rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p q 1 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 151 ADORA2B(2), ADORA3(2), ADRA1A(1), ADRB2(1), AGTR2(2), AVPR1B(3), AVPR2(1), BDKRB1(4), BDKRB2(3), BRS3(1), CCKBR(1), CCR3(2), CCR6(1), CCR8(1), CCR9(1), CHML(3), CHRM2(4), CHRM3(3), CHRM5(1), CXCR3(2), DRD1(2), DRD3(1), EDNRA(1), F2R(2), F2RL2(1), FPR1(1), FSHR(4), GALR1(1), GHSR(1), GPR173(1), GPR174(1), GPR35(1), GPR37(2), GPR37L1(1), GPR4(2), GPR50(2), GPR77(1), GRPR(1), HCRTR1(1), HCRTR2(1), HRH1(1), HTR1A(2), HTR1E(2), HTR1F(3), HTR2A(3), HTR2C(4), HTR4(2), HTR5A(2), HTR6(1), LHCGR(3), MAS1(1), MC3R(2), MC4R(1), MC5R(2), MLNR(1), MTNR1A(1), NMBR(1), NMUR2(2), OPN1SW(2), OPRD1(2), OPRK1(1), OR10A5(1), OR11A1(1), OR12D3(2), OR5V1(3), OR7C1(2), OR8B8(1), P2RY10(2), P2RY12(1), P2RY13(4), P2RY2(2), P2RY6(1), PPYR1(2), PTGDR(1), PTGFR(3), RRH(1), SSTR1(1), SUCNR1(1) 48728343 135 103 135 30 22 12 52 38 11 0 1.57e-06 0.00097 2 HSA04080_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION Genes involved in neuroactive ligand-receptor interaction ADCYAP1R1, ADORA1, ADORA2A, ADORA2B, ADORA3, ADRA1A, ADRA1B, ADRA2A, ADRA2B, ADRA2C, ADRB1, ADRB2, ADRB3, AGTR1, AGTR2, AGTRL1, AVPR1A, AVPR1B, AVPR2, BDKRB1, BDKRB2, BRS3, C3AR1, C5AR1, CALCR, CALCRL, CCKAR, CCKBR, CGA, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, CNR1, CNR2, CRHR1, CRHR2, CTSG, CYSLTR1, CYSLTR2, DRD1, DRD2, DRD3, DRD4, DRD5, EDG1, EDG2, EDG3, EDG4, EDG5, EDG6, EDG7, EDG8, EDNRA, EDNRB, F2, F2R, F2RL1, F2RL2, F2RL3, FPR1, FPRL1, FPRL2, FSHB, FSHR, GABBR1, GABBR2, GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GABRB1, GABRB2, GABRB3, GABRD, GABRE, GABRG1, GABRG2, GABRG3, GABRP, GABRQ, GABRR1, GABRR2, GALR1, GALR2, GALR3, GCGR, GH1, GH2, GHR, GHRHR, GHSR, GIPR, GLP1R, GLP2R, GLRA1, GLRA2, GLRA3, GLRB, GNRHR, GPR156, GPR23, GPR35, GPR50, GPR63, GPR83, GRIA1, GRIA2, GRIA3, GRIA4, GRID1, GRID2, GRIK1, GRIK2, GRIK3, GRIK4, GRIK5, GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, GRIN3A, GRIN3B, GRM1, GRM2, GRM3, GRM4, GRM5, GRM6, GRM7, GRM8, GRPR, GZMA, HCRTR1, HCRTR2, HRH1, HRH2, HRH3, HRH4, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, KISS1R, LEP, LEPR, LHB, LHCGR, LTB4R, LTB4R2, MAS1, MC1R, MC2R, MC3R, MC4R, MC5R, MCHR1, MCHR2, MLNR, MTNR1A, MTNR1B, NMBR, NMUR1, NMUR2, NPBWR1, NPBWR2, NPFFR1, NPFFR2, NPY1R, NPY2R, NPY5R, NR3C1, NTSR1, NTSR2, OPRD1, OPRK1, OPRL1, OPRM1, OXTR, P2RX1, P2RX2, P2RX3, P2RX4, P2RX5, P2RX7, P2RXL1, P2RY1, P2RY10, P2RY11, P2RY13, P2RY14, P2RY2, P2RY4, P2RY5, P2RY6, P2RY8, PARD3, PPYR1, PRL, PRLHR, PRLR, PRSS1, PRSS2, PRSS3, PTAFR, PTGDR, PTGER1, PTGER2, PTGER3, PTGER4, PTGFR, PTGIR, PTH2R, PTHR1, RXFP1, RXFP2, SCTR, SSTR1, SSTR2, SSTR3, SSTR4, SSTR5, TAAR1, TAAR2, TAAR5, TAAR6, TAAR8, TAAR9, TACR1, TACR2, TACR3, TBXA2R, THRA, THRB, TRHR, TRPV1, TSHB, TSHR, TSPO, UTS2R, VIPR1, VIPR2 220 ADCYAP1R1(1), ADORA2B(2), ADORA3(2), ADRA1A(1), ADRA2B(3), ADRB2(1), AGTR2(2), AVPR1B(3), AVPR2(1), BDKRB1(4), BDKRB2(3), BRS3(1), C5AR1(2), CALCR(3), CALCRL(1), CCKBR(1), CGA(1), CHRM2(4), CHRM3(3), CHRM5(1), CTSG(1), CYSLTR1(1), DRD1(2), DRD3(1), EDNRA(1), F2(3), F2R(2), F2RL2(1), FPR1(1), FSHB(1), FSHR(4), GABBR1(2), GABBR2(2), GABRA1(2), GABRA2(2), GABRA3(1), GABRA4(1), GABRA5(1), GABRB1(2), GABRB3(1), GABRE(3), GABRG1(2), GABRG2(2), GABRQ(2), GALR1(1), GH2(1), GHR(1), GHRHR(1), GHSR(1), GLP2R(1), GLRA1(1), GLRA2(1), GLRA3(4), GPR156(1), GPR35(1), GPR50(2), GRIA1(1), GRIA2(2), GRIA3(2), GRIA4(3), GRID1(3), GRID2(2), GRIK1(1), GRIK2(2), GRIK3(2), GRIK5(2), GRIN2A(3), GRIN2B(3), GRIN2C(1), GRIN2D(3), GRIN3A(3), GRM1(4), GRM3(1), GRM4(1), GRM5(2), GRM6(1), GRM7(4), GRM8(3), GRPR(1), GZMA(2), HCRTR1(1), HCRTR2(1), HRH1(1), HRH4(2), HTR1A(2), HTR1E(2), HTR1F(3), HTR2A(3), HTR2C(4), HTR4(2), HTR5A(2), HTR6(1), LEPR(1), LHCGR(3), MAS1(1), MC2R(3), MC3R(2), MC4R(1), MC5R(2), MCHR2(2), MLNR(1), MTNR1A(1), NMBR(1), NMUR2(2), NPBWR1(1), NPFFR2(2), NR3C1(2), OPRD1(2), OPRK1(1), P2RX1(1), P2RX5(1), P2RY10(2), P2RY13(4), P2RY2(2), P2RY6(1), PARD3(2), PPYR1(2), PRLHR(1), PRLR(2), PRSS2(1), PRSS3(1), PTGDR(1), PTGFR(3), PTH2R(1), RXFP2(1), SCTR(1), SSTR1(1), TAAR6(2), TACR1(1), TACR2(2), TACR3(1), TRPV1(1), TSHR(4), VIPR2(1) 92059511 241 147 240 74 46 26 84 64 21 0 6.59e-06 0.0020 3 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 127 ACTG1(2), ACTN2(3), ACTN3(2), AMOTL1(1), ASH1L(3), CASK(2), CGN(2), CLDN10(1), CLDN11(2), CLDN15(1), CLDN16(1), CLDN17(2), CLDN18(2), CLDN2(1), CLDN6(1), CLDN9(1), CSDA(1), CSNK2A1(1), CSNK2B(1), CTNNA1(2), CTNNA3(1), CTNNB1(2), CTTN(1), EPB41(2), EPB41L3(5), EXOC3(1), EXOC4(4), F11R(2), GNAI2(1), INADL(2), JAM3(1), KRAS(2), LLGL2(3), MAGI1(2), MAGI2(4), MAGI3(3), MLLT4(2), MPDZ(4), MPP5(1), MRAS(1), MYH1(9), MYH10(3), MYH11(7), MYH13(6), MYH14(2), MYH15(5), MYH2(5), MYH3(4), MYH4(9), MYH7(3), MYH7B(5), MYH8(3), MYH9(3), MYL2(1), NRAS(2), PARD3(2), PARD6A(1), PPP2CA(2), PPP2R1A(4), PPP2R2A(1), PPP2R2B(1), PPP2R3A(2), PPP2R4(1), PRKCA(1), PRKCE(1), PRKCG(1), PRKCH(1), PRKCI(2), PRKCQ(3), PRKCZ(2), PTEN(2), RAB3B(1), RHOA(2), RRAS(1), SPTAN1(5), TJAP1(1), TJP1(3), TJP3(1), YES1(1) 82023148 185 138 183 38 29 15 64 50 27 0 0.000014 0.0028 4 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 96 ADCY1(4), ADCY2(6), ADCY3(2), ADCY4(1), ADCY5(3), ADCY7(1), ADCY9(5), CALM3(1), CAMK2B(2), CAMK2D(1), CAMK2G(1), CREB3L1(1), CREB3L4(1), CREBBP(7), CTNNB1(2), DCT(2), DVL3(1), EP300(1), FZD5(2), FZD7(2), GNAI2(1), GNAS(3), GSK3B(1), KIT(7), KITLG(1), KRAS(2), MITF(2), NRAS(2), PLCB1(4), PLCB2(4), PLCB3(2), PLCB4(1), POMC(1), PRKACG(1), PRKCA(1), PRKCG(1), TCF7L2(2), TYR(1), WNT11(2), WNT16(3), WNT2(1), WNT2B(1), WNT4(1), WNT6(2), WNT7A(2), WNT7B(2), WNT8A(1), WNT9A(2), WNT9B(1) 43571057 101 86 96 28 21 14 30 20 16 0 0.000070 0.011 5 AMIPATHWAY Endogenous anti-thrombosis pathways are overwhelmed in plaque-narrowed blood vessels, resulting in potentially lethal myocardial infarction. ADCY1, CD3D, CD3E, CD3G, CD3Z, CD4, CREBBP, CSK, GNAS, GNB1, GNGT1, HLA-DRA, HLA-DRB1, LCK, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTPRC, TRA@, TRB@, ZAP70 21 ADCY1(4), CD3E(2), CD4(1), CREBBP(7), CSK(1), GNAS(3), HLA-DRA(1), HLA-DRB1(1), LCK(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PTPRC(3), ZAP70(1) 9488232 28 28 27 3 5 3 6 6 8 0 0.00033 0.033 6 CSKPATHWAY Csk inhibits T-cell activation by phosphorylating Lck; Csk is regulated by cAMP-dependent kinases and is opposed by the T-cell activator CD45. ADCY1, CD3D, CD3E, CD3G, CD3Z, CD4, CREBBP, CSK, GNAS, GNB1, GNGT1, HLA-DRA, HLA-DRB1, LCK, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTPRC, TRA@, TRB@, ZAP70 21 ADCY1(4), CD3E(2), CD4(1), CREBBP(7), CSK(1), GNAS(3), HLA-DRA(1), HLA-DRB1(1), LCK(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PTPRC(3), ZAP70(1) 9488232 28 28 27 3 5 3 6 6 8 0 0.00033 0.033 7 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 125 ALCAM(1), CADM1(2), CADM3(2), CD22(3), CD274(1), CD276(1), CD34(1), CD4(1), CD80(1), CD86(2), CD8A(1), CDH1(2), CDH2(2), CDH3(2), CDH4(2), CDH5(1), CLDN10(1), CLDN11(2), CLDN15(1), CLDN16(1), CLDN17(2), CLDN18(2), CLDN2(1), CLDN6(1), CLDN9(1), CNTN1(3), CNTN2(1), CNTNAP1(5), CNTNAP2(8), F11R(2), GLG1(3), HLA-A(1), HLA-DRA(1), HLA-DRB1(1), HLA-E(1), HLA-G(3), ICAM1(1), ICAM2(1), ICAM3(1), ITGA4(3), ITGA6(1), ITGA8(3), ITGAL(3), ITGAV(2), ITGB2(2), ITGB7(4), JAM3(1), L1CAM(5), MPZ(2), MPZL1(2), NCAM1(2), NCAM2(4), NEGR1(1), NFASC(3), NLGN1(1), NLGN3(2), NRCAM(2), NRXN1(5), NRXN2(2), NRXN3(2), PDCD1(1), PECAM1(2), PTPRC(3), PTPRF(4), PTPRM(1), PVRL1(1), SDC1(4), SDC2(2), SELE(3), SELP(3), SIGLEC1(2), SPN(1), VCAN(6) 63587893 154 111 153 35 22 28 53 34 17 0 0.00038 0.033 8 HSA04630_JAK_STAT_SIGNALING_PATHWAY Genes involved in Jak-STAT signaling pathway AKT1, AKT2, AKT3, BCL2L1, CBL, CBLB, CBLC, CCND1, CCND2, CCND3, CISH, CLCF1, CNTF, CNTFR, CREBBP, CRLF2, CSF2, CSF2RA, CSF2RB, CSF3, CSF3R, CTF1, EP300, EPO, EPOR, GH1, GH2, GHR, GRB2, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IFNE1, IFNG, IFNGR1, IFNGR2, IFNK, IFNW1, IL10, IL10RA, IL10RB, IL11, IL11RA, IL12A, IL12B, IL12RB1, IL12RB2, IL13, IL13RA1, IL13RA2, IL15, IL15RA, IL19, IL2, IL20, IL20RA, IL21, IL21R, IL22, IL22RA1, IL22RA2, IL23A, IL23R, IL24, IL26, IL28A, IL28B, IL28RA, IL29, IL2RA, IL2RB, IL2RG, IL3, IL3RA, IL4, IL4R, IL5, IL5RA, IL6, IL6R, IL6ST, IL7, IL7R, IL9, IL9R, IRF9, JAK1, JAK2, JAK3, LEP, LEPR, LIF, LIFR, MPL, MYC, OSM, OSMR, PIAS1, PIAS2, PIAS3, PIAS4, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIM1, PRL, PRLR, PTPN11, PTPN6, SOCS1, SOCS2, SOCS3, SOCS4, SOCS5, SOCS7, SOS1, SOS2, SPRED1, SPRED2, SPRY1, SPRY2, SPRY3, SPRY4, STAM, STAM2, STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6, TPO, TSLP, TYK2 142 CBLB(1), CBLC(3), CNTFR(2), CREBBP(7), CSF2RB(3), CSF3(1), CSF3R(1), EP300(1), EPOR(1), GH2(1), GHR(1), GRB2(2), IFNA1(2), IFNA13(2), IFNA5(1), IFNA8(1), IFNAR2(1), IFNB1(1), IL10RA(1), IL10RB(1), IL11RA(1), IL12RB2(3), IL13(2), IL19(1), IL20RA(2), IL21R(3), IL22(1), IL24(1), IL28A(1), IL28RA(1), IL2RA(2), IL2RB(1), IL4R(2), IL5RA(1), IL6R(1), IL7R(3), IRF9(1), JAK2(2), JAK3(3), LEPR(1), LIFR(2), OSMR(2), PIAS2(1), PIK3CA(2), PIK3CB(1), PIK3CG(3), PIK3R1(1), PIK3R2(2), PIK3R5(1), PRLR(2), SOCS2(1), SOCS4(1), SOCS5(1), SOS1(3), SOS2(1), SPRED1(1), SPRED2(2), SPRY1(1), SPRY2(1), SPRY4(1), STAM(1), STAM2(1), STAT1(2), STAT2(1), STAT3(1), STAT4(1), STAT5A(2), STAT5B(3), STAT6(2), TPO(4), TYK2(2) 61397096 117 96 117 36 12 14 40 36 15 0 0.00053 0.041 9 GPCRDB_OTHER ADORA3, ALG6, C5R1, CCKBR, CCR2, CCR3, CCR5, CELSR1, CELSR2, CELSR3, CHRM2, CHRM3, CIDEB, CXCR3, DRD4, EBI2, EDG1, EDNRA, ELA3A, EMR2, EMR3, F2R, FSHR, FY, GHRHR, GNRHR, GPR, GPR116, GPR132, GPR133, GPR135, GPR143, GPR145, GPR17, GPR18, GPR55, GPR56, GPR61, GPR73L1, GPR77, GPR84, GPR88, GRCA, GRM1, GRPR, HRH4, IL8RA, IL8RB, LGR6, LGR7, LPHN2, LPHN3, LTB4R2, MASS1, NTSR1, OR2A9P, OR2M4, OR5E1P, OR7E19P, OR7E47P, OR7E37P, OR7E18P, OR7E35P, LOC441453, OR8G1, LOC442754, OR8G2, P2RY11, P2RY13, PTGFR, RLN3R1, SMO, SSTR2, TAAR5, TSHR, VN1R1 50 ADORA3(2), CCKBR(1), CCR3(2), CELSR1(1), CELSR2(4), CELSR3(6), CHRM2(4), CHRM3(3), CXCR3(2), EDNRA(1), EMR2(1), EMR3(5), F2R(2), FSHR(4), GHRHR(1), GPR116(1), GPR132(2), GPR133(2), GPR55(1), GPR77(1), GRM1(4), GRPR(1), HRH4(2), LGR6(3), LPHN2(1), LPHN3(4), OR8G2(1), P2RY13(4), PTGFR(3), TSHR(4) 25452491 73 60 73 20 11 10 27 19 6 0 0.00064 0.042 10 FXRPATHWAY The nuclear receptor transcription factors FXR and LXR are activated by cholesterol metabolites and regulate cholesterol homeostasis. FABP6, LDLR, NR0B2, NR1H3, NR1H4, RXRA 6 LDLR(3), NR1H3(4), NR1H4(3), RXRA(2) 2264708 12 12 12 0 2 2 3 2 3 0 0.00069 0.042 11 CALCINEURIN_NF_AT_SIGNALING Mouse genes associated with signal transduction through calcium, calcineurin, and NF-AT. ACTB, BAD, BCL2, CABIN1, CALM1, CALM2, CALM3, CAMK2B, CAMK4, CD3E, CD3G, CD3Z, CD69, CDKN1A, CEBPB, CNR1, CREBBP, CSF2, CSNK2A1, CSNK2B, CTLA4, EGR2, EGR3, EP300, FCER1A, FCGR3A, FKBP1B, FLJ14639, FOS, FOSL1, GAPD, GATA3, GATA4, GRLF1, GSK3A, GSK3B, HRAS, ICOS, IFNA1, IFNB1, IFNG, IL10, IL13, IL1B, IL2, IL2RA, IL3, IL4, IL6, IL8, IL8RA, ITK, JUNB, KPNA5, KPNB3, MAP2K7, MAPK14, MAPK8, MAPK9, MEF2A, MEF2B, MEF2D, MYF5, NCK2, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NFKB2, NFKBIB, NFKBIE, NPPB, NUP214, OPRD1, P2RX7, PAK1, PIN1, PPIA, PPP3CB, PPP3CC, PPP3R1, PTPRC, RELA, RPL13A, SFN, SLA, SP1, SP3, TGFB1, TNF, TNFSF5, TNFSF6, TRAF2, TRPV6, VAV1, VAV2, VAV3, VEGF, XPO5 89 CABIN1(2), CALM3(1), CAMK2B(2), CAMK4(3), CD3E(2), CDKN1A(1), CREBBP(7), CSNK2A1(1), CSNK2B(1), EP300(1), FOS(1), FOSL1(1), GATA3(1), GRLF1(6), GSK3A(2), GSK3B(1), IFNA1(2), IFNB1(1), IL13(2), IL2RA(2), IL8(1), ITK(5), KPNA5(1), MAPK14(1), MAPK8(1), MAPK9(1), MEF2A(1), MEF2D(1), MYF5(2), NCK2(1), NFAT5(1), NFATC1(1), NFATC2(1), NFATC4(1), NPPB(2), NUP214(1), OPRD1(2), PPP3CC(1), PTPRC(3), RELA(1), SLA(1), TNF(1), TRAF2(1), TRPV6(2), VAV1(2), VAV2(4), VAV3(3) 38005796 83 69 82 25 6 13 28 22 14 0 0.00082 0.046 12 HSA04340_HEDGEHOG_SIGNALING_PATHWAY Genes involved in Hedgehog signaling pathway BMP2, BMP4, BMP5, BMP6, BMP7, BMP8A, BMP8B, BTRC, CSNK1A1, CSNK1A1L, CSNK1D, CSNK1E, CSNK1G1, CSNK1G2, CSNK1G3, DHH, FBXW11, GAS1, GLI1, GLI2, GLI3, GSK3B, HHIP, IHH, LRP2, PRKACA, PRKACB, PRKACG, PRKX, PRKY, PTCH1, PTCH2, RAB23, SHH, SMO, STK36, SUFU, WNT1, WNT10A, WNT10B, WNT11, WNT16, WNT2, WNT2B, WNT3, WNT3A, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A, WNT8B, WNT9A, WNT9B, ZIC2 54 BMP2(1), BMP5(1), BMP6(1), BTRC(2), CSNK1A1L(1), CSNK1E(1), FBXW11(1), GLI1(5), GLI2(10), GLI3(2), GSK3B(1), HHIP(2), LRP2(16), PRKACG(1), PTCH1(6), PTCH2(1), STK36(1), WNT11(2), WNT16(3), WNT2(1), WNT2B(1), WNT4(1), WNT6(2), WNT7A(2), WNT7B(2), WNT8A(1), WNT9A(2), WNT9B(1) 24713567 71 61 70 10 10 14 26 15 6 0 0.00098 0.049 13 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 89 ADCY1(4), ADCY2(6), ADCY3(2), ADCY4(1), ADCY5(3), ADCY7(1), ADCY9(5), CACNA1C(9), CACNA1D(6), CACNA1F(4), CACNA1S(5), CALM3(1), CAMK2B(2), CAMK2D(1), CAMK2G(1), CGA(1), EGFR(7), ELK1(2), FSHB(1), GNA11(1), GNAS(3), GRB2(2), ITPR1(3), ITPR2(5), ITPR3(3), KRAS(2), MAP2K3(1), MAP2K4(1), MAP2K6(1), MAP3K1(1), MAP3K2(2), MAP3K3(1), MAP3K4(2), MAPK14(1), MAPK8(1), MAPK9(1), MMP2(1), NRAS(2), PLA2G12A(1), PLA2G12B(1), PLA2G2F(1), PLA2G4A(1), PLA2G6(1), PLCB1(4), PLCB2(4), PLCB3(2), PLCB4(1), PLD1(1), PLD2(1), PRKACG(1), PRKCA(1), PTK2B(1), SOS1(3), SOS2(1) 53589912 121 97 117 33 16 14 46 30 15 0 0.0010 0.049 14 HSA03320_PPAR_SIGNALING_PATHWAY Genes involved in PPAR signaling pathway ACAA1, ACADL, ACADM, ACOX1, ACOX2, ACOX3, ACSL1, ACSL3, ACSL4, ACSL5, ACSL6, ADIPOQ, ANGPTL4, APOA1, APOA2, APOA5, APOC3, AQP7, CD36, CPT1A, CPT1B, CPT1C, CPT2, CYP27A1, CYP4A11, CYP4A22, CYP7A1, CYP8B1, DBI, EHHADH, FABP1, FABP2, FABP3, FABP4, FABP5, FABP5L1, FABP6, FABP7, FADS2, GK, GK2, HMGCS2, ILK, LOC642956, LPL, ME1, MMP1, NR1H3, OLR1, PCK1, PCK2, PDPK1, PLIN, PLTP, PPARA, PPARD, PPARG, RXRA, RXRB, RXRG, SCD, SCP2, SLC27A1, SLC27A2, SLC27A4, SLC27A5, SLC27A6, SORBS1, UBC, UCP1 65 ACADM(1), ACOX1(2), ACSL1(2), ACSL3(2), ACSL4(1), ACSL6(1), ADIPOQ(1), ANGPTL4(2), CPT1A(2), CPT1B(2), CPT1C(1), CPT2(1), CYP27A1(1), CYP4A11(4), CYP4A22(1), CYP7A1(1), CYP8B1(2), DBI(1), EHHADH(2), FABP2(1), FABP3(2), FABP4(1), FADS2(2), GK2(2), HMGCS2(1), LPL(1), ME1(2), MMP1(1), NR1H3(4), OLR1(1), PDPK1(1), PPARA(1), PPARD(2), RXRA(2), RXRB(2), SCP2(1), SLC27A2(1), SLC27A4(1), SORBS1(2), UBC(3), UCP1(1) 28493267 65 60 64 14 6 10 27 11 11 0 0.0016 0.070 15 WNTPATHWAY The Wnt glycoprotein binds to membrane-bound receptors such as Frizzled to activate a number of signaling pathways, including that of beta-catenin. APC, AXIN1, BTRC, CCND1, CREBBP, CSNK1A1, CSNK1D, CSNK2A1, CTBP1, CTNNB1, DVL1, FRAT1, FZD1, GSK3B, HDAC1, MADH4, MAP3K7, MAP3K7IP1, MYC, NLK, PPARD, PPP2CA, TCF1, TLE1, WIF1, WNT1 21 APC(8), BTRC(2), CREBBP(7), CSNK2A1(1), CTBP1(1), CTNNB1(2), GSK3B(1), HDAC1(1), MAP3K7(3), NLK(1), PPARD(2), PPP2CA(2), TLE1(1), WIF1(3) 12038874 35 30 35 8 0 5 9 12 9 0 0.0020 0.080 16 HSA04360_AXON_GUIDANCE Genes involved in axon guidance ABL1, ABLIM1, ABLIM2, ABLIM3, ARHGEF12, CDC42, CDK5, CFL1, CFL2, CHP, CXCL12, CXCR4, DCC, DPYSL2, DPYSL5, EFNA1, EFNA2, EFNA3, EFNA4, EFNA5, EFNB1, EFNB2, EFNB3, EPHA1, EPHA2, EPHA3, EPHA4, EPHA5, EPHA6, EPHA7, EPHA8, EPHB1, EPHB2, EPHB3, EPHB4, EPHB6, FES, FYN, GNAI1, GNAI2, GNAI3, GSK3B, HRAS, ITGB1, KRAS, L1CAM, LIMK1, LIMK2, LRRC4C, MAPK1, MAPK3, MET, NCK1, NCK2, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NGEF, NRAS, NRP1, NTN1, NTN2L, NTN4, NTNG1, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PLXNA1, PLXNA2, PLXNA3, PLXNB1, PLXNB2, PLXNB3, PLXNC1, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PTK2, RAC1, RAC2, RAC3, RASA1, RGS3, RHOA, RHOD, RND1, ROBO1, ROBO2, ROBO3, ROCK1, ROCK2, SEMA3A, SEMA3B, SEMA3C, SEMA3D, SEMA3E, SEMA3F, SEMA3G, SEMA4A, SEMA4B, SEMA4C, SEMA4D, SEMA4F, SEMA4G, SEMA5A, SEMA5B, SEMA6A, SEMA6B, SEMA6C, SEMA6D, SEMA7A, SLIT1, SLIT2, SLIT3, SRGAP1, SRGAP2, SRGAP3, UNC5A, UNC5B, UNC5C, UNC5D 122 ABL1(1), ABLIM1(1), ABLIM3(1), ARHGEF12(1), DCC(3), DPYSL5(2), EFNA4(1), EFNB1(1), EFNB2(1), EPHA1(4), EPHA2(2), EPHA3(3), EPHA5(1), EPHA6(2), EPHA7(7), EPHB1(4), EPHB2(1), EPHB3(4), EPHB4(1), EPHB6(1), FES(3), GNAI2(1), GSK3B(1), KRAS(2), L1CAM(5), LIMK1(1), LIMK2(1), LRRC4C(2), MET(4), NCK2(1), NFAT5(1), NFATC1(1), NFATC2(1), NFATC4(1), NGEF(3), NRAS(2), NRP1(1), NTN4(1), NTNG1(3), PAK2(1), PAK3(5), PAK6(2), PAK7(1), PLXNA1(1), PLXNA2(3), PLXNA3(1), PLXNB1(2), PLXNC1(1), PPP3CC(1), PTK2(1), RASA1(1), RHOA(2), RND1(2), ROBO1(4), ROBO2(2), ROBO3(3), SEMA3A(2), SEMA3D(2), SEMA3E(1), SEMA3G(2), SEMA4A(1), SEMA4B(1), SEMA4C(1), SEMA4D(1), SEMA4F(2), SEMA4G(1), SEMA5B(1), SEMA6A(1), SEMA6C(1), SLIT1(5), SLIT2(2), SLIT3(6), SRGAP1(2), SRGAP2(2), UNC5A(1), UNC5B(3), UNC5C(3), UNC5D(2) 78278978 153 127 151 53 27 21 57 36 12 0 0.0021 0.080 17 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 239 ACVR1(2), ACVR1B(1), ACVR2B(3), AMHR2(1), BMP2(1), BMPR1A(1), BMPR1B(1), BMPR2(3), CCL15(1), CCL17(1), CCL27(1), CCL28(1), CCL7(1), CCR3(2), CCR6(1), CCR8(1), CCR9(1), CNTFR(2), CSF1(1), CSF1R(1), CSF2RB(3), CSF3(1), CSF3R(1), CXCL13(1), CXCL9(1), CXCR3(2), EDA(2), EGFR(7), EPOR(1), FLT1(2), FLT3(2), FLT4(3), GH2(1), GHR(1), HGF(2), IFNA1(2), IFNA13(2), IFNA5(1), IFNA8(1), IFNAR2(1), IFNB1(1), IL10RA(1), IL10RB(1), IL11RA(1), IL12RB2(3), IL13(2), IL17RA(1), IL17RB(2), IL18R1(2), IL18RAP(2), IL19(1), IL20RA(2), IL21R(3), IL22(1), IL24(1), IL25(1), IL28A(1), IL28RA(1), IL2RA(2), IL2RB(1), IL4R(2), IL5RA(1), IL6R(1), IL7R(3), IL8(1), INHBA(3), KDR(1), KIT(7), KITLG(1), LEPR(1), LIFR(2), LTBR(1), MET(4), NGFR(1), OSMR(2), PDGFC(1), PDGFRA(3), PDGFRB(3), PPBP(2), PRLR(2), TGFBR2(3), TNF(1), TNFRSF10A(2), TNFRSF10D(1), TNFRSF1A(1), TNFRSF9(1), TNFSF10(1), TNFSF13B(1), TNFSF14(1), TNFSF8(1), TPO(4), VEGFA(1), XCL2(1) 75845175 155 119 154 31 18 24 49 49 15 0 0.0022 0.080 18 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 87 ADCY1(4), ADCY2(6), ADCY3(2), ADCY4(1), ADCY5(3), ADCY7(1), ADCY9(5), DRD1(2), EGFR(7), GJA1(2), GJD2(1), GNA11(1), GNAI2(1), GNAS(3), GRB2(2), GRM1(4), GRM5(2), GUCY1A3(1), GUCY2C(3), HTR2A(3), HTR2C(4), ITPR1(3), ITPR2(5), ITPR3(3), KRAS(2), MAP3K2(2), NPR1(1), NPR2(2), NRAS(2), PDGFC(1), PDGFRA(3), PDGFRB(3), PLCB1(4), PLCB2(4), PLCB3(2), PLCB4(1), PRKACG(1), PRKCA(1), PRKCG(1), PRKG1(1), SOS1(3), SOS2(1), TJP1(3), TUBA3C(3), TUBA4A(3), TUBB1(1), TUBB3(2), TUBB4(2), TUBB8(2) 54935770 120 97 116 36 19 13 45 32 11 0 0.0034 0.12 19 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 11 CREBBP(7), DAXX(1), PAX3(5), RARA(1), SP100(4), TNF(1), TNFRSF1A(1) 6853720 20 19 20 3 2 2 5 5 6 0 0.0038 0.12 20 CREMPATHWAY The transcription factor CREM activates a post-meiotic transcriptional cascade culminating in spermatogenesis. ADCY1, CREM, FHL5, FSHB, FSHR, GNAS, XPO1 7 ADCY1(4), FHL5(2), FSHB(1), FSHR(4), GNAS(3) 3965423 14 14 13 3 4 0 2 5 3 0 0.0042 0.12 21 CTLA4PATHWAY T cell activation requires interaction with an antigen-MHC-I complex on an antigen-presenting cell (APC), as well as CD28 interaction with the APC's CD80 or 86. CD28, CD3D, CD3E, CD3G, CD3Z, CD80, CD86, CTLA4, GRB2, HLA-DRA, HLA-DRB1, ICOS, ICOSL, IL2, ITK, LCK, PIK3CA, PIK3R1, PTPN11, TRA@, TRB@ 17 CD3E(2), CD80(1), CD86(2), GRB2(2), HLA-DRA(1), HLA-DRB1(1), ITK(5), LCK(1), PIK3CA(2), PIK3R1(1) 5774211 18 17 18 8 0 3 8 5 2 0 0.0042 0.12 22 SETPATHWAY Cytotoxic T cells release perforin, which to allow entry into target cells of granzyme B, which activates caspases, and granzyme A, which induces caspase-independent apoptosis. ANP32A, APEX1, CREBBP, DFFA, DFFB, GZMA, GZMB, HMGB2, NME1, PRF1, SET 11 APEX1(2), CREBBP(7), GZMA(2), PRF1(2) 4460489 13 13 13 2 2 1 0 5 5 0 0.0044 0.12 23 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 80 ABL1(1), ABL2(1), BRAF(2), CAMK2B(2), CAMK2D(1), CAMK2G(1), CBLB(1), CBLC(3), CDKN1A(1), CDKN1B(1), EGFR(7), EIF4EBP1(1), ELK1(2), ERBB2(4), ERBB3(2), GRB2(2), GSK3B(1), KRAS(2), MAP2K4(1), MAPK8(1), MAPK9(1), NCK2(1), NRAS(2), NRG1(4), NRG2(1), PAK2(1), PAK3(5), PAK6(2), PAK7(1), PIK3CA(2), PIK3CB(1), PIK3CG(3), PIK3R1(1), PIK3R2(2), PIK3R5(1), PLCG2(1), PRKCA(1), PRKCG(1), PTK2(1), RPS6KB2(1), SHC1(1), SHC4(2), SOS1(3), SOS2(1), STAT5A(2), STAT5B(3) 42523072 82 74 79 30 6 12 35 19 10 0 0.0060 0.16 24 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 137 APC(8), AXIN2(1), BTRC(2), CAMK2B(2), CAMK2D(1), CAMK2G(1), CHD8(5), CREBBP(7), CSNK1A1L(1), CSNK1E(1), CSNK2A1(1), CSNK2B(1), CTBP1(1), CTBP2(1), CTNNB1(2), CXXC4(1), DAAM1(2), DAAM2(2), DKK2(2), DVL3(1), EP300(1), FBXW11(1), FOSL1(1), FZD5(2), FZD7(2), GSK3B(1), LRP5(3), LRP6(1), MAP3K7(3), MAPK8(1), MAPK9(1), MMP7(1), NFAT5(1), NFATC1(1), NFATC2(1), NFATC4(1), NLK(1), PLCB1(4), PLCB2(4), PLCB3(2), PLCB4(1), PORCN(2), PPARD(2), PPP2CA(2), PPP2R1A(4), PPP2R2A(1), PPP2R2B(1), PPP3CC(1), PRICKLE1(3), PRICKLE2(2), PRKACG(1), PRKCA(1), PRKCG(1), RHOA(2), SFRP2(1), SFRP5(1), TBL1X(1), TBL1XR1(1), TCF7L2(2), VANGL2(1), WIF1(3), WNT11(2), WNT16(3), WNT2(1), WNT2B(1), WNT4(1), WNT6(2), WNT7A(2), WNT7B(2), WNT8A(1), WNT9A(2), WNT9B(1) 65304893 128 98 127 34 18 21 41 29 19 0 0.0085 0.21 25 HSA04660_T_CELL_RECEPTOR_SIGNALING_PATHWAY Genes involved in T cell receptor signaling pathway AKT1, AKT2, AKT3, BCL10, CARD11, CBL, CBLB, CBLC, CD247, CD28, CD3D, CD3E, CD3G, CD4, CD40LG, CD8A, CD8B, CDC42, CDK4, CHP, CHUK, CSF2, CTLA4, FOS, FYN, GRAP2, GRB2, HRAS, ICOS, IFNG, IKBKB, IKBKG, IL10, IL2, IL4, IL5, ITK, JUN, KRAS, LAT, LCK, LCP2, MALT1, MAP3K14, MAP3K8, NCK1, NCK2, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NRAS, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDCD1, PDK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKCQ, PTPN6, PTPRC, RASGRP1, RHOA, SOS1, SOS2, TEC, TNF, VAV1, VAV2, VAV3, ZAP70 92 CARD11(1), CBLB(1), CBLC(3), CD3E(2), CD4(1), CD8A(1), CHUK(1), FOS(1), GRB2(2), IKBKB(1), ITK(5), KRAS(2), LCK(1), LCP2(1), MAP3K14(1), NCK2(1), NFAT5(1), NFATC1(1), NFATC2(1), NFATC4(1), NFKB1(1), NRAS(2), PAK2(1), PAK3(5), PAK6(2), PAK7(1), PDCD1(1), PDK1(1), PIK3CA(2), PIK3CB(1), PIK3CG(3), PIK3R1(1), PIK3R2(2), PIK3R5(1), PPP3CC(1), PRKCQ(3), PTPRC(3), RASGRP1(1), RHOA(2), SOS1(3), SOS2(1), TEC(1), TNF(1), VAV1(2), VAV2(4), VAV3(3), ZAP70(1) 42827290 79 72 77 32 6 11 33 20 9 0 0.0090 0.21 26 C21_STEROID_HORMONE_METABOLISM AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 10 AKR1C4(1), CYP11A1(1), CYP11B1(7), CYP11B2(1), HSD3B1(2), HSD3B2(1) 3699922 13 13 12 4 1 0 6 5 1 0 0.0092 0.21 27 HSA00140_C21_STEROID_HORMONE_METABOLISM Genes involved in C21-steroid hormone metabolism AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 10 AKR1C4(1), CYP11A1(1), CYP11B1(7), CYP11B2(1), HSD3B1(2), HSD3B2(1) 3699922 13 13 12 4 1 0 6 5 1 0 0.0092 0.21 28 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 45 ACOX1(2), CPT1B(2), CREBBP(7), DUSP1(2), EHHADH(2), EP300(1), HSD17B4(1), LPL(1), ME1(2), MRPL11(1), NCOA1(2), NCOR1(1), NCOR2(1), NR1H3(4), NR2F1(2), PIK3CA(2), PIK3R1(1), PPARA(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PRKCA(1), PTGS2(1), RELA(1), RXRA(2), STAT5A(2), STAT5B(3), TNF(1) 25006718 49 48 49 9 5 7 15 12 10 0 0.010 0.23 29 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 28 ADRA1A(1), ADRB2(1), CHRM2(4), CHRM3(3), CHRM5(1), DRD1(2), DRD3(1), HRH1(1), HTR1A(2), HTR1E(2), HTR1F(3), HTR2A(3), HTR2C(4), HTR4(2), HTR5A(2), HTR6(1) 10112179 33 28 33 4 5 4 15 8 1 0 0.015 0.33 30 HSA00902_MONOTERPENOID_BIOSYNTHESIS Genes involved in monoterpenoid biosynthesis CYP2C19, CYP2C9 2 CYP2C19(4), CYP2C9(1) 942777 5 5 5 1 0 0 1 4 0 0 0.017 0.34 31 HSA04110_CELL_CYCLE Genes involved in cell cycle ABL1, ANAPC1, ANAPC10, ANAPC11, ANAPC2, ANAPC4, ANAPC5, ANAPC7, ATM, ATR, BUB1, BUB1B, BUB3, CCNA1, CCNA2, CCNB1, CCNB2, CCNB3, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCNH, CDC14A, CDC14B, CDC16, CDC2, CDC20, CDC23, CDC25A, CDC25B, CDC25C, CDC26, CDC27, CDC45L, CDC6, CDC7, CDK2, CDK4, CDK6, CDK7, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CHEK1, CHEK2, CREBBP, CUL1, DBF4, E2F1, E2F2, E2F3, EP300, ESPL1, FZR1, GADD45A, GADD45B, GADD45G, GSK3B, hCG_1982709, HDAC1, HDAC2, LOC440917, LOC728919, MAD1L1, MAD2L1, MAD2L2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, PKMYT1, PLK1, PRKDC, PTTG1, PTTG2, RB1, RBL1, RBL2, RBX1, SFN, SKP1, SKP2, SMAD2, SMAD3, SMAD4, SMC1A, SMC1B, TFDP1, TGFB1, TGFB2, TGFB3, TP53, WEE1, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ 104 ABL1(1), ANAPC1(1), ANAPC2(1), ANAPC4(1), ANAPC5(1), ATM(5), ATR(2), BUB1(1), BUB1B(2), BUB3(1), CCNA1(2), CCNA2(1), CCNB3(3), CCNH(1), CDC20(1), CDC25B(2), CDC27(4), CDC6(1), CDC7(2), CDK2(1), CDKN1A(1), CDKN1B(1), CDKN2C(2), CDKN2D(1), CHEK2(1), CREBBP(7), E2F2(1), EP300(1), GADD45A(1), GADD45B(1), GSK3B(1), HDAC1(1), MAD2L2(1), MCM2(2), MCM3(1), MCM4(2), MCM5(2), ORC1L(1), ORC4L(1), PRKDC(8), RBL1(1), RBL2(3), SKP2(2), SMC1A(5), SMC1B(3), TFDP1(2), YWHAB(1), YWHAE(2), YWHAG(2) 57817333 92 83 92 25 13 12 29 23 15 0 0.019 0.37 32 NICOTINATE_AND_NICOTINAMIDE_METABOLISM AOX1, CD38, ENPP1, ENPP3, NADSYN1, NMNAT1, NMNAT2, NNMT, NNT, NP, NT5C, NT5E, NT5M, QPRT 13 AOX1(4), CD38(2), ENPP1(2), ENPP3(2), NADSYN1(1), NNMT(1), NNT(4), NT5E(2) 6608001 18 17 18 2 2 2 4 7 3 0 0.021 0.40 33 PEPTIDE_GPCRS AGTR1, AGTR2, ATP8A1, AVPR1A, AVPR1B, AVPR2, BDKRB1, BDKRB2, BLR1, BRS3, C3AR1, C5R1, CCKAR, CCKBR, CCR1, CCR10, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CX3CR1, CXCR3, CXCR4, CXCR6, EDNRA, EDNRB, ELA3A, FPR1, FPRL1, FPRL2, FSHR, FY, GALR1, GALR2, GALR3, GALT, GHSR, GNB2L1, GNRHR, GPR77, GRPR, IL8RA, IL8RB, LHCGR, MC1R, MC2R, MC3R, MC4R, MC5R, NMBR, NPY1R, NPY2R, NPY5R, NPY6R, NTSR1, NTSR2, OPRD1, OPRK1, OPRL1, OPRM1, OXTR, PPYR1, SSTR1, SSTR2, SSTR3, SSTR4, TAC4, TACR1, TACR2, TACR3, TRHR, TSHR 63 AGTR2(2), AVPR1B(3), AVPR2(1), BDKRB1(4), BDKRB2(3), BRS3(1), CCKBR(1), CCR3(2), CCR6(1), CCR8(1), CXCR3(2), EDNRA(1), FPR1(1), FSHR(4), GALR1(1), GHSR(1), GPR77(1), GRPR(1), LHCGR(3), MC2R(3), MC3R(2), MC4R(1), MC5R(2), NMBR(1), OPRD1(2), OPRK1(1), PPYR1(2), SSTR1(1), TACR1(1), TACR2(2), TACR3(1), TSHR(4) 21138845 57 46 57 13 12 4 20 16 5 0 0.022 0.41 34 LYSINE_BIOSYNTHESIS AADAT, AASDH, AASDHPPT, AASS, KARS 5 AASDH(5), AASDHPPT(1), AASS(2), KARS(1) 3198163 9 9 9 1 0 0 3 4 2 0 0.023 0.41 35 HSA04612_ANTIGEN_PROCESSING_AND_PRESENTATION Genes involved in antigen processing and presentation B2M, CALR, CANX, CD4, CD74, CD8A, CD8B, CIITA, CREB1, CTSB, CTSL1, CTSS, HLA-A, HLA-A29.1, HLA-B, HLA-C, HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-E, HLA-F, HLA-G, HSP90AA1, HSP90AB1, HSPA5, IFI30, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, KIR3DL1, KIR3DL2, KIR3DL3, KLRC1, KLRC2, KLRC3, KLRC4, KLRD1, LGMN, LTA, NFYA, NFYB, NFYC, PDIA3, PSME1, PSME2, RFX5, RFXANK, RFXAP, TAP1, TAP2, TAPBP 73 B2M(2), CD4(1), CD8A(1), CIITA(1), CTSL1(3), HLA-A(1), HLA-DRA(1), HLA-DRB1(1), HLA-E(1), HLA-G(3), HSP90AA1(2), HSPA5(2), IFNA1(2), IFNA13(2), IFNA5(1), IFNA8(1), KIR2DL1(1), KIR2DL3(2), KIR2DL4(2), KIR3DL1(2), KIR3DL2(1), KIR3DL3(3), KLRC2(2), KLRC3(1), PDIA3(2), PSME1(2), RFX5(1), RFXANK(1), RFXAP(1), TAPBP(3) 20221146 49 43 48 13 4 10 12 14 9 0 0.024 0.42 36 NTHIPATHWAY Hemophilus influenzae infections activate NF-kB via several pathways, inducing the inflammatory response. CHUK, CREBBP, DUSP1, EP300, IKBKB, IL1B, IL8, MADH3, MADH4, MAP2K3, MAP2K6, MAP3K14, MAP3K7, MAPK11, MAPK14, MYD88, NFKB1, NFKBIA, NR3C1, RELA, TGFBR1, TGFBR2, TLR2, TNF 21 CHUK(1), CREBBP(7), DUSP1(2), EP300(1), IKBKB(1), IL8(1), MAP2K3(1), MAP2K6(1), MAP3K14(1), MAP3K7(3), MAPK14(1), NFKB1(1), NR3C1(2), RELA(1), TGFBR2(3), TNF(1) 12852953 28 27 28 5 4 4 6 10 4 0 0.025 0.43 37 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 65 ADCY1(4), BRAF(2), CACNA1C(9), CALM3(1), CAMK2B(2), CAMK2D(1), CAMK2G(1), CAMK4(3), CREBBP(7), EP300(1), GRIA1(1), GRIA2(2), GRIN2A(3), GRIN2B(3), GRIN2C(1), GRIN2D(3), GRM1(4), GRM5(2), ITPR1(3), ITPR2(5), ITPR3(3), KRAS(2), NRAS(2), PLCB1(4), PLCB2(4), PLCB3(2), PLCB4(1), PPP1R12A(2), PPP3CC(1), PRKACG(1), PRKCA(1), PRKCG(1), RPS6KA1(1), RPS6KA2(1) 42616889 84 69 81 27 14 10 24 25 11 0 0.027 0.43 38 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 122 ACACB(4), BRAF(2), CALM3(1), CBLB(1), CBLC(3), EIF4EBP1(1), ELK1(2), G6PC(1), GRB2(2), GSK3B(1), GYS1(1), IKBKB(1), INPP5D(4), INSR(6), IRS1(6), IRS4(5), KRAS(2), LIPE(1), MAPK8(1), MAPK9(1), MKNK1(1), NRAS(2), PDE3A(4), PDPK1(1), PFKP(2), PHKA1(3), PHKA2(2), PIK3CA(2), PIK3CB(1), PIK3CG(3), PIK3R1(1), PIK3R2(2), PIK3R5(1), PKLR(1), PPARGC1A(2), PPP1R3A(8), PPP1R3B(1), PRKAA2(2), PRKACG(1), PRKAG3(1), PRKAR2A(1), PRKAR2B(1), PRKCI(2), PRKCZ(2), PTPRF(4), PYGM(3), RAPGEF1(2), RPS6(1), RPS6KB2(1), SHC1(1), SHC4(2), SLC2A4(1), SOCS2(1), SOCS4(1), SORBS1(2), SOS1(3), SOS2(1), TRIP10(1), TSC1(3), TSC2(2) 63860487 122 96 120 28 12 17 50 29 14 0 0.027 0.43 39 HSA04650_NATURAL_KILLER_CELL_MEDIATED_CYTOTOXICITY Genes involved in natural killer cell mediated cytotoxicity ARAF, BID, BRAF, CASP3, CD244, CD247, CD48, CHP, CSF2, FAS, FASLG, FCER1G, FCGR3A, FCGR3B, FYN, GRB2, GZMB, HCST, HLA-A, HLA-B, HLA-C, HLA-E, HLA-G, HRAS, ICAM1, ICAM2, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IFNG, IFNGR1, IFNGR2, ITGAL, ITGB2, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DS1, KIR2DS2, KIR3DL1, KIR3DL2, KLRC1, KLRC2, KLRC3, KLRD1, KLRK1, KRAS, LAT, LCK, LCP2, LOC652578, MAP2K1, MAP2K2, MAPK1, MAPK3, MICA, MICB, NCR1, NCR2, NCR3, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NRAS, PAK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PLCG2, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRF1, PRKCA, PRKCB1, PRKCG, PTK2B, PTPN11, PTPN6, RAC1, RAC2, RAC3, RAF1, SH2D1A, SH2D1B, SH3BP2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SYK, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFSF10, TYROBP, ULBP1, ULBP2, ULBP3, VAV1, VAV2, VAV3, ZAP70 122 BID(1), BRAF(2), CD244(1), GRB2(2), HLA-A(1), HLA-E(1), HLA-G(3), ICAM1(1), ICAM2(1), IFNA1(2), IFNA13(2), IFNA5(1), IFNA8(1), IFNAR2(1), IFNB1(1), ITGAL(3), ITGB2(2), KIR2DL1(1), KIR2DL3(2), KIR2DL4(2), KIR3DL1(2), KIR3DL2(1), KLRC2(2), KLRC3(1), KRAS(2), LCK(1), LCP2(1), MICB(1), NCR1(1), NCR2(1), NCR3(1), NFAT5(1), NFATC1(1), NFATC2(1), NFATC4(1), NRAS(2), PIK3CA(2), PIK3CB(1), PIK3CG(3), PIK3R1(1), PIK3R2(2), PIK3R5(1), PLCG2(1), PPP3CC(1), PRF1(2), PRKCA(1), PRKCG(1), PTK2B(1), SH3BP2(1), SHC1(1), SHC4(2), SOS1(3), SOS2(1), TNF(1), TNFRSF10A(2), TNFRSF10D(1), TNFSF10(1), TYROBP(1), VAV1(2), VAV2(4), VAV3(3), ZAP70(1) 47079132 92 74 90 31 7 13 33 27 12 0 0.028 0.43 40 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 85 ACVR1(2), ACVR1B(1), ACVR1C(2), ACVR2B(3), AMHR2(1), BMP2(1), BMP5(1), BMP6(1), BMPR1A(1), BMPR1B(1), BMPR2(3), CHRD(1), COMP(3), CREBBP(7), E2F5(1), EP300(1), INHBA(3), LTBP1(3), PITX2(1), PPP2CA(2), PPP2R1A(4), PPP2R2A(1), PPP2R2B(1), RBL1(1), RBL2(3), RHOA(2), RPS6KB2(1), SMAD1(1), SMAD7(1), SMURF1(1), TFDP1(2), TGFBR2(3), THBS1(2), THBS2(4), THBS3(3), THBS4(1), TNF(1), ZFYVE9(2) 42288370 73 65 72 21 9 11 22 16 15 0 0.028 0.43 41 HSA00150_ANDROGEN_AND_ESTROGEN_METABOLISM Genes involved in androgen and estrogen metabolism AKR1C4, AKR1D1, ARSD, ARSE, CARM1, CYP11B1, CYP11B2, CYP19A1, HEMK1, HSD11B1, HSD11B2, HSD17B1, HSD17B12, HSD17B2, HSD17B3, HSD17B7, HSD17B8, HSD3B1, HSD3B2, LCMT1, LCMT2, METTL2B, METTL6, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, SRD5A1, SRD5A2, STS, SULT1E1, SULT2A1, SULT2B1, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, WBSCR22 53 AKR1C4(1), CYP11B1(7), CYP11B2(1), HSD17B2(1), HSD3B1(2), HSD3B2(1), METTL6(1), PRMT5(2), PRMT8(3), SRD5A2(1), SULT1E1(1), SULT2A1(1), UGT1A10(2), UGT1A3(1), UGT1A5(1), UGT1A7(1), UGT1A8(2), UGT1A9(2), UGT2A1(3), UGT2A3(1), UGT2B10(2), UGT2B11(1), UGT2B17(1), UGT2B4(1), UGT2B7(1), WBSCR22(1) 20724733 42 42 41 12 3 4 14 15 6 0 0.031 0.44 42 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 B3GNT2(1), B3GNT7(1), B4GALT2(1), CHST2(5), CHST6(1), FUT8(1), ST3GAL2(2), ST3GAL3(3) 4877454 15 15 15 1 4 3 3 4 1 0 0.032 0.44 43 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), ADH1C(1), ADH4(1), ADH5(1), ADH6(1), ADHFE1(1), AKR1C1(2), AKR1C4(1), ALDH3A1(1), CYP1A1(2), CYP1A2(1), CYP1B1(1), CYP2B6(1), CYP2C18(2), CYP2C19(4), CYP2C9(1), CYP2E1(1), CYP2F1(1), CYP3A43(1), DHDH(1), EPHX1(3), GSTA1(1), GSTA2(1), GSTA5(1), GSTM1(1), GSTM5(1), GSTO2(1), MGST1(1), MGST2(1), UGT1A10(2), UGT1A3(1), UGT1A5(1), UGT1A7(1), UGT1A8(2), UGT1A9(2), UGT2A1(3), UGT2A3(1), UGT2B10(2), UGT2B11(1), UGT2B17(1), UGT2B4(1), UGT2B7(1) 24291455 56 47 56 16 1 8 21 16 10 0 0.033 0.44 44 PAR1PATHWAY Activated extracellular thrombin cleaves and activates the G-protein coupled receptors PAR1 and PAR4, which activate platelets. ADCY1, ARHA, ARHGEF1, F2, F2R, F2RL3, GNA12, GNA13, GNAI1, GNAQ, GNB1, GNGT1, MAP3K7, PIK3CA, PIK3R1, PLCB1, PPP1R12B, PRKCA, PRKCB1, PTK2B, ROCK1 18 ADCY1(4), ARHGEF1(3), F2(3), F2R(2), GNA12(1), MAP3K7(3), PIK3CA(2), PIK3R1(1), PLCB1(4), PPP1R12B(4), PRKCA(1), PTK2B(1) 11080969 29 27 29 5 8 7 7 6 1 0 0.033 0.44 45 GSK3PATHWAY Bacterial lipopolysaccharide activates AKT to promote the survival and activation of macrophages and inhibits Gsk3-beta to promote beta-catenin accumulation in the nucleus. AKT1, APC, AXIN1, CCND1, CD14, CTNNB1, DVL1, FZD1, GJA1, GNAI1, GSK3B, IRAK1, LBP, LEF1, LY96, MYD88, NFKB1, PDPK1, PIK3CA, PIK3R1, PPP2CA, PRKR, RELA, TIRAP, TLR4, TOLLIP, WNT1 24 APC(8), CTNNB1(2), GJA1(2), GSK3B(1), IRAK1(2), LBP(2), NFKB1(1), PDPK1(1), PIK3CA(2), PIK3R1(1), PPP2CA(2), RELA(1), TIRAP(1), TLR4(4) 12004974 30 27 30 10 3 5 12 6 4 0 0.033 0.44 46 WNT_SIGNALING Wnt signaling genes APC, ARHA, AXIN1, C2orf31, CCND1, CCND2, CCND3, CSNK1E, CSNK1E, LOC400927, CTNNB1, DIPA, DVL1, DVL2, DVL3, FBXW2, FOSL1, FRAT1, FZD1, FZD10, FZD2, FZD3, FZD5, FZD6, FZD7, FZD8, FZD9, GSK3B, JUN, LDLR, MAPK10, MAPK9, MYC, PAFAH1B1, PLAU, PPP2R5C, PPP2R5E, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCI, PRKCM, PRKCQ, PRKCZ, PRKD1, RAC1, RHOA, SFRP4, TCF7, WNT1, WNT10A, WNT10B, WNT11, WNT16, WNT2, WNT2B, WNT3, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B 57 APC(8), CSNK1E(1), CTNNB1(2), DVL3(1), FOSL1(1), FZD5(2), FZD7(2), GSK3B(1), LDLR(3), MAPK9(1), PLAU(2), PPP2R5C(1), PRKCA(1), PRKCE(1), PRKCG(1), PRKCH(1), PRKCI(2), PRKCQ(3), PRKCZ(2), PRKD1(2), RHOA(2), WNT11(2), WNT16(3), WNT2(1), WNT2B(1), WNT4(1), WNT6(2), WNT7A(2), WNT7B(2) 23439976 54 48 53 17 10 9 16 12 7 0 0.034 0.44 47 HSA04640_HEMATOPOIETIC_CELL_LINEAGE Genes involved in hematopoietic cell lineage ANPEP, CD14, CD19, CD1A, CD1B, CD1C, CD1D, CD1E, CD2, CD22, CD24, CD33, CD34, CD36, CD37, CD38, CD3D, CD3E, CD3G, CD4, CD44, CD5, CD55, CD59, CD7, CD8A, CD8B, CD9, CR1, CR2, CSF1, CSF1R, CSF2, CSF2RA, CSF3, CSF3R, DNTT, EPO, EPOR, FCER2, FCGR1A, FLT3, FLT3LG, GP1BA, GP1BB, GP5, GP9, GYPA, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, IL11, IL11RA, IL1A, IL1B, IL1R1, IL1R2, IL2RA, IL3, IL3RA, IL4, IL4R, IL5, IL5RA, IL6, IL6R, IL7, IL7R, IL9R, ITGA1, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGAM, ITGB3, KIT, KITLG, MME, MS4A1, TFRC, THPO, TNF, TPO 80 ANPEP(2), CD19(2), CD1B(2), CD1C(2), CD22(3), CD34(1), CD38(2), CD3E(2), CD4(1), CD44(1), CD5(1), CD55(1), CD8A(1), CD9(1), CR1(2), CR2(1), CSF1(1), CSF1R(1), CSF3(1), CSF3R(1), DNTT(2), EPOR(1), FCGR1A(2), FLT3(2), GP5(1), HLA-DRA(1), HLA-DRB1(1), IL11RA(1), IL2RA(2), IL4R(2), IL5RA(1), IL6R(1), IL7R(3), ITGA1(1), ITGA2B(4), ITGA3(2), ITGA4(3), ITGA5(1), ITGA6(1), KIT(7), KITLG(1), MME(2), MS4A1(2), TFRC(3), THPO(1), TNF(1), TPO(4) 35829400 82 66 82 18 12 12 31 20 7 0 0.035 0.44 48 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 34 ACTN2(3), ACTN3(2), DMD(6), MYBPC1(3), MYBPC2(4), MYBPC3(3), MYH3(4), MYH7(3), MYH8(3), MYL2(1), MYL4(3), MYOM1(4), NEB(7), TNNT1(1), TPM2(1), TTN(72), VIM(2) 59289691 122 90 122 31 20 15 39 34 14 0 0.036 0.44 49 IL7PATHWAY IL-7 is required for B and T cell development and proliferation and may contribute to activation of VDJ recombination. BCL2, CREBBP, EP300, FYN, IL2RG, IL7, IL7R, JAK1, JAK3, LCK, NMI, PIK3CA, PIK3R1, PTK2B, STAT5A, STAT5B 16 CREBBP(7), EP300(1), IL7R(3), JAK3(3), LCK(1), PIK3CA(2), PIK3R1(1), PTK2B(1), STAT5A(2), STAT5B(3) 11985301 24 24 24 7 2 3 6 7 6 0 0.036 0.44 50 HSA00740_RIBOFLAVIN_METABOLISM Genes involved in riboflavin metabolism ACP1, ACP2, ACP5, ACP6, ACPP, ACPT, ENPP1, ENPP3, FLAD1, LHPP, MTMR1, MTMR2, MTMR6, PHPT1, RFK, TYR 15 ACP2(1), ACP6(2), ACPP(2), ENPP1(2), ENPP3(2), FLAD1(3), MTMR1(2), MTMR6(2), TYR(1) 6674015 17 17 17 4 3 1 4 5 4 0 0.036 0.44 51 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 11 ACTN2(3), ACTN3(2), CSK(1), CTNNA1(2), CTNNB1(2), PECAM1(2), PTK2(1), PXN(5), VCL(2) 7784670 20 20 20 4 2 3 7 3 5 0 0.037 0.44 52 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 EGFR(7), ERBB3(2), NRG1(4) 4746778 13 13 13 5 0 2 6 4 1 0 0.038 0.44 53 CTLPATHWAY Cytotoxic T lymphocytes induce apoptosis in infected cells presenting antigen-MHC-I complexes via the perforin and Fas/Fas ligand pathways. B2M, CD3D, CD3E, CD3G, CD3Z, GZMB, HLA-A, ICAM1, ITGAL, ITGB2, PRF1, TNFRSF6, TNFSF6, TRA@, TRB@ 10 B2M(2), CD3E(2), HLA-A(1), ICAM1(1), ITGAL(3), ITGB2(2), PRF1(2) 3586909 13 11 12 2 2 1 3 5 2 0 0.042 0.44 54 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 23 AKR1B1(3), UGDH(2), UGT1A10(2), UGT1A3(1), UGT1A5(1), UGT1A7(1), UGT1A8(2), UGT1A9(2), UGT2A1(3), UGT2A3(1), UGT2B10(2), UGT2B11(1), UGT2B17(1), UGT2B4(1), UGT2B7(1), XYLB(1) 10765241 25 24 25 6 2 5 7 6 5 0 0.042 0.44 55 ALKPATHWAY Activin receptor-like kinase 3 (ALK3) is required during gestation for cardiac muscle development. ACVR1, APC, ATF2, AXIN1, BMP10, BMP2, BMP4, BMP5, BMP7, BMPR1A, BMPR2, CHRD, CTNNB1, DVL1, FZD1, GATA4, GSK3B, MADH1, MADH4, MADH5, MADH6, MAP3K7, MEF2C, MYL2, NKX2-5, NOG, NPPA, NPPB, RFC1, TCF1, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3, WNT1 30 ACVR1(2), APC(8), BMP10(2), BMP2(1), BMP5(1), BMPR1A(1), BMPR2(3), CHRD(1), CTNNB1(2), GSK3B(1), MAP3K7(3), MEF2C(1), MYL2(1), NPPA(1), NPPB(2), RFC1(2), TGFBR2(3), TGFBR3(2) 15265984 37 31 37 14 3 5 15 10 4 0 0.042 0.44 56 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(2), ACAT1(2), ACAT2(1), ALDH1A1(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), AOC2(4), AOC3(1), AOX1(4), CAT(1), CYP1A1(2), CYP1A2(1), CYP2A13(3), CYP2A6(2), CYP2A7(3), CYP2B6(1), CYP2C18(2), CYP2C19(4), CYP2C9(1), CYP2E1(1), CYP2F1(1), CYP2J2(1), DDC(1), ECHS1(1), EHHADH(2), HAAO(1), HADHA(1), KMO(2), MAOA(2), MAOB(1), WARS(1) 24176324 54 48 54 18 2 8 20 16 8 0 0.042 0.44 57 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(7), EP300(1), NCOA3(4), PRKACG(1), PRKAR2A(1), PRKAR2B(1), RARA(1), RXRA(2) 8841720 18 18 18 2 1 1 3 7 6 0 0.042 0.44 58 HSA00604_GLYCOSPHINGOLIPID_BIOSYNTHESIS_GANGLIOSERIES Genes involved in glycosphingolipid biosynthesis - ganglioseries B3GALT4, B4GALNT1, GLB1, HEXA, HEXB, LCT, SLC33A1, ST3GAL1, ST3GAL2, ST3GAL5, ST6GALNAC3, ST6GALNAC4, ST6GALNAC5, ST6GALNAC6, ST8SIA1, ST8SIA5 16 B3GALT4(2), GLB1(2), HEXA(2), HEXB(1), LCT(6), ST3GAL2(2), ST6GALNAC3(2), ST8SIA1(2), ST8SIA5(1) 7165599 20 19 20 4 1 2 11 4 2 0 0.042 0.44 59 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 129 ACTG1(2), CHAD(1), COL11A1(5), COL11A2(4), COL17A1(3), COL1A1(1), COL1A2(2), COL2A1(1), COL3A1(4), COL4A1(3), COL4A2(1), COL4A4(3), COL4A6(5), COL5A1(1), COL5A2(2), COL5A3(7), COL6A3(11), COL6A6(6), COMP(3), DSC1(3), DSC2(1), DSC3(2), DSG1(3), DSG2(1), DSG3(3), DSG4(3), FN1(1), GJA1(2), GJA5(1), GJA8(2), GJB4(1), GJB5(1), GJB6(1), GJC3(1), GJD2(1), INA(1), ITGA6(1), KRT1(1), KRT12(1), KRT13(1), KRT2(1), KRT23(1), KRT24(1), KRT25(2), KRT27(1), KRT28(1), KRT31(1), KRT32(1), KRT33A(1), KRT35(1), KRT4(3), KRT6A(3), KRT6B(3), KRT6C(2), KRT71(1), KRT72(4), KRT73(2), KRT77(2), KRT78(2), KRT79(2), KRT82(1), KRT85(2), KRT9(1), LAMA1(6), LAMA2(8), LAMA3(7), LAMA4(2), LAMB1(5), LAMB2(3), LAMB3(1), LAMB4(4), LAMC1(3), LAMC2(1), LAMC3(4), LMNA(4), LMNB1(1), NES(5), RELN(8), SPP1(1), THBS1(2), THBS2(4), THBS3(3), THBS4(1), TNC(1), TNN(4), TNR(3), TNXB(4), VIM(2), VWF(4) 102137276 227 147 227 59 24 41 81 49 32 0 0.042 0.44 60 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 41 CSK(1), DAG1(3), EPHB2(1), FBXW7(4), GRB2(2), ITK(5), ITPKB(4), LCK(1), LCP2(1), NFAT5(1), NFKB1(1), PAK2(1), PAK3(5), PAK6(2), PAK7(1), PTPRC(3), RASGRP1(1), RASGRP2(1), RASGRP3(2), SOS1(3), SOS2(1), VAV1(2), ZAP70(1) 22947628 47 45 47 16 6 6 20 10 5 0 0.047 0.48 61 HSA04730_LONG_TERM_DEPRESSION Genes involved in long-term depression ARAF, BRAF, C7orf16, CACNA1A, CRH, CRHR1, GNA11, GNA12, GNA13, GNAI1, GNAI2, GNAI3, GNAO1, GNAQ, GNAS, GNAZ, GRIA1, GRIA2, GRIA3, GRID2, GRM1, GRM5, GUCY1A2, GUCY1A3, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, HRAS, IGF1, IGF1R, ITPR1, ITPR2, ITPR3, KRAS, LYN, MAP2K1, MAP2K2, MAPK1, MAPK3, NOS1, NOS2A, NOS3, NPR1, NPR2, NRAS, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCB1, PLCB2, PLCB3, PLCB4, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, PRKCA, PRKCB1, PRKCG, PRKG1, PRKG2, RAF1, RYR1 73 BRAF(2), C7orf16(1), CACNA1A(5), GNA11(1), GNA12(1), GNAI2(1), GNAS(3), GRIA1(1), GRIA2(2), GRIA3(2), GRID2(2), GRM1(4), GRM5(2), GUCY1A3(1), GUCY2C(3), IGF1R(1), ITPR1(3), ITPR2(5), ITPR3(3), KRAS(2), LYN(1), NOS1(2), NOS3(2), NPR1(1), NPR2(2), NRAS(2), PLA2G12A(1), PLA2G12B(1), PLA2G2F(1), PLA2G4A(1), PLA2G6(1), PLCB1(4), PLCB2(4), PLCB3(2), PLCB4(1), PPP2CA(2), PPP2R1A(4), PPP2R2A(1), PPP2R2B(1), PRKCA(1), PRKCG(1), PRKG1(1), RYR1(11) 47091944 93 77 90 32 14 11 30 26 12 0 0.048 0.48 62 DNAFRAGMENTPATHWAY DNA fragmentation during apoptosis is effected by DFF, a caspase-activated DNAse, and by endonuclease G. CASP3, CASP7, DFFA, DFFB, ENDOG, GZMB, HMGB1, HMGB2, TOP2A, TOP2B 9 CASP7(1), HMGB1(1), TOP2A(6), TOP2B(1) 4097459 9 9 9 2 0 0 3 1 5 0 0.050 0.50 63 MYOSINPATHWAY Myosin light chain kinase phosphorylates myosin and promotes muscle contraction and platelet formation; myosin phosphatase antagonizes these processes. ARHGAP5, ARHGEF1, GNA12, GNA13, GNAQ, GNB1, GNGT1, MYL2, MYLK, PLCB1, PPP1R12B, PRKCA, PRKCB1, PRKCL1, ROCK1 13 ARHGAP5(2), ARHGEF1(3), GNA12(1), MYL2(1), MYLK(6), PLCB1(4), PPP1R12B(4), PRKCA(1) 9217804 22 22 22 2 4 3 8 6 1 0 0.052 0.51 64 HSA00750_VITAMIN_B6_METABOLISM Genes involved in vitamin B6 metabolism AOX1, PDXK, PDXP, PNPO, PSAT1 5 AOX1(4), PDXK(1), PDXP(1), PSAT1(1) 2140556 7 7 7 1 0 1 3 2 1 0 0.055 0.51 65 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 192 ACTN2(3), ACTN3(2), APC(8), ARHGEF1(3), ARHGEF12(1), ARHGEF4(2), ARHGEF7(2), ARPC1A(1), ARPC3(1), BDKRB1(4), BDKRB2(3), BRAF(2), CHRM2(4), CHRM3(3), CHRM5(1), CSK(1), CYFIP1(5), CYFIP2(2), DIAPH2(4), DIAPH3(2), DOCK1(4), EGFR(7), F2(3), F2R(2), FGD1(3), FGD3(1), FGF12(1), FGF2(1), FGF23(2), FGF5(1), FGF6(1), FGFR4(1), FN1(1), GNA12(1), GRLF1(6), GSN(1), IQGAP1(2), IQGAP2(6), IQGAP3(2), ITGA1(1), ITGA10(2), ITGA2B(4), ITGA3(2), ITGA4(3), ITGA5(1), ITGA6(1), ITGA8(3), ITGAD(1), ITGAE(1), ITGAL(3), ITGAV(2), ITGAX(1), ITGB2(2), ITGB6(1), ITGB7(4), KRAS(2), LIMK1(1), LIMK2(1), MOS(1), MRAS(1), MSN(2), MYH10(3), MYH14(2), MYH9(3), MYL2(1), MYLK(6), MYLK2(1), NCKAP1(2), NCKAP1L(3), NRAS(2), PAK2(1), PAK3(5), PAK6(2), PAK7(1), PDGFRA(3), PDGFRB(3), PFN2(1), PFN4(1), PIK3CA(2), PIK3CB(1), PIK3CG(3), PIK3R1(1), PIK3R2(2), PIK3R5(1), PIP4K2A(1), PIP4K2B(1), PIP5K1A(1), PIP5K1C(1), PPP1R12A(2), PPP1R12B(4), PTK2(1), PXN(5), RHOA(2), RRAS(1), SCIN(2), SOS1(3), SOS2(1), SSH1(4), SSH2(1), SSH3(3), TIAM1(1), TIAM2(3), VAV1(2), VAV2(4), VAV3(3), VCL(2), WAS(1), WASF2(1) 116072989 240 159 237 64 31 29 88 64 28 0 0.056 0.51 66 TYROSINE_METABOLISM ABP1, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, AOX1, COMT, DBH, DCT, DDC, FAH, GOT1, GOT2, GSTZ1, HGD, HPD, MAOA, MAOB, PNMT, TAT, TH, TPO, TYR 31 ABP1(2), ADH1B(1), ADH1C(1), ADH4(1), ADH6(1), ADHFE1(1), ALDH3A1(1), AOC2(4), AOC3(1), AOX1(4), DBH(2), DCT(2), DDC(1), MAOA(2), MAOB(1), TAT(2), TPO(4), TYR(1) 13306647 32 29 32 10 3 3 9 12 5 0 0.056 0.51 67 BADPATHWAY When phosphorylated, BAD is inhibited by sequestration; when non-phosphorylated, it promotes apoptosis by inactivating pro-survival BCL-XL and BCL-2. ADCY1, AKT1, BAD, BAX, BCL2, BCL2L1, CSF2RB, IGF1, IGF1R, IL3, IL3RA, KIT, KITLG, PIK3CA, PIK3R1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, YWHAH 21 ADCY1(4), CSF2RB(3), IGF1R(1), KIT(7), KITLG(1), PIK3CA(2), PIK3R1(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1) 8988473 22 22 22 7 7 3 3 6 3 0 0.057 0.51 68 HSA00232_CAFFEINE_METABOLISM Genes involved in caffeine metabolism CYP1A2, CYP2A13, CYP2A6, CYP2A7, NAT1, NAT2, XDH 7 CYP1A2(1), CYP2A13(3), CYP2A6(2), CYP2A7(3), NAT2(1), XDH(1) 3618823 11 11 11 5 0 3 5 3 0 0 0.058 0.51 69 ALKALOID_BIOSYNTHESIS_II ABP1, AOC2, AOC3, CES1, ESD 5 ABP1(2), AOC2(4), AOC3(1), CES1(1) 2553721 8 8 8 3 1 0 2 2 3 0 0.058 0.51 70 HSA00511_N_GLYCAN_DEGRADATION Genes involved in N-glycan degradation AGA, FLJ21865, FUCA1, FUCA2, GLB1, HEXA, HEXB, LCT, MAN2B1, MAN2B2, MAN2C1, MANBA, NEU1, NEU2, NEU3, NEU4 14 FUCA2(1), GLB1(2), HEXA(2), HEXB(1), LCT(6), MAN2B1(3), MAN2B2(3), MAN2C1(1), MANBA(1), NEU1(1), NEU3(1) 8442092 22 21 22 5 1 3 10 6 2 0 0.058 0.51 71 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 15 BCAT2(2), COASY(1), DPYD(3), DPYS(1), ENPP1(2), ENPP3(2), ILVBL(1), PANK3(1), UPB1(1), VNN1(3) 7033922 17 17 17 5 1 0 7 3 6 0 0.062 0.53 72 ANDROGEN_AND_ESTROGEN_METABOLISM AKR1C4, AKR1D1, ARSB, ARSD, ARSE, CYP11B1, CYP11B2, HSD11B1, HSD11B2, HSD17B2, HSD17B3, HSD17B8, HSD3B1, HSD3B2, SRD5A1, SRD5A2, STS, SULT1E1, SULT2A1, UGT1A10, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A9, UGT2B15, UGT2B4 29 AKR1C4(1), CYP11B1(7), CYP11B2(1), HSD17B2(1), HSD3B1(2), HSD3B2(1), SRD5A2(1), SULT1E1(1), SULT2A1(1), UGT1A10(2), UGT1A3(1), UGT1A5(1), UGT1A7(1), UGT1A8(2), UGT1A9(2), UGT2B4(1) 11603165 26 26 25 6 1 3 7 11 4 0 0.063 0.53 73 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 40 AGL(1), AMY2A(1), ENPP1(2), ENPP3(2), G6PC(1), GAA(2), GANAB(1), GPI(2), GYS1(1), HK1(1), HK2(1), HK3(3), MGAM(5), PYGM(3), SI(10), UGDH(2), UGT1A10(2), UGT1A3(1), UGT1A5(1), UGT1A7(1), UGT1A8(2), UGT1A9(2), UGT2B4(1), UXS1(2) 24130556 50 46 49 12 6 7 17 13 7 0 0.063 0.53 74 HSA00590_ARACHIDONIC_ACID_METABOLISM Genes involved in arachidonic acid metabolism AKR1C3, ALOX12, ALOX12B, ALOX15, ALOX15B, ALOX5, CBR1, CBR3, CYP2B6, CYP2C18, CYP2C19, CYP2C8, CYP2C9, CYP2E1, CYP2J2, CYP2U1, CYP4A11, CYP4A22, CYP4F2, CYP4F3, DHRS4, EPHX2, GGT1, GGTL3, GGTL4, GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, LTA4H, LTC4S, PGDS, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PTGDS, PTGES, PTGES2, PTGIS, PTGS1, PTGS2, TBXAS1 49 ALOX12(1), ALOX15(1), ALOX15B(2), ALOX5(1), CYP2B6(1), CYP2C18(2), CYP2C19(4), CYP2C9(1), CYP2E1(1), CYP2J2(1), CYP4A11(4), CYP4A22(1), CYP4F2(1), DHRS4(1), EPHX2(1), GPX6(3), PLA2G12A(1), PLA2G12B(1), PLA2G2F(1), PLA2G4A(1), PLA2G6(1), PTGDS(1), PTGIS(3), PTGS1(1), PTGS2(1), TBXAS1(2) 16484463 39 37 38 7 3 7 17 7 5 0 0.065 0.54 75 HSA04670_LEUKOCYTE_TRANSENDOTHELIAL_MIGRATION Genes involved in Leukocyte transendothelial migration ACTN1, ACTN2, ACTN3, ACTN4, ARHGAP5, BCAR1, CD99, CDC42, CDH5, CLDN1, CLDN10, CLDN11, CLDN14, CLDN15, CLDN16, CLDN17, CLDN18, CLDN19, CLDN2, CLDN20, CLDN22, CLDN23, CLDN3, CLDN4, CLDN5, CLDN6, CLDN7, CLDN8, CLDN9, CTNNA1, CTNNA2, CTNNA3, CTNNB1, CTNND1, CXCL12, CXCR4, CYBA, CYBB, ESAM, EZR, F11R, GNAI1, GNAI2, GNAI3, GRLF1, ICAM1, ITGA4, ITGAL, ITGAM, ITGB1, ITGB2, ITK, JAM2, JAM3, MAPK11, MAPK12, MAPK13, MAPK14, MLLT4, MMP2, MMP9, MRCL3, MRLC2, MSN, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLPF, NCF1, NCF2, NCF4, NOX1, NOX3, OCLN, PECAM1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PLCG2, PRKCA, PRKCB1, PRKCG, PTK2, PTK2B, PTPN11, PXN, RAC1, RAC2, RAP1A, RAP1B, RAPGEF3, RAPGEF4, RASSF5, RHOA, RHOH, ROCK1, ROCK2, SIPA1, THY1, TXK, VASP, VAV1, VAV2, VAV3, VCAM1, VCL 103 ACTN2(3), ACTN3(2), ARHGAP5(2), CDH5(1), CLDN10(1), CLDN11(2), CLDN15(1), CLDN16(1), CLDN17(2), CLDN18(2), CLDN2(1), CLDN6(1), CLDN9(1), CTNNA1(2), CTNNA3(1), CTNNB1(2), F11R(2), GNAI2(1), GRLF1(6), ICAM1(1), ITGA4(3), ITGAL(3), ITGB2(2), ITK(5), JAM3(1), MAPK14(1), MLLT4(2), MMP2(1), MSN(2), MYL2(1), NCF2(4), NCF4(2), NOX1(1), NOX3(1), PECAM1(2), PIK3CA(2), PIK3CB(1), PIK3CG(3), PIK3R1(1), PIK3R2(2), PIK3R5(1), PLCG2(1), PRKCA(1), PRKCG(1), PTK2(1), PTK2B(1), PXN(5), RASSF5(1), RHOA(2), RHOH(1), VAV1(2), VAV2(4), VAV3(3), VCL(2) 51867953 101 81 101 35 11 14 34 26 16 0 0.065 0.54 76 HSA00601_GLYCOSPHINGOLIPID_BIOSYNTHESIS_LACTOSERIES Genes involved in glycosphingolipid biosynthesis - lactoseries ABO, B3GALT1, B3GALT2, B3GALT5, B3GNT5, FUT1, FUT2, FUT3, ST3GAL3, ST3GAL4 10 ABO(1), B3GALT1(1), B3GALT2(2), B3GNT5(1), FUT1(1), ST3GAL3(3) 3040139 9 9 9 1 3 1 3 0 2 0 0.070 0.56 77 GPCRDB_CLASS_C_METABOTROPIC_GLUTAMATE_PHEROMONE CASR, GABBR1, GPCR5A, GPR51, GPRC5A, GPRC5B, GPRC5C, GPRC5D, GRM1, GRM2, GRM3, GRM4, GRM5, GRM7, GRM8 13 CASR(4), GABBR1(2), GPRC5A(1), GPRC5C(2), GPRC5D(1), GRM1(4), GRM3(1), GRM4(1), GRM5(2), GRM7(4), GRM8(3) 9045165 25 25 25 9 8 3 9 4 1 0 0.071 0.56 78 HSA04664_FC_EPSILON_RI_SIGNALING_PATHWAY Genes involved in Fc epsilon RI signaling pathway AKT1, AKT2, AKT3, BTK, CSF2, FCER1A, FCER1G, FYN, GAB2, GRB2, HRAS, IL13, IL3, IL4, IL5, INPP5D, KRAS, LAT, LCP2, LYN, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK8, MAPK9, MS4A2, NRAS, PDK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCG1, PLCG2, PRKCA, PRKCB1, PRKCD, PRKCE, RAC1, RAC2, RAC3, RAF1, SOS1, SOS2, SYK, TNF, VAV1, VAV2, VAV3 69 BTK(1), GAB2(4), GRB2(2), IL13(2), INPP5D(4), KRAS(2), LCP2(1), LYN(1), MAP2K3(1), MAP2K4(1), MAP2K6(1), MAPK14(1), MAPK8(1), MAPK9(1), MS4A2(1), NRAS(2), PDK1(1), PIK3CA(2), PIK3CB(1), PIK3CG(3), PIK3R1(1), PIK3R2(2), PIK3R5(1), PLA2G12A(1), PLA2G12B(1), PLA2G2F(1), PLA2G4A(1), PLA2G6(1), PLCG2(1), PRKCA(1), PRKCE(1), SOS1(3), SOS2(1), TNF(1), VAV1(2), VAV2(4), VAV3(3) 29873766 59 51 57 19 5 9 22 17 6 0 0.072 0.56 79 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(8), CDH1(2), CREBBP(7), EP300(1), MAP3K7(3), SKIL(1), TGFBR2(3) 11613959 25 22 25 6 1 5 4 10 5 0 0.073 0.56 80 SIG_PIP3_SIGNALING_IN_CARDIAC_MYOCTES Genes related to PIP3 signaling in cardiac myocytes AKT1, AKT2, AKT3, BAD, BCL2L1, CDC42, CDK2, CDKN1B, CDKN2A, CREB1, CREB3, CREB5, EBP, ERBB4, F2RL2, FOXO3A, FRAP1, GAB1, GADD45A, GRB2, GSK3A, GSK3B, IFI27, IGF1, IGFBP1, INPPL1, IRS1, IRS2, IRS4, MET, MYC, NOLC1, P101-PI3K, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PARD3, PARD6A, PDK1, PIK3CA, PIK3CD, PPP1R13B, PREX1, PSCD3, PTEN, PTK2, PTPN1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SFN, SHC1, SLC2A4, SOS1, SOS2, TSC1, TSC2, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ 62 CDK2(1), CDKN1B(1), F2RL2(1), GADD45A(1), GRB2(2), GSK3A(2), GSK3B(1), INPPL1(1), IRS1(6), IRS4(5), MET(4), NOLC1(1), PAK2(1), PAK3(5), PAK6(2), PAK7(1), PARD3(2), PARD6A(1), PDK1(1), PIK3CA(2), PREX1(3), PTEN(2), PTK2(1), RPS6KA1(1), RPS6KA2(1), SHC1(1), SLC2A4(1), SOS1(3), SOS2(1), TSC1(3), TSC2(2), YWHAB(1), YWHAE(2), YWHAG(2) 31490586 65 56 65 20 6 11 29 11 8 0 0.074 0.56 81 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(3), FOS(1), GRB2(2), JAK2(2), SHC1(1), SOS1(3), STAT5A(2), STAT5B(3) 7111349 17 17 17 4 1 1 11 2 2 0 0.075 0.56 82 HSA02010_ABC_TRANSPORTERS_GENERAL Genes involved in ABC transporters - general ABCA1, ABCA10, ABCA12, ABCA13, ABCA2, ABCA3, ABCA4, ABCA5, ABCA6, ABCA7, ABCA8, ABCA9, ABCB1, ABCB10, ABCB11, ABCB4, ABCB5, ABCB6, ABCB7, ABCB8, ABCB9, ABCC1, ABCC10, ABCC11, ABCC12, ABCC2, ABCC3, ABCC4, ABCC5, ABCC6, ABCC8, ABCC9, ABCD1, ABCD2, ABCD3, ABCD4, ABCG1, ABCG2, ABCG4, ABCG5, ABCG8, CFTR, TAP1, TAP2 42 ABCA1(5), ABCA10(2), ABCA12(7), ABCA13(5), ABCA3(4), ABCA4(4), ABCA5(2), ABCA6(3), ABCA8(2), ABCA9(4), ABCB1(3), ABCB11(3), ABCB4(3), ABCB5(3), ABCB6(1), ABCB7(2), ABCB8(2), ABCB9(1), ABCC1(5), ABCC10(4), ABCC11(1), ABCC12(2), ABCC2(1), ABCC4(1), ABCC5(2), ABCC6(1), ABCC8(1), ABCC9(2), ABCD2(2), ABCG1(2), ABCG4(2), CFTR(2) 49676141 84 76 84 17 14 14 29 20 7 0 0.075 0.56 83 PURINE_METABOLISM 1_Sep, ADA, ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADK, ADSL, ADSS, AK1, AK2, AK5, ALLC, AMPD1, AMPD2, AMPD3, APRT, ATIC, ATP1B1, ATP5A1, ATP5B, ATP5C1, ATP5D, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5H, ATP5I, ATP5J, ATP5J2, CANT1, DCK, DGUOK, ECGF1, ENPP1, ENPP3, ENTPD1, ENTPD2, FHIT, GART, GDA, GMPS, GUCY1A2, GUCY1A3, GUCY1B2, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, GUK1, HPRT1, IMPDH1, IMPDH2, ITPA, NME1, NME2, NP, NPR1, NPR2, NT5C, NT5E, NT5M, NUDT2, PAICS, PAPSS1, PAPSS2, PDE1A, PDE4A, PDE4B, PDE4C, PDE4D, PDE5A, PDE6B, PDE6C, PDE6G, PDE7B, PDE8A, PDE9A, PFAS, PKLR, PKM2, POLA, POLB, POLD1, POLD2, POLE, POLG, POLL, POLQ, POLR1B, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLRMT, POLS, PPAT, PRPS1, PRPS1L1, PRPS2, PRUNE, RRM1, RRM2, SAC 106 ADA(1), ADCY1(4), ADCY2(6), ADCY3(2), ADCY4(1), ADCY5(3), ADCY7(1), ADK(1), ADSL(1), AK2(1), ALLC(2), AMPD1(2), AMPD2(2), AMPD3(1), ATIC(2), ATP1B1(1), ATP5B(2), ATP5G2(1), ATP5J2(1), DCK(1), ENPP1(2), ENPP3(2), ENTPD1(2), GART(3), GDA(1), GMPS(2), GUCY1A3(1), GUCY2C(3), IMPDH1(1), ITPA(1), NPR1(1), NPR2(2), NT5E(2), PAPSS2(1), PDE1A(1), PDE4A(2), PDE4C(1), PDE6B(2), PDE6C(2), PDE7B(1), PDE8A(1), PFAS(2), PKLR(1), POLB(1), POLD1(1), POLD2(2), POLE(2), POLG(1), POLQ(3), POLR2B(2), POLR2C(1), POLR2I(1), PRPS1L1(2), PRUNE(1) 54841511 90 78 87 30 16 14 26 18 16 0 0.076 0.56 84 AKAPCENTROSOMEPATHWAY Protein Kinase A at the Centrosome AKAP9, ARHA, CDC2, MAP2, PCNT1, PCNT2, PPP1CA, PPP2CA, PRKACB, PRKACG, PRKAG1, PRKAR2A, PRKAR2B, PRKCE, PRKCL1 10 AKAP9(5), MAP2(7), PPP2CA(2), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PRKCE(1) 8072884 18 17 18 6 1 0 8 6 3 0 0.076 0.56 85 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 CD3E(2), CXCR3(2), ETV5(1), IL12RB2(3), IL18R1(2), JAK2(2), MAP2K6(1), MAPK14(1), MAPK8(1), STAT4(1), TYK2(2) 8053562 18 18 18 4 1 5 4 7 1 0 0.077 0.56 86 HSA00630_GLYOXYLATE_AND_DICARBOXYLATE_METABOLISM Genes involved in glyoxylate and dicarboxylate metabolism ACO1, ACO2, AFMID, CS, GRHPR, HAO1, HAO2, HYI, LOC441996, MDH1, MDH2, MTHFD1, MTHFD1L, MTHFD2 13 ACO1(2), ACO2(1), AFMID(1), CS(1), HAO1(2), HAO2(1), HYI(1), MDH2(1), MTHFD1(2), MTHFD1L(3) 6081689 15 15 15 0 3 2 5 3 2 0 0.078 0.56 87 HSA00480_GLUTATHIONE_METABOLISM Genes involved in glutathione metabolism ANPEP, G6PD, GCLC, GCLM, GGT1, GGTL3, GGTL4, GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, GSR, GSS, GSTA1, GSTA2, GSTA3, GSTA4, GSTA5, GSTK1, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, IDH1, IDH2, MGST1, MGST2, MGST3, OPLAH, TXNDC12 34 ANPEP(2), G6PD(4), GCLM(1), GPX6(3), GSR(2), GSS(3), GSTA1(1), GSTA2(1), GSTA5(1), GSTM1(1), GSTM5(1), GSTO2(1), MGST1(1), MGST2(1), TXNDC12(1) 8661487 24 21 24 5 0 6 10 5 3 0 0.078 0.56 88 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 77 AGL(1), AMY2A(1), ASCC3(5), ATP13A2(3), DDX18(1), DDX23(1), DDX4(1), DDX41(1), DDX47(1), DDX52(2), DDX54(2), DDX55(1), ENPP1(2), ENPP3(2), ENTPD7(1), EP400(2), ERCC2(1), G6PC(1), GAA(2), GBA(1), GPI(2), GYS1(1), HK1(1), HK2(1), HK3(3), IFIH1(1), MGAM(5), MOV10L1(2), NUDT5(1), PYGM(3), RAD54L(2), SETX(2), SI(10), SKIV2L2(1), SMARCA2(2), TREH(1), UGDH(2), UGT1A10(2), UGT1A3(1), UGT1A5(1), UGT1A7(1), UGT1A8(2), UGT1A9(2), UGT2A1(3), UGT2A3(1), UGT2B10(2), UGT2B11(1), UGT2B17(1), UGT2B4(1), UGT2B7(1), UXS1(2) 52294535 93 79 92 19 11 10 37 24 11 0 0.080 0.56 89 HSA00400_PHENYLALANINE_TYROSINE_AND_TRYPTOPHAN_BIOSYNTHESIS Genes involved in phenylalanine, tyrosine and tryptophan biosynthesis FARS2, FARSA, FARSB, GOT1, GOT2, PAH, TAT, YARS, YARS2 9 FARSA(4), FARSB(1), PAH(3), TAT(2) 3998421 10 10 10 3 1 1 2 4 2 0 0.081 0.56 90 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(1), ICAM1(1), ITGA4(3), ITGAL(3), ITGB2(2), PECAM1(2), SELE(3) 5803736 15 14 15 3 2 2 5 4 2 0 0.081 0.56 91 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 25 CASP2(1), FADD(1), LMNA(4), LMNB1(1), MADD(6), MAP2K4(1), MAP3K1(1), MAP3K7(3), MAPK8(1), PAK2(1), PRKDC(8), SPTAN1(5), TNF(1), TNFRSF1A(1), TRAF2(1) 15818743 36 34 36 4 5 10 7 8 6 0 0.084 0.56 92 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 ACAA2(1), ACADM(1), ACADSB(2), ACADVL(2), ACAT1(2), ACAT2(1), ACOX1(2), ACSL1(2), ACSL3(2), ACSL4(1), ACSL6(1), ADH1B(1), ADH1C(1), ADH4(1), ADH5(1), ADH6(1), ADHFE1(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ALDH7A1(1), CPT1A(2), CPT1B(2), CPT1C(1), CPT2(1), CYP4A11(4), CYP4A22(1), ECHS1(1), EHHADH(2), HADHA(1), HSD17B4(1) 21413911 44 38 43 11 2 8 17 8 9 0 0.084 0.56 93 HSA00780_BIOTIN_METABOLISM Genes involved in biotin metabolism BTD, HLCS, SPCS1, SPCS3 4 HLCS(2), SPCS1(1), SPCS3(2) 1385811 5 5 5 0 0 1 2 2 0 0 0.086 0.56 94 INSULINPATHWAY Insulin regulates glucose levels via Ras-mediated transcriptional activation. CSNK2A1, ELK1, FOS, GRB2, HRAS, INS, INSR, IRS1, JUN, MAP2K1, MAPK3, MAPK8, PIK3CA, PIK3R1, PTPN11, RAF1, RASA1, SHC1, SLC2A4, SOS1, SRF 20 CSNK2A1(1), ELK1(2), FOS(1), GRB2(2), INSR(6), IRS1(6), MAPK8(1), PIK3CA(2), PIK3R1(1), RASA1(1), SHC1(1), SLC2A4(1), SOS1(3), SRF(1) 10677923 29 24 29 7 0 5 16 6 2 0 0.088 0.56 95 RIBOFLAVIN_METABOLISM ACP1, ACP2, ACP5, ACPP, ACPT, ENPP1, ENPP3, FLAD1, RFK, TYR 10 ACP2(1), ACPP(2), ENPP1(2), ENPP3(2), FLAD1(3), TYR(1) 4339938 11 11 11 2 1 0 4 3 3 0 0.088 0.56 96 ACE_INHIBITOR_PATHWAY_PHARMGKB ACE, AGT, AGTR1, AGTR2, BDKRB2, KNG1, NOS3, REN 8 ACE(3), AGTR2(2), BDKRB2(3), KNG1(1), NOS3(2) 3776727 11 11 11 2 4 2 2 3 0 0 0.091 0.56 97 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(1), ICAM1(1), ITGA4(3), ITGAL(3), ITGB2(2), PECAM1(2), SELE(3), SELP(3) 7578637 18 17 18 5 2 2 6 5 3 0 0.092 0.56 98 HSA04140_REGULATION_OF_AUTOPHAGY Genes involved in regulation of autophagy ATG12, ATG3, ATG5, ATG7, BECN1, GABARAP, GABARAPL1, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNG, INS, LOC441925, PIK3C3, PIK3R4, PRKAA1, PRKAA2, ULK1, ULK2, ULK3 27 ATG3(3), BECN1(1), IFNA1(2), IFNA13(2), IFNA5(1), IFNA8(1), PIK3R4(4), PRKAA2(2), ULK2(1) 8413746 17 17 17 4 0 2 8 6 1 0 0.093 0.56 99 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 CD80(1), CR1(2), CR2(1), HLA-DRA(1), HLA-DRB1(1), ICAM1(1), ITGAL(3), ITGB2(2), PTPRC(3) 6542065 15 15 15 2 2 3 2 5 3 0 0.094 0.56 100 DNA_REPLICATION_REACTOME ASK, CDC45L, CDC6, CDC7, CDK2, CDT1, DIAPH2, GMNN, MCM10, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, NACA, NACA, FKSG17, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, POLA, POLA2, POLD1, POLD2, POLD3, POLD4, POLE, POLE2, PRIM1, PRIM2A, RFC1, RFC2, RFC3, RFC4, RFC5, RPA1, RPA2, RPA3, RPA4, RPS27A, RPS27A, LOC388720, LOC389425, UBA52, UBB, UBC 41 CDC6(1), CDC7(2), CDK2(1), DIAPH2(4), GMNN(1), MCM10(1), MCM2(2), MCM3(1), MCM4(2), MCM5(2), NACA(4), ORC1L(1), ORC4L(1), POLD1(1), POLD2(2), POLD3(1), POLE(2), POLE2(1), RFC1(2), RPA1(2), RPA2(1), RPA4(1), RPS27A(1), UBC(3) 21582663 40 38 40 7 4 3 16 10 7 0 0.094 0.56 101 GLYOXYLATE_AND_DICARBOXYLATE_METABOLISM ACO1, ACO2, CS, GRHPR, HAO1, HAO2, HYI, MDH1, MDH2, MTHFD1, MTHFD1L, MTHFD2 12 ACO1(2), ACO2(1), CS(1), HAO1(2), HAO2(1), HYI(1), MDH2(1), MTHFD1(2), MTHFD1L(3) 5795835 14 14 14 0 3 2 4 3 2 0 0.094 0.56 102 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 CD3E(2), CD8A(1), ICAM1(1), ITGAL(3), ITGB2(2), PTPRC(3) 4679845 12 12 12 2 3 2 4 2 1 0 0.095 0.56 103 NUCLEAR_RECEPTORS ALK, AR, ESR1, ESR2, ESRRA, HNF4A, NPM1, NR0B1, NR1D2, NR1H2, NR1H3, NR1I2, NR1I3, NR2C2, NR2E1, NR2F1, NR2F2, NR2F6, NR3C1, NR4A1, NR4A2, NR5A1, NR5A2, PGR, PPARA, PPARD, PPARG, RARA, RARB, RARG, ROR1, RORA, RORC, RXRA, RXRB, RXRG, THRA, THRA, NR1D1, THRB, VDR 38 ALK(3), AR(1), NR1D2(1), NR1H3(4), NR1I2(1), NR1I3(1), NR2F1(2), NR2F2(1), NR3C1(2), NR4A2(3), NR5A2(1), PGR(1), PPARA(1), PPARD(2), RARA(1), RARG(1), ROR1(4), RORA(2), RORC(1), RXRA(2), RXRB(2), VDR(1) 17446169 38 37 38 8 6 4 13 10 5 0 0.096 0.56 104 TCRAPATHWAY The kinases Lck and Fyn phosphorylate and activate the T cell receptor, which recognizes antigen-bound MHCII and leads to T cell activation. CD3D, CD3E, CD3G, CD3Z, CD4, FYN, HLA-DRA, HLA-DRB1, LCK, PTPRC, TRA@, TRB@, ZAP70 10 CD3E(2), CD4(1), HLA-DRA(1), HLA-DRB1(1), LCK(1), PTPRC(3), ZAP70(1) 4122167 10 10 10 2 0 2 5 1 2 0 0.097 0.56 105 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 38 APH1A(1), CREBBP(7), CTBP1(1), CTBP2(1), DLL4(1), DTX1(1), DTX2(1), DTX3L(2), DVL3(1), EP300(1), HDAC1(1), HES1(1), MAML1(2), MAML2(3), MAML3(1), NCOR2(1), NOTCH2(4), NOTCH3(4), NOTCH4(5), NUMB(2), NUMBL(2), PSENEN(1), PTCRA(2), RBPJL(2), SNW1(1) 24419214 49 45 49 14 10 6 13 14 6 0 0.098 0.56 106 FOLATE_BIOSYNTHESIS ALPI, ALPL, ALPP, ALPP, ALPPL2, ALPPL2, DHFR, FPGS, GCH1, GGH, SPR 9 ALPL(2), ALPP(2), FPGS(1), SPR(2) 2149074 7 7 7 0 2 4 0 0 1 0 0.098 0.56 107 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), CD3E(2), CD4(1), CD8A(1), CSF3(1), IL8(1), KITLG(1) 2853376 8 8 8 3 1 1 4 1 1 0 0.099 0.56 108 IGF1MTORPATHWAY Growth factor IGF-1 activates AKT, Gsk3-beta, and mTOR to promote muscle hypertrophy. AKT1, EIF2B5, EIF2S1, EIF2S2, EIF2S3, EIF4E, EIF4EBP1, FRAP1, GSK3B, IGF1, IGF1R, INPPL1, PDK2, PDPK1, PIK3CA, PIK3R1, PPP2CA, PTEN, RPS6, RPS6KB1 19 EIF2B5(4), EIF2S1(1), EIF4EBP1(1), GSK3B(1), IGF1R(1), INPPL1(1), PDPK1(1), PIK3CA(2), PIK3R1(1), PPP2CA(2), PTEN(2), RPS6(1) 8486033 18 18 18 4 2 2 8 2 4 0 0.10 0.56 109 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 11 CSF1R(1), EGFR(7), GRB2(2), MET(4), PDGFRA(3), PRKCA(1), SH3GLB2(2) 8415900 20 19 20 7 1 3 8 7 1 0 0.10 0.56 110 G_PROTEIN_SIGNALING ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, AKAP1, AKAP10, AKAP11, AKAP12, AKAP2, PALM2_AKAP2, AKAP3, AKAP4, AKAP5, AKAP6, AKAP7, AKAP8, AKAP9, ARHGEF1, CALM1, CALM2, CALM3, CHMP1B, GNA11, GNA12, GNA13, GNA14, GNA15, GNAI2, GNAI3, GNAL, GNAO1, GNAQ, GNAZ, GNB1, GNB2, GNB3, GNB5, GNG10, GNG10, LOC552891, GNG12, GNG13, GNG3, GNG4, GNG5, GNG7, GNGT1, GNGT2, HRAS, IL18BP, ITPR1, KCNJ3, KRAS, MGC11266, NRAS, PALM2, PALM2_AKAP2, PALM2_AKAP2, PDE1A, PDE1B, PDE1C, PDE4A, PDE4B, PDE4C, PDE4D, PDE7A, PDE7B, PDE8A, PDE8B, PLCB3, PPP3CA, PPP3CC, PRKACA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCI, PRKCQ, PRKCZ, PRKD1, PRKD3, RHOA, RRAS, SARA1, SLC9A1, USP5 92 ADCY1(4), ADCY2(6), ADCY3(2), ADCY4(1), ADCY5(3), ADCY7(1), ADCY9(5), AKAP1(1), AKAP10(1), AKAP12(1), AKAP3(1), AKAP4(1), AKAP6(4), AKAP8(2), AKAP9(5), ARHGEF1(3), CALM3(1), CHMP1B(2), GNA11(1), GNA12(1), GNA14(2), GNAI2(1), GNAL(1), GNB2(2), GNG13(1), ITPR1(3), KRAS(2), NRAS(2), PALM2(1), PDE1A(1), PDE1B(1), PDE4A(2), PDE4C(1), PDE7B(1), PDE8A(1), PLCB3(2), PPP3CC(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PRKCA(1), PRKCE(1), PRKCG(1), PRKCH(1), PRKCI(2), PRKCQ(3), PRKCZ(2), PRKD1(2), PRKD3(3), RHOA(2), RRAS(1), USP5(1) 50747341 94 77 91 25 21 12 23 26 12 0 0.10 0.56 111 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), DYRK1B(2), GLI2(10), GLI3(2), GSK3B(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1) 6802508 19 17 19 2 4 3 7 4 1 0 0.10 0.56 112 ST_P38_MAPK_PATHWAY p38 is a MAP kinase regulated by cytokines and cellular stress. AKT1, ATF1, CDC42, CREB1, CREB3, CREB5, DUSP1, DUSP10, EEF2K, EIF4E, ELK1, GADD45A, HSPB1, IL1R1, MAP2K3, MAP2K4, MAP2K6, MAP3K10, MAP3K4, MAP3K5, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAPK1, MAPK11, MAPK12, MAPK13, MAPK14, MAPKAPK2, MAPKAPK5, MKNK1, MKNK2, MYEF2, NFKB1, NR2C2, SRF, TRAF6 32 ATF1(3), DUSP1(2), EEF2K(2), ELK1(2), GADD45A(1), MAP2K3(1), MAP2K4(1), MAP2K6(1), MAP3K10(2), MAP3K4(2), MAP3K5(2), MAP3K7(3), MAPK14(1), MAPKAPK5(1), MKNK1(1), MYEF2(1), NFKB1(1), SRF(1), TRAF6(2) 14196059 30 29 30 4 5 4 10 6 5 0 0.10 0.56 113 RELAPATHWAY Acetylated NF-kB proteins are immune to IkB regulation and promote transcription until the histone deacetylase HDAC3 deacetylates the RelA subunit of NF-kB. CHUK, CREBBP, EP300, FADD, HDAC3, IKBKB, IKBKG, NFKB1, NFKBIA, RELA, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TRADD, TRAF6 14 CHUK(1), CREBBP(7), EP300(1), FADD(1), HDAC3(2), IKBKB(1), NFKB1(1), RELA(1), TNF(1), TNFRSF1A(1), TRAF6(2) 9773832 19 19 19 3 2 4 4 4 5 0 0.11 0.56 114 HSA05110_CHOLERA_INFECTION Genes involved in cholera - infection ACTG1, ACTG2, ADCY3, ADCY9, AK1, ARF1, ARF3, ARF4, ARF5, ARF6, ARL4D, ATP6V0A1, ATP6V0A2, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0D1, ATP6V0D2, ATP6V0E1, ATP6V1A, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1E2, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, ERO1L, GNAS, PDIA4, PLCG1, PLCG2, PRKCA, SEC61A1, SEC61A2, SEC61B, SEC61G, TRIM23 41 ACTG1(2), ADCY3(2), ADCY9(5), ARF5(1), ARF6(1), ARL4D(1), ATP6V0A2(1), ATP6V0D1(1), ATP6V1C2(2), ATP6V1D(1), ATP6V1E2(1), ATP6V1F(1), ERO1L(1), GNAS(3), PDIA4(3), PLCG2(1), PRKCA(1), SEC61A1(2), SEC61A2(1), TRIM23(3) 15934186 34 33 32 7 6 3 10 9 6 0 0.11 0.56 115 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 HTR2C(4), PLCB1(4), TUB(1) 3237978 9 9 9 0 0 3 3 3 0 0 0.11 0.56 116 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 27 EGFR(7), ELK1(2), GNAS(3), GRB2(2), IGF1R(1), KLK2(1), MKNK1(1), NGFR(1), PDGFRA(3), PPP2CA(2), PTPRR(1), RPS6KA1(1), RPS6KA5(1), SHC1(1), SOS1(3), STAT3(1) 13754897 31 29 30 12 0 4 15 7 5 0 0.11 0.56 117 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 10 DNM1(2), GABRA1(2), GABRA2(2), GABRA3(1), GABRA4(1), GABRA5(1), GPHN(2) 4506379 11 11 11 3 3 1 1 4 2 0 0.11 0.56 118 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 73 ACTG1(2), ACTN2(3), ACTN3(2), ACVR1B(1), ACVR1C(2), CDH1(2), CREBBP(7), CSNK2A1(1), CSNK2B(1), CTNNA1(2), CTNNA3(1), CTNNB1(2), EGFR(7), EP300(1), ERBB2(4), FARP2(1), IGF1R(1), INSR(6), IQGAP1(2), MAP3K7(3), MET(4), MLLT4(2), NLK(1), PARD3(2), PTPRB(1), PTPRF(4), PTPRJ(1), PTPRM(1), PVRL1(1), PVRL4(2), RHOA(2), SNAI1(2), SNAI2(1), SORBS1(2), SSX2IP(1), TCF7L2(2), TGFBR2(3), TJP1(3), VCL(2), WAS(1), WASF2(1), YES1(1) 52240552 91 73 90 21 8 15 29 25 14 0 0.11 0.56 119 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(4), CD38(2), ENPP1(2), ENPP3(2), NADK(1), NADSYN1(1), NNMT(1), NNT(4), NT5C1A(1), NT5C1B(1), NT5C3(1), NT5E(2) 9598148 22 20 22 3 4 2 4 9 3 0 0.11 0.56 120 FLUMAZENILPATHWAY Flumazenil is a benzodiazepine receptor antagonist that may induce protective preconditioning in ischemic cardiomyocytes. GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GPX1, PRKCE, SOD1 8 GABRA1(2), GABRA2(2), GABRA3(1), GABRA4(1), GABRA5(1), PRKCE(1) 2988449 8 8 8 2 2 0 1 3 2 0 0.11 0.56 121 HSA01030_GLYCAN_STRUCTURES_BIOSYNTHESIS_1 Genes involved in glycan structures - biosynthesis 1 A4GNT, ALG1, ALG10, ALG10B, ALG11, ALG12, ALG13, ALG14, ALG2, ALG3, ALG6, ALG8, ALG9, B3GALT6, B3GNT1, B3GNT2, B3GNT6, B3GNT7, B4GALT1, B4GALT2, B4GALT3, B4GALT4, B4GALT5, B4GALT7, C1GALT1, C1GALT1C1, ChGn, CHPF, CHST1, CHST11, CHST12, CHST13, CHST14, CHST2, CHST3, CHST4, CHST6, CHST7, CHSY-2, CHSY1, CSGlcA-T, DAD1, DDOST, DPAGT1, EXT1, EXT2, EXTL1, EXTL2, EXTL3, FUT11, FUT8, GALNAC4S-6ST, GALNACT-2, GALNT1, GALNT10, GALNT11, GALNT12, GALNT13, GALNT14, GALNT17, GALNT2, GALNT3, GALNT4, GALNT5, GALNT6, GALNT7, GALNT8, GALNT9, GALNTL1, GALNTL2, GALNTL4, GALNTL5, GANAB, GCNT1, GCNT3, GCNT4, GCS1, HS2ST1, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, HS3ST5, HS6ST1, HS6ST2, HS6ST3, LOC728969, MAN1A1, MAN1A2, MAN1B1, MAN1C1, MAN2A1, MGAT1, MGAT2, MGAT3, MGAT4A, MGAT4B, MGAT5, MGAT5B, NDST1, NDST2, NDST3, NDST4, OGT, RPN1, RPN2, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4, ST6GAL1, ST6GALNAC1, STT3B, UST, WBSCR17, XYLT1, XYLT2 103 ALG1(1), ALG10B(4), ALG11(2), ALG2(2), ALG8(2), ALG9(1), B3GNT2(1), B3GNT7(1), B4GALT2(1), B4GALT5(1), CHPF(1), CHST2(5), CHST6(1), DAD1(2), DPAGT1(1), EXT1(1), EXTL1(1), EXTL3(2), FUT8(1), GALNT1(3), GALNT10(1), GALNT12(1), GALNT13(2), GALNT14(3), GALNT2(1), GALNT3(1), GALNT4(1), GALNT6(2), GALNT8(2), GALNTL2(1), GALNTL5(1), GANAB(1), GCNT4(2), HS3ST3A1(1), HS3ST5(1), HS6ST3(1), MAN1A1(1), MAN1B1(1), MAN2A1(1), MGAT1(2), MGAT4B(1), MGAT5(3), MGAT5B(2), NDST1(1), NDST2(2), OGT(2), RPN1(2), RPN2(1), ST3GAL2(2), ST3GAL3(3), UST(2), WBSCR17(1), XYLT1(4) 46500228 87 74 86 22 18 12 24 20 13 0 0.11 0.56 122 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 62 ADAM10(1), ATP6AP1(4), ATP6V0A2(1), ATP6V0D1(1), ATP6V1C2(2), ATP6V1D(1), ATP6V1E2(1), ATP6V1F(1), CHUK(1), CSK(1), EGFR(7), F11R(2), IKBKB(1), IL8(1), JAM3(1), LYN(1), MAP2K4(1), MAP3K14(1), MAPK14(1), MAPK8(1), MAPK9(1), MET(4), NFKB1(1), NOD1(2), PLCG2(1), PTPRZ1(7), RELA(1), TCIRG1(3), TJP1(3) 29682299 54 51 53 14 5 8 14 20 7 0 0.11 0.56 123 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 CD3E(2), CD4(1), ICAM1(1), ITGAL(3), ITGB2(2), PTPRC(3) 4972456 12 12 12 2 2 2 5 2 1 0 0.11 0.56 124 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 BDKRB2(3), CALM3(1), CHRNA1(1), FLT1(2), FLT4(3), KDR(1), NOS3(2), PDE2A(2), PDE3A(4), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PRKG1(1), RYR2(15) 16793594 38 35 38 10 3 4 14 14 3 0 0.12 0.56 125 CFTRPATHWAY The cAMP-regulated chloride channel CFTR (deficient in cystic fibrosis) is regulated by the surface-localized beta-adrenergic receptor. ADCY1, ADRB2, CFTR, GNAS, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, SLC9A3R1, VIL2 11 ADCY1(4), ADRB2(1), CFTR(2), GNAS(3), PRKACG(1), PRKAR2A(1), PRKAR2B(1) 5265656 13 13 12 0 5 0 3 2 3 0 0.12 0.56 126 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 12 IL10RA(1), IL22(1), JAK2(2), JAK3(3), STAT1(2), STAT3(1), STAT5A(2), STAT5B(3), TYK2(2) 7596702 17 17 17 4 2 1 8 4 2 0 0.12 0.56 127 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), EGFR(7), HGS(1), TF(1), TFRC(3) 5695943 13 13 13 6 1 1 4 6 1 0 0.12 0.56 128 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 136 ADCY1(4), ADCY2(6), ADCY3(2), ADCY4(1), ADCY5(3), ADCY7(1), ADCY9(5), ADRA1A(1), ADRB2(1), ANXA6(1), ATP1A4(1), ATP1B1(1), ATP2A2(1), ATP2A3(1), ATP2B1(1), ATP2B2(4), ATP2B3(1), CACNA1A(5), CACNA1B(1), CACNA1C(9), CACNA1D(6), CACNA1E(4), CACNA1S(5), CACNB1(1), CALM3(1), CAMK2B(2), CAMK2D(1), CAMK2G(1), CAMK4(3), CASQ1(1), CHRM2(4), CHRM3(3), CHRM5(1), FXYD2(1), GJA1(2), GJA5(1), GJB4(1), GJB5(1), GJB6(1), GNA11(1), GNAI2(1), GNB2(2), GNG13(1), GRK5(1), GRK6(1), ITPR1(3), ITPR2(5), ITPR3(3), KCNB1(1), MIB1(5), PLCB3(2), PRKAR2A(1), PRKAR2B(1), PRKCA(1), PRKCE(1), PRKCG(1), PRKCH(1), PRKCQ(3), PRKCZ(2), PRKD1(2), RGS18(2), RGS4(2), RGS7(4), RGS9(2), RYR1(11), RYR2(15), RYR3(4), SLC8A1(2), SLC8A3(1), USP5(1), YWHAB(1) 80751388 174 122 173 47 38 16 57 44 19 0 0.12 0.56 129 RAC1PATHWAY Rac-1 is a Rho family G protein that stimulates formation of actin-dependent structures such as filopodia and lamellopodia. ARFIP2, CDK5, CDK5R1, CFL1, CHN1, LIMK1, MAP3K1, MYL2, MYLK, NCF2, PAK1, PDGFRA, PIK3CA, PIK3R1, PLD1, PPP1R12B, RAC1, RALBP1, RPS6KB1, TRIO, VAV1, WASF1 22 CHN1(2), LIMK1(1), MAP3K1(1), MYL2(1), MYLK(6), NCF2(4), PDGFRA(3), PIK3CA(2), PIK3R1(1), PLD1(1), PPP1R12B(4), TRIO(2), VAV1(2) 15629999 30 29 30 9 3 2 9 14 2 0 0.12 0.57 130 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 ACP2(1), ACPP(2), ALPL(2), ALPP(2), CYP1A1(2), CYP1A2(1), CYP2A13(3), CYP2A6(2), CYP2A7(3), CYP2B6(1), CYP2C18(2), CYP2C19(4), CYP2C9(1), CYP2E1(1), CYP2F1(1), CYP2J2(1) 12324532 29 27 29 10 0 7 12 8 2 0 0.12 0.57 131 ST_WNT_CA2_CYCLIC_GMP_PATHWAY Some Wnt glycoprotein/Frizzled receptor interactions increase intracellular calcium and decrease cGMP. BF, CAMK2A, CAMK2B, CAMK2D, CAMK2G, DAG1, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, NFAT5, PDE6A, PDE6B, PDE6C, PDE6D, PDE6G, PDE6H, SLC6A13, TF 18 CAMK2B(2), CAMK2D(1), CAMK2G(1), DAG1(3), ITPKB(4), ITPR1(3), ITPR2(5), ITPR3(3), NFAT5(1), PDE6A(3), PDE6B(2), PDE6C(2), PDE6H(1), TF(1) 14994531 32 30 32 5 3 4 8 8 9 0 0.12 0.57 132 TCRMOLECULE T Cell Receptor and CD3 Complex CD3D, CD3E, CD3G, CD3Z, TRA@, TRB@ 3 CD3E(2) 542387 2 2 2 1 0 0 2 0 0 0 0.12 0.57 133 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_NEOLACTOSERIES ABO, B3GNT1, FUT1, FUT2, FUT9, GCNT2, ST8SIA1 7 ABO(1), FUT1(1), FUT9(1), GCNT2(2), ST8SIA1(2) 2495432 7 7 7 1 1 2 1 1 2 0 0.12 0.57 134 O_GLYCAN_BIOSYNTHESIS GALNT1, GALNT10, GALNT2, GALNT3, GALNT4, GALNT6, GALNT7, GALNT8, GALNT9, GCNT1, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, WBSCR17 13 GALNT1(3), GALNT10(1), GALNT2(1), GALNT3(1), GALNT4(1), GALNT6(2), GALNT8(2), ST3GAL2(2), WBSCR17(1) 6288236 14 14 14 4 1 3 3 5 2 0 0.12 0.57 135 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(2), ACADM(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ALDH7A1(1), AOC2(4), AOC3(1), DPYD(3), DPYS(1), ECHS1(1), EHHADH(2), GAD1(1), GAD2(1), HADHA(1), SMS(1), UPB1(1) 11796437 25 25 25 6 2 1 7 8 7 0 0.13 0.58 136 HSA00670_ONE_CARBON_POOL_BY_FOLATE Genes involved in one carbon pool by folate ALDH1L1, AMT, ATIC, DHFR, FTCD, GART, MTFMT, MTHFD1, MTHFD1L, MTHFD2, MTHFR, MTHFS, MTR, SHMT1, SHMT2, TYMS 15 ALDH1L1(3), ATIC(2), GART(3), MTFMT(3), MTHFD1(2), MTHFD1L(3), SHMT1(1), SHMT2(1) 8280255 18 18 17 2 1 4 7 2 4 0 0.13 0.58 137 CREBPATHWAY CREB is a transcription factor that binds to cAMP-responsive elements (CREs) to activate transcription in response to extracellular signaling. ADCY1, AKT1, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CREB1, GNAS, GRB2, HRAS, MAPK1, MAPK14, MAPK3, PIK3CA, PIK3R1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, RAC1, RPS6KA1, RPS6KA5, SOS1 26 ADCY1(4), CAMK2B(2), CAMK2D(1), CAMK2G(1), GNAS(3), GRB2(2), MAPK14(1), PIK3CA(2), PIK3R1(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PRKCA(1), RPS6KA1(1), RPS6KA5(1), SOS1(3) 12115797 26 25 25 9 7 1 8 6 4 0 0.13 0.58 138 N_GLYCAN_DEGRADATION AGA, FLJ21865, FUCA1, FUCA2, GLB1, HEXA, HEXB, LCT, MAN2C1, MANBA, NEU1, NEU2, NEU3, NEU4 12 FUCA2(1), GLB1(2), HEXA(2), HEXB(1), LCT(6), MAN2C1(1), MANBA(1), NEU1(1), NEU3(1) 6901890 16 16 16 2 1 3 7 3 2 0 0.13 0.58 139 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(7), EP300(1), LPL(1), NCOA1(2), NCOA2(1), RXRA(2) 8061660 14 14 14 2 0 2 2 5 5 0 0.13 0.58 140 GCRPATHWAY Corticosteroids activate the glucocorticoid receptor (GR), which inhibits NF-kB and activates Annexin-1, thus inhibiting the inflammatory response. ADRB2, AKT1, ANXA1, CALM1, CALM2, CALM3, CRN, GNAS, GNB1, GNGT1, HSPCA, NFKB1, NOS3, NPPA, NR3C1, PIK3CA, PIK3R1, RELA, SYT1 17 ADRB2(1), CALM3(1), GNAS(3), NFKB1(1), NOS3(2), NPPA(1), NR3C1(2), PIK3CA(2), PIK3R1(1), RELA(1) 7079993 15 15 14 7 1 1 5 4 4 0 0.13 0.58 141 NUCLEOTIDE_SUGARS_METABOLISM GALE, GALT, TGDS, UGDH, UXS1 5 GALE(1), UGDH(2), UXS1(2) 1771511 5 5 4 0 0 1 2 1 1 0 0.14 0.59 142 IL2PATHWAY IL-2 promotes proliferation via JAK and MAP kinase and has surface receptors on activated B cells, LPS-treated monocytes, and many T cells. CSNK2A1, ELK1, FOS, GRB2, HRAS, IL2, IL2RA, IL2RB, IL2RG, JAK1, JAK3, JUN, LCK, MAP2K1, MAPK3, MAPK8, RAF1, SHC1, SOS1, STAT5A, STAT5B, SYK 22 CSNK2A1(1), ELK1(2), FOS(1), GRB2(2), IL2RA(2), IL2RB(1), JAK3(3), LCK(1), MAPK8(1), SHC1(1), SOS1(3), STAT5A(2), STAT5B(3) 9940917 23 22 23 4 2 4 14 2 1 0 0.14 0.59 143 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(2), BMPR1A(1), BMPR1B(1), BMPR2(3) 2802426 7 7 7 1 0 2 2 3 0 0 0.14 0.59 144 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 32 BRAF(2), DAG1(3), EGFR(7), EPHB2(1), GRB2(2), ITPKB(4), ITPR1(3), ITPR2(5), ITPR3(3), KCNJ9(1), PIK3CB(1), PITX2(1), PLCB1(4), PLCB2(4), PLCB3(2), PLCB4(1), SHC1(1), SOS1(3), SOS2(1), STAT3(1) 24797706 50 46 50 18 3 7 19 16 5 0 0.14 0.59 145 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(1), ICAM1(1), ITGAL(3), ITGB2(2), PECAM1(2), SELE(3) 5128781 12 12 12 3 2 2 4 3 1 0 0.14 0.59 146 HSA04662_B_CELL_RECEPTOR_SIGNALING_PATHWAY Genes involved in B cell receptor signaling pathway AKT1, AKT2, AKT3, BCL10, BLNK, BTK, CARD11, CD19, CD22, CD72, CD79A, CD79B, CD81, CHP, CHUK, CR2, FCGR2B, FOS, GSK3B, HRAS, IFITM1, IKBKB, IKBKG, INPP5D, JUN, KRAS, LILRB3, LYN, MALT1, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NRAS, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG2, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKCB1, PTPN6, RAC1, RAC2, RAC3, RASGRP3, SYK, VAV1, VAV2, VAV3 60 BTK(1), CARD11(1), CD19(2), CD22(3), CD79A(1), CHUK(1), CR2(1), FOS(1), GSK3B(1), IKBKB(1), INPP5D(4), KRAS(2), LILRB3(1), LYN(1), NFAT5(1), NFATC1(1), NFATC2(1), NFATC4(1), NFKB1(1), NRAS(2), PIK3CA(2), PIK3CB(1), PIK3CG(3), PIK3R1(1), PIK3R2(2), PIK3R5(1), PLCG2(1), PPP3CC(1), RASGRP3(2), VAV1(2), VAV2(4), VAV3(3) 30508389 51 48 49 23 6 6 15 17 7 0 0.14 0.59 147 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 6 CDK2(1), FBXW7(4), TFDP1(2) 2814579 7 7 7 1 2 2 1 0 2 0 0.14 0.59 148 HSA04320_DORSO_VENTRAL_AXIS_FORMATION Genes involved in dorso-ventral axis formation BRAF, CPEB1, EGFR, ERBB2, ERBB4, ETS1, ETS2, ETV6, ETV7, FMN2, GRB2, KRAS, MAP2K1, MAPK1, MAPK3, NOTCH1, NOTCH2, NOTCH3, NOTCH4, PIWIL1, PIWIL2, PIWIL3, PIWIL4, RAF1, SOS1, SOS2, SPIRE1, SPIRE2 26 BRAF(2), CPEB1(1), EGFR(7), ERBB2(4), ETS1(1), ETS2(1), ETV6(1), ETV7(1), FMN2(3), GRB2(2), KRAS(2), NOTCH2(4), NOTCH3(4), NOTCH4(5), PIWIL1(1), PIWIL3(3), SOS1(3), SOS2(1), SPIRE1(1) 20900550 47 40 45 21 4 6 26 9 2 0 0.14 0.59 149 HSA00710_CARBON_FIXATION Genes involved in carbon fixation ALDOA, ALDOB, ALDOC, FBP1, FBP2, GOT1, GOT2, GPT, GPT2, MDH1, MDH2, ME1, ME3, PGK1, PGK2, PKLR, PKM2, RPE, RPIA, TKT, TKTL1, TKTL2, TPI1 22 ALDOC(1), MDH2(1), ME1(2), ME3(1), PGK1(2), PGK2(1), PKLR(1), RPIA(1), TKT(2), TKTL1(5), TKTL2(1) 8462158 18 18 18 3 2 3 8 3 2 0 0.14 0.59 150 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 32 APC(8), AR(1), BRAF(2), CCL15(1), DAG1(3), EGFR(7), GNA11(1), ITPKB(4), ITPR1(3), ITPR2(5), ITPR3(3), KCNJ9(1), MAPK14(1), PHKA2(2), PIK3CA(2), PIK3R1(1), PITX2(1) 22289824 46 40 46 15 2 5 10 19 10 0 0.14 0.59 151 EICOSANOID_SYNTHESIS ALOX12, ALOX15, ALOX15B, ALOX5, ALOX5AP, DPEP1, GGT1, IPLA2(GAMMA), LTA4H, LTC4S, PLA2G2A, PLA2G6, PTGDS, PTGES, PTGIS, PTGS1, PTGS2, TBXAS1 15 ALOX12(1), ALOX15(1), ALOX15B(2), ALOX5(1), ALOX5AP(1), PLA2G6(1), PTGDS(1), PTGIS(3), PTGS1(1), PTGS2(1), TBXAS1(2) 5949100 15 14 15 0 1 5 4 2 3 0 0.15 0.59 152 SA_DIACYLGLYCEROL_SIGNALING DAG (diacylglycerol) signaling activity ESR1, ESR2, ITPKA, PDE1A, PDE1B, PLCB1, PLCB2, PRL, TRH, VIP 9 PDE1A(1), PDE1B(1), PLCB1(4), PLCB2(4), TRH(1) 4678660 11 11 11 0 0 3 4 4 0 0 0.15 0.59 153 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 41 ADH1B(1), ADH1C(1), ADH4(1), ADH6(1), ADHFE1(1), AGPAT3(1), AGPAT4(2), AKR1B1(3), ALDH1A1(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), DGKA(3), DGKB(3), DGKD(2), DGKE(1), DGKH(3), GLB1(2), LCT(6), LIPG(1), LPL(1), PNLIP(2), PNLIPRP1(1), PNLIPRP2(1), PPAP2A(1) 19782752 43 38 43 11 2 9 15 12 5 0 0.15 0.59 154 NFKBPATHWAY Inactive nuclear factor kB (NF-kB) is inhibited by the IkB family in the cytoplasm; active NF-kB is localized in the nucleus and regulates transcription of a variety of genes. CHUK, FADD, IKBKB, IKBKG, IL1A, IL1R1, IRAK1, MAP3K1, MAP3K14, MAP3K7, MAP3K7IP1, MYD88, NFKB1, NFKBIA, RELA, RIPK1, TLR4, TNF, TNFAIP3, TNFRSF1A, TNFRSF1B, TRADD, TRAF6 20 CHUK(1), FADD(1), IKBKB(1), IRAK1(2), MAP3K1(1), MAP3K14(1), MAP3K7(3), NFKB1(1), RELA(1), TLR4(4), TNF(1), TNFAIP3(4), TNFRSF1A(1), TRAF6(2) 10258386 24 22 24 3 4 7 7 6 0 0 0.15 0.59 155 HSA04620_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY Genes involved in Toll-like receptor signaling pathway AKT1, AKT2, AKT3, CASP8, CCL3, CCL4, CCL5, CD14, CD40, CD80, CD86, CHUK, CXCL10, CXCL11, CXCL9, FADD, FOS, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IKBKB, IKBKE, IKBKG, IL12A, IL12B, IL1B, IL6, IL8, IRAK1, IRAK4, IRF3, IRF5, IRF7, JUN, LBP, LY96, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAP3K8, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK8, MAPK9, MYD88, NFKB1, NFKB2, NFKBIA, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, RAC1, RELA, RIPK1, SPP1, STAT1, TBK1, TICAM1, TICAM2, TIRAP, TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TNF, TOLLIP, TRAF3, TRAF6 93 CD80(1), CD86(2), CHUK(1), CXCL9(1), FADD(1), FOS(1), IFNA1(2), IFNA13(2), IFNA5(1), IFNA8(1), IFNAR2(1), IFNB1(1), IKBKB(1), IKBKE(1), IL8(1), IRAK1(2), IRAK4(1), IRF3(2), LBP(2), MAP2K3(1), MAP2K4(1), MAP2K6(1), MAP3K7(3), MAPK14(1), MAPK8(1), MAPK9(1), NFKB1(1), PIK3CA(2), PIK3CB(1), PIK3CG(3), PIK3R1(1), PIK3R2(2), PIK3R5(1), RELA(1), SPP1(1), STAT1(2), TBK1(1), TIRAP(1), TLR1(1), TLR3(2), TLR4(4), TLR5(1), TLR6(2), TLR7(1), TLR8(2), TNF(1), TRAF6(2) 37185452 67 58 67 17 5 14 16 27 5 0 0.15 0.59 156 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 IFNA1(2), IFNB1(1), IL13(2), IL16(3), IL8(1), TNF(1) 4465560 10 10 10 3 0 1 3 6 0 0 0.15 0.59 157 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 16 AKR1B1(3), UGDH(2), UGT1A10(2), UGT1A3(1), UGT1A5(1), UGT1A7(1), UGT1A8(2), UGT1A9(2), UGT2B4(1) 6935112 15 15 15 4 1 4 2 5 3 0 0.15 0.59 158 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 66 ACACB(4), ACSL1(2), ACSL3(2), ACSL4(1), ACSL6(1), ADIPOQ(1), CHUK(1), CPT1A(2), CPT1B(2), CPT1C(1), CPT2(1), G6PC(1), IKBKB(1), IRS1(6), IRS4(5), JAK2(2), JAK3(3), LEPR(1), MAPK8(1), MAPK9(1), NFKB1(1), POMC(1), PPARA(1), PPARGC1A(2), PRKAA2(2), PRKAG3(1), PRKCQ(3), RELA(1), RXRA(2), RXRB(2), SLC2A1(1), SLC2A4(1), STAT3(1), TNF(1), TNFRSF1A(1), TRAF2(1), TYK2(2) 34612403 63 54 63 12 8 14 17 13 11 0 0.16 0.60 159 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(3), F2R(2), F5(3), F7(1), FGA(3), FGB(2), PROC(1), PROS1(1), SERPINC1(1) 7103688 17 15 17 3 3 4 3 6 1 0 0.16 0.60 160 GLUCOCORTICOID_MINERALOCORTICOID_METABOLISM CPN2, CYP11A1, CYP11B2, CYP17A1, HSD11B1, HSD11B2, HSD3B1, HSD3B2 8 CPN2(3), CYP11A1(1), CYP11B2(1), HSD3B1(2), HSD3B2(1) 3066758 8 8 8 5 0 1 4 2 1 0 0.16 0.60 161 MITOCHONDRIAL_FATTY_ACID_BETAOXIDATION ACADL, ACADM, ACADS, ACADVL, ACSL1, ACSL3, ACSL4, CPT1A, CPT2, DCI, EHHADH, HADHA, HADHSC, MGC5139, PECR, SCP2, SLC25A20 15 ACADM(1), ACADVL(2), ACSL1(2), ACSL3(2), ACSL4(1), CPT1A(2), CPT2(1), EHHADH(2), HADHA(1), SCP2(1) 7381905 15 14 15 3 1 3 7 1 3 0 0.16 0.61 162 HSA00785_LIPOIC_ACID_METABOLISM Genes involved in lipoic acid metabolism LIAS, LIPT1, LOC387787 2 LIAS(2) 689704 2 2 2 0 0 0 1 0 1 0 0.16 0.61 163 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(2), F2(3), F2R(2), FGA(3), FGB(2), PLAU(2), SERPINE1(1) 6161353 16 14 16 2 3 4 5 4 0 0 0.16 0.61 164 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(2), CA1(1), CA12(1), CA14(3), CA4(2), CA5A(1), CA6(1), CA9(2), CPS1(4), GLS(1), GLS2(1), HAL(1) 8489310 20 17 20 10 1 2 9 4 4 0 0.17 0.62 165 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 ACOT11(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ALDH7A1(1), CYP2C19(4), CYP2C9(1), DHRS2(1), DHRS7(1), ECHS1(1), EHHADH(2), HADHA(1), MYST3(3), MYST4(5), YOD1(3) 13494562 28 26 28 6 0 3 7 11 7 0 0.17 0.62 166 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 54 ABP1(2), ADH1B(1), ADH1C(1), ADH4(1), ADH5(1), ADH6(1), ADHFE1(1), ALDH3A1(1), AOC2(4), AOC3(1), AOX1(4), DBH(2), DCT(2), DDC(1), ECH1(2), MAOA(2), MAOB(1), METTL6(1), MYST3(3), MYST4(5), PRMT5(2), PRMT8(3), TAT(2), TPO(4), TYR(1), WBSCR22(1) 25235022 50 43 50 15 4 4 13 21 8 0 0.17 0.62 167 VOBESITYPATHWAY The adipose tissue of obese individuals overexpresses a key glucocorticoid-metabolizing enzyme, activating inactive circulating corticosteroids and inducing insulin resistance. APM1, HSD11B1, LPL, NR3C1, PPARG, RETN, RXRA, TNF 7 LPL(1), NR3C1(2), RXRA(2), TNF(1) 2478019 6 6 6 2 0 1 2 2 1 0 0.17 0.63 168 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(2), ACADM(1), ACADSB(2), ALDH1A1(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), AOC2(4), AOC3(1), DPYD(3), DPYS(1), ECHS1(1), EHHADH(2), GAD1(1), GAD2(1), HADHA(1), SMS(1), UPB1(1) 12839218 27 26 27 8 2 3 8 7 7 0 0.17 0.63 169 CHREBPPATHWAY Carbohydrate responsive element binding protein (chREBP) is a transcription factor inhibited by cAMP and activated by high carbohydrate levels. ADCY1, BG1, BUCS1, GNAS, GNB1, GNGT1, PPP2CA, PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKACB, PRKACG, PRKAG1, PRKAG2, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, WBSCR14 17 ADCY1(4), GNAS(3), PPP2CA(2), PRKAA2(2), PRKACG(1), PRKAR2A(1), PRKAR2B(1) 6308374 14 14 13 0 5 0 2 4 3 0 0.17 0.63 170 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 GSR(2), GSS(3), IL8(1), NFKB1(1), NOX1(1), RELA(1), TNF(1), XDH(1) 4567299 11 11 11 2 1 1 7 1 1 0 0.17 0.63 171 HSA00602_GLYCOSPHINGOLIPID_BIOSYNTHESIS_NEO_LACTOSERIES Genes involved in glycosphingolipid biosynthesis - neo-lactoseries ABO, B3GNT1, B3GNT2, B3GNT3, B3GNT4, B3GNT5, B4GALT1, B4GALT2, B4GALT3, B4GALT4, FUT1, FUT2, FUT3, FUT4, FUT5, FUT6, FUT7, FUT9, GCNT2, ST3GAL6, ST8SIA1 18 ABO(1), B3GNT2(1), B3GNT4(2), B3GNT5(1), B4GALT2(1), FUT1(1), FUT9(1), GCNT2(2), ST3GAL6(1), ST8SIA1(2) 5826445 13 13 13 1 3 3 1 3 3 0 0.18 0.63 172 PHENYLALANINE_METABOLISM ABP1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, DDC, EPX, GOT1, GOT2, HPD, LPO, MAOA, MAOB, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TAT, TPO 22 ABP1(2), ALDH3A1(1), AOC2(4), AOC3(1), DDC(1), EPX(2), LPO(1), MAOA(2), MAOB(1), TAT(2), TPO(4) 9489878 21 20 21 5 2 1 7 6 5 0 0.18 0.63 173 TOLLPATHWAY Toll-like receptors are activated by bacterial lipoproteins, lipopolysaccharides, and other surface molecules, and activate pro-inflammatory factors such as NF-kB. CD14, CHUK, ELK1, FOS, IKBKB, IKBKG, IRAK1, JUN, LY96, MAP2K3, MAP2K4, MAP2K6, MAP3K1, MAP3K14, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAPK14, MAPK8, MYD88, NFKB1, NFKBIA, PGLYRP, PPARA, PRKR, RELA, SITPEC, TIRAP, TLR10, TLR2, TLR3, TLR4, TLR6, TLR7, TLR9, TOLLIP, TRAF6 30 CHUK(1), ELK1(2), FOS(1), IKBKB(1), IRAK1(2), MAP2K3(1), MAP2K4(1), MAP2K6(1), MAP3K1(1), MAP3K14(1), MAP3K7(3), MAPK14(1), MAPK8(1), NFKB1(1), PPARA(1), RELA(1), TIRAP(1), TLR3(2), TLR4(4), TLR6(2), TLR7(1), TRAF6(2) 15409974 32 29 32 3 6 7 9 9 1 0 0.18 0.64 174 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 DOCK1(4), ELK1(2), FOS(1), GRB2(2), HGF(2), ITGA1(1), MAP4K1(1), MAPK8(1), MET(4), PIK3CA(2), PIK3R1(1), PTEN(2), PTK2(1), PTK2B(1), PXN(5), RASA1(1), SOS1(3), STAT3(1) 18933380 35 34 35 11 3 4 17 4 7 0 0.18 0.64 175 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_LACTOSERIES ABO, FUT1, FUT2, FUT3, FUT5, FUT6, SIAT6, ST3GAL3 6 ABO(1), FUT1(1), ST3GAL3(3) 1549273 5 5 5 0 3 0 1 0 1 0 0.18 0.64 176 NUCLEOTIDE_GPCRS ADORA1, ADORA2A, ADORA2B, ADORA3, GPR23, LTB4R, P2RY1, P2RY2, P2RY5, P2RY6 8 ADORA2B(2), ADORA3(2), P2RY2(2), P2RY6(1) 2497606 7 7 7 2 1 1 2 3 0 0 0.18 0.64 177 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 11 CDK2(1), CDKN1B(1), SKP2(2), TFDP1(2), UBE2M(1) 2953688 7 7 7 2 1 3 1 0 2 0 0.19 0.64 178 SA_B_CELL_RECEPTOR_COMPLEXES Antigen binding to B cell receptors activates protein tyrosine kinases, such as the Src family, which ultimate activate MAP kinases. ATF2, BCR, BLNK, ELK1, FOS, GRB2, HRAS, JUN, LYN, MAP2K1, MAP3K1, MAPK1, MAPK3, MAPK8IP3, PAPPA, RAC1, RPS6KA1, RPS6KA3, SHC1, SOS1, SYK, VAV1, VAV2, VAV3 23 BCR(1), ELK1(2), FOS(1), GRB2(2), LYN(1), MAP3K1(1), PAPPA(3), RPS6KA1(1), SHC1(1), SOS1(3), VAV1(2), VAV2(4), VAV3(3) 12610660 25 24 25 9 2 1 14 6 2 0 0.19 0.64 179 HSA00230_PURINE_METABOLISM Genes involved in purine metabolism ADA, ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ADK, ADSL, ADSS, ADSSL1, AK1, AK2, AK3L1, AK5, AK7, ALLC, AMPD1, AMPD2, AMPD3, APRT, ATIC, CANT1, DCK, DGUOK, ECGF1, ENPP1, ENPP3, ENTPD1, ENTPD2, ENTPD3, ENTPD4, ENTPD5, ENTPD6, ENTPD8, FHIT, GART, GDA, GMPR, GMPR2, GMPS, GUCY1A2, GUCY1A3, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, GUK1, HPRT1, IMPDH1, IMPDH2, ITPA, NME1, NME2, NME4, NME6, NME7, NP, NPR1, NPR2, NT5C, NT5C1A, NT5C1B, NT5C2, NT5C3, NT5E, NT5M, NUDT2, NUDT5, NUDT9, PAICS, PAPSS1, PAPSS2, PDE10A, PDE11A, PDE1A, PDE1C, PDE2A, PDE3B, PDE4A, PDE4B, PDE4C, PDE4D, PDE5A, PDE6D, PDE6G, PDE6H, PDE7A, PDE7B, PDE8A, PDE8B, PDE9A, PFAS, PKLR, PKM2, PNPT1, POLA1, POLA2, POLD1, POLD2, POLD3, POLD4, POLE, POLE2, POLE3, POLE4, POLR1A, POLR1B, POLR1C, POLR1D, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLR3A, POLR3B, POLR3G, POLR3GL, POLR3H, POLR3K, PPAT, PRIM1, PRIM2, PRPS1, PRPS1L1, PRPS2, PRUNE, RFC5, RRM1, RRM2, RRM2B, SAC, XDH, ZNRD1 138 ADA(1), ADCY1(4), ADCY2(6), ADCY3(2), ADCY4(1), ADCY5(3), ADCY7(1), ADCY9(5), ADK(1), ADSL(1), ADSSL1(3), AK2(1), AK7(1), ALLC(2), AMPD1(2), AMPD2(2), AMPD3(1), ATIC(2), DCK(1), ENPP1(2), ENPP3(2), ENTPD1(2), ENTPD3(1), ENTPD5(1), GART(3), GDA(1), GMPR2(3), GMPS(2), GUCY1A3(1), GUCY2C(3), IMPDH1(1), ITPA(1), NPR1(1), NPR2(2), NT5C1A(1), NT5C1B(1), NT5C3(1), NT5E(2), NUDT5(1), PAPSS2(1), PDE10A(3), PDE11A(4), PDE1A(1), PDE2A(2), PDE4A(2), PDE4C(1), PDE6H(1), PDE7B(1), PDE8A(1), PFAS(2), PKLR(1), POLA1(2), POLD1(1), POLD2(2), POLD3(1), POLE(2), POLE2(1), POLR1C(1), POLR2B(2), POLR2C(1), POLR2I(1), PRPS1L1(2), PRUNE(1), RRM2B(2), XDH(1) 71181527 112 92 110 39 19 11 35 29 18 0 0.19 0.64 180 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 CD3E(2), CD4(1), CXCR3(2), IL12RB2(3), JAK2(2), STAT4(1), TYK2(2) 6293247 13 13 13 2 1 3 4 4 1 0 0.19 0.65 181 CASPASEPATHWAY Caspases are cysteine proteases active in apoptosis; caspase-8 and 9 cleave and activate other caspases, while 3, 6, and 7 cleave cellular targets. ADPRT, APAF1, ARHGDIB, BIRC2, BIRC3, BIRC4, CASP1, CASP10, CASP2, CASP3, CASP4, CASP6, CASP7, CASP8, CASP9, CYCS, DFFA, DFFB, GZMB, LMNA, LMNB1, LMNB2, PRF1 20 APAF1(2), BIRC3(2), CASP1(2), CASP2(1), CASP4(1), CASP6(1), CASP7(1), CASP9(1), LMNA(4), LMNB1(1), PRF1(2) 8247645 18 17 18 5 2 2 5 8 1 0 0.19 0.65 182 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 7 CCNA1(2), CDK2(1), SKP2(2), TFDP1(2) 2909535 7 7 7 3 0 3 1 1 2 0 0.19 0.65 183 SIG_INSULIN_RECEPTOR_PATHWAY_IN_CARDIAC_MYOCYTES Genes related to the insulin receptor pathway AKT1, AKT2, AKT3, BRD4, CAP1, CBL, CDC42, CDKN2A, F2RL2, FLOT1, FLOT2, FOXO1A, GRB2, GSK3A, GSK3B, IGFBP1, INPPL1, IRS1, IRS2, IRS4, LNPEP, MAPK1, MAPK3, PARD3, PARD6A, PDK1, PIK3CA, PIK3CD, PIK3R1, PPYR1, PSCD3, PTEN, PTPN1, RAF1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SERPINB6, SFN, SHC1, SLC2A4, SORBS1, SOS1, SOS2, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ 48 BRD4(1), CAP1(1), F2RL2(1), GRB2(2), GSK3A(2), GSK3B(1), INPPL1(1), IRS1(6), IRS4(5), LNPEP(2), PARD3(2), PARD6A(1), PDK1(1), PIK3CA(2), PIK3R1(1), PPYR1(2), PTEN(2), RPS6KA1(1), RPS6KA2(1), SHC1(1), SLC2A4(1), SORBS1(2), SOS1(3), SOS2(1), YWHAB(1), YWHAE(2), YWHAG(2) 24717861 48 43 48 17 5 8 20 7 8 0 0.19 0.65 184 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(3), EIF2AK4(1), EIF2B5(4), EIF2S1(1), GSK3B(1) 4970970 10 10 10 1 1 1 5 2 1 0 0.19 0.65 185 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 CALM3(1), CAMK4(3), CREBBP(7), F2(3), FGF2(1), GSK3B(1), MAPK14(1), MAPK8(1), MEF2C(1), MYH2(5), NFATC1(1), NFATC2(1), NFATC4(1), NPPA(1), PIK3CA(2), PIK3R1(1), PPP3CC(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1) 21165109 35 35 35 16 5 6 8 12 4 0 0.20 0.65 186 TRANSLATION_FACTORS ANKHD1, ANKHD1, MASK_BP3, EEF1A2, EEF1B2, EEF1D, EEF1G, EEF2, EEF2K, EIF1AX, EIF1AY, EIF2AK1, EIF2AK2, EIF2AK3, EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5, EIF2S1, EIF2S2, EIF2S3, EIF3S1, EIF3S10, EIF3S2, EIF3S3, EIF3S4, EIF3S5, EIF3S6, EIF3S7, EIF3S8, EIF3S9, EIF4A1, EIF4A2, EIF4E, EIF4EBP1, EIF4EBP2, EIF4G1, EIF4G3, EIF5, EIF5A, EIF5B, ETF1, GSPT2, ITGB4BP, KIAA0664, PABPC1, PABPC3, PABPC1, LOC341315, PAIP1, PAIP1, LOC388345, SLC35A4, SUI1, WBSCR1 35 EEF1D(1), EEF1G(2), EEF2K(2), EIF1AX(1), EIF2AK2(2), EIF2AK3(3), EIF2B2(1), EIF2B4(1), EIF2B5(4), EIF2S1(1), EIF4A1(1), EIF4A2(2), EIF4EBP1(1), EIF4G3(1), EIF5B(1), ETF1(1), GSPT2(1), KIAA0664(1), PABPC1(2), PABPC3(4), PAIP1(1) 18064618 34 32 34 9 2 4 16 8 4 0 0.20 0.65 187 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 54 ASH1L(3), ASH2L(1), CTCFL(2), EHMT2(1), EZH1(4), HCFC1(3), JMJD6(2), KDM6A(2), MEN1(1), MLL(5), MLL2(1), MLL3(7), MLL4(4), MLL5(3), NSD1(2), OGT(2), PAXIP1(1), PRDM2(1), PRDM7(2), PRDM9(5), PRMT1(1), PRMT5(2), PRMT8(3), SETD2(6), SETD7(1), SETDB1(3), SETDB2(1), SETMAR(1), STK38(3), SUV39H2(1), SUV420H1(2), WHSC1(2), WHSC1L1(1) 49388924 79 69 78 20 4 5 34 25 11 0 0.20 0.65 188 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 EGFR(7), MAP3K1(1), MAPK14(1), NCOR2(1), RARA(1), RXRA(2) 6496514 13 13 13 5 1 1 3 5 3 0 0.20 0.65 189 RANKLPATHWAY RANK is a TNF-type receptor that promotes osteoclast differentiation and consequent bone resorbtion on binding RANK ligand produced by osteoblasts. FOS, FOSL1, FOSL2, IFNAR1, IFNAR2, IFNB1, ISGF3G, MAPK8, NFKB1, PRKR, RELA, TNFRSF11A, TNFSF11, TRAF6 12 FOS(1), FOSL1(1), FOSL2(2), IFNAR2(1), IFNB1(1), MAPK8(1), NFKB1(1), RELA(1), TRAF6(2) 4880303 11 11 11 1 2 3 2 4 0 0 0.20 0.65 190 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 CDKN1A(1), ELK1(2), GRB2(2), NGFR(1), NTRK1(4), PIK3CA(2), SHC1(1), SOS1(3) 6211558 16 14 16 8 3 2 10 1 0 0 0.20 0.65 191 SYNTHESIS_AND_DEGRADATION_OF_KETONE_BODIES ACAT1, ACAT2, BDH, HMGCL, OXCT1 4 ACAT1(2), ACAT2(1), OXCT1(2) 1563470 5 4 5 2 0 1 2 2 0 0 0.20 0.65 192 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(1) 1108511 3 3 3 0 0 1 1 0 1 0 0.21 0.66 193 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 19 ATM(5), ATR(2), BRCA2(11), CHEK2(1), FANCA(3), FANCC(2), FANCD2(1), FANCE(1), FANCG(1), HUS1(1), RAD1(1), RAD50(2), RAD51(1) 17736736 32 27 32 3 2 2 7 8 12 1 0.21 0.66 194 GSPATHWAY Activated G-protein coupled receptors stimulate cAMP production and thus activate protein kinase A, involved in a number of signal transduction pathways. ADCY1, GNAS, GNB1, GNGT1, PRKACA, PRKAR1A 6 ADCY1(4), GNAS(3) 2545359 7 7 6 0 4 0 1 0 2 0 0.21 0.67 195 GANGLIOSIDE_BIOSYNTHESIS B3GALT4, GALGT, SIAT4A, SIAT4B, SIAT7B, SIAT7D, SIAT9, ST3GAL1, ST3GAL2, ST3GAL4, ST3GAL5, ST6GALNAC2, ST6GALNAC4, ST8SIA1 8 B3GALT4(2), ST3GAL2(2), ST8SIA1(2) 2333143 6 6 6 0 1 1 3 1 0 0 0.21 0.67 196 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(3), COL4A2(1), COL4A3(1), COL4A4(3), COL4A5(4), COL4A6(5), F2(3), F2R(2), F5(3), F8(4), F9(1), FGA(3), FGB(2), KLKB1(2), PROC(1), PROS1(1), SERPINC1(1) 19578286 40 35 40 11 5 11 11 10 3 0 0.21 0.67 197 GLYCINE_SERINE_AND_THREONINE_METABOLISM ABP1, AGXT, AGXT2, ALAS1, ALAS2, AMT, AOC2, AOC3, ATP6V0C, SHMT1, BHMT, CBS, CHDH, CHKA, CHKB, CHKB, CPT1B, CTH, DAO, DLD, DMGDH, GAMT, GARS, GATM, GCAT, GLDC, MAOA, MAOB, PEMT, PISD, PLCB2, PLCG1, PLCG2, PSPH, SARDH, SARS, SHMT1, SHMT2, TARS 36 ABP1(2), AGXT(1), AGXT2(2), ALAS1(1), AOC2(4), AOC3(1), BHMT(1), CHDH(1), CHKA(1), CHKB(1), CPT1B(2), DMGDH(2), GARS(1), GLDC(2), MAOA(2), MAOB(1), PLCB2(4), PLCG2(1), PSPH(1), SHMT1(1), SHMT2(1), TARS(2) 17446160 35 33 35 12 3 3 10 10 9 0 0.22 0.67 198 MTORPATHWAY Mammalian target of rapamycin (mTOR) senses mitogenic factors and nutrients, including ATP, and induces cell proliferation. AKT1, EIF3S10, EIF4A1, EIF4A2, EIF4B, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FKBP1A, FRAP1, MKNK1, PDK2, PDPK1, PIK3CA, PIK3R1, PPP2CA, PTEN, RPS6, RPS6KB1, TSC1, TSC2 21 EIF4A1(1), EIF4A2(2), EIF4EBP1(1), EIF4G2(1), EIF4G3(1), MKNK1(1), PDPK1(1), PIK3CA(2), PIK3R1(1), PPP2CA(2), PTEN(2), RPS6(1), TSC1(3), TSC2(2) 11251173 21 20 21 7 0 2 9 4 6 0 0.22 0.67 199 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(3), CALCRL(1), CD97(2), ELTD1(1), EMR1(1), EMR2(1), GHRHR(1), GLP2R(1), LPHN1(2), LPHN2(1), LPHN3(4), SCTR(1), VIPR2(1) 11697863 21 21 21 5 3 0 7 9 2 0 0.22 0.67 200 INFLAMPATHWAY Interleukins and TNF serve as signals to coordinate the inflammatory response, in which macrophages recruit and activate neutrophils, fibroblasts, and T cells. CD4, CSF1, CSF2, CSF3, HLA-DRA, HLA-DRB1, IFNA1, IFNB1, IFNG, IL10, IL11, IL12A, IL12B, IL13, IL15, IL1A, IL2, IL3, IL4, IL5, IL6, IL7, IL8, LTA, PDGFA, TGFB1, TGFB2, TGFB3, TNF 27 CD4(1), CSF1(1), CSF3(1), HLA-DRA(1), HLA-DRB1(1), IFNA1(2), IFNB1(1), IL13(2), IL8(1), TNF(1) 5803202 12 12 12 2 1 2 2 5 2 0 0.22 0.67 201 TH1TH2PATHWAY Helper T subtype Th1 produces pro-inflammatory cytokines that stimulate phagocytosis, while Th2 cells promote antibody production and activate eosinophils. CD28, CD86, HLA-DRA, HLA-DRB1, IFNG, IFNGR1, IFNGR2, IL12A, IL12B, IL12RB1, IL12RB2, IL18, IL18R1, IL2, IL2RA, IL4, IL4R, TNFRSF5, TNFSF5 17 CD86(2), HLA-DRA(1), HLA-DRB1(1), IL12RB2(3), IL18R1(2), IL2RA(2), IL4R(2) 5847740 13 12 13 0 0 6 3 3 1 0 0.22 0.67 202 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(2), ASRGL1(1), CA1(1), CA12(1), CA14(3), CA4(2), CA5A(1), CA6(1), CA9(2), CPS1(4), GLS(1), GLS2(1), HAL(1) 9435780 21 18 21 11 1 2 10 4 4 0 0.22 0.67 203 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 52 ALG2(2), BAK1(1), BFAR(2), BTK(1), CAD(5), CASP8AP2(1), DAXX(1), DEDD2(1), DIABLO(1), EGFR(7), EPHB2(1), FADD(1), IL8(1), MAP2K4(1), MAP3K1(1), MAP3K5(2), MAPK8(1), MAPK8IP1(1), MAPK9(1), MET(4), NFAT5(1), NFKB1(1), PFN2(1), PTPN13(4), TPX2(1), TRAF2(1), TUFM(1) 28874110 46 44 46 15 6 9 13 12 6 0 0.22 0.67 204 KERATAN_SULFATE_BIOSYNTHESIS B3GNT1, B4GALT1, B4GALT2, B4GALT3, B4GALT5, FUT8, SIAT4A, SIAT4B, SIAT6, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4 10 B4GALT2(1), B4GALT5(1), FUT8(1), ST3GAL2(2), ST3GAL3(3) 3374528 8 8 8 0 3 1 2 2 0 0 0.22 0.67 205 ST_PAC1_RECEPTOR_PATHWAY The signaling peptide PACAP binds to its receptor, PAC1R, which activates adenylyl cyclase and phospholipase C. ASAH1, CAMP, DAG1, GAS, GNAQ, ITPKA, ITPKB, PACAP 5 DAG1(3), ITPKB(4) 2271516 7 6 7 0 2 1 2 1 1 0 0.22 0.67 206 HSA00360_PHENYLALANINE_METABOLISM Genes involved in phenylalanine metabolism ABP1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, ARD1A, DDC, EPX, ESCO1, ESCO2, GOT1, GOT2, HPD, LPO, LYCAT, MAOA, MAOB, MIF, MPO, MYST3, MYST4, NAT5, NAT6, PNPLA3, PRDX6, SH3GLB1, TAT, TPO 26 ABP1(2), ALDH3A1(1), AOC2(4), AOC3(1), DDC(1), EPX(2), LPO(1), MAOA(2), MAOB(1), MYST3(3), MYST4(5), TAT(2), TPO(4) 15041308 29 28 29 8 2 2 8 10 7 0 0.22 0.67 207 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(3), ABCB4(3), ABCC1(5) 6479479 14 13 14 5 3 0 3 6 2 0 0.22 0.67 208 HSA00563_GLYCOSYLPHOSPHATIDYLINOSITOL_ANCHOR_BIOSYNTHESIS Genes involved in glycosylphosphatidylinositol(GPI)-anchor biosynthesis GPAA1, GPLD1, PGAP1, PIGA, PIGB, PIGC, PIGF, PIGG, PIGH, PIGK, PIGL, PIGM, PIGN, PIGO, PIGP, PIGQ, PIGS, PIGT, PIGU, PIGV, PIGW, PIGX, PIGZ 22 GPLD1(1), PGAP1(5), PIGA(1), PIGB(2), PIGG(3), PIGH(1), PIGK(1), PIGO(3), PIGX(1), PIGZ(2) 10098155 20 19 19 9 3 6 0 7 4 0 0.23 0.67 209 GATA3PATHWAY GATA-3 is a transcription factor that promotes differentiation of helper T cells into Th2 cells, which secrete cytokines IL4, IL5, and IL13. GATA3, IL13, IL4, IL5, JUNB, MAF, MAP2K3, MAPK14, NFATC1, NFATC2, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B 15 GATA3(1), IL13(2), MAP2K3(1), MAPK14(1), NFATC1(1), NFATC2(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1) 4365219 10 10 10 5 3 1 0 6 0 0 0.23 0.67 210 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(2), GRM1(4), PLCB1(4), PPP2CA(2), PRKACG(1), PRKAR2A(1), PRKAR2B(1) 6790287 15 14 15 4 2 1 7 4 1 0 0.23 0.68 211 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 GRB2(2), IL4R(2), IRS1(6), JAK3(3), SHC1(1), STAT6(2) 6074163 16 13 16 4 2 6 5 1 2 0 0.23 0.68 212 HSA00730_THIAMINE_METABOLISM Genes involved in thiamine metabolism LHPP, MTMR1, MTMR2, MTMR6, NFS1, PHPT1, THTPA, TPK1 7 MTMR1(2), MTMR6(2), NFS1(1), TPK1(1) 2805444 6 6 6 0 2 1 0 2 1 0 0.23 0.68 213 GLOBOSIDE_METABOLISM A4GALT, FUT1, FUT2, FUT9, GBGT1, GLA, HEXA, HEXB, NAGA, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, ST8SIA1 13 FUT1(1), FUT9(1), HEXA(2), HEXB(1), ST3GAL2(2), ST8SIA1(2) 4082655 9 9 9 1 2 1 3 3 0 0 0.23 0.68 214 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(2), ACAT1(2), ACAT2(1), AFMID(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ALDH7A1(1), AOC2(4), AOC3(1), AOX1(4), CAT(1), CYP1A1(2), CYP1A2(1), CYP1B1(1), DDC(1), ECHS1(1), EHHADH(2), HAAO(1), HADHA(1), HSD17B4(1), INMT(1), KMO(2), MAOA(2), MAOB(1), METTL6(1), NFX1(1), OGDH(2), PRMT5(2), PRMT8(3), TPH2(1), WARS(1), WBSCR22(1) 26340135 50 44 50 15 3 6 19 14 8 0 0.24 0.68 215 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 51 ADH1B(1), ADH1C(1), ADH4(1), ADH5(1), ADH6(1), ADHFE1(1), AGK(1), AGPAT3(1), AGPAT4(2), AGPAT6(1), AKR1B1(3), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ALDH7A1(1), DGKA(3), DGKB(3), DGKD(2), DGKE(1), DGKH(3), DGKI(1), GK2(2), GLB1(2), GPAM(1), LCT(6), LIPG(1), LPL(1), PNLIP(2), PNLIPRP1(1), PNLIPRP2(1), PPAP2A(1) 24462409 50 43 50 10 3 9 19 13 6 0 0.24 0.68 216 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 ABP1(2), AOC2(4), AOC3(1), CES1(1), CES7(3), DDHD1(1), MYST3(3), MYST4(5), PLA1A(1) 11233304 21 20 21 6 1 2 5 7 6 0 0.24 0.68 217 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(2), ACY1(1), ADC(2), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ALDH7A1(1), AOC2(4), AOC3(1), ARG1(1), ASS1(1), CPS1(4), MAOA(2), MAOB(1), ODC1(1), OTC(1), SMS(1) 12834117 27 24 27 8 1 2 7 10 7 0 0.24 0.68 218 FEEDERPATHWAY Sugars such as mannose, galactose, and fructose are enzymatically converted to glucose via feeder pathways that lead to glycolysis. HK1, KHK, LCT, MPI, PGM1, PYGL, PYGM, TPI1, TREH 9 HK1(1), KHK(1), LCT(6), MPI(1), PYGM(3), TREH(1) 5978088 13 13 13 2 1 1 8 2 1 0 0.25 0.69 219 HSA01031_GLYCAN_STRUCTURES_BIOSYNTHESIS_2 Genes involved in glycan structures - biosynthesis 2 A4GALT, ABO, B3GALNT1, B3GALT1, B3GALT2, B3GALT4, B3GALT5, B3GNT1, B3GNT2, B3GNT3, B3GNT4, B3GNT5, B4GALNT1, B4GALT1, B4GALT2, B4GALT3, B4GALT4, B4GALT6, FUT1, FUT2, FUT3, FUT4, FUT5, FUT6, FUT7, FUT9, GBGT1, GCNT2, PIGA, PIGB, PIGC, PIGF, PIGG, PIGH, PIGK, PIGL, PIGM, PIGN, PIGO, PIGP, PIGQ, PIGS, PIGT, PIGU, PIGV, PIGX, PIGZ, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4, ST3GAL5, ST3GAL6, ST6GALNAC3, ST6GALNAC4, ST6GALNAC5, ST6GALNAC6, ST8SIA1, ST8SIA5, UGCG, UGCGL1, UGCGL2 56 ABO(1), B3GALT1(1), B3GALT2(2), B3GALT4(2), B3GNT2(1), B3GNT4(2), B3GNT5(1), B4GALT2(1), FUT1(1), FUT9(1), GCNT2(2), PIGA(1), PIGB(2), PIGG(3), PIGH(1), PIGK(1), PIGO(3), PIGX(1), PIGZ(2), ST3GAL2(2), ST3GAL3(3), ST3GAL6(1), ST6GALNAC3(2), ST8SIA1(2), ST8SIA5(1) 19535253 40 35 40 11 9 10 8 7 6 0 0.25 0.69 220 PITX2PATHWAY The bicoid-related transcription factor Pitx2 is activated by Wnt binding to the Frizzled receptor and induces tissue-specific cell proliferation. APC, AXIN1, CREBBP, CTNNB1, DVL1, EP300, FZD1, GSK3B, HDAC1, HTATIP, LDB1, LEF1, PITX2, PPARBP, TRRAP, WNT1 13 APC(8), CREBBP(7), CTNNB1(2), EP300(1), GSK3B(1), HDAC1(1), LDB1(1), PITX2(1), TRRAP(3) 14006937 25 23 25 12 1 4 6 8 6 0 0.25 0.69 221 IL1RPATHWAY The cytokine IL-1 stimulates its primary receptor, IL-1R1, which induces transcription of inflammation-related genes such as interferons. CHUK, IFNA1, IFNB1, IKBKB, IL1A, IL1B, IL1R1, IL1RAP, IL1RN, IL6, IRAK1, IRAK2, IRAK3, JUN, MAP2K3, MAP2K6, MAP3K1, MAP3K14, MAP3K7, MAP3K7IP1, MAPK14, MAPK8, MYD88, NFKB1, NFKBIA, RELA, SITPEC, TGFB1, TGFB2, TGFB3, TNF, TOLLIP, TRAF6 30 CHUK(1), IFNA1(2), IFNB1(1), IKBKB(1), IL1RN(1), IRAK1(2), IRAK2(1), IRAK3(2), MAP2K3(1), MAP2K6(1), MAP3K1(1), MAP3K14(1), MAP3K7(3), MAPK14(1), MAPK8(1), NFKB1(1), RELA(1), TNF(1), TRAF6(2) 12578171 25 24 25 4 5 7 6 7 0 0 0.25 0.69 222 LDLPATHWAY Low density lipoproteins (LDL) are present in blood plasma, contain cholesterol and triglycerides, and contribute to atherogenic plaque formation. ACAT1, CCL2, CSF1, IL6, LDLR, LPL 6 ACAT1(2), CSF1(1), LDLR(3), LPL(1) 2420573 7 6 7 1 1 2 3 1 0 0 0.25 0.69 223 HSA00520_NUCLEOTIDE_SUGARS_METABOLISM Genes involved in nucleotide sugars metabolism GALE, GALT, TGDS, UGDH, UGP2, UXS1 6 GALE(1), UGDH(2), UXS1(2) 2266027 5 5 4 0 0 1 2 1 1 0 0.25 0.69 224 GLEEVECPATHWAY The drug Gleevec specifically targets the abnormal bcr-abl protein, an apoptosis inhibitor present in chronic myeloid leukemia. AKT1, BCL2, BCR, CRKL, FOS, GRB2, HRAS, JAK2, JUN, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, MYC, PIK3CA, PIK3R1, RAF1, SOS1, STAT1, STAT5A, STAT5B 22 BCR(1), FOS(1), GRB2(2), JAK2(2), MAP2K4(1), MAP3K1(1), MAPK8(1), PIK3CA(2), PIK3R1(1), SOS1(3), STAT1(2), STAT5A(2), STAT5B(3) 11655572 22 21 22 6 2 2 11 4 3 0 0.25 0.69 225 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 7 GRB2(2), HBXIP(1), PTK2B(1), SHC1(1), SOS1(3) 3456280 8 8 8 3 0 1 7 0 0 0 0.26 0.69 226 PROSTAGLANDIN_SYNTHESIS_REGULATION ANXA1, ANXA2, ANXA3, ANXA4, ANXA5, ANXA6, ANXA8, CYP11A1, EDN1, EDNRA, EDNRB, HPGD, HSD11B1, HSD11B2, PLA2G4A, PRL, PTGDR, PTGDS, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, PTGIS, PTGS1, PTGS2, S100A6, SCGB1A1, TBXAS1 27 ANXA2(2), ANXA5(1), ANXA6(1), CYP11A1(1), EDNRA(1), PLA2G4A(1), PTGDR(1), PTGDS(1), PTGFR(3), PTGIS(3), PTGS1(1), PTGS2(1), TBXAS1(2) 9121645 19 19 19 4 4 2 7 2 4 0 0.26 0.69 227 VEGFPATHWAY Vascular endothelial growth factor (VEGF) is upregulated by hypoxic conditions and promotes normal blood vessel formation and angiogenesis related to tumor growth or cardiac disease. ARNT, EIF1, EIF1A, EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5, EIF2S1, EIF2S2, EIF2S3, ELAVL1, FLT1, FLT4, HIF1A, HRAS, KDR, NOS3, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, PTK2, PXN, SHC1, VEGF, VHL 25 EIF2B2(1), EIF2B4(1), EIF2B5(4), EIF2S1(1), FLT1(2), FLT4(3), KDR(1), NOS3(2), PIK3CA(2), PIK3R1(1), PRKCA(1), PTK2(1), PXN(5), SHC1(1) 13990352 26 26 26 11 3 6 7 8 2 0 0.26 0.69 228 PANTOTHENATE_AND_COA_BIOSYNTHESIS BCAT1, COASY, DPYD, DPYS, ENPP1, ENPP3, PANK1, PANK2, PANK3, PANK4, PPCS, UPB1 11 COASY(1), DPYD(3), DPYS(1), ENPP1(2), ENPP3(2), PANK3(1), UPB1(1) 5535166 11 11 11 3 1 0 4 2 4 0 0.26 0.69 229 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 CD3E(2), CD4(1) 1283778 3 3 3 1 0 0 3 0 0 0 0.26 0.69 230 PTENPATHWAY PTEN suppresses AKT-induced cell proliferation and antagonizes the action of PI3K. AKT1, BCAR1, CDKN1B, FOXO3A, GRB2, ILK, ITGB1, MAPK1, MAPK3, PDK2, PDPK1, PIK3CA, PIK3R1, PTEN, PTK2, SHC1, SOS1, TNFSF6 15 CDKN1B(1), GRB2(2), PDPK1(1), PIK3CA(2), PIK3R1(1), PTEN(2), PTK2(1), SHC1(1), SOS1(3) 7785917 14 14 14 10 0 3 7 1 3 0 0.26 0.70 231 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 23 AKR1B1(3), B4GALT2(1), G6PC(1), GAA(2), GALE(1), GANAB(1), GLB1(2), HK1(1), HK2(1), HK3(3), LCT(6), MGAM(5), PFKP(2) 13582242 29 27 29 6 4 5 9 7 4 0 0.26 0.70 232 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 B4GALT2(1), B4GALT5(1), DPAGT1(1), DPM1(1), FUT8(1), MAN1A1(1), MAN1B1(1), MGAT1(2), MGAT4B(1), MGAT5(3), RPN1(2), RPN2(1) 8068818 16 16 16 4 3 1 4 5 3 0 0.26 0.70 233 HSA00030_PENTOSE_PHOSPHATE_PATHWAY Genes involved in pentose phosphate pathway ALDOA, ALDOB, ALDOC, DERA, FBP1, FBP2, G6PD, GPI, H6PD, PFKL, PFKM, PFKP, PGD, PGLS, PGM1, PGM3, PRPS1, PRPS1L1, PRPS2, RBKS, RPE, RPIA, TALDO1, TKT, TKTL1, TKTL2 25 ALDOC(1), G6PD(4), GPI(2), H6PD(1), PFKP(2), PGD(1), PGLS(1), PRPS1L1(2), RPIA(1), TKT(2), TKTL1(5), TKTL2(1) 9962601 23 21 23 3 3 6 10 2 2 0 0.26 0.70 234 EGFPATHWAY The epidermal growth factor (EGF) peptide stimulates the EGF receptor to promote cell proliferation via the MAP kinase and Ras pathways. CSNK2A1, EGF, EGFR, ELK1, FOS, GRB2, HRAS, JAK1, JUN, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, RAF1, RASA1, SHC1, SOS1, SRF, STAT1, STAT3, STAT5A 26 CSNK2A1(1), EGFR(7), ELK1(2), FOS(1), GRB2(2), MAP2K4(1), MAP3K1(1), MAPK8(1), PIK3CA(2), PIK3R1(1), PRKCA(1), RASA1(1), SHC1(1), SOS1(3), SRF(1), STAT1(2), STAT3(1), STAT5A(2) 16382118 31 29 31 11 3 4 15 6 3 0 0.27 0.70 235 GLYCOSAMINOGLYCAN_DEGRADATION ARSB, GALNS, GLB1, GNS, GUSB, HEXA, HEXB, IDS, IDUA, LCT, NAGLU 10 GLB1(2), HEXA(2), HEXB(1), LCT(6), NAGLU(1) 5833589 12 12 12 2 0 1 6 2 3 0 0.27 0.70 236 HSA04512_ECM_RECEPTOR_INTERACTION Genes involved in ECM-receptor interaction AGRN, CD36, CD44, CD47, CHAD, COL11A1, COL11A2, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A2, COL4A4, COL4A6, COL5A1, COL5A2, COL5A3, COL6A1, COL6A2, COL6A3, COL6A6, DAG1, FN1, FNDC1, FNDC3A, FNDC4, FNDC5, GP1BA, GP1BB, GP5, GP6, GP9, HMMR, HSPG2, IBSP, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAV, ITGB1, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, LAMA1, LAMA2, LAMA3, LAMA4, LAMA5, LAMB1, LAMB2, LAMB3, LAMB4, LAMC1, LAMC2, LAMC3, RELN, SDC1, SDC2, SDC3, SDC4, SPP1, SV2A, SV2B, SV2C, THBS1, THBS2, THBS3, THBS4, TNC, TNN, TNR, TNXB, VTN, VWF 82 CD44(1), CD47(1), CHAD(1), COL11A1(5), COL11A2(4), COL1A1(1), COL1A2(2), COL2A1(1), COL3A1(4), COL4A1(3), COL4A2(1), COL4A4(3), COL4A6(5), COL5A1(1), COL5A2(2), COL5A3(7), COL6A3(11), COL6A6(6), DAG1(3), FN1(1), FNDC1(2), FNDC4(1), FNDC5(1), GP5(1), HSPG2(7), ITGA1(1), ITGA10(2), ITGA2B(4), ITGA3(2), ITGA4(3), ITGA5(1), ITGA6(1), ITGA8(3), ITGAV(2), ITGB6(1), ITGB7(4), LAMA1(6), LAMA2(8), LAMA3(7), LAMA4(2), LAMB1(5), LAMB2(3), LAMB3(1), LAMB4(4), LAMC1(3), LAMC2(1), LAMC3(4), RELN(8), SDC1(4), SDC2(2), SPP1(1), SV2A(3), SV2B(2), THBS1(2), THBS2(4), THBS3(3), THBS4(1), TNC(1), TNN(4), TNR(3), TNXB(4), VWF(4) 92544547 189 127 188 56 23 33 77 35 21 0 0.27 0.70 237 HSA04742_TASTE_TRANSDUCTION Genes involved in taste transduction ACCN1, ADCY4, ADCY6, ADCY8, CACNA1A, CACNA1B, GNAS, GNAT3, GNB1, GNB3, GNG13, GNG3, GRM4, ITPR3, KCNB1, PDE1A, PLCB2, PRKACA, PRKACB, PRKACG, PRKX, PRKY, SCNN1A, SCNN1B, SCNN1G, TAS1R1, TAS1R2, TAS1R3, TAS2R1, TAS2R10, TAS2R13, TAS2R14, TAS2R16, TAS2R3, TAS2R38, TAS2R39, TAS2R4, TAS2R40, TAS2R41, TAS2R42, TAS2R43, TAS2R44, TAS2R45, TAS2R46, TAS2R48, TAS2R49, TAS2R5, TAS2R50, TAS2R60, TAS2R7, TAS2R8, TAS2R9, TRPM5 46 ACCN1(3), ADCY4(1), CACNA1A(5), CACNA1B(1), GNAS(3), GNAT3(1), GNG13(1), GRM4(1), ITPR3(3), KCNB1(1), PDE1A(1), PLCB2(4), PRKACG(1), SCNN1B(1), SCNN1G(2), TAS1R1(1), TAS1R2(1), TAS2R1(3), TAS2R14(1), TAS2R16(1), TAS2R42(2), TAS2R43(1), TAS2R46(1), TAS2R50(2), TAS2R8(2), TAS2R9(1) 23131501 45 40 44 5 4 4 18 11 8 0 0.28 0.72 238 OVARIAN_INFERTILITY_GENES ATM, BMPR1B, CCND2, CDK4, CDKN1B, CEBPB, DAZL, DMC1, EGR1, ESR2, FSHR, GJA4, INHA, LHCGR, MLH1, MSH5, NCOR1, NR5A1, NRIP1, PGR, PRLR, PTGER2, SMPD1, VDR, ZP2 23 ATM(5), BMPR1B(1), CDKN1B(1), EGR1(2), FSHR(4), INHA(1), LHCGR(3), MLH1(2), MSH5(2), NCOR1(1), PGR(1), PRLR(2), VDR(1), ZP2(1) 15367645 27 25 27 5 1 3 7 12 4 0 0.28 0.72 239 GLYCOLYSISPATHWAY Glycolysis is an evolutionarily conserved pathway by which one glucose molecule is converted to two pyruvate molecules for a gain of 2 ATP. ALDOB, ENO1, GAPD, GPI, HK1, PFKL, PGAM1, PGK1, PKLR, TPI1 8 GPI(2), HK1(1), PGK1(2), PKLR(1) 3307936 6 6 6 2 0 0 4 1 1 0 0.28 0.72 240 CELLCYCLEPATHWAY Cyclins interact with cyclin-dependent kinases to form active kinase complexes that regulate progression through the cell cycle. CCNA1, CCNB1, CCND1, CCND2, CCND3, CCNE1, CCNH, CDC2, CDC25A, CDK2, CDK4, CDK6, CDK7, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, CDKN2D, E2F1, RB1, RBL1, TFDP1 21 CCNA1(2), CCNH(1), CDK2(1), CDKN1A(1), CDKN1B(1), CDKN2C(2), CDKN2D(1), RBL1(1), TFDP1(2) 6029998 12 12 12 7 2 3 5 1 1 0 0.28 0.73 241 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 28 B4GALT5(1), GALNT1(3), GALNT10(1), GALNT12(1), GALNT13(2), GALNT14(3), GALNT2(1), GALNT3(1), GALNT4(1), GALNT6(2), GALNT8(2), GALNTL2(1), GALNTL5(1), GCNT4(2), OGT(2), ST3GAL2(2), WBSCR17(1) 14374411 27 26 26 7 4 4 9 7 3 0 0.28 0.73 242 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(3), COL4A2(1), COL4A3(1), COL4A4(3), COL4A5(4), COL4A6(5), SLC23A1(1), SLC23A2(2), SLC2A1(1), SLC2A3(1) 10865339 22 21 22 6 2 6 8 4 2 0 0.29 0.73 243 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 BCR(1), BTK(1), CD19(2), CD22(3), CR2(1), CSK(1), DAG1(3), GRB2(2), GSK3A(2), GSK3B(1), INPP5D(4), ITPR1(3), ITPR2(5), ITPR3(3), LYN(1), MAP4K1(1), NFATC1(1), NFATC2(1), PDK1(1), PIK3CA(2), PIK3R1(1), PLCG2(1), PPP3CC(1), PTPRC(3), SHC1(1), SOS1(3), SOS2(1), VAV1(2) 30882356 52 48 52 20 4 7 21 13 7 0 0.29 0.73 244 ST_PHOSPHOINOSITIDE_3_KINASE_PATHWAY The phosphoinositide-3 kinase pathway produces the lipid second messenger PIP3 and regulates cell growth, survival, and movement. A1BG, AKT1, AKT2, AKT3, BAD, BTK, CDKN2A, CSL4, DAF, DAPP1, FOXO1A, GRB2, GSK3A, GSK3B, IARS, IGFBP1, INPP5D, P14, PDK1, PIK3CA, PPP1R13B, PSCD3, PTEN, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SFN, SHC1, SOS1, SOS2, TEC, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ 33 BTK(1), GRB2(2), GSK3A(2), GSK3B(1), IARS(1), INPP5D(4), PDK1(1), PIK3CA(2), PTEN(2), RPS6KA1(1), RPS6KA2(1), SHC1(1), SOS1(3), SOS2(1), TEC(1), YWHAB(1), YWHAE(2), YWHAG(2) 15614212 29 29 29 12 3 4 16 3 3 0 0.29 0.73 245 HSA04610_COMPLEMENT_AND_COAGULATION_CASCADES Genes involved in complement and coagulation cascades A2M, BDKRB1, BDKRB2, C1QA, C1QB, C1QC, C1R, C1S, C2, C3, C3AR1, C4A, C4B, C4BPA, C4BPB, C5, C5AR1, C6, C7, C8A, C8B, C8G, C9, CD46, CD55, CD59, CFB, CFD, CFH, CFI, CPB2, CR1, CR2, F10, F11, F12, F13A1, F13B, F2, F2R, F3, F5, F7, F8, F9, FGA, FGB, FGG, KLKB1, KNG1, MASP1, MASP2, MBL2, PLAT, PLAU, PLAUR, PLG, PROC, PROS1, SERPINA1, SERPINA5, SERPINC1, SERPIND1, SERPINE1, SERPINF2, SERPING1, TFPI, THBD, VWF 64 A2M(1), BDKRB1(4), BDKRB2(3), C2(1), C3(2), C4BPA(1), C4BPB(1), C5(1), C5AR1(2), C6(2), C7(3), C8A(1), C8B(1), CD55(1), CPB2(1), CR1(2), CR2(1), F13A1(2), F2(3), F2R(2), F5(3), F7(1), F8(4), F9(1), FGA(3), FGB(2), KLKB1(2), KNG1(1), MASP1(1), MASP2(2), PLAU(2), PLAUR(1), PROC(1), PROS1(1), SERPINA5(2), SERPINC1(1), SERPINE1(1), VWF(4) 39995553 68 57 68 20 11 10 22 18 7 0 0.29 0.73 246 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 FUT1(1), FUT9(1), HEXA(2), HEXB(1), ST3GAL2(2), ST8SIA1(2) 4373885 9 9 9 1 2 1 3 3 0 0 0.29 0.73 247 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 CCR3(2), HLA-DRA(1), HLA-DRB1(1) 1374193 4 3 4 2 0 1 1 1 1 0 0.29 0.73 248 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), GRB2(2), INSR(6), IRS1(6), JAK2(2), PIK3CA(2), PIK3R1(1), PRKCA(1), RPS6KA1(1), SHC1(1), SLC2A4(1), SOS1(3), SRF(1), STAT5A(2), STAT5B(3) 13986290 33 26 33 9 2 4 18 6 3 0 0.29 0.73 249 KERATINOCYTEPATHWAY Keratinocyte differentiation, which models the differentiation of epidermal cells, requires the four main MAP kinase pathways. BCL2, CEBPA, CHUK, DAXX, EGF, EGFR, ETS1, ETS2, FOS, HOXA7, HRAS, IKBKB, JUN, MAP2K1, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAP3K1, MAP3K14, MAP3K5, MAPK1, MAPK13, MAPK14, MAPK3, MAPK8, NFKB1, NFKBIA, PPP2CA, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCQ, RAF1, RELA, RIPK1, SP1, TNF, TNFRSF1A, TNFRSF1B, TNFRSF6, TNFSF6, TRAF2 41 CHUK(1), DAXX(1), EGFR(7), ETS1(1), ETS2(1), FOS(1), HOXA7(1), IKBKB(1), MAP2K3(1), MAP2K4(1), MAP2K6(1), MAP3K1(1), MAP3K14(1), MAP3K5(2), MAPK14(1), MAPK8(1), NFKB1(1), PPP2CA(2), PRKCA(1), PRKCE(1), PRKCG(1), PRKCH(1), PRKCQ(3), RELA(1), TNF(1), TNFRSF1A(1), TRAF2(1) 21040124 37 37 37 12 5 7 9 9 7 0 0.29 0.73 250 CD40PATHWAY The CD40 receptor is a TNF-type receptor that regulates immunoglobulin expression in B cells and moderates T cell activation via T-cell expression of its ligand. CHUK, DUSP1, IKBKAP, IKBKB, IKBKG, MAP3K1, MAP3K14, NFKB1, NFKBIA, RELA, TNFAIP3, TNFRSF5, TNFSF5, TRAF3, TRAF6 12 CHUK(1), DUSP1(2), IKBKAP(1), IKBKB(1), MAP3K1(1), MAP3K14(1), NFKB1(1), RELA(1), TNFAIP3(4), TRAF6(2) 7958068 15 15 15 4 4 2 5 4 0 0 0.30 0.73 251 ONE_CARBON_POOL_BY_FOLATE ALDH1L1, AMT, ATIC, ATP6V0C, SHMT1, DHFR, GART, MTHFD1, MTHFD1L, MTHFD2, MTHFR, MTHFS, MTR, SHMT1, SHMT2, TYMS 15 ALDH1L1(3), ATIC(2), GART(3), MTHFD1(2), MTHFD1L(3), SHMT1(1), SHMT2(1) 8116034 15 15 14 2 1 3 5 2 4 0 0.30 0.73 252 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), CD80(1), HLA-DRA(1), HLA-DRB1(1) 1858767 4 4 4 0 0 1 1 1 1 0 0.30 0.73 253 HSA05050_DENTATORUBROPALLIDOLUYSIAN_ATROPHY Genes involved in dentatorubropallidoluysian atrophy (DRPLA) ATN1, BAIAP2, CASP1, CASP3, CASP7, CASP8, GAPDH, INS, INSR, ITCH, MAGI1, MAGI2, RERE, WWP1, WWP2 14 ATN1(2), CASP1(2), CASP7(1), INSR(6), MAGI1(2), MAGI2(4), RERE(3) 10127031 20 20 20 3 4 2 7 6 1 0 0.30 0.74 254 HSA01032_GLYCAN_STRUCTURES_DEGRADATION Genes involved in degradation of glycan structures AGA, ARSB, FLJ21865, FUCA1, FUCA2, GALNS, GBA, GLB1, GNS, GUSB, HEXA, HEXB, HGSNAT, HPSE, HPSE2, HYAL1, HYAL2, IDS, IDUA, LCT, MAN2B1, MAN2B2, MAN2C1, MANBA, NAGLU, NEU1, NEU2, NEU3, NEU4, SPAM1 27 FUCA2(1), GBA(1), GLB1(2), HEXA(2), HEXB(1), HPSE(1), HPSE2(1), LCT(6), MAN2B1(3), MAN2B2(3), MAN2C1(1), MANBA(1), NAGLU(1), NEU1(1), NEU3(1), SPAM1(2) 13895063 28 26 28 9 1 4 10 9 4 0 0.30 0.74 255 AKTPATHWAY Second messenger PIP3 promotes cell survival by activating the anti-apoptotic kinase AKT. AKT1, BAD, CASP9, CHUK, FOXO1A, FOXO3A, GH1, GHR, HSPCA, MLLT7, NFKB1, NFKBIA, PDPK1, PIK3CA, PIK3R1, PPP2CA, RELA, TNFSF6, YWHAH 14 CASP9(1), CHUK(1), GHR(1), NFKB1(1), PDPK1(1), PIK3CA(2), PIK3R1(1), PPP2CA(2), RELA(1) 6104266 11 11 11 5 1 1 4 3 2 0 0.31 0.74 256 MAPKPATHWAY The mitogen-activated protein (MAP) kinase pathway is a common signaling mechanism and has four main sub-pathways: Erk, JNK/SAPK, p53, and ERK5. ARAF1, ATF2, BRAF, CEBPA, CHUK, CREB1, DAXX, ELK1, FOS, GRB2, HRAS, IKBKB, JUN, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K5, MAP2K6, MAP2K7, MAP3K1, MAP3K10, MAP3K11, MAP3K12, MAP3K13, MAP3K14, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K6, MAP3K7, MAP3K8, MAP3K9, MAP4K1, MAP4K2, MAP4K3, MAP4K4, MAP4K5, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK4, MAPK6, MAPK7, MAPK8, MAPK9, MAPKAPK2, MAPKAPK3, MAPKAPK5, MAX, MEF2A, MEF2B, MEF2C, MEF2D, MKNK1, MKNK2, MYC, NFKB1, NFKBIA, PAK1, PAK2, PDZGEF1, RAC1, RAF1, RELA, RIPK1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA4, RPS6KA5, RPS6KB1, RPS6KB2, SHC1, SP1, STAT1, TGFB1, TGFB2, TGFB3, TGFBR1, TRADD, TRAF2 79 BRAF(2), CHUK(1), DAXX(1), ELK1(2), FOS(1), GRB2(2), IKBKB(1), MAP2K3(1), MAP2K4(1), MAP2K6(1), MAP3K1(1), MAP3K10(2), MAP3K12(1), MAP3K13(2), MAP3K14(1), MAP3K2(2), MAP3K3(1), MAP3K4(2), MAP3K5(2), MAP3K6(1), MAP3K7(3), MAP3K9(1), MAP4K1(1), MAP4K3(3), MAPK14(1), MAPK6(1), MAPK8(1), MAPK9(1), MAPKAPK3(1), MAPKAPK5(1), MEF2A(1), MEF2C(1), MEF2D(1), MKNK1(1), NFKB1(1), PAK2(1), RELA(1), RPS6KA1(1), RPS6KA2(1), RPS6KA4(1), RPS6KA5(1), RPS6KB2(1), SHC1(1), STAT1(2), TRAF2(1) 39676496 58 56 58 13 6 10 19 15 8 0 0.31 0.74 257 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 25 CASP6(1), CASP7(1), DAXX(1), FADD(1), LMNA(4), LMNB1(1), MAP2K4(1), MAP3K1(1), MAP3K7(3), MAPK8(1), PAK2(1), PRKDC(8), PTPN13(4), RIPK2(1), SPTAN1(5) 17236756 34 30 34 4 3 7 8 11 5 0 0.31 0.74 258 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 62 ATM(5), CCNA1(2), CCNG2(1), CCNH(1), CDK2(1), CDKN1A(1), CDKN1B(1), CDKN2C(2), CDKN2D(1), CREB3L1(1), CREB3L4(1), E2F2(1), E2F5(1), GADD45A(1), GBA2(2), MCM2(2), MCM3(1), MCM4(2), MCM5(2), MNAT1(1), MYT1(2), NACA(4), ORC1L(1), ORC4L(1), POLE(2), POLE2(1), RBL1(1), RPA1(2), RPA2(1), TFDP1(2), TNXB(4) 31260267 51 48 51 21 9 6 18 9 9 0 0.31 0.74 259 BIOPEPTIDESPATHWAY Extracellular signaling peptides exert biological effects via G-protein coupled receptors (GPCRs), which activate intracellular GTPases. AGT, AGTR2, BDK, CALM1, CALM2, CALM3, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CDK5, F2, FYN, GNA11, GNAI1, GNB1, GNGT1, GRB2, HRAS, JAK2, MAP2K1, MAP2K2, MAPK1, MAPK14, MAPK3, MAPK8, MAPT, MYLK, PLCG1, PRKCA, PRKCB1, PTK2B, RAF1, SHC1, SOS1, STAT1, STAT3, STAT5A, SYT1 36 AGTR2(2), CALM3(1), CAMK2B(2), CAMK2D(1), CAMK2G(1), F2(3), GNA11(1), GRB2(2), JAK2(2), MAPK14(1), MAPK8(1), MYLK(6), PRKCA(1), PTK2B(1), SHC1(1), SOS1(3), STAT1(2), STAT3(1), STAT5A(2) 18089105 34 33 34 9 6 3 14 7 4 0 0.31 0.74 260 FOSBPATHWAY FOSB gene expression and drug abuse CDK5, FOSB, GRIA2, JUND, PPP1R1B 4 FOSB(1), GRIA2(2) 1466129 3 3 3 2 0 0 0 2 1 0 0.31 0.74 261 METHANE_METABOLISM ADH5, ATP6V0C, SHMT1, CAT, EPX, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, SHMT1, SHMT2, TPO 13 ADH5(1), CAT(1), EPX(2), LPO(1), SHMT1(1), SHMT2(1), TPO(4) 4986774 11 11 11 3 3 0 4 2 2 0 0.31 0.74 262 HSA00300_LYSINE_BIOSYNTHESIS Genes involved in lysine biosynthesis AADAT, AASDHPPT, AASS, KARS 4 AASDHPPT(1), AASS(2), KARS(1) 2175443 4 4 4 1 0 0 1 3 0 0 0.32 0.74 263 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 BHMT(1), DNMT1(2), DNMT3A(3), DNMT3B(2), MARS(2), MARS2(3), MTFMT(3), TAT(2) 8969405 18 18 18 4 1 5 7 5 0 0 0.32 0.74 264 HSA00510_N_GLYCAN_BIOSYNTHESIS Genes involved in N-glycan biosynthesis ALG1, ALG10, ALG10B, ALG11, ALG12, ALG13, ALG14, ALG2, ALG3, ALG5, ALG6, ALG8, ALG9, B4GALT1, B4GALT2, B4GALT3, DAD1, DDOST, DHDDS, DOLPP1, DPAGT1, DPM1, FUT8, GANAB, GCS1, MAN1A1, MAN1A2, MAN1B1, MAN1C1, MAN2A1, MGAT1, MGAT2, MGAT3, MGAT4A, MGAT4B, MGAT5, MGAT5B, RFT1, RPN1, RPN2, ST6GAL1, STT3B 41 ALG1(1), ALG10B(4), ALG11(2), ALG2(2), ALG8(2), ALG9(1), B4GALT2(1), DAD1(2), DPAGT1(1), DPM1(1), FUT8(1), GANAB(1), MAN1A1(1), MAN1B1(1), MAN2A1(1), MGAT1(2), MGAT4B(1), MGAT5(3), MGAT5B(2), RPN1(2), RPN2(1) 17929942 33 31 33 9 6 2 8 9 8 0 0.32 0.74 265 ST_WNT_BETA_CATENIN_PATHWAY Beta-catenin is degraded in the absence of Wnt signaling; when extracellular Wnt binds Frizzled receptors, beta-catenin accumulates in the nucleus and may promote cell survival. AKT1, AKT2, AKT3, ANKRD6, APC, AXIN1, AXIN2, C22orf2, CER1, CSNK1A1, CTNNB1, DACT1, DKK1, DKK2, DKK3, DKK4, DVL1, FRAT1, FSTL1, GSK3A, GSK3B, IDAX, LAMR1, LRP1, MVP, NKD1, NKD2, PIN1, PSEN1, PTPRA, SENP2, SFRP1, TSHB, WIF1 28 ANKRD6(3), APC(8), AXIN2(1), CTNNB1(2), DACT1(1), DKK2(2), DKK3(1), GSK3A(2), GSK3B(1), LRP1(7), MVP(2), WIF1(3) 16601452 33 31 33 9 6 1 12 9 5 0 0.32 0.74 266 HSA00680_METHANE_METABOLISM Genes involved in methane metabolism ADH5, CAT, EPX, LPO, MPO, MTHFR, PRDX6, SHMT1, SHMT2, TPO 10 ADH5(1), CAT(1), EPX(2), LPO(1), SHMT1(1), SHMT2(1), TPO(4) 4996138 11 11 11 3 3 0 4 2 2 0 0.32 0.74 267 HSA00940_PHENYLPROPANOID_BIOSYNTHESIS Genes involved in phenylpropanoid biosynthesis EPX, GBA, GBA3, LPO, MPO, PRDX6, TPO 7 EPX(2), GBA(1), LPO(1), TPO(4) 3614017 8 8 8 3 1 0 4 1 2 0 0.32 0.74 268 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 230 ACVR1B(1), ACVR1C(2), BRAF(2), CACNA1A(5), CACNA1B(1), CACNA1C(9), CACNA1D(6), CACNA1E(4), CACNA1F(4), CACNA1G(3), CACNA1S(5), CACNA2D1(4), CACNA2D2(1), CACNA2D3(1), CACNA2D4(1), CACNB1(1), CACNB2(1), CACNB4(1), CACNG3(1), CACNG6(2), CDC25B(2), CHUK(1), DAXX(1), DDIT3(2), DUSP1(2), DUSP7(1), DUSP9(2), ECSIT(1), EGFR(7), ELK1(2), FGF12(1), FGF2(1), FGF23(2), FGF5(1), FGF6(1), FGFR4(1), FLNA(1), FLNB(3), FLNC(3), FOS(1), GADD45A(1), GADD45B(1), GNA12(1), GRB2(2), IKBKB(1), KRAS(2), MAP2K3(1), MAP2K4(1), MAP2K6(1), MAP3K1(1), MAP3K10(2), MAP3K12(1), MAP3K13(2), MAP3K14(1), MAP3K2(2), MAP3K3(1), MAP3K4(2), MAP3K5(2), MAP3K6(1), MAP3K7(3), MAP4K1(1), MAP4K3(3), MAPK14(1), MAPK8(1), MAPK8IP1(1), MAPK9(1), MAPKAPK3(1), MAPKAPK5(1), MEF2C(1), MKNK1(1), MOS(1), MRAS(1), NFATC2(1), NFATC4(1), NFKB1(1), NLK(1), NRAS(2), NTF3(1), NTRK1(4), NTRK2(1), PAK2(1), PDGFRA(3), PDGFRB(3), PLA2G12A(1), PLA2G12B(1), PLA2G2F(1), PLA2G4A(1), PLA2G6(1), PPP3CC(1), PPP5C(1), PRKACG(1), PRKCA(1), PRKCG(1), PTPN5(3), PTPRR(1), RAPGEF2(1), RASA1(1), RASA2(2), RASGRF1(2), RASGRF2(4), RASGRP1(1), RASGRP2(1), RASGRP3(2), RPS6KA1(1), RPS6KA2(1), RPS6KA4(1), RPS6KA5(1), RRAS(1), SOS1(3), SOS2(1), SRF(1), STK4(1), TAOK1(1), TAOK3(1), TGFBR2(3), TNF(1), TNFRSF1A(1), TRAF2(1), TRAF6(2) 113573898 202 146 200 50 31 27 69 51 24 0 0.32 0.74 269 EPOPATHWAY Erythropoietin, which activates the MAPK pathway, stimulates erythrocyte production and is an effective treatment for anemia. CSNK2A1, ELK1, EPO, EPOR, FOS, GRB2, HRAS, JAK2, JUN, MAP2K1, MAPK3, MAPK8, PLCG1, PTPN6, RAF1, SHC1, SOS1, STAT5A, STAT5B 19 CSNK2A1(1), ELK1(2), EPOR(1), FOS(1), GRB2(2), JAK2(2), MAPK8(1), SHC1(1), SOS1(3), STAT5A(2), STAT5B(3) 9180117 19 18 19 2 1 3 11 3 1 0 0.33 0.74 270 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 20 BTK(1), DLG4(2), EPHB2(1), F2(3), F2RL2(1), MAPK8(1), MYEF2(1), PLD1(1), PLD2(1), PTK2(1), RASAL1(6), TEC(1), VAV1(2) 11528638 22 22 22 11 3 7 3 5 4 0 0.33 0.74 271 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 6 CREBBP(7), EP300(1), PELP1(1) 6044532 9 9 9 2 0 1 1 3 4 0 0.33 0.74 272 PLCEPATHWAY Gs-coupled receptors activate adenylyl cyclase, which activates Epac1, leading to the stimulation of PLC and subsequent DAG and IP3 production. ADCY1, ADRB2, GNAS, PLCE1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTGER1, RAP2B 11 ADCY1(4), ADRB2(1), GNAS(3), PLCE1(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1) 5857361 12 12 11 2 5 0 1 3 3 0 0.33 0.74 273 TPOPATHWAY Thrombopoietin binds to its receptor and activates cell growth through the Erk and JNK MAP kinase pathways, protein kinase C, and JAK/STAT activation. CSNK2A1, FOS, GRB2, HRAS, JAK2, JUN, MAP2K1, MAPK3, MPL, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, RAF1, RASA1, SHC1, SOS1, STAT1, STAT3, STAT5A, STAT5B, THPO 22 CSNK2A1(1), FOS(1), GRB2(2), JAK2(2), PIK3CA(2), PIK3R1(1), PRKCA(1), RASA1(1), SHC1(1), SOS1(3), STAT1(2), STAT3(1), STAT5A(2), STAT5B(3), THPO(1) 13126097 24 23 24 6 2 2 13 5 2 0 0.33 0.74 274 HSA00592_ALPHA_LINOLENIC_ACID_METABOLISM Genes involved in alpha-Linolenic acid metabolism ACOX1, ACOX3, FADS2, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6 15 ACOX1(2), FADS2(2), PLA2G12A(1), PLA2G12B(1), PLA2G2F(1), PLA2G4A(1), PLA2G6(1) 4448820 9 9 9 1 1 2 4 0 2 0 0.33 0.74 275 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 CYP1A2(1), CYP2E1(1), NR1I3(1), PTGS1(1), PTGS2(1) 2412823 5 5 5 2 1 1 3 0 0 0 0.34 0.74 276 DEATHPATHWAY Death receptors such as Fas and DR3, 4, and 5 transduce pro-apoptotic signaling by oligomerizing to activate the caspase cascade. APAF1, BCL2, BID, BIRC2, BIRC3, BIRC4, CASP10, CASP3, CASP6, CASP7, CASP8, CASP9, CFLAR, CHUK, CYCS, DFFA, DFFB, FADD, GAS2, LMNA, MAP3K14, NFKB1, NFKBIA, RELA, RIPK1, SPTAN1, TNFRSF10A, TNFRSF10B, TNFRSF25, TNFSF10, TNFSF12, TRADD, TRAF2 31 APAF1(2), BID(1), BIRC3(2), CASP6(1), CASP7(1), CASP9(1), CHUK(1), FADD(1), GAS2(1), LMNA(4), MAP3K14(1), NFKB1(1), RELA(1), SPTAN1(5), TNFRSF10A(2), TNFSF10(1), TRAF2(1) 14347455 27 27 27 8 4 4 11 7 1 0 0.34 0.74 277 SA_PTEN_PATHWAY PTEN is a tumor suppressor that dephosphorylates the lipid messenger phosphatidylinositol triphosphate. AKT1, AKT2, AKT3, BPNT1, GRB2, ILK, MAPK1, MAPK3, PDK1, PIK3CA, PIK3CD, PIP3-E, PTEN, PTK2B, RBL2, SHC1, SOS1 16 BPNT1(1), GRB2(2), PDK1(1), PIK3CA(2), PTEN(2), PTK2B(1), RBL2(3), SHC1(1), SOS1(3) 8583775 16 16 16 8 1 2 10 2 1 0 0.34 0.74 278 ST_DIFFERENTIATION_PATHWAY_IN_PC12_CELLS Rat-derived PC12 cells respond to nerve growth factor (NGF) and PACAP to differentiate into neuronal cells. AKT1, ASAH1, ATF1, BRAF, CAMP, CREB1, CREB3, CREB5, CREBBP, CRKL, DAG1, EGR1, EGR2, EGR3, EGR4, ELK1, FRS2, GAS, GNAQ, GRF2, JUN, MAP1B, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK3, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, NTRK1, OPN1LW, PACAP, PIK3C2G, PIK3CA, PIK3CD, PIK3R1, PTPN11, RPS6KA3, SH2B, SHC1, SRC, TERF2IP, TH, TUBA3 37 ATF1(3), BRAF(2), CREBBP(7), DAG1(3), EGR1(2), EGR4(1), ELK1(2), MAP2K4(1), MAPK8(1), MAPK8IP1(1), MAPK9(1), NTRK1(4), OPN1LW(1), PIK3CA(2), PIK3R1(1), SHC1(1) 19615099 33 31 33 14 5 4 8 10 6 0 0.34 0.74 279 ACE2PATHWAY Angiotensin-converting enzyme 2 (ACE2) digests the blood-pressure regulator angiotensin II (AGT) ultimately to the vasodilator AGT1-7. ACE2, AGT, AGTR1, AGTR2, CMA1, COL4A1, COL4A2, COL4A3, COL4A4, COL4A5, COL4A6, REN 12 ACE2(2), AGTR2(2), COL4A1(3), COL4A2(1), COL4A3(1), COL4A4(3), COL4A5(4), COL4A6(5) 11212233 21 20 21 6 3 6 5 5 2 0 0.34 0.74 280 IL5PATHWAY Pro-inflammatory IL-5 is secretes by activated T cells, eosinophils, and mast cells, and stimulates the proliferation and activation of eosinophils in bone marrow. CCL11, CCR3, CD4, HLA-DRA, HLA-DRB1, IL1B, IL4, IL5, IL5RA, IL6 10 CCR3(2), CD4(1), HLA-DRA(1), HLA-DRB1(1), IL5RA(1) 2491679 6 5 6 0 1 1 2 1 1 0 0.34 0.74 281 TNFR2PATHWAY Tumor necrosis factor beta, produced by activated lymphocytes, binds to its receptor TNFR2 to induce activation in immune cells and apoptosis in many other cells. CHUK, DUSP1, IKBKAP, IKBKB, IKBKG, LTA, MAP3K1, MAP3K14, NFKB1, NFKBIA, RELA, RIPK1, TANK, TNFAIP3, TNFRSF1B, TRAF1, TRAF2, TRAF3 17 CHUK(1), DUSP1(2), IKBKAP(1), IKBKB(1), MAP3K1(1), MAP3K14(1), NFKB1(1), RELA(1), TNFAIP3(4), TRAF1(4), TRAF2(1) 9722476 18 18 18 4 4 2 5 6 1 0 0.34 0.74 282 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), CCNA2(1), CDK2(1), CDKN1B(1), E2F2(1), PRB1(1) 3550246 7 7 7 6 1 2 1 3 0 0 0.34 0.74 283 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 134 ADCY1(4), ADCY2(6), ADCY3(2), ADCY4(1), ADCY5(3), ADCY7(1), ADCY9(5), ATF1(3), ATP2A2(1), ATP2A3(1), CALM3(1), CAMK2B(2), CAMK2D(1), CAMK2G(1), CORIN(1), ETS2(1), FOS(1), GABPA(2), GBA2(2), GJA1(2), GNB2(2), GNG13(1), GRK5(1), GRK6(1), GUCY1A3(1), IGFBP6(1), ITPR1(3), ITPR2(5), ITPR3(3), MIB1(5), MYL2(1), MYL4(3), MYLK2(1), NFKB1(1), NOS1(2), NOS3(2), PLCB3(2), PLCG2(1), PRKAR2A(1), PRKAR2B(1), PRKCA(1), PRKCE(1), PRKCH(1), PRKCQ(3), PRKCZ(2), PRKD1(2), RGS18(2), RGS4(2), RGS7(4), RGS9(2), RYR1(11), RYR2(15), RYR3(4), SLC8A1(2), TNXB(4), USP5(1), YWHAB(1) 72563205 137 104 136 40 30 8 48 39 12 0 0.34 0.74 284 EPHA4PATHWAY Eph Kinases and ephrins support platelet aggregation ACTA1, EPHA4, EPHB1, FYN, ITGA1, ITGB1, L1CAM, LYN, RAP1B, SELP 10 EPHB1(4), ITGA1(1), L1CAM(5), LYN(1), SELP(3) 7046462 14 13 14 6 3 2 4 3 2 0 0.34 0.74 285 IRINOTECAN_PATHWAY_PHARMGKB ABCC1, ABCC2, ABCG2, BCHE, CES1, CES2, CES4, CYP3A4, CYP3A5, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6 17 ABCC1(5), ABCC2(1), BCHE(4), CES1(1), UGT1A10(2), UGT1A3(1), UGT1A5(1), UGT1A7(1), UGT1A8(2), UGT1A9(2) 10445971 20 19 20 8 1 2 8 7 2 0 0.35 0.74 286 BIOGENIC_AMINE_SYNTHESIS AANAT, ACHE, CHAT, COMT, DBH, DDC, DXYS155E, GAD1, GAD2, HDC, MAOA, PAH, PNMT, SLC18A3, TH, TPH1 14 DBH(2), DDC(1), GAD1(1), GAD2(1), MAOA(2), PAH(3), SLC18A3(1) 5736161 11 11 11 7 1 0 4 3 3 0 0.35 0.74 287 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 IFNA1(2), IFNAR2(1), IFNB1(1), STAT1(2), STAT2(1), TYK2(2) 4634719 9 9 9 2 0 0 3 6 0 0 0.35 0.74 288 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 46 AGPAT3(1), AGPAT4(2), CDS1(1), CHKA(1), CHKB(1), CPT1B(2), DGKA(3), DGKB(3), DGKD(2), DGKE(1), DGKH(3), GNPAT(4), GPD2(1), LCAT(2), LYPLA2(1), PAFAH2(2), PLA2G4A(1), PLA2G6(1), PLCB2(4), PLCG2(1), PPAP2A(1) 19968929 38 36 38 11 2 7 11 14 4 0 0.35 0.74 289 LAIRPATHWAY The local acute inflammatory response is mediated by activated macrophages and mast cells or by complement activation. BDK, C3, C5, C6, C7, ICAM1, IL1A, IL6, IL8, ITGA4, ITGAL, ITGB1, ITGB2, SELP, SELPLG, TNF, VCAM1 16 C3(2), C5(1), C6(2), C7(3), ICAM1(1), IL8(1), ITGA4(3), ITGAL(3), ITGB2(2), SELP(3), TNF(1) 10857154 22 19 22 6 2 3 5 8 4 0 0.35 0.74 290 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 ACP2(1), ACP6(2), ACPP(2), ALPL(2), ALPP(2), CYP3A43(1), DHRS2(1), DHRS7(1), PON3(1) 7245219 13 13 13 4 0 5 2 2 4 0 0.35 0.74 291 HSA00053_ASCORBATE_AND_ALDARATE_METABOLISM Genes involved in ascorbate and aldarate metabolism ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, MIOX, UGDH 9 ALDH2(1), ALDH3A1(1), ALDH3A2(2), ALDH7A1(1), UGDH(2) 3569998 7 7 7 1 0 2 0 3 2 0 0.35 0.74 292 HSA04614_RENIN_ANGIOTENSIN_SYSTEM Genes involved in renin-angiotensin system ACE, ACE2, AGT, AGTR1, AGTR2, ANPEP, CMA1, CPA3, CTSA, CTSG, ENPEP, LNPEP, MAS1, MME, NLN, REN, THOP1 16 ACE(3), ACE2(2), AGTR2(2), ANPEP(2), CTSA(1), CTSG(1), LNPEP(2), MAS1(1), MME(2) 9036210 16 16 16 5 2 3 5 5 1 0 0.36 0.74 293 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(2), G6PD(4), GCLM(1), GSS(3), GSTA1(1), GSTA2(1), GSTM1(1), GSTM5(1), GSTO2(1), MGST1(1), MGST2(1), PGD(1) 7718240 18 15 18 5 0 5 9 3 1 0 0.36 0.74 294 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 14 B3GAT1(3), B3GAT2(1), B3GAT3(1), CHPF(1), DSE(1), UST(2), XYLT1(4) 5385313 13 12 13 2 4 3 4 1 1 0 0.36 0.74 295 HSA00550_PEPTIDOGLYCAN_BIOSYNTHESIS Genes involved in peptidoglycan biosynthesis GLUL, PGLYRP2 2 PGLYRP2(2) 808930 2 2 2 1 0 0 2 0 0 0 0.36 0.74 296 IGF1PATHWAY Growth factor IGF-1 stimulates growth and inhibits apoptosis by activating the MAP kinase pathway in a variety of cell types. CSNK2A1, ELK1, FOS, GRB2, HRAS, IGF1, IGF1R, IRS1, JUN, MAP2K1, MAPK3, MAPK8, PIK3CA, PIK3R1, PTPN11, RAF1, RASA1, SHC1, SOS1, SRF 20 CSNK2A1(1), ELK1(2), FOS(1), GRB2(2), IGF1R(1), IRS1(6), MAPK8(1), PIK3CA(2), PIK3R1(1), RASA1(1), SHC1(1), SOS1(3), SRF(1) 10427694 23 19 23 5 0 5 12 4 2 0 0.36 0.74 297 HSA00072_SYNTHESIS_AND_DEGRADATION_OF_KETONE_BODIES Genes involved in synthesis and degradation of ketone bodies ACAT1, ACAT2, BDH1, BDH2, HMGCL, HMGCS1, HMGCS2, OXCT1, OXCT2 9 ACAT1(2), ACAT2(1), BDH1(1), HMGCS2(1), OXCT1(2) 3242833 7 6 7 3 0 1 3 2 1 0 0.36 0.74 298 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 PSMA4(1), PSMB1(1), PSMB4(1), PSMB5(1), PSMB6(1), PSMC3(4), RPN1(2), RPN2(1) 5964778 12 11 12 4 1 0 3 5 3 0 0.36 0.74 299 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 APAF1(2), ATM(5), BID(1), CASP6(1), CASP7(1), CASP9(1), EIF2S1(1), PRKCA(1), PTK2(1), PXN(5), STAT1(2), TLN1(1) 11895055 22 21 22 4 2 2 11 5 2 0 0.36 0.74 300 PS1PATHWAY Presenilin is required for gamma-secretase activity to activate Notch signaling; presenilin also inhibits beta-catenin in the Wnt/Frizzled pathway. ADAM17, APC, AXIN1, BTRC, CTNNB1, DLL1, DVL1, FZD1, GSK3B, NOTCH1, PSEN1, RBPSUH, TCF1, WNT1 10 APC(8), BTRC(2), CTNNB1(2), GSK3B(1) 6851948 13 12 13 7 0 2 4 5 2 0 0.36 0.75 301 PLCPATHWAY Phospholipase C hydrolyzes the membrane lipid PIP2 to DAG, which activates protein kinase C, and IP3, which causes calcium influx. AKT1, PIK3CA, PIK3R1, PLCB1, PLCG1, PRKCA, PRKCB1, VAV1 7 PIK3CA(2), PIK3R1(1), PLCB1(4), PRKCA(1), VAV1(2) 5724666 10 10 10 4 1 2 2 4 1 0 0.37 0.75 302 CHONDROITIN B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 8 B3GAT3(1), HS3ST3A1(1), XYLT1(4) 2478547 6 6 6 2 2 1 2 1 0 0 0.37 0.75 303 HEPARAN_SULFATE_BIOSYNTHESIS B3GAT3, B4GALT7, HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, XYLT1, XYLT2 8 B3GAT3(1), HS3ST3A1(1), XYLT1(4) 2478547 6 6 6 2 2 1 2 1 0 0 0.37 0.75 304 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(4), GLS(1) 3357119 6 6 6 5 0 1 4 0 1 0 0.37 0.75 305 P38MAPKPATHWAY The Rho family GTPases activate the p38 MAPKs under environmental stress or in the presence of pro-inflammatory cytokines. ATF2, CDC42, CREB1, DAXX, DDIT3, ELK1, GRB2, HMGN1, HRAS, HSPB1, HSPB2, MAP2K4, MAP2K6, MAP3K1, MAP3K5, MAP3K7, MAP3K9, MAPK14, MAPKAPK2, MAPKAPK5, MAX, MEF2A, MEF2B, MEF2C, MEF2D, MKNK1, MYC, PDZGEF1, PLA2G4A, RAC1, RIPK1, RPS6KA5, SHC1, STAT1, TGFB1, TGFB2, TGFB3, TGFBR1, TRADD, TRAF2 37 DAXX(1), DDIT3(2), ELK1(2), GRB2(2), MAP2K4(1), MAP2K6(1), MAP3K1(1), MAP3K5(2), MAP3K7(3), MAP3K9(1), MAPK14(1), MAPKAPK5(1), MEF2A(1), MEF2C(1), MEF2D(1), MKNK1(1), PLA2G4A(1), RPS6KA5(1), SHC1(1), STAT1(2), TRAF2(1) 16052954 28 28 28 8 1 5 11 5 6 0 0.37 0.75 306 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 IL13(2), IL4R(2), JAK2(2), TYK2(2) 4480421 8 8 8 3 0 2 0 5 1 0 0.37 0.75 307 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 IL13(2), IL4R(2), JAK2(2), TYK2(2) 4480421 8 8 8 3 0 2 0 5 1 0 0.37 0.75 308 TRKAPATHWAY Nerve growth factor (NGF) promotes neuronal survival and proliferation by binding its receptor TrkA, which activates PI3K/AKT, Ras, and the MAP kinase pathway. AKT1, DPM2, GRB2, HRAS, KLK2, NGFB, NTRK1, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, SHC1, SOS1 12 GRB2(2), KLK2(1), NTRK1(4), PIK3CA(2), PIK3R1(1), PRKCA(1), SHC1(1), SOS1(3) 6760845 15 13 15 8 3 3 7 1 1 0 0.37 0.75 309 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 60 AGPAT3(1), AGPAT4(2), AGPAT6(1), CDS1(1), CHKA(1), CHKB(1), CRLS1(1), DGKA(3), DGKB(3), DGKD(2), DGKE(1), DGKH(3), DGKI(1), ETNK2(2), GNPAT(4), GPAM(1), GPD2(1), LCAT(2), LYPLA2(1), MYST3(3), MYST4(5), PLA2G12A(1), PLA2G12B(1), PLA2G2F(1), PLA2G4A(1), PLA2G6(1), PLD1(1), PLD2(1), PPAP2A(1), PTDSS1(1) 27356663 49 44 49 15 4 6 17 16 6 0 0.38 0.75 310 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 30 AASDH(5), AASDHPPT(1), AASS(2), ACAT1(2), ACAT2(1), ALDH1A1(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), DLST(1), ECHS1(1), EHHADH(2), EHMT2(1), HADHA(1), PLOD1(1), PLOD2(1), PLOD3(3), SHMT1(1), SHMT2(1), TMLHE(1) 14859141 30 26 30 9 4 4 8 9 5 0 0.38 0.75 311 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 108 ATP12A(2), ATP4A(1), ATP5B(2), ATP5G2(1), ATP5J2(1), ATP5O(1), ATP6AP1(4), ATP6V0A2(1), ATP6V0D1(1), ATP6V1C2(2), ATP6V1D(1), ATP6V1E2(1), ATP6V1F(1), COX10(1), COX15(1), COX6B1(1), CYC1(1), NDUFA7(1), NDUFA9(1), NDUFB11(1), NDUFB2(1), NDUFB9(1), NDUFS1(1), NDUFS4(1), NDUFV3(2), PPA2(1), SDHA(1), TCIRG1(3), UQCRB(1), UQCRC1(1) 24165707 39 39 37 11 5 4 13 11 6 0 0.39 0.78 312 TOB1PATHWAY TGF-beta signaling activates SMADs, which interact with intracellular Tob to maintain unstimulated T cells by repressing IL-2 expression. CD28, CD3D, CD3E, CD3G, CD3Z, IFNG, IL2, IL2RA, IL4, MADH3, MADH4, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3, TOB1, TOB2, TRA@, TRB@ 16 CD3E(2), IL2RA(2), TGFBR2(3), TGFBR3(2), TOB1(1) 4811608 10 9 10 4 1 1 6 1 1 0 0.39 0.78 313 HSA00860_PORPHYRIN_AND_CHLOROPHYLL_METABOLISM Genes involved in porphyrin and chlorophyll metabolism ALAD, ALAS1, ALAS2, BLVRA, BLVRB, COX10, COX15, CP, CPOX, EARS2, EPRS, FECH, FTH1, FTMT, GUSB, HCCS, HMBS, HMOX1, HMOX2, MMAB, PPOX, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, UROD, UROS 40 ALAS1(1), BLVRA(1), COX10(1), COX15(1), CPOX(1), FTH1(1), FTMT(1), HMBS(1), PPOX(2), UGT1A10(2), UGT1A3(1), UGT1A5(1), UGT1A7(1), UGT1A8(2), UGT1A9(2), UGT2A1(3), UGT2A3(1), UGT2B10(2), UGT2B11(1), UGT2B17(1), UGT2B4(1), UGT2B7(1) 17527352 29 28 28 11 2 6 8 6 7 0 0.40 0.78 314 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 GRB2(2), IARS(1), IL4R(2), INPP5D(4), JAK2(2), JAK3(3), PIK3CA(2), SERPINA4(2), SHC1(1), SOS1(3), SOS2(1), STAT6(2), TYK2(2) 15352642 27 26 27 12 3 5 12 4 3 0 0.40 0.78 315 HSA00260_GLYCINE_SERINE_AND_THREONINE_METABOLISM Genes involved in glycine, serine and threonine metabolism ABP1, AGXT, AGXT2, AKR1B10, ALAS1, ALAS2, AMT, AOC2, AOC3, BHMT, CBS, CHDH, CHKA, CHKB, CTH, DAO, DLD, DMGDH, GAMT, GARS, GATM, GCAT, GLDC, GNMT, HSD3B7, MAOA, MAOB, PEMT, PHGDH, PIPOX, PISD, PSAT1, PSPH, RDH11, RDH12, RDH13, RDH14, SARDH, SARS, SARS2, SDS, SHMT1, SHMT2, TARS, TARS2 44 ABP1(2), AGXT(1), AGXT2(2), ALAS1(1), AOC2(4), AOC3(1), BHMT(1), CHDH(1), CHKA(1), CHKB(1), DMGDH(2), GARS(1), GLDC(2), MAOA(2), MAOB(1), PSAT1(1), PSPH(1), RDH12(1), RDH13(1), SARS2(1), SHMT1(1), SHMT2(1), TARS(2), TARS2(2) 18279579 34 31 34 12 4 3 10 7 10 0 0.40 0.78 316 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 85 CAPN10(1), CAPN11(1), CAPN5(1), CAPN6(2), CAPN7(1), CAPN9(2), CSK(1), DOCK1(4), GRB2(2), ITGA10(2), ITGA2B(4), ITGA3(2), ITGA4(3), ITGA5(1), ITGA6(1), ITGA8(3), ITGAD(1), ITGAE(1), ITGAL(3), ITGAV(2), ITGAX(1), ITGB2(2), ITGB6(1), ITGB7(4), MAP2K3(1), MAP2K6(1), MAPK6(1), MYLK2(1), PAK2(1), PAK3(5), PAK6(2), PDPK1(1), PIK3R2(2), PTK2(1), PXN(5), RAPGEF1(2), SHC1(1), SORBS1(2), SOS1(3), TLN1(1), TNS1(3), VAV2(4), VAV3(3), VCL(2) 56019859 88 76 87 24 10 7 36 23 12 0 0.40 0.78 317 CAPROLACTAM_DEGRADATION AKR1A1, ECHS1, EHHADH, HADHA, SDS 5 ECHS1(1), EHHADH(2), HADHA(1) 2127357 4 4 4 1 0 0 3 0 1 0 0.40 0.78 318 HSA00950_ALKALOID_BIOSYNTHESIS_I Genes involved in alkaloid biosynthesis I DDC, GOT1, GOT2, TAT, TYR 5 DDC(1), TAT(2), TYR(1) 2156312 4 4 4 3 0 1 1 2 0 0 0.41 0.79 319 HSA00531_GLYCOSAMINOGLYCAN_DEGRADATION Genes involved in glycosaminoglycan degradation ARSB, GALNS, GLB1, GNS, GUSB, HEXA, HEXB, HGSNAT, HPSE, HPSE2, HYAL1, HYAL2, IDS, IDUA, LCT, NAGLU, SPAM1 16 GLB1(2), HEXA(2), HEXB(1), HPSE(1), HPSE2(1), LCT(6), NAGLU(1), SPAM1(2) 8366998 16 15 16 4 0 2 6 5 3 0 0.41 0.79 320 HSA00624_1_AND_2_METHYLNAPHTHALENE_DEGRADATION Genes involved in 1- and 2-methylnaphthalene degradation ACAD8, ACAD9, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, ARD1A, DHRS1, DHRS2, DHRS3, DHRS7, DHRSX, ESCO1, ESCO2, LYCAT, MYST3, MYST4, NAT5, NAT6, PNPLA3, SH3GLB1 21 ACAD8(1), ACAD9(2), ADH1B(1), ADH1C(1), ADH4(1), ADH5(1), ADH6(1), ADHFE1(1), DHRS2(1), DHRS7(1), MYST3(3), MYST4(5) 10940233 19 18 19 6 0 4 4 5 6 0 0.41 0.79 321 HSA00062_FATTY_ACID_ELONGATION_IN_MITOCHONDRIA Genes involved in fatty acid elongation in mitochondria ACAA2, ECHS1, HADH, HADHA, HADHB, HSD17B10, HSD17B4, MECR, PPT1, PPT2 10 ACAA2(1), ECHS1(1), HADHA(1), HSD17B4(1), MECR(2), PPT1(1) 3813499 7 7 7 2 2 0 2 2 1 0 0.41 0.79 322 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 CDK2(1), CDKN1A(1), CDKN1B(1), E2F2(1), NXT1(1), PRB1(1) 2908928 6 6 6 5 2 2 1 1 0 0 0.41 0.79 323 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 48 ACTG1(2), APAF1(2), BID(1), BIRC3(2), CASP2(1), CASP6(1), CASP7(1), CASP9(1), CHUK(1), DAXX(1), FADD(1), GSN(1), LMNA(4), LMNB1(1), MAP3K1(1), MAP3K14(1), MAP3K5(2), MAPK8(1), NFKB1(1), NUMA1(4), PAK2(1), PRKDC(8), PTK2(1), RASA1(1), RELA(1), SPTAN1(5), TNF(1), TNFRSF1A(1), TRAF1(4), TRAF2(1) 28666739 54 46 54 12 6 12 13 15 8 0 0.42 0.79 324 STILBENE_COUMARINE_AND_LIGNIN_BIOSYNTHESIS EPX, GBA3, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TPO, TYR 10 EPX(2), LPO(1), TPO(4), TYR(1) 4112949 8 8 8 3 1 0 4 2 1 0 0.42 0.80 325 EIF4PATHWAY The eIF-4F complex recognizes 5' mRNA caps, recruits RNA helicases, and maintains mRNA-ribosome bridging. AKT1, EIF4A1, EIF4A2, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FRAP1, GHR, IRS1, MAPK1, MAPK14, MAPK3, MKNK1, PABPC1, PDK2, PDPK1, PIK3CA, PIK3R1, PRKCA, PRKCB1, PTEN, RPS6KB1 22 EIF4A1(1), EIF4A2(2), EIF4EBP1(1), EIF4G2(1), EIF4G3(1), GHR(1), IRS1(6), MAPK14(1), MKNK1(1), PABPC1(2), PDPK1(1), PIK3CA(2), PIK3R1(1), PRKCA(1), PTEN(2) 12111501 24 20 24 8 2 3 9 6 4 0 0.43 0.81 326 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 30 AKR1B1(3), B4GALT2(1), G6PC(1), GAA(2), GALE(1), GLB1(2), HK1(1), HK2(1), HK3(3), LCT(6), MGAM(5), PFKP(2), RDH12(1), RDH13(1) 15620630 30 28 30 4 5 5 9 7 4 0 0.43 0.81 327 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 26 DUSP1(2), GORASP1(2), MAP2K4(1), MAPK14(1), MAPK8(1), MAPK8IP1(1), MAPK9(1), MAPKAPK5(1), NFKB1(1), PIK3CA(2), PIK3R1(1), TRAF2(1), TRAF5(1), TRAF6(2) 11136168 18 18 18 7 4 4 3 4 3 0 0.43 0.82 328 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 ALOX15(1), ALOX5(1), CYP1A2(1), CYP2C18(2), CYP2C19(4), CYP2C9(1), CYP2E1(1), CYP2J2(1), CYP3A43(1), PLA2G12A(1), PLA2G12B(1), PLA2G2F(1), PLA2G4A(1), PLA2G6(1), RDH12(1), RDH13(1) 10582968 20 19 20 6 2 2 10 4 2 0 0.44 0.82 329 SIG_IL4RECEPTOR_IN_B_LYPHOCYTES Genes related to IL4 rceptor signaling in B lymphocytes AKT1, AKT2, AKT3, BAD, BCL2, GRB2, GSK3A, GSK3B, IL4R, IRS1, IRS2, JAK1, JAK3, MAP4K1, MAPK1, MAPK3, PDK1, PIK3CA, PIK3CD, PIK3R1, PPP1R13B, RAF1, SHC1, SOCS1, SOS1, SOS2, STAT6 25 GRB2(2), GSK3A(2), GSK3B(1), IL4R(2), IRS1(6), JAK3(3), MAP4K1(1), PDK1(1), PIK3CA(2), PIK3R1(1), SHC1(1), SOS1(3), SOS2(1), STAT6(2) 14548954 28 25 28 13 2 8 13 2 3 0 0.44 0.82 330 TALL1PATHWAY APRIL and BAFF bind to BCMA and TACI receptors on B cell surfaces, promoting immunoglobulin production and cell proliferation. CHUK, MAP3K14, MAPK14, MAPK8, NFKB1, RELA, TNFRSF13B, TNFRSF13C, TNFRSF17, TNFSF13, TNFSF13B, TRAF2, TRAF3, TRAF5, TRAF6 14 CHUK(1), MAP3K14(1), MAPK14(1), MAPK8(1), NFKB1(1), RELA(1), TNFSF13B(1), TRAF2(1), TRAF5(1), TRAF6(2) 6150369 11 11 11 3 2 3 4 2 0 0 0.44 0.82 331 ST_GRANULE_CELL_SURVIVAL_PATHWAY The survival and differentiation of granule cells in the brain is controlled by pro-growth PACAP and pro-apoptotic ceramides. ADPRT, APC, ASAH1, CAMP, CASP3, CERK, CREB1, CREB3, CREB5, CXCL2, DAG1, EPHB2, FOS, GNAQ, IL8RB, ITPKA, ITPKB, JUN, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, PACAP 21 APC(8), DAG1(3), EPHB2(1), FOS(1), ITPKB(4), MAP2K4(1), MAPK8(1), MAPK8IP1(1), MAPK9(1) 10547207 21 18 21 7 2 3 5 8 3 0 0.44 0.82 332 PYRIMIDINE_METABOLISM AK3, AK3L1, AK3L1, AK3L2, CAD, CANT1, CDA, CMPK, CTPS, CTPS2, DCK, DCTD, DHODH, DPYD, DPYS, DTYMK, DUT, ECGF1, ENTPD1, ITPA, NME1, NME2, NP, NT5C, NT5E, NT5M, NUDT2, POLA, POLB, POLD1, POLD2, POLE, POLG, POLL, POLQ, POLR1B, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLRMT, POLS, RRM1, RRM2, TK1, TK2, TXNRD1, TYMS, UCK1, UCK2, UMPS, UNG, UPB1, UPP1 53 AK3(2), CAD(5), CDA(1), CTPS2(1), DCK(1), DCTD(1), DHODH(1), DPYD(3), DPYS(1), ENTPD1(2), ITPA(1), NT5E(2), POLB(1), POLD1(1), POLD2(2), POLE(2), POLG(1), POLQ(3), POLR2B(2), POLR2C(1), POLR2I(1), UCK2(1), UMPS(1), UNG(1), UPB1(1), UPP1(1) 24226493 40 37 40 10 7 4 15 8 6 0 0.44 0.82 333 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 CXCR3(2), EGFR(7), ITGA1(1), MYL2(1), MYLK(6), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PTK2(1), PXN(5), TLN1(1) 14438758 27 24 27 11 5 2 9 8 3 0 0.44 0.82 334 STATIN_PATHWAY_PHARMGKB ABCA1, APOA1, APOA1, LOC440837, APOA4, APOC1, APOC2, APOC3, APOC3, LOC440838, APOE, CETP, CYP7A1, DGAT1, HMGCR, LCAT, LDLR, LIPC, LPL, LRP1, SCARB1, SOAT1 14 ABCA1(5), CYP7A1(1), HMGCR(1), LCAT(2), LDLR(3), LPL(1), LRP1(7) 10976763 20 20 20 2 5 1 8 4 2 0 0.45 0.82 335 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 NFKB1(1), PLCB1(4), PRKCA(1), RELA(1) 3696182 7 7 7 1 2 1 3 1 0 0 0.45 0.82 336 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 16 EGFR(7), GRB2(2), PTPRB(1), RASA1(1), SHC1(1), SOS1(3), SPRY1(1), SPRY2(1), SPRY4(1) 10477578 18 18 18 8 2 2 9 4 1 0 0.45 0.82 337 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), ADH1C(1), ADH4(1), ADH5(1), ADH6(1), ADHFE1(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ALDH7A1(1) 5896766 11 10 11 3 0 2 2 4 3 0 0.45 0.82 338 SIG_CHEMOTAXIS Genes related to chemotaxis ACTR2, ACTR3, AKT1, AKT2, AKT3, ANGPTL2, ARHGAP1, ARHGAP4, ARHGEF11, BTK, CDC42, CFL1, CFL2, GDI1, GDI2, INPPL1, ITPR1, ITPR2, ITPR3, LIMK1, MYLK, MYLK2, P101-PI3K, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDK1, PIK3CA, PIK3CD, PIK3CG, PIK3R1, PITX2, PPP1R13B, PTEN, RACGAP1, RHO, ROCK1, ROCK2, RPS4X, SAG, WASF1, WASL 44 ANGPTL2(1), ARHGAP1(1), ARHGEF11(2), BTK(1), INPPL1(1), ITPR1(3), ITPR2(5), ITPR3(3), LIMK1(1), MYLK(6), MYLK2(1), PAK2(1), PAK3(5), PAK6(2), PAK7(1), PDK1(1), PIK3CA(2), PIK3CG(3), PIK3R1(1), PITX2(1), PTEN(2), SAG(1) 29722180 45 44 45 14 2 5 17 15 6 0 0.45 0.82 339 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(2), RELN(8), VLDLR(1) 6388360 11 11 11 4 1 3 3 3 1 0 0.46 0.83 340 NGFPATHWAY Nerve growth factor (NGF) stimulates neural survival and proliferation via the TrkA and p75 receptors, which induce DAG and IP3 production and activate Ras. CSNK2A1, DPM2, ELK1, FOS, GRB2, HRAS, JUN, KLK2, MAP2K1, MAPK3, MAPK8, NGFB, NGFR, PIK3CA, PIK3R1, PLCG1, RAF1, SHC1, SOS1 18 CSNK2A1(1), ELK1(2), FOS(1), GRB2(2), KLK2(1), MAPK8(1), NGFR(1), PIK3CA(2), PIK3R1(1), SHC1(1), SOS1(3) 8183579 16 14 16 5 0 4 8 3 1 0 0.46 0.83 341 MSPPATHWAY Macrophage stimulating protein is synthesized as pro-MSP by the liver and, on proteolysis, binds to monocyte receptor kinase RON to induce macrophage development. CCL2, CSF1, IL1B, MST1, MST1R, TNF 6 CSF1(1), MST1R(3), TNF(1) 2405880 5 5 5 1 1 1 3 0 0 0 0.47 0.84 342 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 29 ADCY3(2), ADRBK2(2), CALM3(1), CAMK2B(2), CAMK2D(1), CAMK2G(1), CLCA1(2), CLCA2(2), CLCA4(1), CNGA3(5), CNGB1(2), GNAL(1), PRKACG(1), PRKG1(1) 13316774 24 24 24 3 3 2 10 5 4 0 0.47 0.84 343 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 ACAT1(2), ACAT2(1), ACOT11(1), DHRS2(1), DHRS7(1), ECHS1(1), EHHADH(2), HADHA(1), MYST3(3), MYST4(5), YOD1(3) 11241811 21 18 21 5 0 3 7 5 6 0 0.47 0.85 344 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 ACAA2(1), ADH1B(1), ADH1C(1), ADH4(1), ADH6(1), ADHFE1(1), AKR1C4(1), ALDH1A1(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), BAAT(1), CYP27A1(1), CYP7A1(1), SOAT2(2), SRD5A2(1) 10225508 18 17 18 8 0 4 5 6 3 0 0.47 0.85 345 STRESSPATHWAY Tumor necrosis factor receptor TNFR1 promotes apoptosis and activates the pro-inflammatory NF-kB, while TNFR2 activates stress-activated protein kinases (SAPKs). ATF1, CASP2, CHUK, CRADD, IKBKB, IKBKG, JUN, LTA, MAP2K3, MAP2K4, MAP2K6, MAP3K1, MAP3K14, MAP4K2, MAPK14, MAPK8, NFKB1, NFKBIA, RELA, RIPK1, TANK, TNF, TNFRSF1A, TRADD, TRAF2 23 ATF1(3), CASP2(1), CHUK(1), IKBKB(1), MAP2K3(1), MAP2K4(1), MAP2K6(1), MAP3K1(1), MAP3K14(1), MAPK14(1), MAPK8(1), NFKB1(1), RELA(1), TNF(1), TNFRSF1A(1), TRAF2(1) 10059042 18 18 18 5 3 5 5 4 1 0 0.48 0.85 346 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 CLOCK(1), CRY1(2), CSNK1E(1), PER1(2) 3537733 6 6 6 2 0 1 2 2 1 0 0.48 0.85 347 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 68 CALM3(1), CDS1(1), DGKA(3), DGKB(3), DGKD(2), DGKE(1), DGKH(3), DGKI(1), INPP1(1), INPP4A(1), INPP4B(1), INPP5D(4), INPPL1(1), ITPK1(1), ITPKB(4), ITPR1(3), ITPR2(5), ITPR3(3), OCRL(1), PI4KA(1), PI4KB(2), PIK3C2A(3), PIK3C2B(3), PIK3CA(2), PIK3CB(1), PIK3CG(3), PIK3R1(1), PIK3R2(2), PIK3R5(1), PIP4K2A(1), PIP4K2B(1), PIP5K1A(1), PIP5K1C(1), PLCB1(4), PLCB2(4), PLCB3(2), PLCB4(1), PLCD4(2), PLCE1(1), PLCG2(1), PLCZ1(1), PRKCA(1), PRKCG(1), PTEN(2), SYNJ1(2) 51645361 85 71 85 24 7 16 28 25 9 0 0.48 0.85 348 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(2) 1383611 2 2 2 0 1 0 0 1 0 0 0.48 0.85 349 HSA00565_ETHER_LIPID_METABOLISM Genes involved in ether lipid metabolism AGPAT1, AGPAT2, AGPAT3, AGPAT4, AGPAT6, AGPS, CHPT1, ENPP2, ENPP6, LYCAT, PAFAH1B1, PAFAH1B2, PAFAH1B3, PAFAH2, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLD1, PLD2, PPAP2A, PPAP2B, PPAP2C 29 AGPAT3(1), AGPAT4(2), AGPAT6(1), ENPP2(3), PAFAH1B3(1), PAFAH2(2), PLA2G12A(1), PLA2G12B(1), PLA2G2F(1), PLA2G4A(1), PLA2G6(1), PLD1(1), PLD2(1), PPAP2A(1) 10146738 18 18 18 4 3 4 5 5 1 0 0.49 0.86 350 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 JAK2(2), JAK3(3), STAT3(1), TYK2(2) 4857650 8 8 8 4 1 1 1 3 2 0 0.49 0.86 351 CCR3PATHWAY CCR3 is a G-protein coupled receptor that recruits eosinophils to inflammation sites via chemokine ligands. ARHA, CCL11, CCR3, CFL1, GNAQ, GNAS, GNB1, GNGT1, HRAS, LIMK1, MAP2K1, MAPK1, MAPK3, MYL2, NOX1, PIK3C2G, PLCB1, PPP1R12B, PRKCA, PRKCB1, PTK2, RAF1, ROCK2 21 CCR3(2), GNAS(3), LIMK1(1), MYL2(1), NOX1(1), PLCB1(4), PPP1R12B(4), PRKCA(1), PTK2(1) 11018345 18 18 17 8 1 1 10 3 3 0 0.49 0.86 352 HSA00401_NOVOBIOCIN_BIOSYNTHESIS Genes involved in novobiocin biosynthesis GOT1, GOT2, TAT 3 TAT(2) 1217953 2 2 2 1 0 1 0 1 0 0 0.49 0.86 353 LIMONENE_AND_PINENE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, ECHS1, EHHADH, HADHA, SDS 12 ALDH1A1(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ECHS1(1), EHHADH(2), HADHA(1) 5313211 9 9 9 4 0 2 3 2 2 0 0.50 0.86 354 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 20 ADCY1(4), ITGAV(2), PDGFRA(3), PIK3CA(2), PIK3R1(1), PLCB1(4), PRKCA(1), PTK2(1), SPHK1(1) 11431562 19 19 19 9 5 3 4 5 2 0 0.50 0.86 355 MITOCHONDRIAPATHWAY Pro-apoptotic signaling induces mitochondria to release cytochrome c, which stimulates Apaf-1 to activate caspase 9. APAF1, BAK1, BAX, BCL2, BCL2L1, BID, BIK, BIRC2, BIRC3, BIRC4, CASP3, CASP6, CASP7, CASP8, CASP9, CYCS, DFFA, DFFB, DIABLO, ENDOG, PDCD8 18 APAF1(2), BAK1(1), BID(1), BIRC3(2), CASP6(1), CASP7(1), CASP9(1), DIABLO(1) 5944434 10 10 10 6 0 1 6 3 0 0 0.50 0.86 356 BETAOXIDATIONPATHWAY Beta-Oxidation of Fatty Acids ACADL, ACADM, ACADS, ACAT1, ECHS1, HADHA 6 ACADM(1), ACAT1(2), ECHS1(1), HADHA(1) 2304868 5 4 5 1 1 1 2 0 1 0 0.50 0.86 357 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 ANGPTL2(1), DAG1(3), DGKA(3), GCA(1), ITPKB(4), ITPR1(3), ITPR2(5), ITPR3(3), NR1I3(1), PDE3A(4), PIK3CA(2), PIK3R1(1), PSME1(2), RIPK3(2) 20841276 35 32 35 13 2 4 13 9 7 0 0.50 0.86 358 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 21 ADCY1(4), CAP1(1), GNAS(3), MYT1(2), PRKACG(1), PRKAR2A(1), PRKAR2B(1), RPS6KA1(1) 7845498 14 14 13 3 5 0 2 5 2 0 0.51 0.86 359 CYSTEINE_METABOLISM CARS, CTH, GOT1, GOT2, LDHA, LDHB, LDHC, MPST 7 CARS(3), LDHB(1), LDHC(1) 2970053 5 5 5 1 0 0 3 2 0 0 0.51 0.86 360 HSA00252_ALANINE_AND_ASPARTATE_METABOLISM Genes involved in alanine and aspartate metabolism AARS, AARS2, ABAT, ACY3, ADSL, ADSS, ADSSL1, AGXT, AGXT2, ASL, ASNS, ASPA, ASRGL1, ASS1, CAD, CRAT, DARS, DARS2, DDO, DLAT, DLD, GAD1, GAD2, GOT1, GOT2, GPT, GPT2, NARS, NARS2, PC, PDHA1, PDHA2, PDHB 32 AARS(1), AARS2(1), ADSL(1), ADSSL1(3), AGXT(1), AGXT2(2), ASNS(2), ASRGL1(1), ASS1(1), CAD(5), DARS(1), DARS2(1), DDO(3), DLAT(1), GAD1(1), GAD2(1), NARS2(2) 16012567 28 27 28 13 4 2 11 9 2 0 0.51 0.86 361 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 CALM3(1), CAMK2B(2), CAMK2D(1), CAMK2G(1), CAMK4(3), HDAC5(1), MEF2A(1), MEF2C(1), MEF2D(1), PPARA(1), PPP3CC(1), SLC2A4(1) 8556433 15 15 15 6 1 2 8 3 1 0 0.51 0.86 362 HSA00340_HISTIDINE_METABOLISM Genes involved in histidine metabolism ABP1, ACY3, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH7A1, ALDH9A1, AMDHD1, AOC2, AOC3, ASPA, CARM1, CNDP1, DDC, FTCD, HAL, HARS, HARS2, HDC, HEMK1, HNMT, LCMT1, LCMT2, MAOA, MAOB, METTL2B, METTL6, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, PRPS1, PRPS2, UROC1, WBSCR22 40 ABP1(2), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ALDH7A1(1), AMDHD1(1), AOC2(4), AOC3(1), DDC(1), HAL(1), HNMT(1), MAOA(2), MAOB(1), METTL6(1), PRMT5(2), PRMT8(3), UROC1(2), WBSCR22(1) 16708635 28 27 28 9 3 1 8 11 5 0 0.51 0.86 363 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 IL8(1) 667417 1 1 1 0 0 0 0 1 0 0 0.51 0.86 364 HSA00970_AMINOACYL_TRNA_BIOSYNTHESIS Genes involved in aminoacyl-tRNA biosynthesis AARS, AARS2, CARS, CARS2, DARS, DARS2, EARS2, EPRS, FARS2, FARSA, FARSB, GARS, HARS, HARS2, IARS, IARS2, KARS, LARS, LARS2, MARS, MARS2, MTFMT, NARS, NARS2, PARS2, QARS, RARS, RARS2, SARS, SARS2, TARS, TARS2, VARS, VARS2, WARS, WARS2, YARS, YARS2 38 AARS(1), AARS2(1), CARS(3), DARS(1), DARS2(1), FARSA(4), FARSB(1), GARS(1), IARS(1), IARS2(2), KARS(1), MARS(2), MARS2(3), MTFMT(3), NARS2(2), PARS2(1), QARS(1), RARS(1), RARS2(2), SARS2(1), TARS(2), TARS2(2), VARS(1), VARS2(3), WARS(1) 24300098 42 38 42 12 6 7 19 8 2 0 0.51 0.86 365 SRCRPTPPATHWAY Activation of Src by Protein-tyrosine phosphatase alpha CCNB1, CDC2, CDC25A, CDC25B, CDC25C, CSK, GRB2, PRKCA, PRKCB1, PTPRA, SRC 8 CDC25B(2), CSK(1), GRB2(2), PRKCA(1) 3659937 6 6 6 1 1 0 4 0 1 0 0.51 0.86 366 HSA00791_ATRAZINE_DEGRADATION Genes involved in atrazine degradation ADAR, APOBEC1, APOBEC2, APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3F, APOBEC3G, APOBEC4 9 ADAR(4), APOBEC3A(1), APOBEC3B(1) 3322067 6 6 6 0 2 2 1 1 0 0 0.51 0.86 367 SIG_REGULATION_OF_THE_ACTIN_CYTOSKELETON_BY_RHO_GTPASES Genes related to regulation of the actin cytoskeleton ACTG1, ACTG2, ACTR2, ACTR3, AKT1, ANGPTL2, CDC42, CFL1, CFL2, FLNA, FLNC, FSCN1, FSCN2, FSCN3, GDI1, GDI2, LIMK1, MYH2, MYLK, MYLK2, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PFN1, PFN2, RHO, ROCK1, ROCK2, RPS4X, VASP, WASF1, WASL 34 ACTG1(2), ANGPTL2(1), FLNA(1), FLNC(3), FSCN3(1), LIMK1(1), MYH2(5), MYLK(6), MYLK2(1), PAK2(1), PAK3(5), PAK6(2), PAK7(1), PFN2(1) 18413045 31 31 31 7 4 1 14 10 2 0 0.52 0.86 368 AGPCRPATHWAY G-protein coupled receptors (GPCRs) transduce extracellular signals across the plasma membrane; attenuation occurs by signal molecule degradation or receptor-mediated endocytosis. ARRB1, GNAS, GNB1, GNGT1, GPRK2L, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1 11 GNAS(3), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PRKCA(1) 3880714 7 7 6 0 2 0 1 2 2 0 0.52 0.86 369 1_AND_2_METHYLNAPHTHALENE_DEGRADATION ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1 7 ADH1B(1), ADH1C(1), ADH4(1), ADH6(1), ADHFE1(1) 2609919 5 4 5 2 0 1 2 1 1 0 0.52 0.86 370 STEMPATHWAY In the absence of infection, bone marrow stromal cells release hematopoietic cytokines; activated macrophages and Th cells induce hematopoiesis during infection. CD4, CD8A, CSF1, CSF2, CSF3, EPO, IL11, IL2, IL3, IL4, IL5, IL6, IL7, IL8, IL9 14 CD4(1), CD8A(1), CSF1(1), CSF3(1), IL8(1) 2701009 5 5 5 2 2 0 1 1 1 0 0.52 0.86 371 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 13 EGFR(7), IGF1R(1), PPP2CA(2), PRKCA(1), TEP1(5), TERF1(1), TERT(1), TNKS(1) 11132654 19 19 19 7 3 1 7 4 4 0 0.52 0.86 372 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 29 ARHGAP1(1), ARHGAP5(2), ARHGAP6(1), ARHGEF1(3), ARHGEF11(2), ARPC1A(1), ARPC3(1), GSN(1), LIMK1(1), MYL2(1), MYLK(6), OPHN1(3), PIP5K1A(1), PPP1R12B(4), TLN1(1), VCL(2) 19274394 31 31 31 6 3 5 13 9 1 0 0.52 0.86 373 PTDINSPATHWAY Phosphoinositide 3 kinase (PI3K) phosphorylate inositol rings of phosphoinositide lipids, influencing vesicle trafficking, cell proliferation, and migration. AKT1, AP2A1, AP2M1, ARF1, BAD, BTK, EEA1, GRASP, GSK3A, GSK3B, LYN, PDPK1, PFKL, PFKM, PFKP, PFKX, PLCG1, PRKCE, PRKCZ, RAB5A, RAC1, RPS6KB1, VAV2 21 AP2A1(2), BTK(1), EEA1(1), GSK3A(2), GSK3B(1), LYN(1), PDPK1(1), PFKP(2), PRKCE(1), PRKCZ(2), VAV2(4) 9792746 18 17 18 4 3 2 9 4 0 0 0.52 0.86 374 AMINOSUGARS_METABOLISM CMAS, CYB5R3, GCK, GFPT1, GNE, GNPDA1, GNPDA2, HEXA, HEXB, HK1, HK2, HK3, PGM3, RENBP, UAP1 15 CMAS(1), GNPDA2(1), HEXA(2), HEXB(1), HK1(1), HK2(1), HK3(3), RENBP(2), UAP1(2) 7342680 14 12 14 1 1 2 5 4 2 0 0.52 0.86 375 PDGFPATHWAY Platelet-derived growth factor (PDGF) receptor is phosphorylated on ligand binding and promotes cell proliferation. CSNK2A1, ELK1, FOS, GRB2, HRAS, JAK1, JUN, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, PDGFA, PDGFRA, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, RAF1, RASA1, SHC1, SOS1, SRF, STAT1, STAT3, STAT5A 25 CSNK2A1(1), ELK1(2), FOS(1), GRB2(2), MAP2K4(1), MAP3K1(1), MAPK8(1), PDGFRA(3), PIK3CA(2), PIK3R1(1), PRKCA(1), RASA1(1), SHC1(1), SOS1(3), SRF(1), STAT1(2), STAT3(1), STAT5A(2) 15043225 27 24 27 8 3 4 13 5 2 0 0.52 0.86 376 ST_ERK1_ERK2_MAPK_PATHWAY The Erk1 and Erk2 MAP kinase pathways are regulated by Raf, Mos, and Tpl-2. ARAF1, ATF1, BAD, BRAF, COPEB, CREB1, CREB3, CREB5, DUSP4, DUSP6, DUSP9, EEF2K, EIF4E, GRB2, HTATIP, MAP2K1, MAP2K2, MAP3K8, MAPK1, MAPK3, MKNK1, MKNK2, MOS, NFKB1, RAP1A, RPS6KA1, RPS6KA2, RPS6KA3, SHC1, SOS1, SOS2, TRAF3 28 ATF1(3), BRAF(2), DUSP9(2), EEF2K(2), GRB2(2), MKNK1(1), MOS(1), NFKB1(1), RPS6KA1(1), RPS6KA2(1), SHC1(1), SOS1(3), SOS2(1) 12735845 21 21 21 9 1 2 9 5 4 0 0.53 0.86 377 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 ACAA2(1), ACAD8(1), ACAD9(2), ADH1B(1), ADH1C(1), ADH4(1), ADH5(1), ADH6(1), ADHFE1(1), AKR1C4(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ALDH7A1(1), BAAT(1), CYP27A1(1), CYP7A1(1), RDH12(1), RDH13(1), SOAT2(2), SRD5A2(1) 13798749 24 22 24 8 1 4 6 7 6 0 0.53 0.87 378 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(2), ALDH1A1(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), AOC2(4), AOC3(1), DDC(1), HAL(1), HNMT(1), MAOA(2), MAOB(1) 10873040 18 18 18 8 1 2 4 6 5 0 0.54 0.87 379 D4GDIPATHWAY D4-GDI inhibits the pro-apoptotic Rho GTPases and is cleaved by caspase-3. ADPRT, APAF1, ARHGAP5, ARHGDIB, CASP1, CASP10, CASP3, CASP8, CASP9, CYCS, GZMB, JUN, PRF1 12 APAF1(2), ARHGAP5(2), CASP1(2), CASP9(1), PRF1(2) 5756868 9 9 9 3 1 2 1 4 1 0 0.54 0.87 380 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 CALM3(1), CAMK2B(2), CAMK2D(1), CAMK2G(1), CAMK4(3) 4889723 8 8 8 4 1 1 3 2 1 0 0.54 0.87 381 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 19 ATM(5), ATR(2), CDC25B(2), CDKN1A(1), CDKN2D(1), CHEK2(1), EP300(1), GADD45A(1), MYT1(2), PRKDC(8), RPS6KA1(1) 16701039 25 24 25 4 2 3 6 10 4 0 0.54 0.87 382 FATTY_ACID_BIOSYNTHESIS_PATH_2 ACAA1, ACAA2, ACAT1, ACAT2, ECHS1, EHHADH, HADHA, HADHB, SDS 9 ACAA2(1), ACAT1(2), ACAT2(1), ECHS1(1), EHHADH(2), HADHA(1) 3733981 8 6 8 4 0 1 5 1 1 0 0.54 0.87 383 IGF1RPATHWAY Insulin-like growth factor receptor IGF-1R promotes cell growth and inhibits apoptosis on binding of ligands IGF-1 and 2 via Ras activation and the AKT pathway. AKT1, BAD, GRB2, HRAS, IGF1R, IRS1, MAP2K1, MAPK1, MAPK3, PIK3CA, PIK3R1, RAF1, SHC1, SOS1, YWHAH 15 GRB2(2), IGF1R(1), IRS1(6), PIK3CA(2), PIK3R1(1), SHC1(1), SOS1(3) 7909616 16 13 16 6 0 4 8 2 2 0 0.54 0.87 384 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 10 FOS(1), FXYD2(1), KEAP1(1), MAPK14(1), MAPK8(1), PRKCA(1) 3597758 6 6 6 3 1 2 1 2 0 0 0.56 0.89 385 SARSPATHWAY The SARS coronavirus has a 30kb RNA genome containing rep, a large gene encoding viral protease Mpro. ANPEP, CKM, EIF4E, FBL, GPT, LDHA, LDHB, LDHC, MAPK14, NCL 9 ANPEP(2), FBL(1), LDHB(1), LDHC(1), MAPK14(1) 3783741 6 6 6 4 0 2 2 2 0 0 0.56 0.89 386 IL10PATHWAY The cytokine IL-10 inhibits the inflammatory response by macrophages via activation of heme oxygenase 1. BLVRA, BLVRB, HMOX1, IL10, IL10RA, IL10RB, IL1A, IL6, JAK1, STAT1, STAT3, STAT5A, TNF 13 BLVRA(1), IL10RA(1), IL10RB(1), STAT1(2), STAT3(1), STAT5A(2), TNF(1) 5353975 9 9 9 4 1 1 5 1 1 0 0.56 0.89 387 SA_G2_AND_M_PHASES Cdc25 activates the cdc2/cyclin B complex to induce the G2/M transition. CDC2, CDC25A, CDC25B, CDK7, CDKN1A, CHEK1, NEK1, WEE1 7 CDC25B(2), CDKN1A(1), NEK1(2) 3203612 5 5 5 1 2 0 2 1 0 0 0.56 0.90 388 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 INPP1(1), INPP4A(1), INPP4B(1), INPPL1(1), ITPKB(4), OCRL(1), PIK3C2A(3), PIK3C2B(3), PIK3CA(2), PIK3CB(1), PIK3CG(3), PLCB1(4), PLCB2(4), PLCB3(2), PLCB4(1), PLCG2(1) 19109252 33 31 33 11 3 8 11 10 1 0 0.57 0.90 389 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 FOS(1), GRB2(2), IL2RA(2), IL2RB(1), IRS1(6), JAK3(3), PIK3CA(2), PIK3R1(1), SHC1(1), SOS1(3), STAT5A(2), STAT5B(3) 14800824 27 24 27 9 2 6 13 3 3 0 0.57 0.90 390 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 F2(3), F5(3), F7(1), F8(4), F9(1), FGA(3), FGB(2), LPA(2), PLAU(2), SERPINE1(1), VWF(4) 15347354 26 24 26 10 4 3 10 6 3 0 0.57 0.90 391 ATP_SYNTHESIS ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H 21 ATP5O(1), ATP6AP1(4), ATP6V0D1(1), ATP6V1C2(2), ATP6V1D(1), ATP6V1F(1), SHMT1(1) 6853412 11 11 10 2 3 0 2 5 1 0 0.58 0.90 392 FLAGELLAR_ASSEMBLY ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H 21 ATP5O(1), ATP6AP1(4), ATP6V0D1(1), ATP6V1C2(2), ATP6V1D(1), ATP6V1F(1), SHMT1(1) 6853412 11 11 10 2 3 0 2 5 1 0 0.58 0.90 393 TYPE_III_SECRETION_SYSTEM ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H 21 ATP5O(1), ATP6AP1(4), ATP6V0D1(1), ATP6V1C2(2), ATP6V1D(1), ATP6V1F(1), SHMT1(1) 6853412 11 11 10 2 3 0 2 5 1 0 0.58 0.90 394 METHIONINE_METABOLISM AHCY, BHMT, CBS, CTH, DNMT1, DNMT2, DNMT3A, DNMT3B, MARS, MARS2, MAT1A, MAT2B, MTR 12 BHMT(1), DNMT1(2), DNMT3A(3), DNMT3B(2), MARS(2), MARS2(3) 7584595 13 13 13 3 1 3 5 4 0 0 0.58 0.90 395 SODDPATHWAY Some members of the tumor necrosis factor receptor family have cytoplasmic death domains that promote apoptosis when active and are repressed by silencers called SODDs. BAG4, BIRC3, CASP8, FADD, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TRADD, TRAF2 9 BIRC3(2), FADD(1), TNF(1), TNFRSF1A(1), TRAF2(1) 3425831 6 6 6 2 0 2 4 0 0 0 0.58 0.91 396 CARDIACEGFPATHWAY Cardiac hypertrophy, a response to high blood pressure, is stimulated by GPCR ligands such as angiotensin II that activate the EGF pathway. ADAM12, AGT, AGTR2, ARHA, EDN1, EDNRA, EDNRB, EGF, EGFR, FOS, HRAS, JUN, MYC, NFKB1, PLCG1, PRKCA, PRKCB1, RELA 16 ADAM12(1), AGTR2(2), EDNRA(1), EGFR(7), FOS(1), NFKB1(1), PRKCA(1), RELA(1) 9209570 15 15 15 8 4 2 4 4 1 0 0.59 0.91 397 IL6PATHWAY IL-6 binding to its receptor activates JAK kinases and a variety of transcription factors, with effects in neuronal differentiation, bone loss, and inflammation. CEBPB, CSNK2A1, ELK1, FOS, GRB2, HRAS, IL6, IL6R, IL6ST, JAK1, JAK2, JAK3, JUN, MAP2K1, MAPK3, PTPN11, RAF1, SHC1, SOS1, SRF, STAT3 20 CSNK2A1(1), ELK1(2), FOS(1), GRB2(2), IL6R(1), JAK2(2), JAK3(3), SHC1(1), SOS1(3), SRF(1), STAT3(1) 10230094 18 16 18 7 2 2 9 3 2 0 0.59 0.91 398 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 28 CMAS(1), CYB5R1(1), GFPT2(1), GNPDA2(1), HEXA(2), HEXB(1), HK1(1), HK2(1), HK3(3), MTMR1(2), MTMR6(2), NANS(1), RENBP(2), UAP1(2) 12323838 21 19 21 5 4 3 5 5 4 0 0.59 0.91 399 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 23 ABL1(1), ATM(5), ATR(2), CCNA1(2), CDK2(1), CDKN1A(1), CDKN1B(1), GSK3B(1), HDAC1(1), SKP2(2), TFDP1(2) 12074531 19 18 19 5 1 5 5 5 3 0 0.60 0.91 400 SULFUR_METABOLISM BPNT1, PAPSS1, PAPSS2, SULT1A2, SULT1A3, SULT1A3, SULT1A4, SULT1E1, SULT2A1, SUOX 7 BPNT1(1), PAPSS2(1), SULT1E1(1), SULT2A1(1) 2774113 4 4 4 0 0 0 1 2 1 0 0.60 0.91 401 SA_PROGRAMMED_CELL_DEATH Programmed cell death, or apoptosis, eliminates damaged or unneeded cells. APAF1, BAD, BAK1, BAX, BCL10, BCL2, BCL2L1, BCL2L11, BID, CASP8AP2, CASP9, CES1 12 APAF1(2), BAK1(1), BID(1), CASP8AP2(1), CASP9(1), CES1(1) 4612714 7 7 7 3 0 1 4 2 0 0 0.60 0.91 402 RASPATHWAY Ras activation stimulates many signaling cascades, including PI3K/AKT activation to inhibit apoptosis. AKT1, ARHA, BAD, BCL2L1, CASP9, CDC42, CHUK, ELK1, H2AFX, HRAS, MAP2K1, MAPK3, MLLT7, NFKB1, PIK3CA, PIK3R1, RAC1, RAF1, RALA, RALBP1, RALGDS, RELA, RHOA 21 CASP9(1), CHUK(1), ELK1(2), NFKB1(1), PIK3CA(2), PIK3R1(1), RALGDS(1), RELA(1), RHOA(2) 7852662 12 12 12 5 1 2 4 3 2 0 0.60 0.91 403 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(2), CD5(1), IFNA1(2), IFNB1(1), IL13(2), ITGAX(1), TLR4(4), TLR7(1) 8216955 14 13 14 4 0 4 3 7 0 0 0.60 0.91 404 CARBON_FIXATION ALDOA, ALDOB, ALDOC, FBP1, FBP2, GOT1, GOT2, GPT, GPT2, MDH1, MDH2, ME1, ME2, ME3, PGK1, PKLR, PKM2, RPE, RPE, LOC440001, RPIA, TKT, TPI1 20 ALDOC(1), MDH2(1), ME1(2), ME3(1), PGK1(2), PKLR(1), RPIA(1), TKT(2) 7516569 11 11 11 2 2 1 4 3 1 0 0.60 0.91 405 HSA00430_TAURINE_AND_HYPOTAURINE_METABOLISM Genes involved in taurine and hypotaurine metabolism BAAT, CDO1, CSAD, GAD1, GAD2, GGT1, GGTL3, GGTL4 6 BAAT(1), CSAD(1), GAD1(1), GAD2(1) 2461360 4 4 4 0 1 0 1 1 1 0 0.60 0.91 406 NKCELLSPATHWAY Natural killer (NK) lymphocytes are inhibited by MHC and activated by surface glycoproteins on tumor or virus-infected cells, which undergo perforin-mediated lysis. B2M, HLA-A, IL18, ITGB1, KLRC1, KLRC2, KLRC3, KLRC4, KLRD1, LAT, MAP2K1, MAPK3, PAK1, PIK3CA, PIK3R1, PTK2B, PTPN6, RAC1, SYK, VAV1 20 B2M(2), HLA-A(1), KLRC2(2), KLRC3(1), PIK3CA(2), PIK3R1(1), PTK2B(1), VAV1(2) 8176796 12 11 11 7 0 1 1 7 3 0 0.61 0.92 407 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 ALDOC(1), G6PD(4), GPI(2), H6PD(1), PFKP(2), PGD(1), PGLS(1), PRPS1L1(2), RPIA(1), TKT(2) 8736340 17 15 17 2 3 4 7 2 1 0 0.61 0.92 408 HSA00460_CYANOAMINO_ACID_METABOLISM Genes involved in cyanoamino acid metabolism ASRGL1, GBA, GBA3, GGT1, GGTL3, GGTL4, SHMT1, SHMT2 6 ASRGL1(1), GBA(1), SHMT1(1), SHMT2(1) 2265880 4 4 4 1 1 0 1 1 1 0 0.61 0.92 409 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 15 DNAJA3(2), IKBKB(1), JAK2(2), LIN7A(1), NFKB1(1), RELA(1), TNF(1), TNFRSF1A(1), USH1C(1) 6748621 11 11 11 2 2 3 3 2 1 0 0.61 0.92 410 BENZOATE_DEGRADATION_VIA_COA_LIGATION ACAT1, ACAT2, ACYP1, ACYP2, ECHS1, EHHADH, GCDH, HADHA, SDHB, SDS 10 ACAT1(2), ACAT2(1), ECHS1(1), EHHADH(2), HADHA(1) 3453829 7 5 7 2 0 1 4 1 1 0 0.61 0.92 411 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 78 ACVR1(2), ACVR1B(1), BMPR1A(1), BMPR2(3), BUB1(1), CDS1(1), CLK1(1), CLK4(1), CSNK2A1(1), CSNK2B(1), DGKA(3), DGKB(3), DGKD(2), DGKE(1), DGKH(3), INPP1(1), INPP4A(1), INPP4B(1), INPPL1(1), ITPKB(4), MAP3K10(2), MOS(1), NEK1(2), NEK3(1), OCRL(1), PIK3C2A(3), PIK3C2B(3), PIK3CA(2), PIK3CB(1), PIK3CG(3), PLCB1(4), PLCB2(4), PLCB3(2), PLCB4(1), PLCG2(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PRKCA(1), PRKCE(1), PRKCG(1), PRKCH(1), PRKCQ(3), PRKCZ(2), PRKD1(2), PRKG1(1), RPS6KA1(1), RPS6KA2(1), RPS6KA4(1) 47601602 82 66 82 24 13 13 26 23 7 0 0.62 0.92 412 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 CHUK(1), DNAJC3(1), EIF2S1(1), MAP3K14(1), NFKB1(1), RELA(1) 3906009 6 6 6 2 1 0 3 2 0 0 0.62 0.92 413 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 8 GREB1(4), MTA3(2) 3640059 6 6 6 2 1 0 4 1 0 0 0.62 0.92 414 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 APC(8), DAG1(3), DLG4(2), EPHB2(1), ITPR1(3), ITPR2(5), ITPR3(3), KCNJ9(1), PITX2(1), RYR1(11) 20009396 38 32 38 11 5 3 11 16 3 0 0.62 0.92 415 ERK5PATHWAY Signaling between a tissue and its innervating axon stimulates retrograde transport via Trk receptors, which activate Erk5, which induces transcription of anti-apoptotic factors. AKT1, CREB1, GRB2, HRAS, MAPK1, MAPK3, MAPK7, MEF2A, MEF2B, MEF2C, MEF2D, NTRK1, PIK3CA, PIK3R1, PLCG1, RPS6KA1, SHC1 17 GRB2(2), MEF2A(1), MEF2C(1), MEF2D(1), NTRK1(4), PIK3CA(2), PIK3R1(1), RPS6KA1(1), SHC1(1) 8071503 14 13 14 10 2 2 6 3 1 0 0.63 0.92 416 BUTANOATE_METABOLISM AACS, ABAT, ACADS, ACAT1, ACAT2, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH5A1, ALDH9A1, BDH, BUCS1, ECHS1, EHHADH, GAD1, GAD2, HADHA, HMGCL, L2HGDH, OXCT1, PDHA1, PDHA2, PDHB, SDHB, SDS 27 AACS(2), ACAT1(2), ACAT2(1), ALDH1A1(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ECHS1(1), EHHADH(2), GAD1(1), GAD2(1), HADHA(1), L2HGDH(2), OXCT1(2) 11460534 20 18 20 8 0 4 8 6 2 0 0.63 0.92 417 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), DHRS7(1), METTL6(1), PRMT5(2), PRMT8(3), WBSCR22(1) 5959227 9 9 9 2 1 1 3 3 1 0 0.63 0.92 418 PHOTOSYNTHESIS ATP5E, ATP5O, ATP6AP1, ATP6V0A1, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0C, SHMT1, ATP6V0D1, ATP6V0E, ATP6V1A, ATP6V1B1, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1F, ATP6V1G1, ATP6V1G2, ATP6V1G3, ATP6V1H, FDXR 22 ATP5O(1), ATP6AP1(4), ATP6V0D1(1), ATP6V1C2(2), ATP6V1D(1), ATP6V1F(1), SHMT1(1) 7100054 11 11 10 2 3 0 2 5 1 0 0.63 0.92 419 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 CHRNB1(1), MUSK(2), PIK3CA(2), PIK3R1(1), PTK2(1), PTK2B(1), RAPSN(1), TERT(1) 6349040 10 10 10 9 0 2 4 2 2 0 0.63 0.92 420 HSA00625_TETRACHLOROETHENE_DEGRADATION Genes involved in tetrachloroethene degradation AKR1B10, EPHX2, HSD3B7, RDH11, RDH12, RDH13, RDH14 7 EPHX2(1), RDH12(1), RDH13(1) 2076871 3 3 3 0 1 0 1 0 1 0 0.63 0.92 421 HSA00660_C5_BRANCHED_DIBASIC_ACID_METABOLISM Genes involved in C5-branched dibasic acid metabolism ILVBL, SUCLA2 2 ILVBL(1) 927961 1 1 1 1 0 0 0 1 0 0 0.63 0.92 422 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 73 ABL1(1), ANGPTL2(1), ARHGEF7(2), BRAF(2), CSE1L(1), DOCK1(4), EPHB2(1), GRB2(2), GRB7(1), GRLF1(6), ITGA1(1), ITGA10(2), ITGA3(2), ITGA4(3), ITGA5(1), ITGA6(1), ITGA8(3), MAP2K4(1), MAPK8(1), MAPK8IP1(1), MAPK9(1), MRAS(1), MYLK(6), MYLK2(1), PAK2(1), PAK3(5), PAK6(2), PAK7(1), PIK3CA(2), PIK3CB(1), PKLR(1), PLCG2(1), PTEN(2), PTK2(1), SHC1(1), SOS1(3), SOS2(1), TLN1(1), TLN2(3), WAS(1) 50867702 73 66 73 26 8 7 27 18 13 0 0.63 0.92 423 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 13 GTF2B(1), GTF2E1(1), HDAC3(2), NCOA1(2), NCOA2(1), NCOA3(4), NCOR2(1), RARA(1), RXRA(2) 9803822 15 15 15 2 1 1 5 3 5 0 0.64 0.93 424 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 184 ACTG1(2), ACTN2(3), ACTN3(2), ARHGAP5(2), BIRC3(2), BRAF(2), CHAD(1), COL11A1(5), COL11A2(4), COL1A1(1), COL1A2(2), COL2A1(1), COL3A1(4), COL4A1(3), COL4A2(1), COL4A4(3), COL4A6(5), COL5A1(1), COL5A2(2), COL5A3(7), COL6A3(11), COL6A6(6), COMP(3), CTNNB1(2), DOCK1(4), EGFR(7), ELK1(2), ERBB2(4), FARP2(1), FIGF(1), FLNA(1), FLNB(3), FLNC(3), FLT1(2), FN1(1), GRB2(2), GRLF1(6), GSK3B(1), HGF(2), IGF1R(1), ITGA1(1), ITGA10(2), ITGA2B(4), ITGA3(2), ITGA4(3), ITGA5(1), ITGA6(1), ITGA8(3), ITGAV(2), ITGB6(1), ITGB7(4), KDR(1), LAMA1(6), LAMA2(8), LAMA3(7), LAMA4(2), LAMB1(5), LAMB2(3), LAMB3(1), LAMB4(4), LAMC1(3), LAMC2(1), LAMC3(4), MAPK8(1), MAPK9(1), MET(4), MYL2(1), MYLK(6), MYLK2(1), PAK2(1), PAK3(5), PAK6(2), PAK7(1), PDGFC(1), PDGFRA(3), PDGFRB(3), PDPK1(1), PGF(1), PIK3CA(2), PIK3CB(1), PIK3CG(3), PIK3R1(1), PIK3R2(2), PIK3R5(1), PIP5K1C(1), PPP1R12A(2), PRKCA(1), PRKCG(1), PTEN(2), PTK2(1), PXN(5), RAPGEF1(2), RELN(8), RHOA(2), SHC1(1), SHC4(2), SOS1(3), SOS2(1), SPP1(1), THBS1(2), THBS2(4), THBS3(3), THBS4(1), TLN1(1), TLN2(3), TNC(1), TNN(4), TNR(3), TNXB(4), VAV1(2), VAV2(4), VAV3(3), VCL(2), VEGFA(1), VWF(4) 152980066 302 185 300 84 30 47 118 63 44 0 0.64 0.93 425 HSA00272_CYSTEINE_METABOLISM Genes involved in cysteine metabolism CARS, CARS2, CDO1, CTH, GOT1, GOT2, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, MPST, SDS, SULT1B1, SULT1C2, SULT1C4, SULT4A1 16 CARS(3), LDHAL6B(1), LDHB(1), LDHC(1), SULT1C2(1), SULT4A1(1) 5498530 8 8 8 2 0 0 5 3 0 0 0.64 0.93 426 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 ALOX12(1), ALOX15(1), ALOX5(1), CYP4F2(1), EPX(2), LPO(1), PLA2G4A(1), PLA2G6(1), PTGDS(1), PTGIS(3), PTGS1(1), PTGS2(1), TBXAS1(2), TPO(4) 11764879 21 20 21 5 3 3 9 2 4 0 0.65 0.93 427 HSA00240_PYRIMIDINE_METABOLISM Genes involved in pyrimidine metabolism AICDA, AK3, CAD, CANT1, CDA, CMPK, CTPS, CTPS2, DCK, DCTD, DHODH, DPYD, DPYS, DTYMK, DUT, ECGF1, ENTPD1, ENTPD3, ENTPD4, ENTPD5, ENTPD6, ENTPD8, ITPA, NME1, NME2, NME4, NME6, NME7, NP, NT5C, NT5C1A, NT5C1B, NT5C2, NT5C3, NT5E, NT5M, NUDT2, PNPT1, POLA1, POLA2, POLD1, POLD2, POLD3, POLD4, POLE, POLE2, POLE3, POLE4, POLR1A, POLR1B, POLR1C, POLR1D, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLR3A, POLR3B, POLR3G, POLR3GL, POLR3H, POLR3K, PRIM1, PRIM2, RFC5, RRM1, RRM2, RRM2B, TK1, TK2, TXNRD1, TXNRD2, TYMS, UCK1, UCK2, UMPS, UPB1, UPP1, UPP2, UPRT, ZNRD1 83 AICDA(1), AK3(2), CAD(5), CDA(1), CTPS2(1), DCK(1), DCTD(1), DHODH(1), DPYD(3), DPYS(1), ENTPD1(2), ENTPD3(1), ENTPD5(1), ITPA(1), NT5C1A(1), NT5C1B(1), NT5C3(1), NT5E(2), POLA1(2), POLD1(1), POLD2(2), POLD3(1), POLE(2), POLE2(1), POLR1C(1), POLR2B(2), POLR2C(1), POLR2I(1), RRM2B(2), TXNRD2(2), UCK2(1), UMPS(1), UPB1(1), UPP1(1) 35265960 49 45 49 19 10 1 15 14 9 0 0.65 0.93 428 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 RAB27A(1), RAB4A(1), RAB9A(1) 1918809 3 3 3 1 1 1 1 0 0 0 0.65 0.94 429 ALTERNATIVEPATHWAY The alternative complement pathway is an antibody-independent mechanism of immune activation that results in cell lysis via the membrane attack complex. BF, C3, C5, C6, C7, C8A, C9, DF, PFC 6 C3(2), C5(1), C6(2), C7(3), C8A(1) 5623387 9 8 9 3 1 1 2 3 2 0 0.66 0.95 430 STEROID_BIOSYNTHESIS CYP17A1, F13B, HSD17B1, HSD17B2, HSD17B3, HSD17B4, HSD17B7, HSD3B1, HSD3B2 9 HSD17B2(1), HSD17B4(1), HSD3B1(2), HSD3B2(1) 3617463 5 5 5 2 0 1 2 2 0 0 0.66 0.95 431 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 77 AIFM1(2), APAF1(2), ATM(5), BID(1), BIRC3(2), CASP6(1), CASP7(1), CASP9(1), CHUK(1), CSF2RB(3), FADD(1), IKBKB(1), IRAK1(2), IRAK2(1), IRAK3(2), IRAK4(1), MAP3K14(1), NFKB1(1), NTRK1(4), PIK3CA(2), PIK3CB(1), PIK3CG(3), PIK3R1(1), PIK3R2(2), PIK3R5(1), PPP3CC(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1), RELA(1), TNF(1), TNFRSF10A(2), TNFRSF10D(1), TNFRSF1A(1), TNFSF10(1), TRAF2(1) 34854147 55 48 55 22 6 11 20 14 4 0 0.66 0.95 432 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(2), ACO2(1), ACSS1(1), FH(1), MDH2(1) 6045006 9 9 9 0 0 1 4 3 1 0 0.67 0.95 433 PHENYLALANINE_TYROSINE_AND_TRYPTOPHAN_BIOSYNTHESIS ENO1, ENO2, ENO3, FARS2, FARSLB, GOT1, GOT2, PAH, TAT, YARS 9 PAH(3), TAT(2) 3858279 5 5 5 6 0 1 0 2 2 0 0.67 0.95 434 SA_MMP_CYTOKINE_CONNECTION Cytokines can induce activation of matrix metalloproteinases, which degrade extracellular matrix. ACE, CD44, CSF1, FCGR3A, IL1B, IL6R, SELL, SPN, TGFB1, TGFB2, TNF, TNFRSF1A, TNFRSF1B, TNFRSF8, TNFSF8 15 ACE(3), CD44(1), CSF1(1), IL6R(1), SPN(1), TNF(1), TNFRSF1A(1), TNFSF8(1) 5773994 10 10 10 4 3 3 3 1 0 0 0.68 0.96 435 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 62 APAF1(2), BAK1(1), BID(1), BIRC3(2), BNIP3L(1), CASP1(2), CASP2(1), CASP4(1), CASP6(1), CASP7(1), CASP9(1), CHUK(1), FADD(1), IKBKB(1), IRF2(2), IRF3(2), IRF4(1), IRF6(3), MAP2K4(1), MAP3K1(1), NFKB1(1), PRF1(2), RELA(1), TNF(1), TNFRSF1A(1), TNFSF10(1), TRAF1(4), TRAF2(1) 23243025 39 35 39 11 4 8 11 12 4 0 0.68 0.96 436 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 161 ADCY1(4), ADCY2(6), ADCY3(2), ADCY4(1), ADCY7(1), ADCY9(5), ADORA2B(2), ADRA1A(1), ADRB2(1), ATP2A1(2), ATP2A2(1), ATP2A3(1), ATP2B1(1), ATP2B2(4), ATP2B3(1), ATP2B4(2), AVPR1B(3), BDKRB1(4), BDKRB2(3), CACNA1A(5), CACNA1B(1), CACNA1C(9), CACNA1D(6), CACNA1E(4), CACNA1F(4), CACNA1G(3), CACNA1S(5), CALM3(1), CAMK2B(2), CAMK2D(1), CAMK2G(1), CAMK4(3), CCKBR(1), CD38(2), CHRM2(4), CHRM3(3), CHRM5(1), CHRNA7(1), CYSLTR1(1), DRD1(2), EDNRA(1), EGFR(7), ERBB2(4), ERBB3(2), F2R(2), GNA11(1), GNA14(2), GNAL(1), GNAS(3), GRIN2A(3), GRIN2C(1), GRIN2D(3), GRM1(4), GRM5(2), GRPR(1), HRH1(1), HTR2A(3), HTR2C(4), HTR4(2), HTR5A(2), HTR6(1), ITPKB(4), ITPR1(3), ITPR2(5), ITPR3(3), LHCGR(3), MYLK(6), MYLK2(1), NOS1(2), NOS3(2), P2RX1(1), P2RX5(1), PDE1A(1), PDE1B(1), PDGFRA(3), PDGFRB(3), PHKA1(3), PHKA2(2), PLCB1(4), PLCB2(4), PLCB3(2), PLCB4(1), PLCD4(2), PLCE1(1), PLCG2(1), PLCZ1(1), PPP3CC(1), PRKACG(1), PRKCA(1), PRKCG(1), PTGFR(3), PTK2B(1), RYR1(11), RYR2(15), RYR3(4), SLC25A4(1), SLC25A5(1), SLC8A1(2), SLC8A3(1), SPHK1(1), TACR1(1), TACR2(2), TACR3(1), TRPC1(2), VDAC2(1) 112277705 266 148 263 71 39 35 90 72 30 0 0.68 0.96 437 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), DHRS7(1), MYST3(3), MYST4(5) 7137865 10 10 10 3 0 2 1 4 3 0 0.68 0.96 438 CDC42RACPATHWAY PI3 kinase stimulates cell migration by activating cdc42, which activates ARP2/3, which in turn promotes formation of new actin fibers. ACTR2, ACTR3, ARHA, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, CDC42, PAK1, PDGFRA, PIK3CA, PIK3R1, RAC1, WASL 14 ARPC1A(1), ARPC3(1), PDGFRA(3), PIK3CA(2), PIK3R1(1) 6019778 8 8 8 4 0 3 1 3 1 0 0.69 0.96 439 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 39 ALPL(2), ALPP(2), ASCC3(5), ATP13A2(3), DDX18(1), DDX23(1), DDX4(1), DDX41(1), DDX47(1), DDX52(2), DDX54(2), DDX55(1), ENTPD7(1), EP400(2), ERCC2(1), FPGS(1), IFIH1(1), MOV10L1(2), NUDT5(1), QDPR(1), RAD54L(2), SETX(2), SKIV2L2(1), SMARCA2(2), SPR(2) 26095152 41 38 41 6 6 6 17 9 3 0 0.69 0.96 440 1_2_DICHLOROETHANE_DEGRADATION ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A1(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2) 3501749 5 5 5 3 0 2 0 2 1 0 0.69 0.96 441 ASCORBATE_AND_ALDARATE_METABOLISM ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 8 ALDH1A1(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2) 3501749 5 5 5 3 0 2 0 2 1 0 0.69 0.96 442 COMPPATHWAY Both the classic and alternative immune complement pathways promote inflammation, foreign cell lysis, and phagocytosis. BF, C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C9, DF, MASP1, MASP2, MBL2 14 C2(1), C3(2), C5(1), C6(2), C7(3), C8A(1), MASP1(1), MASP2(2) 9566411 13 12 13 7 2 1 3 4 3 0 0.69 0.96 443 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), ME1(2) 3867016 6 6 6 3 0 0 4 2 0 0 0.69 0.96 444 SMALL_LIGAND_GPCRS C9orf47, CNR1, CNR2, DNMT1, EDG1, EDG2, EDG5, EDG6, MTNR1A, MTNR1B, PTAFR, PTGDR, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, TBXA2R 11 DNMT1(2), MTNR1A(1), PTGDR(1), PTGFR(3) 4318168 7 7 7 1 2 0 3 1 1 0 0.69 0.96 445 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 10 ATM(5), CDC25B(2), CDK2(1), MYT1(2) 6758951 10 9 10 2 0 1 5 3 1 0 0.69 0.96 446 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 31 CALM3(1), EGFR(7), ELK1(2), GRB2(2), MAP2K4(1), MAP3K1(1), MAPK8(1), MEF2A(1), MEF2C(1), MEF2D(1), PRKCA(1), PTK2(1), PTK2B(1), SHC1(1), SOS1(3) 14401186 25 22 25 12 2 3 13 4 3 0 0.69 0.96 447 ALANINE_AND_ASPARTATE_METABOLISM AARS, ABAT, ADSL, ADSS, AGXT, AGXT2, ASL, ASNS, ASPA, ASS, CAD, CRAT, DARS, DDO, GAD1, GAD2, GOT1, GOT2, GPT, GPT2, NARS, PC 20 AARS(1), ADSL(1), AGXT(1), AGXT2(2), ASNS(2), CAD(5), DARS(1), DDO(3), GAD1(1), GAD2(1) 10988586 18 17 18 10 3 2 6 5 2 0 0.69 0.96 448 HSA03022_BASAL_TRANSCRIPTION_FACTORS Genes involved in basal transcription factors GTF2A1, GTF2A1L, GTF2A2, GTF2B, GTF2E1, GTF2E2, GTF2F1, GTF2F2, GTF2H1, GTF2H2, GTF2H3, GTF2H4, GTF2I, GTF2IRD1, LOC391764, STON1, TAF1, TAF10, TAF12, TAF13, TAF1L, TAF2, TAF4, TAF4B, TAF5, TAF5L, TAF6, TAF6L, TAF7, TAF7L, TAF9, TAF9B, TBPL1, TBPL2 31 GTF2B(1), GTF2E1(1), GTF2H4(1), GTF2IRD1(3), TAF1(5), TAF12(1), TAF2(2), TAF4(3), TAF5(1), TAF5L(1), TAF6(2), TAF6L(3), TAF9(1) 15721611 25 24 25 8 4 6 8 6 1 0 0.70 0.96 449 HSA00900_TERPENOID_BIOSYNTHESIS Genes involved in terpenoid biosynthesis FDFT1, FDPS, GGPS1, IDI1, IDI2, SQLE 6 GGPS1(1), IDI2(1) 1913062 2 2 2 1 0 0 1 1 0 0 0.70 0.96 450 SELENOAMINO_ACID_METABOLISM AHCY, CBS, CTH, GGT1, MARS, MARS2, MAT1A, MAT2B, PAPSS1, PAPSS2, SCLY, SEPHS1 12 MARS(2), MARS2(3), PAPSS2(1), SCLY(2), SEPHS1(1) 5233572 9 8 9 0 0 1 3 4 1 0 0.70 0.96 451 HSA00031_INOSITOL_METABOLISM Genes involved in inositol metabolism ALDH6A1, TPI1 2 ALDH6A1(1) 703431 1 1 1 0 1 0 0 0 0 0 0.71 0.96 452 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(5), CDC25B(2), MYT1(2) 6178089 9 8 9 2 0 1 4 3 1 0 0.71 0.96 453 HEME_BIOSYNTHESIS ALAD, ALAS1, ALAS2, CPOX, FECH, HMBS, PPOX, UROD, UROS 9 ALAS1(1), CPOX(1), HMBS(1), PPOX(2) 3484115 5 5 4 3 1 2 1 0 1 0 0.71 0.96 454 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 25 BIRC3(2), FADD(1), MAP2K4(1), MAP3K3(1), MAP3K7(3), NFKB1(1), TNF(1), TNFAIP3(4), TNFRSF1A(1), TRAF2(1) 10644511 16 16 16 5 1 3 7 4 1 0 0.71 0.97 455 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 16 ABL1(1), ATM(5), CDKN1A(1), CHEK2(1), GADD45A(1), MAPK8(1), NFKB1(1), RAD50(2), RAD51(1), RBBP8(1), RELA(1) 10730456 16 15 16 3 3 3 5 3 2 0 0.71 0.97 456 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 CALM3(1), DLG4(2), GRIN2A(3), GRIN2B(3), GRIN2C(1), GRIN2D(3), NOS1(2), PPP3CC(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PRKCA(1) 10597436 20 18 19 10 7 4 4 3 2 0 0.72 0.97 457 HSA03060_PROTEIN_EXPORT Genes involved in protein export OXA1L, SEC61A2, SRP19, SRP54, SRP68, SRP72, SRP9, SRPR 8 SEC61A2(1), SRP68(2), SRPR(1) 3412338 4 4 4 2 0 1 2 0 1 0 0.72 0.97 458 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 14 APAF1(2), ATM(5), CDK2(1), CDKN1A(1), GADD45A(1) 6829081 10 9 10 0 1 2 2 4 1 0 0.72 0.97 459 NEUROTRANSMITTERSPATHWAY Biosynthesis of neurotransmitters DBH, GAD1, HDC, PNMT, TH, TPH1 5 DBH(2), GAD1(1) 2260812 3 3 3 3 1 0 0 2 0 0 0.73 0.97 460 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 DHRS2(1), DHRS7(1), PON3(1), RDH12(1), RDH13(1) 3699232 5 5 5 0 1 1 1 0 2 0 0.73 0.97 461 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 39 APAF1(2), BAK1(1), BID(1), BIRC3(2), CASP2(1), CASP6(1), CASP7(1), CASP9(1), FADD(1), MAP2K4(1), MAP3K1(1), MAP3K14(1), NFKB1(1), PRF1(2), RELA(1), TNF(1), TNFRSF1A(1), TNFSF10(1), TRAF1(4), TRAF2(1) 15632457 26 24 26 7 3 5 9 6 3 0 0.73 0.97 462 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 46 AASDHPPT(1), AASS(2), ACAT1(2), ACAT2(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ALDH7A1(1), DLST(1), ECHS1(1), EHHADH(2), EHMT2(1), HADHA(1), HSD17B4(1), NSD1(2), OGDH(2), PLOD1(1), PLOD2(1), PLOD3(3), RDH12(1), RDH13(1), SETD7(1), SETDB1(3), SHMT1(1), SHMT2(1), SPCS1(1), SPCS3(2), SUV39H2(1), TMLHE(1) 24204325 40 35 40 11 5 4 13 14 4 0 0.73 0.97 463 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 PSMA4(1), PSMB1(1), PSMB4(1), PSMB5(1), PSMB6(1), PSMC3(4), PSMD1(1), PSMD13(1) 7352160 11 10 11 4 0 0 5 4 2 0 0.73 0.97 464 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 80 ABL1(1), ATM(5), BUB1(1), BUB1B(2), BUB3(1), CCNA1(2), CCNA2(1), CCNB3(3), CCNH(1), CDAN1(2), CDC20(1), CDC25B(2), CDC6(1), CDC7(2), CDH1(2), CDK2(1), CDKN1A(1), CHEK2(1), E2F2(1), E2F5(1), EP300(1), GADD45A(1), GSK3B(1), HDAC1(1), HDAC3(2), HDAC4(2), HDAC5(1), HDAC6(2), MAD2L2(1), MCM2(2), MCM3(1), MCM4(2), MCM5(2), MPEG1(1), ORC1L(1), ORC4L(1), PRKDC(8), RBL1(1), SKP2(2), TBC1D8(3), TFDP1(2) 47508427 70 58 70 24 9 10 23 19 9 0 0.74 0.97 465 KREBPATHWAY The Krebs (citric acid) cycle takes place in mitochondria, where it extracts energy in the form of electron carriers NADH and FADH2, which drive the electron transport chain. ACO2, CS, FH, IDH2, MDH1, OGDH, SDHA, SUCLA2 8 ACO2(1), CS(1), FH(1), OGDH(2), SDHA(1) 4203499 6 6 6 1 0 2 2 1 1 0 0.74 0.97 466 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 ACAA2(1), ACADM(1), ACADSB(2), ACAT1(2), ACAT2(1), ALDH1A1(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ALDH6A1(1), AOX1(4), ECHS1(1), EHHADH(2), HADHA(1), IVD(2), MCCC2(1), OXCT1(2), PCCB(1) 16142208 27 23 27 12 2 5 8 8 4 0 0.74 0.97 467 DNA_POLYMERASE POLA, POLB, POLD1, POLD2, POLE, POLG, POLL, POLQ, POLS 7 POLB(1), POLD1(1), POLD2(2), POLE(2), POLG(1), POLQ(3) 7158005 10 10 10 4 0 3 6 1 0 0 0.75 0.97 468 HSA04710_CIRCADIAN_RHYTHM Genes involved in circadian rhythm ARNTL, BHLHB2, BHLHB3, CLOCK, CRY1, CRY2, CSNK1D, CSNK1E, NPAS2, NR1D1, PER1, PER2, PER3 11 CLOCK(1), CRY1(2), CSNK1E(1), NPAS2(2), PER1(2), PER2(1), PER3(1) 7064708 10 10 9 4 0 2 2 5 1 0 0.75 0.97 469 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 38 AKR1B1(3), ALDOC(1), FUK(1), HK1(1), HK2(1), HK3(3), KHK(1), MPI(1), MTMR1(2), MTMR6(2), PFKFB2(1), PFKFB3(2), PFKFB4(1), PFKP(2), RDH12(1), RDH13(1) 15159044 24 24 24 7 6 5 8 2 3 0 0.75 0.97 470 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 36 BCR(1), BTK(1), CD19(2), CSK(1), DAG1(3), EPHB2(1), GRB2(2), ITPKB(4), LYN(1), NFAT5(1), NFKB1(1), PIK3CA(2), PIK3R1(1), PLCG2(1), SERPINA4(2), SHC1(1), SOS1(3), SOS2(1), VAV1(2) 20708368 31 29 31 15 3 5 14 6 3 0 0.75 0.97 471 TSP1PATHWAY Thrombospondin-1 (TSP-1) inhibits angiogenesis by inducing caspase-dependent apoptosis in microvascular endothelial cells. CASP3, CD36, FOS, FYN, JUN, MAPK14, THBS1 7 FOS(1), MAPK14(1), THBS1(2) 3212759 4 4 4 3 0 0 2 2 0 0 0.75 0.97 472 CLASSICPATHWAY The classic complement pathway is initiated by antibodies and promotes phagocytosis and lysis of foreign cells as well as activating the inflammatory response. C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C9 11 C2(1), C3(2), C5(1), C6(2), C7(3), C8A(1) 7917696 10 9 10 3 1 1 2 3 3 0 0.75 0.97 473 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), ATM(5), CDKN1A(1), CPB2(1), GADD45A(1), MAPK8(1) 8550367 12 11 12 2 2 2 2 4 2 0 0.75 0.97 474 ETSPATHWAY The Ets transcription factors are activated by Ras and promote macrophage differentiation. CSF1, CSF1R, DDX20, E2F1, E2F4, ETS1, ETS2, ETV3, FOS, HDAC2, HDAC5, HRAS, JUN, NCOR2, RBL1, RBL2, SIN3A, SIN3B 18 CSF1(1), CSF1R(1), ETS1(1), ETS2(1), FOS(1), HDAC5(1), NCOR2(1), RBL1(1), RBL2(3), SIN3A(2), SIN3B(2) 10077364 15 15 15 3 3 1 8 2 1 0 0.75 0.97 475 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) 1841117 2 2 2 1 0 0 2 0 0 0 0.75 0.97 476 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(2), GSN(1), ITGA1(1), MYL2(1), MYLK(6), PIK3CA(2), PIK3R1(1), PTK2(1), PXN(5), SHC1(1), TLN1(1) 16294460 22 22 22 10 3 3 8 5 3 0 0.75 0.97 477 HSA00130_UBIQUINONE_BIOSYNTHESIS Genes involved in ubiquinone biosynthesis COQ2, COQ3, COQ5, COQ6, COQ7, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA12, NDUFA13, NDUFB11 8 COQ5(1), NDUFB11(1) 1814673 2 2 2 2 0 0 1 0 1 0 0.75 0.97 478 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 CDK2(1), CDKN1A(1), CDKN1B(1), NFKB1(1), PIK3CA(2), PIK3R1(1), RELA(1), TFDP1(2) 7767914 10 10 10 7 2 3 2 1 2 0 0.76 0.97 479 HSA00920_SULFUR_METABOLISM Genes involved in sulfur metabolism BPNT1, CHST11, CHST12, CHST13, PAPSS1, PAPSS2, SULT1A1, SULT1A2, SULT1A3, SULT1A4, SULT1E1, SULT2A1, SULT2B1, SUOX 11 BPNT1(1), PAPSS2(1), SULT1A1(1), SULT1E1(1), SULT2A1(1) 3903402 5 5 5 0 0 0 1 3 1 0 0.76 0.97 480 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 57 ATP12A(2), ATP5O(1), ATP6AP1(4), ATP6V0D1(1), ATP6V1C2(2), ATP6V1D(1), ATP6V1F(1), ATP7B(1), COX10(1), COX6B1(1), NDUFB2(1), NDUFS1(1), PPA2(1), SDHA(1), SHMT1(1), UQCRB(1), UQCRC1(1) 15770684 22 22 21 6 4 0 6 8 4 0 0.76 0.97 481 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 LDLR(3), MBTPS1(1), MBTPS2(1), SCAP(1) 4475758 6 6 6 2 1 1 2 2 0 0 0.76 0.97 482 REDUCTIVE_CARBOXYLATE_CYCLE_CO2_FIXATION ACO1, ACO2, FH, IDH1, IDH2, MDH1, MDH2, SDHB, SUCLA2 9 ACO1(2), ACO2(1), FH(1), MDH2(1) 4059691 5 5 5 0 0 1 2 1 1 0 0.76 0.97 483 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 GOSR1(1), STX11(1), STX16(1), STX3(2), STX5(2), STX6(1), VTI1A(1) 7044921 9 9 9 3 1 1 2 2 3 0 0.76 0.97 484 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 14 MAP2K3(1), MAP2K6(1), MAP3K1(1), MAPK14(1), NFKB1(1), PIK3CA(2), PIK3R1(1), RELA(1) 7478570 9 9 9 7 3 1 1 3 1 0 0.76 0.97 485 SIG_PIP3_SIGNALING_IN_B_LYMPHOCYTES Genes related to PIP3 signaling in B lymphocytes AKT1, AKT2, AKT3, BCR, BTK, CD19, CDKN2A, DAPP1, FLOT1, FLOT2, FOXO3A, GAB1, ITPR1, ITPR2, ITPR3, LYN, NR0B2, P101-PI3K, PDK1, PHF11, PIK3CA, PITX2, PLCG2, PPP1R13B, PREX1, PSCD3, PTEN, PTPRC, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SAG, SYK, TEC, VAV1 33 BCR(1), BTK(1), CD19(2), ITPR1(3), ITPR2(5), ITPR3(3), LYN(1), PDK1(1), PIK3CA(2), PITX2(1), PLCG2(1), PREX1(3), PTEN(2), PTPRC(3), RPS6KA1(1), RPS6KA2(1), SAG(1), TEC(1), VAV1(2) 23870337 35 32 35 13 2 4 13 12 4 0 0.76 0.97 486 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 CCR3(2), CD4(1), CXCR3(2), IL12RB2(3), IL18R1(2), IL4R(2) 8730677 12 12 12 0 1 5 4 2 0 0 0.77 0.97 487 HSA00830_RETINOL_METABOLISM Genes involved in retinol metabolism ALDH1A1, ALDH1A2, BCMO1, RDH5 4 ALDH1A1(1), RDH5(1) 1778074 2 2 2 2 0 2 0 0 0 0 0.77 0.97 488 COMPLEMENT_ACTIVATION_CLASSICAL C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C8B, C9, DAF, MASP1 13 C2(1), C3(2), C5(1), C6(2), C7(3), C8A(1), C8B(1), MASP1(1) 9462307 12 11 12 6 2 1 3 3 3 0 0.77 0.97 489 ARGININE_AND_PROLINE_METABOLISM ABP1, AGMAT, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH4A1, ALDH9A1, AMD1, AOC2, AOC3, ARG1, ARG2, ASL, ASS, CKB, CKM, CKMT1, CKMT1B, CKMT1A, CKMT2, CPS1, DAO, GAMT, GATM, GLUD1, GOT1, GOT2, MAOA, MAOB, NOS1, NOS2A, NOS3, OAT, ODC1, OTC, P4HA1, P4HA2, P4HA3, P4HB, PYCR1, RARS, SAT, SMS 40 ABP1(2), ALDH1A1(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), AOC2(4), AOC3(1), ARG1(1), CPS1(4), MAOA(2), MAOB(1), NOS1(2), NOS3(2), ODC1(1), OTC(1), RARS(1), SMS(1) 18068047 28 25 28 16 1 3 9 9 6 0 0.77 0.97 490 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 11 BFAR(2), BRAF(2) 4756747 4 4 4 1 0 1 0 1 2 0 0.77 0.97 491 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 63 CASP9(1), KDR(1), KRAS(2), MAPK14(1), MAPKAPK3(1), NFAT5(1), NFATC1(1), NFATC2(1), NFATC4(1), NOS3(2), NRAS(2), PIK3CA(2), PIK3CB(1), PIK3CG(3), PIK3R1(1), PIK3R2(2), PIK3R5(1), PLA2G12A(1), PLA2G12B(1), PLA2G2F(1), PLA2G4A(1), PLA2G6(1), PLCG2(1), PPP3CC(1), PRKCA(1), PRKCG(1), PTGS2(1), PTK2(1), PXN(5), SPHK1(1), VEGFA(1) 27940856 42 38 40 18 4 10 12 13 3 0 0.78 0.97 492 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 15 ACTN2(3), ACTN3(2), ITGA1(1), PTK2(1), PXN(5), SPTAN1(5), TLN1(1) 12073731 18 18 18 7 4 1 8 2 3 0 0.78 0.97 493 TCRPATHWAY T cell receptors bind to foreign peptides presented by MHC molecules and induce T cell activation. CALM1, CALM2, CALM3, CD3D, CD3E, CD3G, CD3Z, ELK1, FOS, FYN, GRB2, HRAS, JUN, LAT, LCK, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKBIA, PIK3CA, PIK3R1, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCA, PRKCB1, PTPN7, RAC1, RAF1, RASA1, RELA, SHC1, SOS1, SYT1, TRA@, TRB@, VAV1, ZAP70 42 CALM3(1), CD3E(2), ELK1(2), FOS(1), GRB2(2), LCK(1), MAP2K4(1), MAP3K1(1), MAPK8(1), NFATC1(1), NFATC2(1), NFATC4(1), NFKB1(1), PIK3CA(2), PIK3R1(1), PPP3CC(1), PRKCA(1), RASA1(1), RELA(1), SHC1(1), SOS1(3), VAV1(2), ZAP70(1) 20322739 30 27 30 15 4 4 14 6 2 0 0.78 0.97 494 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 17 ACY1(1), ARG1(1), CPS1(4), ODC1(1), OTC(1), SMS(1) 6908209 9 9 9 6 0 1 3 3 2 0 0.78 0.98 495 FRUCTOSE_AND_MANNOSE_METABOLISM AKR1B1, ALDOA, ALDOB, ALDOC, FBP1, FBP2, FPGT, GCK, GMDS, GMPPA, GMPPB, HK1, HK2, HK3, KHK, MPI, PFKFB1, PFKFB3, PFKFB4, PFKM, PFKP, PMM1, PMM2, SORD, TPI1 25 AKR1B1(3), ALDOC(1), HK1(1), HK2(1), HK3(3), KHK(1), MPI(1), PFKFB3(2), PFKFB4(1), PFKP(2) 10315150 16 16 16 6 3 4 6 1 2 0 0.79 0.98 496 PROTEASOME PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMB1, PSMB10, PSMB2, PSMB3, PSMB4, PSMB5, PSMB6, PSMB7, PSMB8, PSMB9 17 PSMA4(1), PSMB1(1), PSMB4(1), PSMB5(1), PSMB6(1) 3939621 5 5 5 3 0 0 2 3 0 0 0.79 0.98 497 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 32 ACTN2(3), ACTN3(2), BCR(1), CSK(1), GRB2(2), ITGA1(1), MAPK8(1), PPP1R12B(4), PTK2(1), PXN(5), SHC1(1), SOS1(3), TLN1(1), VCL(2) 18908964 28 27 28 9 3 3 15 4 3 0 0.79 0.98 498 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 10 IL6R(1), JAK2(2), JAK3(3), PTPRU(1), STAT3(1) 6174631 8 8 8 4 2 1 2 1 2 0 0.79 0.98 499 FCER1PATHWAY In mast cells, Fc epsilon receptor 1 activates BTK, PKC, and the MAP kinase pathway to promote degranulation and arachnidonic acid release. BTK, CALM1, CALM2, CALM3, ELK1, FCER1A, FCER1G, FOS, GRB2, HRAS, JUN, LYN, MAP2K1, MAP2K4, MAP2K7, MAP3K1, MAPK1, MAPK3, MAPK8, NFATC1, NFATC2, NFATC3, NFATC4, PAK2, PIK3CA, PIK3R1, PLA2G4A, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCB1, RAF1, SHC1, SOS1, SYK, SYT1, VAV1 36 BTK(1), CALM3(1), ELK1(2), FOS(1), GRB2(2), LYN(1), MAP2K4(1), MAP3K1(1), MAPK8(1), NFATC1(1), NFATC2(1), NFATC4(1), PAK2(1), PIK3CA(2), PIK3R1(1), PLA2G4A(1), PPP3CC(1), SHC1(1), SOS1(3), VAV1(2) 18129539 26 24 26 13 2 6 11 5 2 0 0.79 0.98 500 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 CABIN1(2), CALM3(1), HDAC5(1), IGF1R(1), INSR(6), MAP2K6(1), MAPK14(1), MEF2A(1), MEF2C(1), MEF2D(1), NFATC1(1), NFATC2(1), PIK3CA(2), PIK3R1(1), PPP3CC(1) 14026829 22 20 22 13 2 2 9 7 2 0 0.80 0.98 501 INOSITOL_METABOLISM ALDH6A1, ALDOA, ALDOB, ALDOC, TPI1 5 ALDH6A1(1), ALDOC(1) 1690173 2 2 2 0 2 0 0 0 0 0 0.80 0.98 502 IFNGPATHWAY IFN gamma signaling pathway IFNG, IFNGR1, IFNGR2, JAK1, JAK2, STAT1 6 JAK2(2), STAT1(2) 3690289 4 4 4 1 0 0 2 1 1 0 0.80 0.99 503 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 49 ABL1(1), ACTG1(2), ARHGEF2(1), CDH1(2), CTNNB1(2), CTTN(1), NCK2(1), PRKCA(1), RHOA(2), TLR4(4), TLR5(1), TUBA3C(3), TUBA4A(3), TUBB1(1), TUBB3(2), TUBB4(2), TUBB8(2), WAS(1) 21643853 32 31 32 10 5 5 11 9 2 0 0.81 0.99 504 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 49 ABL1(1), ACTG1(2), ARHGEF2(1), CDH1(2), CTNNB1(2), CTTN(1), NCK2(1), PRKCA(1), RHOA(2), TLR4(4), TLR5(1), TUBA3C(3), TUBA4A(3), TUBB1(1), TUBB3(2), TUBB4(2), TUBB8(2), WAS(1) 21643853 32 31 32 10 5 5 11 9 2 0 0.81 0.99 505 SLRPPATHWAY Small leucine-rich proteoglycans (SLRPs) interact with and reorganize collagen fibers in the extracellular matrix. BGN, DCN, DSPG3, FMOD, KERA, LUM 5 FMOD(1) 1623106 1 1 1 1 0 0 0 1 0 0 0.81 0.99 506 APOPTOSIS_KEGG APAF1, BAD, BAX, BCL2, BCL2A1, BCL2L1, BCL2L2, BOK, CASP1, CASP1, COPl, CASP10, CASP2, CASP3, CASP4, CASP6, CASP7, CASP8, CASP9, CD40, CD40LG, CRADD, CYCS, DAXX, DFFA, DFFB, FADD, FAS, FASLG, HRK, IKBKE, LTA, MCL1, NFKB1, NFKBIA, NGFB, NGFR, NR3C1, NTRK1, PTPN13, RIPK1, SFRS2IP, TFG, TNF, TNFRSF1A, TNFRSF1B, TRADD, TRAF1, TRAF2, TRAF3, TRAF6 45 APAF1(2), CASP1(2), CASP2(1), CASP4(1), CASP6(1), CASP7(1), CASP9(1), DAXX(1), FADD(1), IKBKE(1), NFKB1(1), NGFR(1), NR3C1(2), NTRK1(4), PTPN13(4), TNF(1), TNFRSF1A(1), TRAF1(4), TRAF2(1), TRAF6(2) 19093637 33 28 33 11 6 7 10 8 2 0 0.81 0.99 507 HSA00251_GLUTAMATE_METABOLISM Genes involved in glutamate metabolism ABAT, ADC, ALDH4A1, ALDH5A1, CAD, CPS1, EARS2, EPRS, GAD1, GAD2, GCLC, GCLM, GFPT1, GFPT2, GLS, GLS2, GLUD1, GLUD2, GLUL, GMPS, GNPNAT1, GOT1, GOT2, GPT, GPT2, GSR, GSS, NADSYN1, NAGK, PPAT, QARS 30 ADC(2), CAD(5), CPS1(4), GAD1(1), GAD2(1), GCLM(1), GFPT2(1), GLS(1), GLS2(1), GMPS(2), GSR(2), GSS(3), NADSYN1(1), QARS(1) 17322351 26 23 26 8 4 1 14 3 4 0 0.82 0.99 508 ST_TYPE_I_INTERFERON_PATHWAY Type I interferon is an antiviral cytokine that induces a JAK-STAT type pathway leading to ISGF3 activation and a cellular antiviral response. IFNAR1, IFNB1, ISGF3G, JAK1, PTPRU, REG1A, STAT1, STAT2, TYK2 8 IFNB1(1), PTPRU(1), STAT1(2), STAT2(1), TYK2(2) 5388667 7 7 7 2 0 0 3 4 0 0 0.82 0.99 509 41BBPATHWAY TNF-type receptor 4-1BB is bound by TRAF1 to activate the MAP kinase pathway in activated T cells. ATF2, CHUK, IFNG, IKBKB, IL2, IL4, JUN, MAP3K1, MAP3K5, MAP4K5, MAPK14, MAPK8, NFKB1, NFKBIA, RELA, TNFRSF9, TNFSF9, TRAF2 17 CHUK(1), IKBKB(1), MAP3K1(1), MAP3K5(2), MAPK14(1), MAPK8(1), NFKB1(1), RELA(1), TNFRSF9(1), TRAF2(1) 8515347 11 11 11 3 2 4 1 3 1 0 0.82 0.99 510 HSA04150_MTOR_SIGNALING_PATHWAY Genes involved in mTOR signaling pathway AKT1, AKT2, AKT3, BRAF, CAB39, DDIT4, EIF4B, EIF4EBP1, FIGF, FRAP1, GBL, HIF1A, IGF1, INS, KIAA1303, LYK5, MAPK1, MAPK3, PDPK1, PGF, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PRKAA1, PRKAA2, RHEB, RICTOR, RPS6, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA6, RPS6KB1, RPS6KB2, STK11, TSC1, TSC2, ULK1, ULK2, ULK3, VEGFA, VEGFB, VEGFC 41 BRAF(2), EIF4EBP1(1), FIGF(1), PDPK1(1), PGF(1), PIK3CA(2), PIK3CB(1), PIK3CG(3), PIK3R1(1), PIK3R2(2), PIK3R5(1), PRKAA2(2), RICTOR(2), RPS6(1), RPS6KA1(1), RPS6KA2(1), RPS6KB2(1), TSC1(3), TSC2(2), ULK2(1), VEGFA(1) 20377950 31 26 31 10 1 7 8 10 5 0 0.82 0.99 511 PTC1PATHWAY The binding of extracellular signaling protein Sonic hedgehog to the Patched receptor (Ptc1) allows progression through G1 and may inhibit the G2/M transition. CCNB1, CCNH, CDC2, CDC25A, CDC25B, CDC25C, CDK7, MNAT1, PTCH, SHH, XPO1 9 CCNH(1), CDC25B(2), MNAT1(1) 3901939 4 4 4 3 0 0 4 0 0 0 0.82 0.99 512 IONPATHWAY Activated phospholipase C hydrolyzes the lipid PIP3 into second messengers DAG, which activates protein kinase C, and IP3, which induces calcium influx into the cytoplasm. P2RY2, PLCG1, PRKCA, PRKCB1, PTK2B 4 P2RY2(2), PRKCA(1), PTK2B(1) 3038990 4 4 4 1 2 0 1 1 0 0 0.82 0.99 513 CYANOAMINO_ACID_METABOLISM ATP6V0C, SHMT1, GBA3, GGT1, SHMT1, SHMT2 5 SHMT1(1), SHMT2(1) 1661782 2 2 2 0 1 0 0 1 0 0 0.83 0.99 514 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 CAT(1), GHR(1), IGF1R(1), PIK3CA(2), PIK3R1(1), SHC1(1) 5609153 7 7 7 4 1 2 2 1 1 0 0.83 0.99 515 ARGININECPATHWAY Related catabolic pathways process arginine, histidine, glutamine, and proline through glutamate to alpha-ketoglutamate, which feeds into the citric acid cycle. ALDH4A1, ARG1, GLS, GLUD1, OAT, PRODH 6 ARG1(1), GLS(1) 2150366 2 2 2 0 0 0 2 0 0 0 0.83 0.99 516 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 METTL6(1), PRMT5(2), PRMT8(3), WBSCR22(1) 5887718 7 7 7 3 1 0 3 3 0 0 0.83 0.99 517 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 ACAA2(1), ACADM(1), ACAT1(2), ACAT2(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ALDH6A1(1), ALDH7A1(1), AOX1(4), BCAT2(2), ECHS1(1), EHHADH(2), HADHA(1), HMGCS2(1), HSD17B4(1), IVD(2), MCCC2(1), OXCT1(2), PCCB(1) 19343617 29 25 29 12 2 3 8 10 6 0 0.83 0.99 518 BOTULINPATHWAY Blockade of Neurotransmitter Relase by Botulinum Toxin CHRM1, CHRNA1, SNAP25, STX1A, VAMP2 5 CHRNA1(1) 1486039 1 1 1 3 0 0 0 0 1 0 0.83 0.99 519 ACTINYPATHWAY The Arp 2/3 complex localizes to the Y-junction of polymerizing actin fibers that enable lamellipod extension and consequent cell motility. ABI-2, ACTA1, ACTR2, ACTR3, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, NCK1, NCKAP1, NTRK1, PIR, PSMA7, RAC1, WASF1, WASF2, WASF3, WASL 18 ARPC1A(1), ARPC3(1), NCKAP1(2), NTRK1(4), PIR(1), WASF2(1) 6897790 10 9 10 3 2 1 5 2 0 0 0.84 0.99 520 HYPERTROPHY_MODEL ADAM10, ANKRD1, ATF3, CYR61, DUSP14, EIF4E, EIF4EBP1, GDF8, HBEGF, IFNG, IFRD1, IL18, IL1A, IL1R1, JUND, MYOG, NR4A3, TCF8, VEGF, WDR1 16 ADAM10(1), EIF4EBP1(1), NR4A3(1), WDR1(2) 4663387 5 5 5 0 1 0 2 2 0 0 0.84 0.99 521 PARKINPATHWAY In Parkinson's disease, dopaminergic neurons contain Lewy bodies consisting of alpha-synuclein and parkin, an E3 ubiquitin ligase that targets glycosylated alpha-synuclein. GPR37, PARK2, PNUTL1, SNCA, SNCAIP, UBE2E2, UBE2F, UBE2G1, UBE2G2, UBE2L3, UBE2L6, UBL1 10 GPR37(2), SNCAIP(1) 2814528 3 3 3 3 0 1 2 0 0 0 0.84 0.99 522 FMLPPATHWAY The fMLP receptor is a G-protein coupled receptor in neutrophils that recognizes formylated bacterial peptides and activates NADPH oxidase. CALM1, CALM2, CALM3, CAMK1, CAMK1G, ELK1, FPR1, GNA15, GNB1, GNGT1, HRAS, MAP2K1, MAP2K2, MAP2K3, MAP2K6, MAP3K1, MAPK1, MAPK14, MAPK3, NCF1, NCF2, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKBIA, PAK1, PIK3C2G, PLCB1, PPP3CA, PPP3CB, PPP3CC, RAC1, RAF1, RELA, SYT1 36 CALM3(1), ELK1(2), FPR1(1), MAP2K3(1), MAP2K6(1), MAP3K1(1), MAPK14(1), NCF2(4), NFATC1(1), NFATC2(1), NFATC4(1), NFKB1(1), PLCB1(4), PPP3CC(1), RELA(1) 16128675 22 22 22 13 5 2 9 6 0 0 0.84 0.99 523 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 37 ANAPC1(1), ANAPC2(1), ANAPC4(1), ANAPC5(1), BTRC(2), CDC20(1), CDC27(4), CUL2(2), CUL3(1), FBXW11(1), FBXW7(4), SKP2(2), SMURF1(1), UBA1(1) 17226266 23 21 23 4 3 4 5 4 7 0 0.84 0.99 524 ERYTHPATHWAY Erythropoietin selectively stimulates erythrocyte differentiation from CFU-GEMM cells in bone marrow. CCL3, CSF2, CSF3, EPO, FLT3, IGF1, IL11, IL1A, IL3, IL6, IL9, KITLG, TGFB1, TGFB2, TGFB3 14 CSF3(1), FLT3(2), KITLG(1) 3684735 4 4 4 2 0 1 1 1 1 0 0.85 0.99 525 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 MARS(2), MARS2(3), METTL6(1), PAPSS2(1), PRMT5(2), PRMT8(3), SCLY(2), SEPHS1(1), WBSCR22(1) 10340611 16 14 16 2 1 1 6 7 1 0 0.85 0.99 526 HSA01040_POLYUNSATURATED_FATTY_ACID_BIOSYNTHESIS Genes involved in polyunsaturated fatty acid biosynthesis ACAA1, ACOX1, ACOX3, ELOVL2, ELOVL5, ELOVL6, FADS1, FADS2, FASN, GPSN2, HADHA, HSD17B12, PECR, SCD 12 ACOX1(2), FADS2(2), HADHA(1) 4801514 5 5 5 1 0 0 3 0 2 0 0.85 0.99 527 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 23 CREBBP(7), EP300(1), GTF2E1(1), HDAC1(1), HDAC3(2), HDAC4(2), HDAC5(1), HDAC6(2), MEF2C(1), NCOR2(1), PELP1(1) 16961928 20 20 20 10 1 1 7 5 6 0 0.85 0.99 528 HSA00650_BUTANOATE_METABOLISM Genes involved in butanoate metabolism AACS, AADAC, ABAT, ACADS, ACAT1, ACAT2, ACSM1, AKR1B10, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH5A1, ALDH7A1, ALDH9A1, BDH1, BDH2, DDHD1, ECHS1, EHHADH, GAD1, GAD2, HADH, HADHA, HMGCL, HMGCS1, HMGCS2, HSD17B10, HSD17B4, HSD3B7, ILVBL, L2HGDH, OXCT1, OXCT2, PDHA1, PDHA2, PDHB, PLA1A, PPME1, PRDX6, RDH11, RDH12, RDH13, RDH14 45 AACS(2), ACAT1(2), ACAT2(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ALDH7A1(1), BDH1(1), DDHD1(1), ECHS1(1), EHHADH(2), GAD1(1), GAD2(1), HADHA(1), HMGCS2(1), HSD17B4(1), ILVBL(1), L2HGDH(2), OXCT1(2), PLA1A(1), RDH12(1), RDH13(1) 18026223 28 24 28 10 1 3 10 9 5 0 0.85 0.99 529 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), GNA12(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1) 4577268 5 5 5 0 2 0 1 2 0 0 0.85 0.99 530 SA_CASPASE_CASCADE Apoptosis is mediated by caspases, cysteine proteases arranged in a proteolytic cascade. ADPRT, APAF1, BIRC2, BIRC3, BIRC4, CASP10, CASP3, CASP7, CASP8, CASP9, DFFA, DFFB, GZMB, PRF1, SCAP, SREBF1, SREBF2, TNFRSF6, TNFSF6 15 APAF1(2), BIRC3(2), CASP7(1), CASP9(1), PRF1(2), SCAP(1) 7347779 9 9 9 5 0 1 3 4 1 0 0.85 0.99 531 GPCRDB_CLASS_A_RHODOPSIN_LIKE2 CYSLTR1, CYSLTR2, GPR109B, GPR161, GPR171, GPR18, GPR34, GPR39, GPR41, GPR42, GPR45, GPR65, GPR68, GPR75, GPR81, LYPDC1 13 CYSLTR1(1), GPR161(1), GPR34(1), GPR45(1), GPR75(1) 4413282 5 5 5 1 1 0 4 0 0 0 0.85 0.99 532 CDK5PATHWAY Cdk5, a regulatory kinase implicated in neuronal development, represses Mek1, which downregulates the MAP kinase pathway. CDK5, CDK5R1, DPM2, EGR1, HRAS, KLK2, MAP2K1, MAP2K2, MAPK1, MAPK3, NGFB, NGFR, RAF1 11 EGR1(2), KLK2(1), NGFR(1) 3101211 4 4 4 2 1 1 1 1 0 0 0.85 0.99 533 NOTCHPATHWAY Proteolysis and Signaling Pathway of Notch ADAM17, DLL1, FURIN, NOTCH1, PSEN1, RBPSUH 4 FURIN(2) 1995317 2 2 2 2 0 1 0 0 1 0 0.85 0.99 534 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 19 F2(3), F2R(2), ITGA1(1), PLA2G4A(1), PLCB1(4), PRKCA(1), PTGS1(1), PTK2(1), TBXAS1(2) 10481864 16 14 16 5 4 5 4 2 1 0 0.85 0.99 535 HSP27PATHWAY Hsp27 oligomers have molecular chaperone activity and protect heat-stressed cells against apoptosis. ACTA1, APAF1, BCL2, CASP3, CASP9, CYCS, DAXX, FAS, FASLG, HSPB1, HSPB2, IL1A, MAPKAPK2, MAPKAPK3, TNF, TNFRSF6 14 APAF1(2), CASP9(1), DAXX(1), MAPKAPK3(1), TNF(1) 4875061 6 6 6 2 0 2 0 3 1 0 0.86 0.99 536 ETCPATHWAY Energy is extracted from carbohydrates via oxidation and transferred to the mitochondrial electron transport chain, which couples ATP synthesis to the reduction of oxygen to water. ATP5A1, CYCS, GPD2, MTCO1, NDUFA1, SDHA, SDHB, SDHC, SDHD, UQCRC1 9 GPD2(1), SDHA(1), UQCRC1(1) 2901740 3 3 3 3 0 1 1 0 1 0 0.86 0.99 537 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 CDKN1A(1), EPOR(1), JAK2(2), NFKB1(1), RELA(1) 5226260 6 6 6 1 2 1 1 1 1 0 0.86 0.99 538 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 21 GBA(1), GLB1(2), LCT(6), NEU1(1), NEU3(1), PPAP2A(1), SPTLC1(1) 9877930 13 13 13 5 1 2 4 2 4 0 0.87 0.99 539 CDMACPATHWAY Cadmium 2+ promotes cell proliferation in cultured macrophages by entering the cell via calcium channels and activating the MAP kinase pathway. CUZD1, FOS, HRAS, JUN, MAP2K1, MAPK1, MAPK3, MYC, NFKB1, NFKBIA, PLCB1, PRKCA, PRKCB1, RAF1, RELA, TNF 15 FOS(1), NFKB1(1), PLCB1(4), PRKCA(1), RELA(1), TNF(1) 6794913 9 9 9 4 2 2 3 2 0 0 0.87 0.99 540 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 BCAT2(2), IARS(1), IARS2(2), ILVBL(1), VARS(1), VARS2(3) 8187423 10 10 10 5 3 0 4 2 1 0 0.87 0.99 541 HSA00521_STREPTOMYCIN_BIOSYNTHESIS Genes involved in streptomycin biosynthesis GCK, HK1, HK2, HK3, IMPA1, IMPA2, ISYNA1, PGM1, PGM3, TGDS 10 HK1(1), HK2(1), HK3(3), ISYNA1(1) 4839654 6 6 6 1 1 2 3 0 0 0 0.87 0.99 542 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(5), ATR(2), CHEK2(1) 7095257 8 7 8 0 1 1 1 4 1 0 0.88 1.00 543 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 ACAT1(2), ACAT2(1), ADH5(1), AKR1B1(3), ALDH1A1(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), DLAT(1), GLO1(2), HAGH(1), LDHB(1), LDHC(1), MDH2(1), ME1(2), ME3(1), PKLR(1) 16020000 23 21 23 11 1 5 9 6 2 0 0.89 1.00 544 PORPHYRIN_AND_CHLOROPHYLL_METABOLISM ALAD, BLVRA, BLVRB, CP, CPOX, EPRS, FECH, GUSB, HCCS, HMBS, HMOX1, HMOX2, PPOX, UGT1A10, UGT1A10, UGT1A8, UGT1A7, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A9, UGT2B15, UGT2B4, UROD, UROS 25 BLVRA(1), CPOX(1), HMBS(1), PPOX(2), UGT1A10(2), UGT1A3(1), UGT1A5(1), UGT1A7(1), UGT1A8(2), UGT1A9(2), UGT2B4(1) 11531667 15 14 14 7 0 4 3 4 4 0 0.89 1.00 545 AMINOACYL_TRNA_BIOSYNTHESIS AARS, CARS, DARS, EPRS, FARS2, FARSLB, GARS, HARS, HARSL, IARS, KARS, LARS, LARS2, MARS, MARS2, NARS, QARS, RARS, SARS, TARS, WARS, WARS2, YARS 21 AARS(1), CARS(3), DARS(1), GARS(1), IARS(1), KARS(1), MARS(2), MARS2(3), QARS(1), RARS(1), TARS(2), WARS(1) 14635826 18 18 18 9 1 3 9 4 1 0 0.89 1.00 546 GLUTAMATE_METABOLISM ABAT, ALDH4A1, ALDH5A1, CAD, CPS1, EPRS, GAD1, GAD2, GCLC, GCLM, GFPT1, GLS, GLS2, GLUD1, GLUL, GMPS, GOT1, GOT2, GPT, GPT2, GSS, NADSYN1, PPAT, QARS 23 CAD(5), CPS1(4), GAD1(1), GAD2(1), GCLM(1), GLS(1), GLS2(1), GMPS(2), GSS(3), NADSYN1(1), QARS(1) 14659618 21 18 21 7 4 1 11 3 2 0 0.89 1.00 547 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 ACACB(4), ACAT1(2), ACAT2(1), ACOT12(2), ACSS1(1), AKR1B1(3), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ALDH7A1(1), DLAT(1), GLO1(2), HAGH(1), LDHAL6B(1), LDHB(1), LDHC(1), MDH2(1), ME1(2), ME3(1), PKLR(1) 20578499 30 27 30 10 2 5 13 8 2 0 0.90 1.00 548 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 38 CBX3(1), CLOCK(1), CRY1(2), EIF4G2(1), ETV6(1), GFRA1(3), NCKAP1(2), NR1D2(1), PER1(2), PER2(1), PSMA4(1), PURA(1), TOB1(1), TUBB3(2) 15605980 20 19 20 7 1 2 5 9 3 0 0.90 1.00 549 HSA00930_CAPROLACTAM_DEGRADATION Genes involved in caprolactam degradation AKR1A1, ASAHL, ECHS1, EHHADH, HADH, HADHA, HSD17B10, HSD17B4, NTAN1, SIRT1, SIRT2, SIRT5, SIRT7, VNN2, VNN3 12 ECHS1(1), EHHADH(2), HADHA(1), HSD17B4(1) 5099472 5 5 5 2 0 0 3 1 1 0 0.90 1.00 550 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 18 EXT1(1), EXTL1(1), EXTL3(2), GLCE(1), HS3ST3A1(1), HS3ST5(1), HS6ST3(1), NDST1(1), NDST2(2) 8843013 11 11 11 6 2 3 3 2 1 0 0.90 1.00 551 NDKDYNAMINPATHWAY Endocytotic role of NDK, Phosphins and Dynamin AMPH, AP2A1, AP2M1, BIN1, CALM1, CALM2, CALM3, DNM1, EPN1, EPS15, NME1, NME2, PICALM, PPP3CA, PPP3CB, PPP3CC, SYNJ1, SYNJ2, SYT1 19 AMPH(2), AP2A1(2), BIN1(1), CALM3(1), DNM1(2), PICALM(1), PPP3CC(1), SYNJ1(2) 9559857 12 12 12 8 3 3 2 3 1 0 0.90 1.00 552 STREPTOMYCIN_BIOSYNTHESIS GCK, HK1, HK2, HK3, IMPA1, PGM1, PGM3, TGDS 8 HK1(1), HK2(1), HK3(3) 4457266 5 5 5 1 1 2 2 0 0 0 0.90 1.00 553 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 35 GADD45A(1), MAP2K4(1), MAP3K1(1), MAP3K10(2), MAP3K12(1), MAP3K13(2), MAP3K2(2), MAP3K3(1), MAP3K4(2), MAP3K5(2), MAP3K7(3), MAP3K9(1), MAPK8(1), MAPK9(1), MYEF2(1), PAPPA(3), SHC1(1), TRAF6(2) 20974112 28 27 28 3 4 6 11 4 3 0 0.91 1.00 554 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 JAK2(2), JAK3(3), PTPRU(1) 5903784 6 6 6 2 1 1 1 1 2 0 0.91 1.00 555 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 24 DAG1(3), ITPKB(4), ITPR1(3), ITPR2(5), ITPR3(3), NFKB1(1), PDK1(1), PHKA2(2), PIK3CB(1), PITX2(1), PLD1(1), PLD2(1) 17861744 26 23 26 8 3 2 6 9 6 0 0.91 1.00 556 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 PRKCA(1), TGM2(1) 2217781 2 2 2 2 1 0 0 1 0 0 0.91 1.00 557 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 JAK2(2), PTPRU(1), STAT1(2) 5026891 5 5 5 1 0 0 3 1 1 0 0.91 1.00 558 GPCRPATHWAY G-protein coupled receptors activate adenylyl cyclase, which converts ATP to cAMP, to activate second messenger pathways. ADCY1, CALM1, CALM2, CALM3, CREB1, ELK1, FOS, GNAI1, GNAQ, GNAS, GNB1, GNGT1, HRAS, JUN, MAP2K1, MAPK3, NFATC1, NFATC2, NFATC3, NFATC4, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, RAF1, RPS6KA3, SYT1 34 ADCY1(4), CALM3(1), ELK1(2), FOS(1), GNAS(3), NFATC1(1), NFATC2(1), NFATC4(1), PPP3CC(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PRKCA(1) 14251803 19 19 18 7 7 1 5 4 2 0 0.91 1.00 559 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 CPT1A(2), LEPR(1), PRKAA2(2) 6628783 5 5 5 2 0 0 2 2 1 0 0.91 1.00 560 UBIQUINONE_BIOSYNTHESIS NDUFA1, NDUFA10, NDUFA11, NDUFA4, NDUFA5, NDUFA8, NDUFB2, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFS1, NDUFS2, NDUFV1, NDUFV2 13 NDUFB2(1), NDUFS1(1) 2959512 2 2 2 1 0 0 0 2 0 0 0.92 1.00 561 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 87 ANK2(8), B3GALT4(2), DGKI(1), PIGK(1), RPL10(1), RPL15(1), RPL32(1), RPLP1(1), RPS18(1), RPS24(1), RPS27A(1), RPS6(1), RPS6KA1(1), RPS6KA2(1), RPS6KB2(1), RPS9(1), SLC36A2(1), TSPAN9(1), UBC(3) 21016616 29 26 29 11 3 5 7 8 6 0 0.92 1.00 562 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 MEF2A(1), MEF2C(1), MEF2D(1) 3473443 3 3 3 3 0 0 2 1 0 0 0.93 1.00 563 NUCLEOTIDE_METABOLISM ADSL, ADSS, DHFR, HPRT1, IMPDH1, MTHFD2, NME2, OAZ1, POLA, POLB, POLD1, POLG, PRPS2, RRM1, SAT, SRM 13 ADSL(1), IMPDH1(1), POLB(1), POLD1(1), POLG(1) 5029639 5 5 5 4 0 3 1 1 0 0 0.93 1.00 564 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 ACADM(1), ACADSB(2), ACAT1(2), ACAT2(1), ALDH1A1(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ALDH6A1(1), ECHS1(1), EHHADH(2), HADHA(1), LDHB(1), LDHC(1), PCCB(1), SUCLG2(1) 14956043 20 18 20 8 2 4 7 4 3 0 0.93 1.00 565 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 BTK(1), CALM3(1), CD79A(1), ELK1(2), FOS(1), GRB2(2), LYN(1), MAP3K1(1), MAPK14(1), MAPK8(1), NFATC1(1), NFATC2(1), NFATC4(1), PPP3CC(1), PRKCA(1), SHC1(1), SOS1(3), VAV1(2) 16330030 23 20 23 12 4 4 10 5 0 0 0.93 1.00 566 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), ADH1C(1), ADH4(1), ADH6(1), ADHFE1(1), ALDH1A1(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ALDOC(1), DLAT(1), G6PC(1), GPI(2), HK1(1), HK2(1), HK3(3), LDHB(1), LDHC(1), PFKP(2), PGK1(2), PKLR(1) 21325915 27 25 27 12 3 6 10 5 3 0 0.93 1.00 567 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), ADH1C(1), ADH4(1), ADH6(1), ADHFE1(1), ALDH1A1(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ALDOC(1), DLAT(1), G6PC(1), GPI(2), HK1(1), HK2(1), HK3(3), LDHB(1), LDHC(1), PFKP(2), PGK1(2), PKLR(1) 21325915 27 25 27 12 3 6 10 5 3 0 0.93 1.00 568 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 GSK3B(1), PPP2CA(2) 3747407 3 3 3 4 0 0 2 0 1 0 0.93 1.00 569 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 61 APAF1(2), ATM(5), ATR(2), BAI1(2), BID(1), CASP9(1), CCNB3(3), CCNG2(1), CD82(1), CDK2(1), CDKN1A(1), CHEK2(1), DDB2(1), EI24(1), GADD45A(1), GADD45B(1), GTSE1(1), PTEN(2), RRM2B(2), SERPINB5(1), SERPINE1(1), SESN1(1), THBS1(2), TSC2(2), ZMAT3(2) 26202066 39 30 39 10 7 4 12 13 3 0 0.94 1.00 570 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 NFKB1(1), PIK3CA(2), PIK3R1(1), PRKCA(1), PTK2(1), PTK2B(1), PXN(5), RELA(1) 11634109 13 13 13 11 3 1 6 1 2 0 0.94 1.00 571 BIOSYNTHESIS_OF_STEROIDS DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, IDI1, LSS, MVD, MVK, NQO1, NQO2, PMVK, SC5DL, SQLE, VKORC1 13 DHCR7(1), HMGCR(1), LSS(1), NQO2(1) 4415379 4 4 4 2 0 1 1 2 0 0 0.94 1.00 572 UBIQUITIN_MEDIATED_PROTEOLYSIS CDC34, HIP2, NRF1, UBE1, UBE2A, UBE2B, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2E1, UBE2E3, UBE2G1, UBE2G2, UBE2G2, TAX1BP3, UBE2H, UBE2I, UBE2J1, UBE2J2, UBE2L3, UBE2L6, UBE2M, UBE2N, UBE2S, UBE3A 22 NRF1(1), UBE2J2(1), UBE2M(1) 4179134 3 3 3 2 1 0 0 2 0 0 0.94 1.00 573 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 25 CALM3(1), GRB2(2), MAP2K3(1), MAP2K4(1), MAP3K1(1), MAPK14(1), MAPK8(1), PRKCA(1), PTK2B(1), SHC1(1), SOS1(3) 11347637 14 13 14 6 3 2 7 1 1 0 0.95 1.00 574 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 CALM3(1), FOS(1), MAPK14(1), MAPK8(1), PRKCA(1), PTK2B(1) 5889135 6 6 6 3 1 1 2 2 0 0 0.95 1.00 575 HSA00010_GLYCOLYSIS_AND_GLUCONEOGENESIS Genes involved in glycolysis and gluconeogenesis ACSS1, ACSS2, ACYP1, ACYP2, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, AKR1A1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH7A1, ALDH9A1, ALDOA, ALDOB, ALDOC, BPGM, DLAT, DLD, ENO1, ENO2, ENO3, FBP1, FBP2, G6PC, G6PC2, GALM, GAPDH, GAPDHS, GCK, GPI, HK1, HK2, HK3, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, PDHA1, PDHA2, PDHB, PFKL, PFKM, PFKP, PGAM1, PGAM2, PGAM4, PGK1, PGK2, PGM1, PGM3, PKLR, PKM2, TPI1 62 ACSS1(1), ADH1B(1), ADH1C(1), ADH4(1), ADH5(1), ADH6(1), ADHFE1(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ALDH7A1(1), ALDOC(1), DLAT(1), G6PC(1), GPI(2), HK1(1), HK2(1), HK3(3), LDHAL6B(1), LDHB(1), LDHC(1), PFKP(2), PGK1(2), PGK2(1), PKLR(1) 24603708 31 28 31 10 3 5 12 7 4 0 0.95 1.00 576 CERAMIDEPATHWAY Ceramide is a lipid signaling molecule that can activate proliferative or apoptotic pathways, depending on signaling context, localization, and cell type. BAD, BAX, BCL2, CASP8, CYCS, FADD, MAP2K1, MAP2K4, MAP3K1, MAPK1, MAPK3, MAPK8, NFKB1, NSMAF, PDCD8, RAF1, RELA, RIPK1, SMPD1, TNFRSF1A, TRADD, TRAF2 20 FADD(1), MAP2K4(1), MAP3K1(1), MAPK8(1), NFKB1(1), NSMAF(1), RELA(1), TNFRSF1A(1), TRAF2(1) 8748649 9 9 9 4 2 3 3 0 1 0 0.95 1.00 577 ACETYLCHOLINE_SYNTHESIS ACHE, CHAT, CHKA, PCYT1A, PDHA1, PDHA2, PEMT, SLC18A3 8 CHKA(1), SLC18A3(1) 2909171 2 2 2 2 0 0 1 1 0 0 0.95 1.00 578 HSA03030_DNA_POLYMERASE Genes involved in DNA polymerase POLA1, POLA2, POLB, POLD1, POLD2, POLD3, POLD4, POLE, POLE2, POLE3, POLE4, POLG, POLG2, POLH, POLI, POLK, POLL, POLM, POLQ, POLS, PRIM1, PRIM2, REV1, REV3L, RFC5 24 POLA1(2), POLB(1), POLD1(1), POLD2(2), POLD3(1), POLE(2), POLE2(1), POLG(1), POLI(2), POLK(1), POLM(2), POLQ(3), REV3L(1) 18375351 20 20 20 11 3 3 10 3 1 0 0.95 1.00 579 ARAPPATHWAY ADP-ribosylation factors (ARFs), members of the Ras superfamily, regulate eukaryotic vesicular trafficking and activate phospholipase D's. ARF1, ARFGAP1, ARFGAP3, ARFGEF2, BIG1, CENTD1, CENTD2, CLTA, CLTB, COP, COPA, DDEF1, DDEF2, GBF1, GPLD1, KDELR1, KDELR2, KDELR3, PSCD1, PSCD2, PSCD3, PSCD4 12 ARFGAP1(2), ARFGEF2(1), COPA(1), GPLD1(1), KDELR2(1), KDELR3(1) 7250271 7 7 7 2 0 2 2 3 0 0 0.95 1.00 580 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 INPP1(1), INPP4A(1), INPP4B(1), INPPL1(1), IPMK(1), ISYNA1(1), ITPK1(1), ITPKB(4), OCRL(1), PI4KA(1), PI4KB(2), PIK3CA(2), PIK3CB(1), PIK3CG(3), PIP4K2A(1), PIP4K2B(1), PIP5K1A(1), PIP5K1C(1), PLCB1(4), PLCB2(4), PLCB3(2), PLCB4(1), PLCD4(2), PLCE1(1), PLCG2(1), PLCZ1(1), PTEN(2), SYNJ1(2) 30169383 45 36 45 13 3 10 15 14 3 0 0.96 1.00 581 DREAMPATHWAY The transcription factor DREAM blocks expression of the prodynorphin gene, which encodes the ligand of an opioid receptor that blocks pain signaling. CREB1, CREM, CSEN, FOS, JUN, MAPK3, OPRK1, POLR2A, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B 13 FOS(1), OPRK1(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1) 5543576 5 5 5 0 1 0 0 4 0 0 0.96 1.00 582 HSA00061_FATTY_ACID_BIOSYNTHESIS Genes involved in fatty acid biosynthesis ACACA, ACACB, FASN, MCAT, OLAH, OXSM 5 ACACB(4), MCAT(1) 5589051 5 5 5 3 1 1 3 0 0 0 0.96 1.00 583 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 ACACB(4), ACADM(1), ACAT1(2), ACAT2(1), ACSS1(1), ALDH2(1), ALDH3A1(1), ALDH3A2(2), ALDH6A1(1), ALDH7A1(1), ECHS1(1), EHHADH(2), HADHA(1), LDHAL6B(1), LDHB(1), LDHC(1), PCCB(1), SUCLG2(1) 17990102 24 21 24 7 3 3 9 6 3 0 0.96 1.00 584 HIFPATHWAY Under normal conditions, hypoxia inducible factor HIF-1 is degraded; under hypoxic conditions, it activates transcription of genes controlled by hpoxic response elements (HREs). ARNT, ASPH, COPS5, CREB1, EDN1, EP300, EPO, HIF1A, HSPCA, JUN, LDHA, NOS3, P4HB, VEGF, VHL 13 ASPH(3), EP300(1), NOS3(2) 7058354 6 6 6 3 0 0 2 3 1 0 0.96 1.00 585 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 MMP2(1), RECK(1) 3292425 2 2 2 3 0 0 1 1 0 0 0.96 1.00 586 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 30 ARG1(1), ASS1(1), CPS1(4), NOS1(2), NOS3(2), OTC(1), PARS2(1), RARS(1), RARS2(2) 14373303 15 15 15 14 0 2 7 4 2 0 0.97 1.00 587 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 63 MRPL13(1), RPL10A(1), RPL10L(1), RPL23A(1), RPL32(1), RPS18(1), RPS24(1), RPS6(1), RPS9(1) 8328378 9 8 9 6 1 1 3 2 2 0 0.97 1.00 588 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 34 ENPP7(1), GBA(1), GLB1(2), LCT(6), NEU1(1), NEU3(1), PPAP2A(1), SGPP2(1), SMPD3(1), SPHK1(1), SPTLC1(1) 13767639 17 16 17 8 2 2 5 4 4 0 0.97 1.00 589 CITRATE_CYCLE_TCA_CYCLE ACO1, ACO2, CS, DLD, DLST, DLSTP, FH, IDH1, IDH2, IDH3A, IDH3B, IDH3G, MDH1, MDH2, PC, PCK1, SDHA, SDHA, SDHAL2, SDHB, SUCLA2, SUCLG1, SUCLG2 20 ACO1(2), ACO2(1), CS(1), DLST(1), FH(1), MDH2(1), SDHA(1), SUCLG2(1) 8979632 9 9 9 3 0 1 3 3 2 0 0.97 1.00 590 AHSPPATHWAY Alpha-hemoglobin stabilizing protein (AHSP) prevents precitipation of hemoglobin alpha-subunits. ALAD, ALAS1, ALAS2, CPO, ERAF, FECH, GATA1, HBA1, HBA2, HBB, HMBS, UROD, UROS 10 ALAS1(1), HMBS(1) 3615635 2 2 2 3 1 0 0 0 1 0 0.97 1.00 591 GLYCOLYSIS_AND_GLUCONEOGENESIS Genes involved in glycolysis and gluconeogenesis ALDOA, ALDOB, ALDOC, DLAT, DLD, ENO1, ENO2, ENO3, FBP1, FBP2, G6PC, GAPDH, GAPDHS, GAPDS, GCK, GOT1, GOT2, GPI, HK1, HK2, HK3, LDHA, LDHAL6B, LDHB, LDHC, MDH1, MDH2, PC, PCK1, PDHA1, PDHA2, PDHB, PDHX, PFKL, PFKM, PFKP, PGAM1, PGAM2, PGK1, PGK2, PKLR, PKM2, TNFAIP1, TPI1 42 ALDOC(1), DLAT(1), G6PC(1), GPI(2), HK1(1), HK2(1), HK3(3), LDHAL6B(1), LDHB(1), LDHC(1), MDH2(1), PFKP(2), PGK1(2), PGK2(1), PKLR(1) 17596225 20 19 20 8 3 3 10 3 1 0 0.97 1.00 592 RNA_POLYMERASE POLR1B, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLRMT 13 POLR2B(2), POLR2C(1), POLR2I(1) 5129945 4 4 4 1 0 1 0 2 1 0 0.97 1.00 593 SALMONELLAPATHWAY Salmonella induces membrane ruffling in infected cells via bacterial proteins including SipA, SipC, and SopE, which alter actin structure. ACTA1, ACTR2, ACTR3, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, CDC42, RAC1, WASF1, WASL 12 ARPC1A(1), ARPC3(1) 3634055 2 2 2 0 0 1 1 0 0 0 0.98 1.00 594 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 CALM3(1), CHUK(1), MAP3K1(1), NFATC1(1), NFATC2(1), NFKB1(1), PPP3CC(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1), RELA(1), VIPR2(1) 11532660 12 12 12 9 4 1 2 5 0 0 0.98 1.00 595 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 23 DHCR7(1), GGCX(1), GGPS1(1), HMGCR(1), IDI2(1), LSS(1), TM7SF2(1) 8031604 7 7 7 3 0 1 3 2 1 0 0.98 1.00 596 RANPATHWAY RanGEF (aka RCC1) and RanGFP regulate the GTP- or GDP-bound state of Ran, creating a Ran gradient across the nuclear membrane that is used in nuclear import. CHC1, RAN, RANBP1, RANBP2, RANGAP1 4 RANBP1(1) 3303680 1 1 1 0 0 0 0 0 1 0 0.98 1.00 597 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 12 ABL1(1), PIK3CA(2), PIK3R1(1), POLR1C(1) 7031738 5 5 5 9 0 1 1 2 1 0 0.98 1.00 598 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(2), ACO2(1), CS(1), DLST(1), FH(1), MDH2(1), OGDH(2), SDHA(1), SUCLG2(1) 13147823 14 14 14 4 0 2 6 4 2 0 0.98 1.00 599 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 HDAC1(1) 2770344 1 1 1 3 0 0 1 0 0 0 0.99 1.00 600 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 NRG2(1), PRKCA(1) 4037719 2 2 2 1 1 0 1 0 0 0 0.99 1.00 601 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(2), CALM3(1), EP300(1), HDAC1(1), MEF2D(1), NFATC1(1), NFATC2(1), PPP3CC(1), PRKCA(1) 10151543 10 9 10 6 3 1 3 1 2 0 0.99 1.00 602 RNA_TRANSCRIPTION_REACTOME CCNH, CDK7, ERCC3, GTF2A2, GTF2B, GTF2E1, GTF2E2, GTF2F2, GTF2H1, GTF2H2, GTF2H4, ILK, MGC9850, MNAT1, POLR1A, POLR1B, POLR2A, POLR2B, POLR2C, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR3B, POLR3D, POLR3E, POLR3H, POLR3K, TAF12, TAF13, TAF5, TAF6, TAF7, TAF9, TBP, VARS2L 35 CCNH(1), GTF2B(1), GTF2E1(1), GTF2H4(1), MNAT1(1), POLR2B(2), POLR2C(1), POLR2I(1), POLR3E(1), TAF12(1), TAF5(1), TAF6(2), TAF9(1) 15120945 15 15 15 12 1 1 6 5 2 0 0.99 1.00 603 CHOLESTEROL_BIOSYNTHESIS C10orf110, CYP51A1, DHCR7, FDFT1, FDPS, FDPS, LOC402397, HMGCR, HMGCS1, IDI1, LSS, MVD, MVK, NSDHL, PMVK, SC4MOL, SC5DL, SQLE 14 DHCR7(1), HMGCR(1), LSS(1) 5387432 3 3 3 2 0 1 1 1 0 0 0.99 1.00 604 CALCINEURINPATHWAY Increased intracellular calcium activates the phosphatase calcineurin in differentiating keratinocytes. CALM1, CALM2, CALM3, CDKN1A, GNAQ, MARCKS, NFATC1, NFATC2, NFATC3, NFATC4, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCA, PRKCB1, SP1, SP3, SYT1 17 CALM3(1), CDKN1A(1), NFATC1(1), NFATC2(1), NFATC4(1), PPP3CC(1), PRKCA(1) 8634058 7 7 7 8 3 1 2 1 0 0 0.99 1.00 605 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 32 ARHGEF11(2), DLG4(2), LPA(2), MAP2K4(1), MAP3K1(1), MAP3K5(2), MAPK8(1), NFKB1(1), PDK1(1), PHKA2(2), PIK3CB(1), PLD1(1), PLD2(1), PTK2(1), SERPINA4(2), SRF(1) 20312243 22 20 22 13 5 4 5 2 6 0 0.99 1.00 606 KREBS_TCA_CYCLE ACO2, CGI_48, CS, DLAT, DLD, DLST, DLST, DLSTP, FH, IDH2, IDH3A, IDH3B, IDH3G, KIAA1348, MDH1, MDH2, OGDH, PC, PDHA1, PDHA2, PDHB, PDHX, PDK1, PDK2, PDK3, PDK4, PDP2, PPM2C, SDHA, SDHA, SDHAL2, SDHB, SDHC, SDHD, SUCLA2, SUCLG1, SUCLG2, WDR50 30 ACO2(1), CS(1), DLAT(1), DLST(1), FH(1), MDH2(1), OGDH(2), PDK1(1), PDK3(1), SDHA(1), SUCLG2(1) 12416313 12 11 12 7 1 2 5 3 1 0 1.00 1.00 607 VALINE_LEUCINE_AND_ISOLEUCINE_BIOSYNTHESIS BCAT1, IARS, LARS, LARS2, PDHA1, PDHA2, PDHB 7 IARS(1) 4641740 1 1 1 3 0 0 1 0 0 0 1.00 1.00 608 MRNA_PROCESSING_REACTOME BRUNOL4, C10orf9, C20orf14, CD2BP2, CDC40, CLK2, CLK3, CLK4, COL2A1, CPSF1, CPSF2, CPSF3, CPSF4, CSTF1, CSTF2, CSTF2T, CSTF3, CUGBP1, CUGBP2, DDIT3, DDX1, DDX20, DHX15, DHX16, DHX38, DHX8, DHX9, DICER1, DNAJC8, FLJ10748, FNBP3, FUS, FUSIP1, GIPC1, HEAB, HNRPA2B1, HNRPA3, HNRPA3P1, HNRPA3, LOC387933, HNRPA3P1, HNRPA3, LOC389395, HNRPAB, HNRPC, HNRPC, HNRPCL1, LOC390615, LOC440563, HNRPD, HNRPH1, HNRPH2, HNRPL, HNRPR, HNRPU, HRMT1L2, LSM2, LSM7, METTL3, NCBP1, NCBP2, NONO, NUDT21, NXF1, PABPN1, PAPOLA, PHF5A, POLR2A, PPM1G, PRPF18, PRPF3, PRPF4, PRPF4B, PRPF8, PSKH1, PTBP1, PTBP2, RBM17, RBM5, RNGTT, RNMT, RNPC2, RNPS1, SF3A1, SF3A2, SF3A3, SF3B1, SF3B2, SF3B4, SF3B5, SF4, SFRS10, SFRS12, SFRS14, SFRS16, SFRS2, SFRS4, SFRS5, SFRS6, SFRS7, SFRS8, SFRS9, SMC1L1, SNRP70, SNRPA, SNRPA1, SNRPB, SNRPB2, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, SNRPN, SNRPN, PAR1, SNRPN, SNURF, SPOP, SRPK1, SRPK2, SRRM1, SUPT5H, TMP21, TXNL4A, U2AF1, U2AF2, WDR57, XRN2 89 CD2BP2(1), CLK4(1), COL2A1(1), CPSF2(2), CSTF2T(1), DDIT3(2), DDX1(1), DHX15(1), DHX16(3), DHX8(2), DHX9(2), DICER1(1), NONO(1), NXF1(1), PABPN1(2), PRPF3(1), PRPF4(1), PRPF4B(1), PRPF8(1), PTBP1(1), RNPS1(2), SF3A1(4), SF3B2(1), SF3B4(2), SNRPA(1), SNRPB(1), SNRPN(1), SPOP(1), SRPK1(1), SRPK2(1), SRRM1(2), SUPT5H(4), U2AF2(1), XRN2(1) 46105882 50 45 50 14 7 10 14 9 10 0 1.00 1.00 609 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 POLR1C(1), POLR2B(2), POLR2C(1), POLR2I(1) 10380306 5 5 5 6 0 1 0 3 1 0 1.00 1.00 610 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 339344 0 0 0 1 0 0 0 0 0 0 1.00 1.00 611 HSA00627_1,4_DICHLOROBENZENE_DEGRADATION Genes involved in 1,4-dichlorobenzene degradation CMBL 1 237871 0 0 0 0 0 0 0 0 0 0 1.00 1.00 612 HSA00643_STYRENE_DEGRADATION Genes involved in styrene degradation FAH, GSTZ1, HGD 3 715548 0 0 0 0 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 1999361 0 0 0 1 0 0 0 0 0 0 1.00 1.00 614 SA_FAS_SIGNALING The TNF-type receptor Fas induces apoptosis on ligand binding. BCL2, CASP3, CASP8, CFL1, CFLAR, P11, PDE6D, TNFRSF6, TNFSF6 6 1679841 0 0 0 0 0 0 0 0 0 0 1.00 1.00 615 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 5 2244780 0 0 0 2 0 0 0 0 0 0 1.00 1.00 616 TERPENOID_BIOSYNTHESIS FDFT1, FDPS, FDPS, LOC402397, IDI1, SQLE 4 1409820 0 0 0 1 0 0 0 0 0 0 1.00 1.00