI2(1), PMVK(1), SC4MOL(1), VKORC1(1) 9544279 7 7 7 1 0 3 3 0 1 0 0.73 0.84 542 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 CHPT1(1), PAFAH1B1(1), PLA2G12A(1), PLA2G6(2), PLD1(1), PLD2(1), PPAP2C(1) 11433514 8 8 8 2 0 1 6 0 1 0 0.74 0.84 543 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 ADRB2(1), GNAS(1), PLCE1(1), PRKACB(1), RAP2B(1) 7019869 5 5 5 2 0 3 1 0 1 0 0.74 0.84 544 GPCRDB_CLASS_B_SECRETIN_LIKE ADCYAP1R1, CALCR, CALCRL, CD97, CRHR1, CRHR2, ELTD1, EMR1, EMR2, GCGR, GHRHR, GIPR, GLP1R, GLP2R, GPR64, LPHN1, LPHN2, LPHN3, PTHR1, PTHR2, SCTR, VIPR1, VIPR2 20 ADCYAP1R1(1), CALCR(1), CD97(1), CRHR2(1), ELTD1(1), GIPR(1), GLP2R(1), LPHN1(1), LPHN3(3) 13618233 11 10 11 2 1 3 6 0 1 0 0.74 0.84 545 PORPHYRIN_AND_CHLOROPHYLL_METABOLISM ALAD, BLVRA, BLVRB, CP, CPOX, EPRS, FECH, GUSB, HCCS, HMBS, HMOX1, HMOX2, PPOX, UGT1A10, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A9, UGT2B15, UGT2B4, UROD, UROS 26 CP(1), EPRS(1), FECH(1), GUSB(2), HMOX1(1), UGT1A1(1), UGT1A7(2), UGT1A8(1), UGT2B15(1) 12759751 11 11 11 4 5 2 1 1 2 0 0.74 0.84 546 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 HRAS(2) 3710742 2 2 2 0 0 1 1 0 0 0 0.74 0.84 547 HSA00920_SULFUR_METABOLISM Genes involved in sulfur metabolism BPNT1, CHST11, CHST12, CHST13, PAPSS1, PAPSS2, SULT1A1, SULT1A2, SULT1A3, SULT1A4, SULT1E1, SULT2A1, SULT2B1, SUOX 12 PAPSS2(1), SULT1A2(1), SUOX(1) 4452086 3 3 3 3 0 2 0 1 0 0 0.75 0.84 548 HEME_BIOSYNTHESIS ALAD, ALAS1, ALAS2, CPOX, FECH, HMBS, PPOX, UROD, UROS 9 ALAS2(1), FECH(1) 3797446 2 2 2 2 1 0 0 0 1 0 0.75 0.84 549 TNFR2PATHWAY Tumor necrosis factor beta, produced by activated lymphocytes, binds to its receptor TNFR2 to induce activation in immune cells and apoptosis in many other cells. CHUK, DUSP1, IKBKAP, IKBKB, IKBKG, LTA, MAP3K1, MAP3K14, NFKB1, NFKBIA, RELA, RIPK1, TANK, TNFAIP3, TNFRSF1B, TRAF1, TRAF2, TRAF3 17 IKBKAP(1), MAP3K1(1), RELA(1), RIPK1(1), TANK(1), TRAF3(1) 11081882 6 6 6 2 0 2 2 0 2 0 0.75 0.84 550 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 SNCAIP(1), UBE2E2(1) 3102891 2 2 2 1 1 1 0 0 0 0 0.75 0.84 551 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_NEOLACTOSERIES ABO, B3GNT1, FUT1, FUT2, FUT9, GCNT2, ST8SIA1 7 GCNT2(1), ST8SIA1(1) 2939076 2 2 2 2 1 0 1 0 0 0 0.75 0.84 552 SA_FAS_SIGNALING The TNF-type receptor Fas induces apoptosis on ligand binding. BCL2, CASP3, CASP8, CFL1, CFLAR, P11, PDE6D, TNFRSF6, TNFSF6 6 CASP8(1) 1862712 1 1 1 0 0 0 1 0 0 0 0.75 0.84 553 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 ITPKA(1), ITPKB(1) 2855343 2 2 2 1 0 2 0 0 0 0 0.76 0.84 554 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(1) 2601171 1 1 1 2 0 0 1 0 0 0 0.76 0.84 555 GPCRDB_CLASS_A_RHODOPSIN_LIKE2 CYSLTR1, CYSLTR2, GPR109B, GPR161, GPR171, GPR18, GPR34, GPR39, GPR41, GPR42, GPR45, GPR65, GPR68, GPR75, GPR81, LYPDC1 13 GPR45(1), GPR65(1), GPR81(1) 4848662 3 3 3 2 0 1 2 0 0 0 0.76 0.85 556 SRCRPTPPATHWAY Activation of Src by Protein-tyrosine phosphatase alpha CCNB1, CDC2, CDC25A, CDC25B, CDC25C, CSK, GRB2, PRKCA, PRKCB1, PTPRA, SRC 9 CDC25A(1), CSK(1), PTPRA(1) 4568919 3 3 3 3 0 1 2 0 0 0 0.76 0.85 557 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 15 CD4(1), IL3(1) 3068160 2 2 2 2 1 1 0 0 0 0 0.77 0.85 558 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 ADH1B(1), ADH5(1), ADHFE1(1), AKR1B10(2), ALDH1B1(2), ALDH3A2(1), CEL(1), HADHB(2), RDH13(1), SOAT2(1) 15762123 13 12 13 4 6 0 4 0 3 0 0.77 0.85 559 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 CALM2(1), CDKN1A(1), NFATC2(1), NFATC3(2), PLCG1(1), PPP3CC(1) 9931680 7 7 7 6 0 4 2 0 1 0 0.77 0.85 560 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(1), HRAS(2), JUN(1), NCOR2(3), RBL2(1), SIN3A(1) 12945129 9 9 9 1 2 1 6 0 0 0 0.77 0.85 561 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 BDH1(1), OXCT1(1) 3554023 2 2 2 1 1 0 0 0 1 0 0.77 0.85 562 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), COASY(1), DPYS(1), ENPP3(2), PANK2(2) 8385050 7 6 7 2 1 1 4 1 0 0 0.77 0.85 563 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 19 BIRC2(2), BIRC3(1), CASP7(1), CASP8(1) 6680587 5 5 5 2 2 1 2 0 0 0 0.77 0.85 564 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 PLCB1(1), RELA(1) 4051481 2 2 2 2 0 0 1 0 1 0 0.78 0.85 565 BENZOATE_DEGRADATION_VIA_COA_LIGATION ACAT1, ACAT2, ACYP1, ACYP2, ECHS1, EHHADH, GCDH, HADHA, SDHB, SDS 10 ECHS1(1), HADHA(1) 3853368 2 2 2 0 0 1 1 0 0 0 0.78 0.85 566 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 ARHGAP1(1), ARHGAP5(1), ARHGEF11(1), ARHGEF5(2), ARPC2(1), ARPC3(1), DIAPH1(1), MYLK(2), PPP1R12B(1), ROCK1(2), TLN1(3), VCL(1) 22850648 17 16 17 3 3 5 7 1 1 0 0.79 0.86 567 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(2), AKT2(2), ARHGEF11(1), GNA13(1), MAP3K1(1), MAP3K5(1), NFKBIB(1), NFKBIL2(1), PDK1(1), PIK3CB(1), PLD1(1), PLD2(1), PLD3(1), PTK2(1), ROCK1(2), SERPINA4(1) 23773686 19 18 19 6 1 7 8 1 2 0 0.79 0.86 568 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 81 ANPEP(3), CD19(1), CD1B(1), CD22(2), CD34(1), CD38(1), CD4(1), CD44(2), CD55(1), CR1(2), CR2(2), CSF1R(1), CSF3R(1), FLT3(1), GP1BA(1), HLA-DRA(1), HLA-DRB1(3), IL1R2(1), IL3(1), IL4R(1), IL6R(1), ITGA1(1), ITGA3(2), ITGA6(2), KITLG(1), MME(1), TPO(1) 39789370 37 31 37 19 5 12 12 1 7 0 0.80 0.86 569 ACE_INHIBITOR_PATHWAY_PHARMGKB ACE, AGT, AGTR1, AGTR2, BDKRB2, KNG1, NOS3, REN 8 ACE(1), NOS3(1), REN(1) 4732682 3 3 3 2 2 1 0 0 0 0 0.80 0.87 570 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 B3GALT2(1), B3GALT4(1), B3GNT3(1), B3GNT5(1), B4GALT4(2), B4GALT6(1), FUT6(1), GCNT2(1), PIGG(1), PIGK(1), PIGM(1), PIGN(1), PIGO(1), PIGQ(2), PIGU(1), ST3GAL3(1), ST3GAL6(1), ST8SIA1(1) 23661756 20 18 20 5 3 6 6 1 4 0 0.80 0.87 571 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 B3GAT2(1), DSE(1), XYLT1(1), XYLT2(1) 6781104 4 4 4 3 0 2 2 0 0 0 0.81 0.87 572 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 RELA(1), TRAF3(1), TRAF5(1), TRAF6(1) 7233248 4 4 4 2 0 1 2 0 1 0 0.82 0.88 573 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(1), ATP6AP1(1), ATP6V0A4(1), ATP6V0D2(1), ATP6V1B1(1), ATP6V1B2(1), CSK(1), EGFR(4), F11R(1), GIT1(2), JUN(1), MAPK10(1), MAPK9(1), MET(1), NOD1(1), PAK1(1), PLCG1(1), PLCG2(1), PTPN11(1), PTPRZ1(3), RELA(1), TJP1(1) 34666598 28 26 28 10 3 10 13 0 2 0 0.82 0.89 574 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 86 AICDA(1), CTPS(1), DCTD(1), DPYS(1), NT5C1B(1), NT5C3(1), POLD1(2), POLD3(1), POLE(1), POLE2(1), POLR1A(1), POLR1C(1), POLR2A(4), POLR2B(1), POLR2I(1), POLR3A(1), POLR3B(5), POLR3G(1), POLR3H(1), PRIM2(1), RRM2(1), TK2(1), UPP2(1), UPRT(1) 40406257 32 30 30 11 3 10 12 1 6 0 0.83 0.89 575 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 ELOVL2(1), FADS2(1), HADHA(1), PECR(1) 6478509 4 4 4 0 0 2 2 0 0 0 0.83 0.89 576 HSA03060_PROTEIN_EXPORT Genes involved in protein export OXA1L, SEC61A2, SRP19, SRP54, SRP68, SRP72, SRP9, SRPR 8 SRP72(2) 3688758 2 2 2 2 0 1 1 0 0 0 0.83 0.89 577 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 CDH1(2), FYN(1), HCLS1(1), ITGB1(2), KRT18(1), NCL(3), ROCK1(2), TLR4(1), TUBA3C(1), TUBA3D(1), TUBA4A(1), TUBAL3(1), TUBB1(1), WASL(2) 25174071 20 19 20 16 3 7 7 1 2 0 0.84 0.89 578 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 CDH1(2), FYN(1), HCLS1(1), ITGB1(2), KRT18(1), NCL(3), ROCK1(2), TLR4(1), TUBA3C(1), TUBA3D(1), TUBA4A(1), TUBAL3(1), TUBB1(1), WASL(2) 25174071 20 19 20 16 3 7 7 1 2 0 0.84 0.89 579 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 ATP6AP1(1), ATP6V0A4(1), ATP6V1B1(1), ATP6V1B2(1), FDXR(1), SHMT1(1) 7926774 6 5 6 4 0 2 3 0 1 0 0.84 0.90 580 CD40PATHWAY The CD40 receptor is a TNF-type receptor that regulates immunoglobulin expression in B cells and moderates T cell activation via T-cell expression of its ligand. CHUK, DUSP1, IKBKAP, IKBKB, IKBKG, MAP3K1, MAP3K14, NFKB1, NFKBIA, RELA, TNFAIP3, TNFRSF5, TNFSF5, TRAF3, TRAF6 12 IKBKAP(1), MAP3K1(1), RELA(1), TRAF3(1), TRAF6(1) 9029476 5 5 5 2 0 2 1 0 2 0 0.85 0.90 581 C21_STEROID_HORMONE_METABOLISM AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 11 CYP11A1(1), CYP11B2(1) 4354661 2 2 2 1 0 1 1 0 0 0 0.85 0.90 582 HSA00140_C21_STEROID_HORMONE_METABOLISM Genes involved in C21-steroid hormone metabolism AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 11 CYP11A1(1), CYP11B2(1) 4354661 2 2 2 1 0 1 1 0 0 0 0.85 0.90 583 IRINOTECAN_PATHWAY_PHARMGKB ABCC1, ABCC2, ABCG2, BCHE, CES1, CES2, CES4, CYP3A4, CYP3A5, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6 17 ABCC1(1), CES1(3), CES2(1), UGT1A1(1), UGT1A7(2), UGT1A8(1) 11174776 9 8 9 3 2 3 2 1 1 0 0.86 0.91 584 METHIONINE_METABOLISM AHCY, BHMT, CBS, CTH, DNMT1, DNMT2, DNMT3A, DNMT3B, MARS, MARS2, MAT1A, MAT2B, MTR 12 DNMT1(2), DNMT3A(2), MARS(1) 8578032 5 5 5 4 0 3 2 0 0 0 0.86 0.91 585 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 10 CASP7(1), HMGB2(1), TOP2A(1) 5126406 3 3 3 1 1 1 0 0 1 0 0.88 0.92 586 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 PSMA3(1), PSMA4(1), PSMA6(1), PSMD1(1), PSMD11(1), PSMD2(1) 7882835 6 5 6 3 1 0 3 2 0 0 0.88 0.92 587 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 DNMT1(2), DNMT3A(2), MARS(1), MTAP(1) 10229229 6 6 6 5 0 4 2 0 0 0 0.89 0.93 588 STREPTOMYCIN_BIOSYNTHESIS GCK, HK1, HK2, HK3, IMPA1, PGM1, PGM3, TGDS 8 HK1(3) 4975759 3 2 3 0 0 1 1 1 0 0 0.89 0.94 589 HSA00061_FATTY_ACID_BIOSYNTHESIS Genes involved in fatty acid biosynthesis ACACA, ACACB, FASN, MCAT, OLAH, OXSM 6 ACACA(3), OLAH(1) 7200836 4 4 4 1 2 0 0 1 1 0 0.90 0.94 590 VALINE_LEUCINE_AND_ISOLEUCINE_BIOSYNTHESIS BCAT1, IARS, LARS, LARS2, PDHA1, PDHA2, PDHB 7 BCAT1(1), IARS(1) 4924924 2 2 2 1 0 0 2 0 0 0 0.90 0.94 591 KERATAN_SULFATE_BIOSYNTHESIS B3GNT1, B4GALT1, B4GALT2, B4GALT3, B4GALT5, FUT8, SIAT4A, SIAT4B, SIAT6, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4 10 ST3GAL3(1) 3812383 1 1 1 1 0 0 0 0 1 0 0.91 0.94 592 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) 2469991 1 1 1 3 0 0 1 0 0 0 0.91 0.95 593 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(1), UBE2A(1) 5114696 2 2 2 0 0 0 2 0 0 0 0.92 0.95 594 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 ATP6AP1(1), ATP6V0A4(1), ATP6V1B1(1), ATP6V1B2(1), SHMT1(1) 7491671 5 4 5 4 0 2 2 0 1 0 0.92 0.95 595 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 ATP6AP1(1), ATP6V0A4(1), ATP6V1B1(1), ATP6V1B2(1), SHMT1(1) 7491671 5 4 5 4 0 2 2 0 1 0 0.92 0.95 596 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 ATP6AP1(1), ATP6V0A4(1), ATP6V1B1(1), ATP6V1B2(1), SHMT1(1) 7491671 5 4 5 4 0 2 2 0 1 0 0.92 0.95 597 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 ADCY9(2), ARF1(1), ATP6V0A4(1), ATP6V0D2(1), ERO1L(1), GNAS(1), PLCG1(1), PLCG2(1), SEC61B(1), TRIM23(1) 18073423 11 11 11 9 0 5 6 0 0 0 0.93 0.96 598 HSA00521_STREPTOMYCIN_BIOSYNTHESIS Genes involved in streptomycin biosynthesis GCK, HK1, HK2, HK3, IMPA1, IMPA2, ISYNA1, PGM1, PGM3, TGDS 10 HK1(3) 5623104 3 2 3 0 0 1 1 1 0 0 0.93 0.96 599 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 CES1(3) 5632490 3 3 3 3 1 2 0 0 0 0 0.94 0.96 600 GLOBOSIDE_METABOLISM A4GALT, FUT1, FUT2, FUT9, GBGT1, GLA, HEXA, HEXB, NAGA, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, ST8SIA1 13 HEXA(1), ST8SIA1(1) 4825521 2 2 2 2 1 1 0 0 0 0 0.95 0.97 601 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 PIGG(1), PIGK(1), PIGM(1), PIGN(1), PIGO(1), PIGQ(2), PIGU(1) 12115980 8 7 8 1 2 3 2 0 1 0 0.96 0.98 602 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 HEXA(1), ST8SIA1(1) 5125130 2 2 2 2 1 1 0 0 0 0 0.96 0.98 603 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 IRAK1(2), JUN(1), MAP2K3(2), MAP3K1(1), MAP3K7(1), RELA(1), TLR10(1), TLR4(1), TLR6(1), TLR7(1), TRAF6(1) 17920265 13 10 13 4 3 0 6 1 3 0 0.97 0.99 604 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 EXT1(1), EXTL3(1), GLCE(1), HS6ST3(1), NDST4(1) 10206650 5 5 5 1 1 1 3 0 0 0 0.97 0.99 605 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 CDS2(1), CHPT1(1), DGKB(1), DGKH(1), DGKQ(1), DGKZ(1), MYST3(4), PLA2G12A(1), PLA2G6(2), PLD1(1), PLD2(1), PNPLA3(1), PPAP2C(1) 32286546 17 16 17 6 1 4 11 0 1 0 0.98 1.00 606 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 CDS2(1), DGKB(1), DGKH(1), DGKQ(1), DGKZ(1), PAFAH1B1(1), PLA2G6(2), PLCB2(1), PLCG1(1), PLCG2(1), PPAP2C(1) 24464749 12 12 12 3 1 2 8 0 1 0 0.99 1.00 607 ACETYLCHOLINE_SYNTHESIS ACHE, CHAT, CHKA, PCYT1A, PDHA1, PDHA2, PEMT, SLC18A3 8 3461122 0 0 0 2 0 0 0 0 0 0 1.00 1.00 608 HSA00031_INOSITOL_METABOLISM Genes involved in inositol metabolism ALDH6A1, TPI1 2 770288 0 0 0 0 0 0 0 0 0 0 1.00 1.00 609 HSA00627_1,4_DICHLOROBENZENE_DEGRADATION Genes involved in 1,4-dichlorobenzene degradation CMBL 1 247866 0 0 0 1 0 0 0 0 0 0 1.00 1.00 610 HSA00643_STYRENE_DEGRADATION Genes involved in styrene degradation FAH, GSTZ1, HGD 3 906038 0 0 0 1 0 0 0 0 0 0 1.00 1.00 611 HSA00660_C5_BRANCHED_DIBASIC_ACID_METABOLISM Genes involved in C5-branched dibasic acid metabolism ILVBL, SUCLA2 2 1054317 0 0 0 1 0 0 0 0 0 0 1.00 1.00 612 HSA00780_BIOTIN_METABOLISM Genes involved in biotin metabolism BTD, HLCS, SPCS1, SPCS3 4 1533192 0 0 0 1 0 0 0 0 0 0 1.00 1.00 613 METHIONINEPATHWAY Catabolic Pathways for Methionine, Isoleucine, Threonine and Valine BCKDHB, BCKDK, CBS, CTH, MUT 5 2372078 0 0 0 0 0 0 0 0 0 0 1.00 1.00 614 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 830307 0 0 0 0 0 0 0 0 0 0 1.00 1.00 615 TCRMOLECULE T Cell Receptor and CD3 Complex CD3D, CD3E, CD3G, CD3Z, TRA@, TRB@ 3 568246 0 0 0 0 0 0 0 0 0 0 1.00 1.00 616 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 2713275 0 0 0 1 0 0 0 0 0 0 1.00 1.00