Development Notch signaling pathway Ageing

PSENEN NUMB NUMBL JAG1 JAG2 DVL1 DVL2 DVL3 LFNG MFNG RFNG DLL3 DLL1 DLL4 NCSTN APH1A APH1B PSEN1 PSEN2 ADAM17 PSENEN NUMB NUMBL JAG1 JAG2 DVL1 DVL2 DVL3 LFNG MFNG RFNG DLL3 DLL1 DLL4 NCSTN APH1A APH1B PSEN1 PSEN2 ADAM17

NCOR2 CREBBP EP300 KAT2A KAT2B MAML3 MAML2 MAML1 HDAC1 HDAC2 CIR1 CTBP1 CTBP2 NOTCH1 NOTCH2 NOTCH3 NOTCH4 NCOR2 CREBBP EP300 KAT2A KAT2B MAML3 MAML2 MAML1 HDAC1 HDAC2 CIR1 CTBP1 CTBP2 NOTCH1 NOTCH2 NOTCH3 NOTCH4

RBPJL RBPJ DTX1 DTX3 DTX4 DTX2 DTX3L RBPJL RBPJ DTX1 DTX3 DTX4 DTX2 DTX3L

HES5 SNW1 PTCRA HES1 HES5 SNW1 PTCRA HES1 Development Renal cell carcinoma Ageing

HGF EGLN1 ARNT ARNT2 CREBBP EP300 EGLN2 EGLN3 CUL2 RBX1 ELOB ELOC VHL FLCN FH RAC1 CDC42 HRAS KRAS NRAS PRCC TFE3 CDKN1A HGF EGLN1 ARNT ARNT2 CREBBP EP300 EGLN2 EGLN3 CUL2 RBX1 ELOB ELOC VHL FLCN FH RAC1 CDC42 HRAS KRAS NRAS PRCC TFE3 CDKN1A

MET EPAS1 HIF1A PAK5 PAK4 BUB1B−PAK6 PAK1 PAK2 PAK3 PAK6 MET EPAS1 HIF1A PAK5 PAK4 BUB1B−PAK6 PAK1 PAK2 PAK3 PAK6

RAF1 BRAF ARAF GAB1 PDGFB TGFB1 TGFB2 TGFB3 VEGFA SLC2A1 TGFA RAF1 BRAF ARAF GAB1 PDGFB TGFB1 TGFB2 TGFB3 VEGFA SLC2A1 TGFA

MAP2K2 MAP2K1 PTPN11 PIK3R2 PIK3R3 PIK3CA PIK3CB PIK3CD PIK3R1 CRK CRKL GRB2 MAP2K2 MAP2K1 PTPN11 PIK3R2 PIK3R3 PIK3CA PIK3CB PIK3CD PIK3R1 CRK CRKL GRB2

MAPK3 MAPK1 AKT2 AKT3 AKT1 RAPGEF1 SOS1 SOS2 MAPK3 MAPK1 AKT2 AKT3 AKT1 RAPGEF1 SOS1 SOS2

ETS1 JUN BAD RAP1B RAP1A ETS1 JUN BAD RAP1B RAP1A Development RNA polymerase Ageing

TWISTNB ZNRD1 TWISTNB ZNRD1 POLR1D POLR3K POLR1C POLR1D POLR3K POLR1C

POLR3B POLR3B POLR2H POLR2G POLR2F POLR2H POLR2G POLR2F POLR3F POLR3F POLR1E POLR1E POLR2J3 POLR2C POLR2A POLR2J3 POLR2C POLR2A POLR2J POLR1A POLR2J POLR1A

POLR1B POLR2J2 POLR3E POLR1B POLR2J2 POLR3E POLR2D POLR2K POLR2D POLR2K

POLR3H POLR2E POLR2B POLR3H POLR2E POLR2B POLR2I POLR2L POLR2I POLR2L

POLR3C POLR3D POLR3A POLR3C POLR3D POLR3A POLR3G POLR3GL POLR3G POLR3GL Development mRNA surveillance pathway Ageing

RBM8A MAGOH MAGOHB EIF4A3 CASC3 ACIN1 RNPS1 SAP18 SRRM1 NXF5 NXF3 NXF2 NXF2B NXF1 PNN ALYREF SMG1 DDX39B PYM1 RNGTT RNMT NUDT21 PAPOLA PAPOLB PAPOLG CLP1 CPSF3 CPSF2 CPSF1 CPSF4 FIP1L1 SYMPK BCL2L2−PABPN1 PABPN1L PABPN1 HBS1L RBM8A MAGOH MAGOHB EIF4A3 CASC3 ACIN1 RNPS1 SAP18 SRRM1 NXF5 NXF3 NXF2 NXF2B NXF1 PNN ALYREF SMG1 DDX39B PYM1 RNGTT RNMT NUDT21 PAPOLA PAPOLB PAPOLG CLP1 CPSF3 CPSF2 CPSF1 CPSF4 FIP1L1 SYMPK BCL2L2−PABPN1 PABPN1L PABPN1 HBS1L

NXT1 NXT2 PPP2R2C PPP2R3A PPP2R5A PPP2R5B PPP2R5C PPP2R5D PPP2R5E PPP2R2D PPP2R3B PPP2R3C PPP2CA PPP2CB PPP2R1A PPP2R1B PPP2R2A PPP2R2B SMG7 CPSF6 CPSF7 PCF11 WDR33 WDR82 PPP1CA PPP1CB PPP1CC SSU72 CSTF1 CSTF2 CSTF2T CSTF3 PELO NXT1 NXT2 PPP2R2C PPP2R3A PPP2R5A PPP2R5B PPP2R5C PPP2R5D PPP2R5E PPP2R2D PPP2R3B PPP2R3C PPP2CA PPP2CB PPP2R1A PPP2R1B PPP2R2A PPP2R2B SMG7 CPSF6 CPSF7 PCF11 WDR33 WDR82 PPP1CA PPP1CB PPP1CC SSU72 CSTF1 CSTF2 CSTF2T CSTF3 PELO

ETF1 SMG6 SMG5 NCBP1 ETF1 SMG6 SMG5 NCBP1

UPF3B UPF3A UPF2 UPF1 NCBP2 UPF3B UPF3A UPF2 UPF1 NCBP2

GSPT2 MSI2 DAZAP1 MSI1 GSPT1 GSPT2 MSI2 DAZAP1 MSI1 GSPT1

PABPC1L PABPC4 PABPC4L PABPC5 PABPC1 PABPC1L2A PABPC3 PABPC1L2B PABPC1L PABPC4 PABPC4L PABPC5 PABPC1 PABPC1L2A PABPC3 PABPC1L2B Development Autophagy − other Ageing

RPTOR BECN2 BECN1 PIK3R4 PIK3C3 ATG9B ATG9A ATG2A ATG2B WIPI2 WIPI1 ATG16L1 RPTOR BECN2 BECN1 PIK3R4 PIK3C3 ATG9B ATG9A ATG2A ATG2B WIPI2 WIPI1 ATG16L1

MTOR ATG7 ATG10 ATG5 MTOR ATG7 ATG10 ATG5

MLST8 ATG12 MLST8 ATG12

IGBP1 ATG4C ATG4D ATG4A ATG4B ATG3 IGBP1 ATG4C ATG4D ATG4A ATG4B ATG3

PPP2CB PPP2CA GABARAP GABARAPL1 GABARAPL2 PPP2CB PPP2CA GABARAP GABARAPL1 GABARAPL2

ULK2 ULK2

ATG13 ATG13

ATG101 ATG101 Development AMPK signaling pathway Ageing

PDPK1 MAP3K7 STK11 CAMKK2 STRADB STRADA CAB39 CAB39L ADRA1A INS IGF1 FOXO1 SIRT1 ADIPOQ CPT1C CPT1A CPT1B PFKL PFKM PFKP FBP1 FBP2 PPP2R3B PPP2R3C PPP2CA PPP2CB PPP2R1A PPP2R1B PPP2R2A PPP2R2B PPP2R2C PPP2R3A PPP2R5A PPP2R5B PPP2R5C PPP2R5D PPP2R5E PPP2R2D LEP PDPK1 MAP3K7 STK11 CAMKK2 STRADB STRADA CAB39 CAB39L ADRA1A INS IGF1 FOXO1 SIRT1 ADIPOQ CPT1C CPT1A CPT1B PFKL PFKM PFKP FBP1 FBP2 PPP2R3B PPP2R3C PPP2CA PPP2CB PPP2R1A PPP2R1B PPP2R2A PPP2R2B PPP2R2C PPP2R3A PPP2R5A PPP2R5B PPP2R5C PPP2R5D PPP2R5E PPP2R2D LEP

CREB5 CREB3 CREB1 CREB3L4 CREB3L2 CREB3L3 CREB3L1 AKT3 AKT1 AKT2 PRKAG3 PRKAB2 PRKAG1 PRKAG2 PRKAA2 PRKAB1 PRKAA1 INSR IGF1R FOXO3 ADIPOR1 ADIPOR2 LEPR CREB5 CREB3 CREB1 CREB3L4 CREB3L2 CREB3L3 CREB3L1 AKT3 AKT1 AKT2 PRKAG3 PRKAB2 PRKAG1 PRKAG2 PRKAA2 PRKAB1 PRKAA1 INSR IGF1R FOXO3 ADIPOR1 ADIPOR2 LEPR

CRTC2 HNF4A TSC2 TSC1 SREBF1 ELAVL1 CFTR MLYCD PFKFB1 PFKFB2 PFKFB3 PFKFB4 EEF2K GYS1 GYS2 ACACB LIPE HMGCR CD36 TBC1D1 IRS1 IRS4 IRS2 CRTC2 HNF4A TSC2 TSC1 SREBF1 ELAVL1 CFTR MLYCD PFKFB1 PFKFB2 PFKFB3 PFKFB4 EEF2K GYS1 GYS2 ACACB LIPE HMGCR CD36 TBC1D1 IRS1 IRS4 IRS2

PCK1 PCK2 G6PC2 G6PC3 G6PC RHEB FASN SCD SCD5 CCNA2 CCNA1 CCND1 ACACA EEF2 PPARGC1A RAB14 RAB2A RAB11B RAB10 RAB8A PIK3CA PIK3CB PIK3CD PIK3R1 PIK3R2 PIK3R3 PCK1 PCK2 G6PC2 G6PC3 G6PC RHEB FASN SCD SCD5 CCNA2 CCNA1 CCND1 ACACA EEF2 PPARGC1A RAB14 RAB2A RAB11B RAB10 RAB8A PIK3CA PIK3CB PIK3CD PIK3R1 PIK3R2 PIK3R3

AKT1S1 MTOR RPTOR SLC2A4 AKT1S1 MTOR RPTOR SLC2A4

PPARG ULK1 RPS6KB1 RPS6KB2 EIF4EBP1 PPARG ULK1 RPS6KB1 RPS6KB2 EIF4EBP1 Development Phospholipase D signaling pathway Ageing

RAF1 LOC102723407 AKT3 AKT1 AKT2 PLCG1 PLCG2 PIP5K1C PIP5K1A PIP5K1B PLA2G4B PLA2G4E PLA2G4F PLA2G4D PLA2G4A PLA2G4C JMJD7−PLA2G4B PLPP1 PLPP2 PLPP3 DGKK DGKA DGKB DGKG DGKH DGKQ DGKZ DGKE DGKD DGKI SPHK2 SPHK1 DNM1 DNM2 DNM3 AGPAT1 AGPAT2 AGPAT5 AGPAT3 AGPAT4 RAF1 LOC102723407 AKT3 AKT1 AKT2 PLCG1 PLCG2 PIP5K1C PIP5K1A PIP5K1B PLA2G4B PLA2G4E PLA2G4F PLA2G4D PLA2G4A PLA2G4C JMJD7−PLA2G4B PLPP1 PLPP2 PLPP3 DGKK DGKA DGKB DGKG DGKH DGKQ DGKZ DGKE DGKD DGKI SPHK2 SPHK1 DNM1 DNM2 DNM3 AGPAT1 AGPAT2 AGPAT5 AGPAT3 AGPAT4

MAP2K1 MAP2K2 MS4A2 FCER1G FCER1A KITLG PDGFA PDGFB PDGFC PDGFD INS EGF TSC1 TSC2 MAP2K1 MAP2K2 MS4A2 FCER1G FCER1A KITLG PDGFA PDGFB PDGFC PDGFD INS EGF TSC1 TSC2

MAPK1 MAPK3 SYK FYN EGFR PDGFRA KIT INSR PDGFRB RHEB MAPK1 MAPK3 SYK FYN EGFR PDGFRA KIT INSR PDGFRB RHEB

AVP CXCL8 GAB2 PTPN11 GRB2 SHC3 SHC2 SHC4 SHC1 GAB1 MTOR AVP CXCL8 GAB2 PTPN11 GRB2 SHC3 SHC2 SHC4 SHC1 GAB1 MTOR

GRM6 GRM7 GRM8 CXCR1 CXCR2 AVPR1A AVPR1B AVPR2 LPAR5 PTGFR LPAR2 LPAR6 AGTR1 LPAR1 F2R LPAR3 LPAR4 GRM1 GRM2 GRM3 GRM4 GRM5 PIK3CD PIK3R1 PIK3R2 PIK3CA PIK3CB SOS2 SOS1 PIK3R3 RAPGEF4 RAPGEF3 GRM6 GRM7 GRM8 CXCR1 CXCR2 AVPR1A AVPR1B AVPR2 LPAR5 PTGFR LPAR2 LPAR6 AGTR1 LPAR1 F2R LPAR3 LPAR4 GRM1 GRM2 GRM3 GRM4 GRM5 PIK3CD PIK3R1 PIK3R2 PIK3CA PIK3CB SOS2 SOS1 PIK3R3 RAPGEF4 RAPGEF3

GNA13 PLCB1 PLCB2 PLCB3 PLCB4 GNAS GNA12 KRAS NRAS MRAS HRAS RRAS RRAS2 GNA13 PLCB1 PLCB2 PLCB3 PLCB4 GNAS GNA12 KRAS NRAS MRAS HRAS RRAS RRAS2

PIK3CG PIK3R6 PIK3R5 ADCY4 ADCY1 ADCY2 ADCY3 ADCY5 ADCY6 ADCY7 ADCY8 ADCY9 PTK2B RALGDS CYTH2 CYTH1 CYTH4 CYTH3 PIK3CG PIK3R6 PIK3R5 ADCY4 ADCY1 ADCY2 ADCY3 ADCY5 ADCY6 ADCY7 ADCY8 ADCY9 PTK2B RALGDS CYTH2 CYTH1 CYTH4 CYTH3

RHOA RALB RALA ARF1 ARF6 PRKCA RHOA RALB RALA ARF1 ARF6 PRKCA

PLD1 PLD2 PLD1 PLD2 Development Longevity regulating pathway − multiple species Ageing

AKT2 AKT3 AKT1 INS IGF1 CLPB AKT2 AKT3 AKT1 INS IGF1 CLPB

HDAC1 HDAC2 PRKAB2 PRKAG1 ADCY3 ADCY5 ADCY6 ADCY7 ADCY8 ADCY9 ADCY4 PRKAG2 PRKAG3 PRKAA1 PRKAA2 ADCY1 ADCY2 PRKAB1 INSR IGF1R HDAC1 HDAC2 PRKAB2 PRKAG1 ADCY3 ADCY5 ADCY6 ADCY7 ADCY8 ADCY9 ADCY4 PRKAG2 PRKAG3 PRKAA1 PRKAA2 ADCY1 ADCY2 PRKAB1 INSR IGF1R

SIRT1 PRKACA PRKACB PRKACG RPTOR MTOR AKT1S1 IRS4 IRS2 IRS1 KRAS NRAS HRAS SIRT1 PRKACA PRKACB PRKACG RPTOR MTOR AKT1S1 IRS4 IRS2 IRS1 KRAS NRAS HRAS

FOXO1 FOXO3 EIF4EBP2 RPS6KB1 RPS6KB2 PIK3CD PIK3CA PIK3R2 PIK3R3 PIK3R1 PIK3CB FOXO1 FOXO3 EIF4EBP2 RPS6KB1 RPS6KB2 PIK3CD PIK3CA PIK3R2 PIK3R3 PIK3R1 PIK3CB

ATG5 CRYAB HSPA1A HSPA1B HSPA1L HSPA2 HSPA6 HSPA8 SOD1 FOXA2 ATG5 CRYAB HSPA1A HSPA1B HSPA1L HSPA2 HSPA6 HSPA8 SOD1 FOXA2

CAT SOD2 CAT SOD2 Development Longevity regulating pathway Ageing

SIRT1 INS KL IGF1 CREB3 CREB1 ATF2 ATF6B CREB3L4 ATF4 CREB3L2 CREB3L3 CREB3L1 CREB5 ADIPOQ SIRT1 INS KL IGF1 CREB3 CREB1 ATF2 ATF6B CREB3L4 ATF4 CREB3L2 CREB3L3 CREB3L1 CREB5 ADIPOQ

TP53 BAX NFKB1 RELA PPARG INSR IGF1R ADIPOR1 ADIPOR2 TP53 BAX NFKB1 RELA PPARG INSR IGF1R ADIPOR1 ADIPOR2

SESN1 SESN2 STK11 SESN3 CAMKK2 IRS1 IRS4 IRS2 HRAS KRAS NRAS APPL1 SESN1 SESN2 STK11 SESN3 CAMKK2 IRS1 IRS4 IRS2 HRAS KRAS NRAS APPL1

AKT1 AKT2 AKT3 PRKAG1 PRKAG3 PRKAG2 PRKAA1 PRKAA2 PRKAB2 PRKAB1 PRKACA PRKACB PRKACG CAMK4 PIK3CA PIK3CB PIK3CD PIK3R1 PIK3R2 PIK3R3 AKT1 AKT2 AKT3 PRKAG1 PRKAG3 PRKAG2 PRKAA1 PRKAA2 PRKAB2 PRKAB1 PRKACA PRKACB PRKACG CAMK4 PIK3CA PIK3CB PIK3CD PIK3R1 PIK3R2 PIK3R3

ADCY7 ADCY8 ADCY1 ADCY2 ADCY9 ADCY4 ADCY3 ADCY5 ADCY6 TSC2 TSC1 FOXO1 FOXO3 EHMT2 EHMT1 PPARGC1A ADCY7 ADCY8 ADCY1 ADCY2 ADCY9 ADCY4 ADCY3 ADCY5 ADCY6 TSC2 TSC1 FOXO1 FOXO3 EHMT2 EHMT1 PPARGC1A

RHEB ATG5 SOD2 CAT RHEB ATG5 SOD2 CAT

AKT1S1 MTOR RPTOR AKT1S1 MTOR RPTOR

RPS6KB2 EIF4EBP1 ULK1 RB1CC1 ATG13 ATG101 RPS6KB1 RPS6KB2 EIF4EBP1 ULK1 RB1CC1 ATG13 ATG101 RPS6KB1

EIF4E EIF4E1B EIF4E2 EIF4E EIF4E1B EIF4E2 Development FoxO signaling pathway Ageing

EGF IGF1 INS SKP2 MDM2 CREBBP EP300 SIRT1 TGFB1 TGFB2 TGFB3 FOXG1 SLC2A4 EGF IGF1 INS SKP2 MDM2 CREBBP EP300 SIRT1 TGFB1 TGFB2 TGFB3 FOXG1 SLC2A4

EGFR IGF1R INSR GRM1 TGFBR2 TGFBR1 SMAD4 EGFR IGF1R INSR GRM1 TGFBR2 TGFBR1 SMAD4

GRB2 IRS1 IRS4 IRS2 AGAP2 HOMER3 HOMER2 HOMER1 SMAD2 SMAD3 GRB2 IRS1 IRS4 IRS2 AGAP2 HOMER3 HOMER2 HOMER1 SMAD2 SMAD3

SOS1 SOS2 PIK3CA PIK3CB PIK3CD PIK3R1 PIK3R2 PIK3R3 SOS1 SOS2 PIK3CA PIK3CB PIK3CD PIK3R1 PIK3R2 PIK3R3

KRAS NRAS HRAS KRAS NRAS HRAS

ARAF RAF1 BRAF PDPK1 ARAF RAF1 BRAF PDPK1

MAP2K1 MAP2K2 IL10 IL6 STK11 AKT1 AKT2 AKT3 MAP2K1 MAP2K2 IL10 IL6 STK11 AKT1 AKT2 AKT3

MAPK1 MAPK3 C8orf44−SGK3 SGK2 SGK3 STAT3 SGK1 PRKAA1 PRKAA2 PRKAB1 PRKAB2 PRKAG1 MAPK9 NLK MAPK14 MAPK11 MAPK13 MAPK12 SETD7 PRMT1 USP7 MAPK10 STK4 CDK2 TPTEP2−CSNK1E CSNK1E MAPK8 PRKAG2 PRKAG3 IKBKB CHUK MAPK1 MAPK3 C8orf44−SGK3 SGK2 SGK3 STAT3 SGK1 PRKAA1 PRKAA2 PRKAB1 PRKAB2 PRKAG1 MAPK9 NLK MAPK14 MAPK11 MAPK13 MAPK12 SETD7 PRMT1 USP7 MAPK10 STK4 CDK2 TPTEP2−CSNK1E CSNK1E MAPK8 PRKAG2 PRKAG3 IKBKB CHUK

FOXO6 FOXO1 FOXO3 FOXO4 PTEN FOXO6 FOXO1 FOXO3 FOXO4 PTEN

G6PC2 G6PC3 CCNB3 CCNB1 CCNB2 CCND1 CCND2 CDKN2B CDKN2D CDKN1A CDKN1B RBL2 PLK4 PLK2 PLK3 PLK1 GADD45G GADD45A GADD45B FASLG BCL2L11 TNFSF10 BCL6 CAT SOD2 ATM IL7R KLF2 S1PR1 S1PR4 RAG1 RAG2 BNIP3 GABARAP GABARAPL2 GABARAPL1 ATG12 FBXO32 FBXO25 CCNG2 PCK1 PCK2 G6PC G6PC2 G6PC3 CCNB3 CCNB1 CCNB2 CCND1 CCND2 CDKN2B CDKN2D CDKN1A CDKN1B RBL2 PLK4 PLK2 PLK3 PLK1 GADD45G GADD45A GADD45B FASLG BCL2L11 TNFSF10 BCL6 CAT SOD2 ATM IL7R KLF2 S1PR1 S1PR4 RAG1 RAG2 BNIP3 GABARAP GABARAPL2 GABARAPL1 ATG12 FBXO32 FBXO25 CCNG2 PCK1 PCK2 G6PC Development Autophagy − animal Ageing

IGF1R INS PTEN ZFYVE1 MTMR3 MTMR4 MTMR14 LAMP1 LAMP2 RAB7B RAB7A CTSD CTSL CTSB IGF1R INS PTEN ZFYVE1 MTMR3 MTMR4 MTMR14 LAMP1 LAMP2 RAB7B RAB7A CTSD CTSL CTSB

RRAS2 MRAS HRAS KRAS NRAS RRAS RRAS2 MRAS HRAS KRAS NRAS RRAS

PRAP1 RAF1 PDPK1 PRAP1 RAF1 PDPK1

PRKACG PRKACA PRKACB STK11 MAP3K7 CAMKK2 MAP2K2 MAP2K1 HIF1A PRKACG PRKACA PRKACB STK11 MAP3K7 CAMKK2 MAP2K2 MAP2K1 HIF1A

PRKAA2 PRKAA1 MAPK3 MAPK1 AKT2 AKT3 AKT1 DDIT4 PRKAA2 PRKAA1 MAPK3 MAPK1 AKT2 AKT3 AKT1 DDIT4

TSC1 TSC2 BNIP3 TSC1 TSC2 BNIP3

RRAGA RRAGB RRAGC RRAGD RHEB RRAGA RRAGB RRAGC RRAGD RHEB

AKT1S1 AKT1S1

DEPTOR RPTOR MLST8 DEPTOR RPTOR MLST8

MTOR MTOR

IGBP1 RPS6KB1 RPS6KB2 IGBP1 RPS6KB1 RPS6KB2

PPP2CA PPP2CB IRS4 IRS2 IRS1 PPP2CA PPP2CB IRS4 IRS2 IRS1

ULK1 PIK3R2 PIK3R3 PIK3CA PIK3CB PIK3CD PIK3R1 ULK1 PIK3R2 PIK3R3 PIK3CA PIK3CB PIK3CD PIK3R1

AMBRA1 AMBRA1

TRAF6 TRAF6

ULK2 SH3GLB1 PRKCD ERN1 ULK2 SH3GLB1 PRKCD ERN1

TP53INP2 ATG2B ATG2A ATG13 SUPT20H UVRAG STX17 MAPK8 MAPK10 MAPK9 BAD TP53INP2 ATG2B ATG2A ATG13 SUPT20H UVRAG STX17 MAPK8 MAPK10 MAPK9 BAD

EIF2AK4 EIF2AK3 WIPI1 RAB33B WIPI2 RB1CC1 VMP1 ATG101 DAPK2 DAPK1 DAPK3 HMGB1 ATG9A ATG9B ITPR1 ATG14 BCL2 BCL2L1 EIF2AK4 EIF2AK3 WIPI1 RAB33B WIPI2 RB1CC1 VMP1 ATG101 DAPK2 DAPK1 DAPK3 HMGB1 ATG9A ATG9B ITPR1 ATG14 BCL2 BCL2L1

ATG7 ATG10 EIF2S1 ATG16L1 ATG16L2 BECN2 BECN1 SNAP29 ATG7 ATG10 EIF2S1 ATG16L1 ATG16L2 BECN2 BECN1 SNAP29

ATG12 PIK3R4 NRBF2 VAMP8 RUBCN ATG12 PIK3R4 NRBF2 VAMP8 RUBCN

CFLAR ATG5 PIK3C3 CFLAR ATG5 PIK3C3

ATG4B ATG4C ATG4D ATG4A PRKCQ ATG3 ATG4B ATG4C ATG4D ATG4A PRKCQ ATG3

GABARAP GABARAPL2 GABARAPL1 GABARAP GABARAPL2 GABARAPL1 Development Adherens junction Ageing

TGFBR2 TGFBR1 FGFR1 CTNNA3 CTNNA2 CTNNA1 MAP3K7 CREBBP EP300 INSR TGFBR2 TGFBR1 FGFR1 CTNNA3 CTNNA2 CTNNA1 MAP3K7 CREBBP EP300 INSR

SMAD4 SMAD2 SMAD3 SNAI1 ACTB NLK SMAD4 SMAD2 SMAD3 SNAI1 ACTB NLK

VCL VCL

SORBS1 SORBS1

AFDN AFDN

NECTIN3 NECTIN3

NECTIN1 NECTIN1

NECTIN2 NECTIN2

NECTIN4 YES1 NECTIN4 YES1

PARD3 SRC PTPRJ PTPN6 FER MET FYN PTPRM EGFR ERBB2 PARD3 SRC PTPRJ PTPN6 FER MET FYN PTPRM EGFR ERBB2

FARP2 RHOA CTNND1 MAPK3 MAPK1 FARP2 RHOA CTNND1 MAPK3 MAPK1

CDC42 SNAI2 CDC42 SNAI2

RAC1 RAC3 RAC2 WASL WAS RAC1 RAC3 RAC2 WASL WAS

BAIAP2 WASF1 WASF2 WASF3 IQGAP1 CDH1 LEF1 TCF7 TCF7L2 TCF7L1 IGF1R CSNK2A1 CSNK2A2 CSNK2B CSNK2A3 PTPN1 PTPRF PTPRB ACP1 BAIAP2 WASF1 WASF2 WASF3 IQGAP1 CDH1 LEF1 TCF7 TCF7L2 TCF7L1 IGF1R CSNK2A1 CSNK2A2 CSNK2B CSNK2A3 PTPN1 PTPRF PTPRB ACP1

ACTG1 CTNNB1 ACTG1 CTNNB1

TJP1 ACTN1 ACTN4 TJP1 ACTN1 ACTN4

LMO7 SSX2IP LMO7 SSX2IP Development Herpes simplex infection Ageing

DDX58 IFIH1 NECTIN1 NECTIN2 PILRA C3 C5 CFP CDK2 CDK1 UBE2R2 CDC34 CUL1 SKP1 SKP2 PML SP100 DAXX CREBBP EP300 TP53 EEF1D NOP53 MCRS1 ARNTL TAF6L MED8 TAF5L GTF2I TBPL2 TAF9B TAF4 TAF4B TAF5 TAF6 TAF10 TAF13 TBP TAF3 TBPL1 GTF2IRD1 HMGN1 PPP1CA PPP1CB PPP1CC OAS1 OAS2 OAS3 ALYREF NXF1 NXF5 NXF3 NXF2 NXF2B TAP1 TAP2 HLA−A HLA−B HLA−C HLA−E HLA−F HLA−G POLR2A CD74 HLA−DMA HLA−DMB HLA−DOA HLA−DOB HLA−DPA1 HLA−DPB1 HLA−DQA1HLA−DQA2HLA−DQB1 HLA−DRA HLA−DRB1 HLA−DRB3 HLA−DRB4 HLA−DRB5 HNRNPK DDX58 IFIH1 NECTIN1 NECTIN2 PILRA C3 C5 CFP CDK2 CDK1 UBE2R2 CDC34 CUL1 SKP1 SKP2 PML SP100 DAXX CREBBP EP300 TP53 EEF1D NOP53 MCRS1 ARNTL TAF6L MED8 TAF5L GTF2I TBPL2 TAF9B TAF4 TAF4B TAF5 TAF6 TAF10 TAF13 TBP TAF3 TBPL1 GTF2IRD1 HMGN1 PPP1CA PPP1CB PPP1CC OAS1 OAS2 OAS3 ALYREF NXF1 NXF5 NXF3 NXF2 NXF2B TAP1 TAP2 HLA−A HLA−B HLA−C HLA−E HLA−F HLA−G POLR2A CD74 HLA−DMA HLA−DMB HLA−DOA HLA−DOB HLA−DPA1 HLA−DPB1 HLA−DQA1HLA−DQA2HLA−DQB1 HLA−DRA HLA−DRB1 HLA−DRB3 HLA−DRB4 HLA−DRB5 HNRNPK

TLR9 TLR2 TLR3 MAVS PTPN11 CSNK2A3 CSNK2A1 CSNK2A2 CSNK2B CLOCK PER1 PER3 PER2 EIF2AK2 EIF2AK3 EIF2AK1 EIF2AK4 RNASEL TLR9 TLR2 TLR3 MAVS PTPN11 CSNK2A3 CSNK2A1 CSNK2A2 CSNK2B CLOCK PER1 PER3 PER2 EIF2AK2 EIF2AK3 EIF2AK1 EIF2AK4 RNASEL

USP7 MYD88 TICAM1 IKBKE TBK1 HCFC1 C1QBP SRPK1 POU2F3 HCFC2 EIF2S1 USP7 MYD88 TICAM1 IKBKE TBK1 HCFC1 C1QBP SRPK1 POU2F3 HCFC2 EIF2S1

TRAF6 LTA TNFSF14 IRF3 IRF7 SRSF4 SRSF5 SRSF6 SRSF7 SRSF9 SRSF8 SRSF1 SRSF2 SRSF3 TRAF6 LTA TNFSF14 IRF3 IRF7 SRSF4 SRSF5 SRSF6 SRSF7 SRSF9 SRSF8 SRSF1 SRSF2 SRSF3

MAP3K7 TNFRSF14 IFNB1 IL15 IFIT1 IFNA14 IFNA16 IFNA17 IFNA21 IFNA1 IFNA2 IFNA4 IFNA5 IFNA6 IFNA7 IFNA8 IFNA10 IFIT1B IFNA13 IFNG MAP3K7 TNFRSF14 IFNB1 IL15 IFIT1 IFNA14 IFNA16 IFNA17 IFNA21 IFNA1 IFNA2 IFNA4 IFNA5 IFNA6 IFNA7 IFNA8 IFNA10 IFIT1B IFNA13 IFNG

IKBKB TAB2 TAB1 TRAF2 TRAF3 TRAF5 TRAF1 IFNAR1 SOCS3 IFNAR2 IFNGR1 IFNGR2 IKBKB TAB2 TAB1 TRAF2 TRAF3 TRAF5 TRAF1 IFNAR1 SOCS3 IFNAR2 IFNGR1 IFNGR2

CHUK NFKBIB NFKBIA IKBKG MAPK9 MAPK8 MAPK10 TYK2 JAK1 JAK2 CHUK NFKBIB NFKBIA IKBKG MAPK9 MAPK8 MAPK10 TYK2 JAK1 JAK2

RELA NFKB1 FOS JUN STAT2 STAT1 RELA NFKB1 FOS JUN STAT2 STAT1

IL1B CCL5 TNF IL12B IL12A FASLG IL6 CCL2 IRF9 IL1B CCL5 TNF IL12B IL12A FASLG IL6 CCL2 IRF9

TNFRSF1A FAS TNFRSF1A FAS

FADD FADD

CASP8 CASP8

CASP3 CYCS CASP3 CYCS Development Protein digestion and absorption Ageing

COL6A5 COL24A1 COL6A5 COL24A1 COL12A1 COL11A2 COL12A1 COL11A2 COL9A3 COL9A3 COL4A6 COL4A5 COL4A4 COL4A6 COL4A5 COL4A4 COL1A2 COL1A1 COL1A2 COL1A1 MEP1B MEP1A MEP1B MEP1A KCNQ1 KCNN4 KCNJ13 KCNQ1 KCNN4 KCNJ13 COL5A1 PGA5 COL9A2 COL5A1 PGA5 COL9A2 CPA1 CELA2A CPA1 CELA2A FXYD2 ATP1B3 ATP1B2 FXYD2 ATP1B3 ATP1B2 COL2A1 SLC8A1 COL11A1 COL2A1 SLC8A1 COL11A1 CPB1 ATP1A2 CPB1 ATP1A2 SLC1A5 SLC6A19 SLC15A1 SLC1A5 SLC6A19 SLC15A1 COL5A3 CELA3A DPP4 COL5A3 CELA3A DPP4 ACE2 CPA2 ACE2 CPA2 ATP1B4 SLC7A8 SLC7A9 COL15A1 ATP1B4 SLC7A8 SLC7A9 COL15A1 SLC3A1 CELA2B SLC3A1 CELA2B COL17A1 MME COL17A1 MME CELA3B PRSS3 SLC16A10 PRCP CELA3B PRSS3 SLC16A10 PRCP SLC38A2 ATP1A1 COL22A1 SLC38A2 ATP1A1 COL22A1 COL13A1 COL13A1 SLC8A3 SLC3A2 SLC7A7 CPA3 SLC8A3 SLC3A2 SLC7A7 CPA3 XPNPEP2 XPNPEP2 PRSS1 PRSS2 SLC1A1 PRSS1 PRSS2 SLC1A1

COL10A1 KCNK5 ATP1A4 ATP1B1 ATP1A3 COL10A1 KCNK5 ATP1A4 ATP1B1 ATP1A3 KCNE3 KCNE3 CTRB1 CTRL COL9A1 CTRB1 CTRL COL9A1

COL5A2 PGA3 PGA4 CPB2 COL5A2 PGA3 PGA4 CPB2 SLC9A3 SLC9A3 SLC36A1 SLC8A2 COL7A1 SLC36A1 SLC8A2 COL7A1

COL3A1 COL4A1 COL4A2 ELN COL3A1 COL4A1 COL4A2 ELN COL4A3 COL4A3 COL6A1 COL6A2 COL6A3 COL6A1 COL6A2 COL6A3

COL14A1 COL18A1 COL21A1 COL27A1 COL6A6 COL14A1 COL18A1 COL21A1 COL27A1 COL6A6 Development Primary immunodeficiency Ageing

RFXAP RFXAP ZAP70 PTPRC ZAP70 PTPRC IL2RG IL7R ADA IL2RG IL7R ADA

TAP2 ICOS TAP2 ICOS IKBKG CD8B CD8A IKBKG CD8B CD8A CD3D CD3D LCK LCK

BLNK CD40LG CD40 BLNK CD40LG CD40 IGLL1 DCLRE1C IGLL1 DCLRE1C

CD3E CD79A ORAI1 CD3E CD79A ORAI1 LOC102723407 BTK LOC102723407 BTK

JAK3 CD4 AIRE JAK3 CD4 AIRE AICDA UNG AICDA UNG

CD19 TNFRSF13B TNFRSF13C CD19 TNFRSF13B TNFRSF13C RAG1 RAG2 RAG1 RAG2

RFXANK CIITA RFX5 RFXANK CIITA RFX5 TAP1 TAP1 Development Linoleic acid metabolism Ageing

CYP1A2 CYP1A2

CYP2C8 CYP2C9 CYP2C19 CYP2C8 CYP2C9 CYP2C19

CYP2J2 CYP2J2

ALOX15 ALOX15

PLA2G4B PLA2G4B

CYP2E1 CYP2E1

CYP3A4 CYP3A4

PLA2G4D PLA2G2C PLB1 PLA2G2D PLA2G16 PLA2G4F PLA2G4E PLA2G5 PLA2G10 PLA2G12B PLA2G2E PLA2G2F JMJD7−PLA2G4B PLA2G3 PLA2G4C PLA2G1B PLA2G2A PLA2G4A PLA2G12A PLA2G6 PLA2G4D PLA2G2C PLB1 PLA2G2D PLA2G16 PLA2G4F PLA2G4E PLA2G5 PLA2G10 PLA2G12B PLA2G2E PLA2G2F JMJD7−PLA2G4B PLA2G3 PLA2G4C PLA2G1B PLA2G2A PLA2G4A PLA2G12A PLA2G6 Development Fat digestion and absorption Ageing

ABCG5 ABCG8 NPC1L1 CD36 APOB CEL PLA2G2D PLA2G2E PLA2G2C PLA2G3 PLA2G1B PLA2G2A PLA2G5 PNLIP PNLIPRP1 PNLIPRP2 PLA2G2F PLA2G12A PLA2G10 PLA2G12B LIPF AGPAT1 AGPAT2 ACAT2 MTTP APOA4 APOA1 ABCA1 CLPS SLC27A4 SCARB1 FABP2 FABP1 GOT2 ABCG5 ABCG8 NPC1L1 CD36 APOB CEL PLA2G2D PLA2G2E PLA2G2C PLA2G3 PLA2G1B PLA2G2A PLA2G5 PNLIP PNLIPRP1 PNLIPRP2 PLA2G2F PLA2G12A PLA2G10 PLA2G12B LIPF AGPAT1 AGPAT2 ACAT2 MTTP APOA4 APOA1 ABCA1 CLPS SLC27A4 SCARB1 FABP2 FABP1 GOT2

MOGAT2 PLPP1 PLPP2 PLPP3 MOGAT3 MOGAT2 PLPP1 PLPP2 PLPP3 MOGAT3

DGAT2 DGAT1 DGAT2 DGAT1