Disease table of GASTRIC CANCER, HEREDITARY DIFFUSE OMIM ID: 137215

Gene-disease associations table

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Gene	Associated with GASTRIC CANCER, HEREDITARY DIFFUSE in	Link to HGNC	Cytogenetic band	Number of associated diseases	Associated diseases
CDH1	ClinVar, OMIM, HUMSAVAR	HGNC link	16q22.1	5	608089, 167000, 176807, 137215, 114480
IL1B	OMIM	HGNC link	2q14.1	2	608316, 137215
IL1RN	OMIM	HGNC link	2q14.1	3	PS603933, 137215, 612852
KRAS	OMIM	HGNC link	12p12.1	14	601626, 600268, 137215, 109800, PS163950, 211980, 114480, PS115150, 613659, 163200, 607785, 614470, 162900, 260350

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Relations among genes:

Tandem repeat annotations from DGD

Cytogenetic band analysis

By sub-band

Shared sub_band	Number of genes associated with the disease	Genes associated with the disease
2q14.1	2	IL1B, IL1RN

By band

Shared band	Number of genes associated with the disease	Genes associated with the disease
2q14	2	IL1B, IL1RN

By region

Shared region	Number of genes associated with the disease	Genes associated with the disease
2q1	2	IL1B, IL1RN

By arm

Shared arm	Number of genes associated with the disease	Genes associated with the disease
2q	2	IL1B, IL1RN

By chromosome

Shared chromosome	Number of genes associated with the disease	Genes associated with the disease
2	2	IL1B, IL1RN

Transcription Factors (TF) annotation from TRRUST

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TF	associated to this disease	# regulated genes	Regulated genes	# regulated genes associated with this disease	Regulated genes associated with this disease
STAT3	NO	129	IFNG, MMP2, CCND3, EGFR, GAST, VEGFA, CHI3L1, CYP19A1, HAMP, POU2F1, COPS5, SLC9A3, IL11, SAA1, F2R, HP, IL10, PIAS3, CDK4, AKT1, CXCL8, OAS1, IL2, LTBP1, PTPN6, TP63, FAAH, MMP9, FLT3, JUNB, ZFP36, BCL2L1, CCL11, FGF1, TWIST2, JAK2, CFLAR, NR0B1, FGF2, MMP7, PTGS2, CCND2, MCL1, UCP2, SOCS3, CFB, HSPB1, HGF, NOX5, NOSTRIN, ESR2, CISH, IKBKE, JAK3, MMP1, CDH1, TIMP1, CYR61, CCL20, CRP, CD46, TRH, IRF1, TERT, ETV6, HIF1A, NANOG, NME1, TYK2, OPRM1, MDC1, A2M, FOS, PHB, IL2RA, OSM, MUC4, CCND1, NDUFA13, SOCS1, MMP14, SHH, IFNAR1, PRDM1, FGG, CSRP1, GFAP, TWIST1, PTEN, ICAM1, VEGFB, LEP, USP7, IL1RN, BST2, HMOX1, KRT17, MMP3, CDKN1B, PGF, MICA, TP53, DDIT3, BIRC5, FGL1, PIM1, MUC1, S1PR1, KLF11, FAS, STS, DNMT1, TGFB1, CDKN1A, VDR, TNFRSF10B, PAX3, LCAT, CTGF, BCL6, LGALS3BP, BCL2, HSPA4, IL21, SALL4, IL6, ROR1, MYC, AKAP12	2	IL1RN, CDH1
KLF4	NO	30	ATF3, IVL, GDF15, KRT19, BIRC5, TP53, MMP2, BDKRB2, IFITM3, GPA33, CCND1, LAMA3, THBD, ALPI, IL1B, CDKN1A, VDR, CDH1, RARA, NANOG, HDC, LXN, CYP1A1, HSPA8, CDKN1C, IL6, CDKN1B, CCNB1, ODC1, CDH5	2	IL1B, CDH1
NFKB1	NO	306	NRF1, VWF, FTH1, PGLYRP2, CDK4, RGS4, IFNG, MMP2, DCST1, AGT, THBD, EGFR, GDNF, CCL4, NCAM1, VEGFA, CR2, CFI, TP53, FOXO3, CYP19A1, BGN, LPL, CXCL12, ELF3, PTHLH, HOXA9, IRF7, TNC, AGER, EDN1, HBEGF, SFTPA1, SAA1, TSLP, GSK3A, IFNB1, GKN2, TRAF2, PLA2G2A, F3, IL10, LIPE, FAF1, IL17A, CEACAM1, AKT1, KLK3, IL1RN, GSTP1, E2F1, CCR5, TAPBP, ADORA2A, CXCL1, PTPN6, MMP3, PIGR, ERAP1, YY1, OLFM4, DEFB4A, CCL2, CD28, SQSTM1, TERT, IL4, NAMPT, BACE1, JUNB, SLC9A2, FASLG, ALOX5, BCL2L1, CD83, TLR3, CCL22, PLIN1, CDKN1A, BIRC3, CSF2, CFLAR, TFPI2, MYB, IL18, SERPINB1, MUC17, TNFRSF10A, PTGFR, TFF3, PTAFR, PTGS2, COX1, SERPINA3, ITGAX, CCND2, MCL1, TLR7, POU2F2, REPS2, CD3G, TFF1, B2M, PLAU, TNF, FOXP3, HDAC7, MUC5B, CCR2, FIGF, HSD11B2, CCL13, IFNA1, NOX5, MAT2A, COL7A1, HMOX1, ADORA1, TNFSF10, AR, COL2A1, TAP1, IL1B, CD74, CD38, MUC5AC, MUC2, TIMP1, CCL19, FGF8, PDK4, CCL20, STK39, CYP3A7, MMP9, GATA3, IRF4, CD58, HES1, PLAUR, SP4, NFKB1, MMP1, NOX4, BDKRB1, CASP3, CYP1A1, PSMB9, PTEN, HPSE, CCNB1, CD40, NOS3, PTGDS, UPP1, HIF1A, TNFRSF9, CD80, TNFSF13B, IL23A, TNFAIP3, TNFSF14, IL12A, TRPC1, CYP2E1, OPRM1, HLA-F, AMH, XIAP, MADCAM1, HYAL1, A2M, CCL11, TBX21, ICAM1, BCL2L11, CHUK, TAP2, IL2RA, CTCF, ABCB1, GSK3B, CCND1, KLF5, CCR7, CCK, DCST2, MMP14, IL17C, FBP1, OPTN, IL1A, LTC4S, COL1A2, NOS1, WT1, BIRC5, PPIG, PTGES, CREB3, CXCL2, CRP, KDM2A, BCL2A1, BRCA2, IKBKB, GFAP, PSMB10, PROX1, COL1A1, TNIP3, NFKBIZ, TLR2, S100A6, DRD2, CXCL8, CD86, TRAF1, PTPN13, CSNK2A1, CARD8, CXCL10, IL6, CFTR, CASP9, ABCG2, BMP2, CRMP1, IL2, IRF1, SOD2, IER3, NFKBIA, FN1, SERPINE1, MICA, TBP, CXCR2, BHMT, NCOR1, SNAI1, BAX, NPPB, CTSB, F8, IL12B, IGF2BP1, LCN2, NOLC1, CD40LG, SELE, NOD2, CCL5, FAS, ALOX5AP, OLR1, CXCR4, SDC1, FLT4, NCOR2, AKT2, CDH1, TGFB1, CCL3, IGF2BP2, HDAC1, SP1, PDE7A, ADORA3, CRHR1, BCL3, MIF, CXCL5, TNFRSF10B, HAX1, CYP27B1, NLRP2, FGF7, PTGER4, TNFRSF13C, CARM1, EBI3, VCAM1, ERAP2, MYC, CSF1, EPCAM, SLC25A27, NOS2, RIPK2, EGR1, BTG2, BCL2, ABCA1, CD69, BIRC2, CCR3, IL21, GCLC, MMP13, GRIN1, SP3, RRM2B, STAT4, TF, MUC6	3	IL1RN, IL1B, CDH1
RELA	NO	302	NRF1, OXTR, FTH1, CDK4, UPP1, IFNG, MMP2, DCST1, AGT, FLT4, EGFR, CCL4, NCAM1, VEGFA, CR2, CFI, TP53, FOXO3, CYP19A1, BGN, LPL, CXCL12, ELF3, PTHLH, IRF7, TNC, AGER, EDN1, SFTPA1, IGF2BP2, PPARA, SAA1, TSLP, GSK3A, IFNB1, GKN2, PLA2G2A, F3, IL10, KLK3, MMP12, IL17A, NR4A1, CEACAM1, AKT1, EPAS1, IL1RN, BAX, TRIB3, E2F1, PCK2, CXCL1, PTPN6, MMP3, CDK6, PIGR, ERAP1, YY1, OLFM4, IL18, LIPE, CD28, MMP9, TERT, IL4, NAMPT, BACE1, JUNB, CCR2, FASLG, ALOX5, BCL2L1, CCL11, PGR, GTF2B, CCL22, PLIN1, AKT2, BIRC3, HBEGF, CCL2, SERPINB1, MUC17, BAD, FGF7, PTGFR, TFF3, PTAFR, PTGS2, COX1, SERPINA3, ITGAX, CCND2, MCL1, TLR7, POU2F2, REPS2, TF, TFF1, SLC9A2, PLAU, TNF, FOXP3, HDAC7, MUC5B, NCOR1, FIGF, CYP3A4, SP1, CCL13, IFNA1, NOX5, MAT2A, COL7A1, HMOX1, ADORA1, TNFSF10, AR, CCR5, COL2A1, TAP1, IL1B, CD74, CD38, MUC5AC, GSTP1, MUC2, TIMP1, CCL19, CXCR4, FGF8, PDK4, CCL20, STK39, CYP3A7, GATA3, IRF4, CD58, HES1, PLAUR, SP4, NFKB1, MMP1, NOX4, BDKRB1, CASP3, CYP1A1, PTEN, HPSE, CCNB1, CD40, NOS3, ABCA1, PPARD, HIF1A, TNFRSF9, CD80, KDM2A, IL23A, TNFAIP3, TNFSF14, IL12A, TRPC1, CYP2E1, RGS4, ADORA2A, AMH, XIAP, MADCAM1, HYAL1, CFLAR, TBX21, ICAM1, BCL2L11, CHUK, TAP2, IL2RA, TLR3, ABCB1, IL17C, CCND1, KLF5, CCR7, CCK, DCST2, MMP14, FBP1, OPTN, IL1A, LTC4S, COL1A2, NOS1, WT1, BIRC5, PPIG, PTGES, THBD, CREB3, VWF, CXCL2, CRP, HLA-A, BCL2A1, BRCA2, IKBKB, GFAP, TWIST1, PSMB10, PROX1, COL1A1, TNIP3, NFKBIZ, TLR2, TNFRSF10A, S100A6, DRD2, CXCL8, BTG2, TRAF1, PTPN13, CD83, CSNK2A1, CARD8, CXCL10, CDKN1A, IL6, CFTR, CASP9, SIRT1, BMP2, IL2, IRF1, SOD2, IER3, NFKBIA, FN1, SERPINE1, MICA, TBP, CXCR2, BHMT, ABCG2, SNAI1, NOS2, PSMB9, CTSB, HSD11B2, F8, IL12B, IGF2BP1, LCN2, NOLC1, CD40LG, SELE, CCL5, FAS, ALOX5AP, OLR1, VCAM1, SDC1, SAA2, NCOR2, DEFB4A, CDH1, TRAF2, CCL3, GNRH2, HDAC1, TAPBP, CSF2, ADORA3, CRHR1, BCL3, MIF, CXCL5, TNFRSF10B, CYP27B1, NLRP2, FAF1, PTGER4, TNFRSF13C, CARM1, EBI3, ERAP2, CSF1, EPCAM, SLC25A27, RIPK2, EGR1, CD86, BCL2, CD69, BIRC2, CCR3, NPPB, GCLC, MMP13, GRIN1, SP3, MYC, STAT4, MUC6	3	IL1RN, IL1B, CDH1
SIRT1	NO	43	ACAN, TBX3, ESRRG, EZH2, CFLAR, NR1I2, FOXO3, SELE, HSF1, ABCB1, TP73, CCND1, NR5A2, CFH, HYOU1, IL1B, SHC1, COL1A2, NBN, CDKN1A, CTNNB1, MCL1, TNFRSF10B, BCL11A, CDH1, PARP1, ICAM1, PAX6, DLL4, SIRT6, NOTCH1, WRN, ADAMTS5, NDRG1, PER1, TNF, MMP9, COL10A1, TP53, EGLN1, MYC, PPARG, HIF1A	2	IL1B, CDH1
HMGA1	NO	17	PTGS2, SP1, CXCL1, XPA, POU1F1, INSR, CRYAB, CDC25A, TWIST1, IL1B, CDH1, CD44, TP53, RAG2, SLC2A3, BRCA1, KL	2	IL1B, CDH1

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regulated gene	associated to this disease	# TFs	TFs
CDH1	YES	49	AR, MTA2, FOXM1, ZEB2, SNAI1, TWIST2, TWIST1, EZH2, RBBP7, FOXA2, TCF3, LMO2, SPDEF, YBX1, KLF4, MTA1, LCOR, HDAC3, DNMT1, FOXQ1, HOXA7, TCF12, ESR1, SIRT1, WT1, ZEB1, FOSB, SMARCA4, VDR, HDAC1, TFAP2A, RELA, PARP1, HMGA2, NFKB1, KLF8, HDGF, STAT3, GATA3, HDAC2, SNAI2, CBX7, SALL4, RB1, HMGA1, KLF6, ZNF217, SIX1, HIF1A
IL1RN	YES	3	STAT3, NFKB1, RELA
IL1B	YES	18	SUGP1, SPI1, HSF1, IRF8, KLF4, REL, NFIL3, NFKBIA, CEBPB, JUN, HMGA1, SIRT1, RELA, AHR, JUNB, NFKB1, E2F1, STAT1
KRAS	YES	1	MYC

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Interactions from BIOGRID - physical

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Gene1	Gene2	Direct Interaction	Number of shared interactors	Shared genes in interaction
CDH1	IL1B	No	1	FYN
IL1RN	IL1B	No	1	IL1R1
IL1B	KRAS	No	2	ELAVL1, APP

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Direct interactions graph
Interactions graph (direct and indirect interactions, when direct are not available)

Interactions from BIOGRID - genetic

Interactions from STRING

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Gene1	Gene2	Direct Interaction	Interaction mode	Number of shared interactors	Shared genes in interaction
CDH1	IL1B	No	-	24	CTGF, IL8, MMP9, BMP7, FGF2, FOS, PTGS2, IL4, NFKB1, SMAD7, PIK3CA, CD44, LEP, STAT3, PSEN1, JUN, CDH2, EP300, IL24, ITGA6, FGF13, IGF1R, PIK3R1, PPARG
CDH1	KRAS	No	-	31	AKT1, BMP4, MAPK3, RET, TP53, EGFR, CTGF, IGF2BP1, BCL2, CCND1, PIK3CA, EPHA2, ERBB2, ERBB3, KIT, IRS2, SLC3A2, PRMT5, UBC, RPS6KB1, IL8, ABL1, SRC, FYN, YES1, NOTCH1, MAPK1, JUN, CDX1, CDX2, EGF
IL1B	KRAS	No	-	10	MAPK11, LGALS3, PIK3CA, JUN, GAST, IL8, CTGF, MAP3K3, VEGFA, MAPK14

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Direct interactions graph
Interactions graph (direct and indirect interactions, when direct are not available)

Interactions from CORUM

Interactions from CENSUS

Interactions from PDB

Interactions from manually curated literature

KEGG pathways annotation: shared terms / NET-GE enrichment

Shared terms

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KEGG term	KEGG term ID	IC	Number of genes with the same term	Genes
Thyroid cancer	hsa05216	7.48	2	KRAS, CDH1
Bladder cancer	hsa05219	7.38	2	KRAS, CDH1
Endometrial cancer	hsa05213	6.81	2	KRAS, CDH1
Melanoma	hsa05218	6.56	2	KRAS, CDH1
Rap1 signaling pathway	hsa04015	4.97	2	KRAS, CDH1
MAPK signaling pathway	hsa04010	4.63	2	KRAS, IL1B
Pathways in cancer	hsa05200	3.98	2	KRAS, CDH1

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NET-GE enrichment

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Term	New enriched term	IC	P value	Genes
Thyroid cancer (hsa05216)	-	7.48	0.01	KRAS, CDH1
Bladder cancer (hsa05219)	-	7.38	0.012	KRAS, CDH1
N-Glycan biosynthesis (hsa00510)	NEW	7.07	0.049	KRAS, CDH1
Endometrial cancer (hsa05213)	-	6.81	0.026	KRAS, CDH1
Melanoma (hsa05218)	-	6.56	0.037	KRAS, CDH1
Hepatitis B (hsa05161)	NEW	5.52	0.016	KRAS, IL1B, CDH1
MicroRNAs in cancer (hsa05206)	NEW	5.38	0.029	KRAS, IL1B, CDH1
Chemokine signaling pathway (hsa04062)	NEW	5.19	0.045	KRAS, IL1B, CDH1

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REACTOME pathways annotation: shared terms / NET-GE enrichment

Shared terms

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REACTOME term	REACTOME term ID	IC	Number of genes with the same term	Genes
Interleukin-1 signaling	R-HSA-446652	7.52	2	IL1RN, IL1B
C-type lectin receptors (CLRs)	R-HSA-5621481	6.06	2	KRAS, IL1B
Signaling by Interleukins	R-HSA-449147	4.71	3	IL1RN, KRAS, IL1B
Cytokine Signaling in Immune system	R-HSA-1280215	3.74	3	IL1RN, KRAS, IL1B
Adaptive Immune System	R-HSA-1280218	3.19	2	KRAS, CDH1
Innate Immune System	R-HSA-168249	3.17	2	KRAS, IL1B
Immune System	R-HSA-168256	2.37	4	KRAS, IL1RN, IL1B, CDH1
Signal Transduction	R-HSA-162582	1.78	2	KRAS, CDH1

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NET-GE enrichment

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Term	New enriched term	IC	P value	Genes
SHC-mediated cascade:FGFR3 (R-HSA-5654704)	NEW	8.81	0.006	KRAS, CDH1
N-glycan antennae elongation in the medial/trans-Golgi (R-HSA-975576)	NEW	8.66	0.015	KRAS, CDH1
SHC-mediated cascade:FGFR1 (R-HSA-5654688)	NEW	8.59	0.01	KRAS, CDH1
Signaling by FGFR3 in disease (R-HSA-5655332)	NEW	8.52	0.009	KRAS, CDH1
SHC-mediated cascade:FGFR2 (R-HSA-5654699)	NEW	8.28	0.016	KRAS, CDH1
Signaling by FGFR2 in disease (R-HSA-5655253)	NEW	8.23	0.014	KRAS, CDH1
Transport to the Golgi and subsequent modification (R-HSA-948021)	NEW	7.81	0.046	KRAS, CDH1
Interleukin-1 signaling (R-HSA-446652)	-	7.52	0.02	IL1RN, IL1B
Signaling by Interleukins (R-HSA-449147)	-	4.71	0.025	KRAS, IL1RN, IL1B, CDH1

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GO - molecular function annotation: shared terms / NET-GE enrichment

Shared terms

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GO	IC	Number of genes with the same GO	Genes
interleukin-1 receptor binding (GO:0005149)	6.85	2	IL1RN, IL1B
growth factor receptor binding (GO:0070851)	4.87	2	IL1RN, IL1B
cytokine activity (GO:0005125)	4.34	2	IL1RN, IL1B
cytokine receptor binding (GO:0005126)	4.14	2	IL1RN, IL1B
protein domain specific binding (GO:0019904)	3.32	2	KRAS, IL1B
receptor binding (GO:0005102)	2.43	2	IL1RN, IL1B
carbohydrate derivative binding (GO:0097367)	2.03	2	KRAS, CDH1
metal ion binding (GO:0046872)	1.41	2	KRAS, CDH1
cation binding (GO:0043169)	1.4	2	KRAS, CDH1
ion binding (GO:0043167)	1.36	2	KRAS, CDH1

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NET-GE enrichment

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Term	New enriched term	IC	P value	Genes
interleukin-1 receptor binding (GO:0005149)	-	6.85	0.0	IL1RN, IL1B
acetylglucosaminyltransferase activity (GO:0008375)	NEW	5.85	0.033	KRAS, CDH1
cytokine receptor activity (GO:0004896)	NEW	5.24	0.002	IL1RN, KRAS, IL1B
growth factor receptor binding (GO:0070851)	-	4.87	0.004	IL1RN, IL1B, CDH1
UDP-glycosyltransferase activity (GO:0008194)	NEW	4.81	0.002	KRAS, IL1B, CDH1
transferase activity, transferring hexosyl groups (GO:0016758)	NEW	4.43	0.007	KRAS, IL1B, CDH1
glycosaminoglycan binding (GO:0005539)	NEW	4.42	0.041	IL1RN, IL1B, CDH1
cytokine receptor binding (GO:0005126)	-	4.14	0.049	KRAS, IL1RN, IL1B, CDH1
transferase activity, transferring glycosyl groups (GO:0016757)	NEW	4.08	0.025	KRAS, IL1B, CDH1
protein domain specific binding (GO:0019904)	-	3.32	0.007	KRAS, IL1B, CDH1

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GO - biological process annotation: shared terms / NET-GE enrichment

Shared terms

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GO	IC	Number of genes with the same GO	Genes
regulation of heterotypic cell-cell adhesion (GO:0034114)	6.84	2	IL1RN, IL1B
positive regulation of monooxygenase activity (GO:0032770)	6.47	2	KRAS, IL1B
positive regulation of oxidoreductase activity (GO:0051353)	5.94	2	KRAS, IL1B
acute-phase response (GO:0006953)	5.94	2	IL1RN, IL1B
social behavior (GO:0035176)	5.9	2	KRAS, IL1B
intraspecies interaction between organisms (GO:0051703)	5.9	2	KRAS, IL1B
regulation of nitric-oxide synthase activity (GO:0050999)	5.9	2	KRAS, IL1B
positive regulation of transcription factor import into nucleus (GO:0042993)	5.78	2	IL1B, CDH1
regulation of monooxygenase activity (GO:0032768)	5.69	2	KRAS, IL1B
multi-organism behavior (GO:0051705)	5.6	2	KRAS, IL1B

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NET-GE enrichment

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Term	New enriched term	IC	P value	Genes
fever generation (GO:0001660)	NEW	9.04	0.0	IL1RN, IL1B
heat generation (GO:0031649)	NEW	8.12	0.001	IL1RN, IL1B
astrocyte cell migration (GO:0043615)	NEW	7.94	0.004	IL1B, CDH1
regulation of organic acid transport (GO:0032890)	NEW	7.78	0.025	IL1RN, IL1B
regulation of vitamin D biosynthetic process (GO:0060556)	NEW	7.53	0.011	IL1B, CDH1
cyclooxygenase pathway (GO:0019371)	NEW	7.33	0.022	KRAS, IL1B
regulation of vitamin metabolic process (GO:0030656)	NEW	7.24	0.02	IL1B, CDH1
chronic inflammatory response (GO:0002544)	NEW	7.16	0.036	IL1RN, IL1B
epithelial tube branching involved in lung morphogenesis (GO:0060441)	NEW	6.9	0.04	KRAS, CDH1
regulation of heterotypic cell-cell adhesion (GO:0034114)	-	6.84	0.038	IL1RN, IL1B

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GO - cellular component annotation: shared terms / NET-GE enrichment

Shared terms

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GO	IC	Number of genes with the same GO	Genes
cell-substrate adherens junction (GO:0005924)	3.83	2	KRAS, CDH1
focal adhesion (GO:0005925)	3.83	2	KRAS, CDH1
cell-substrate junction (GO:0030055)	3.82	2	KRAS, CDH1
adherens junction (GO:0005912)	3.66	2	KRAS, CDH1
anchoring junction (GO:0070161)	3.61	2	KRAS, CDH1
vacuole (GO:0005773)	2.92	2	IL1B, CDH1
cell junction (GO:0030054)	2.75	2	KRAS, CDH1
extracellular space (GO:0005615)	2.63	2	IL1RN, IL1B
intracellular (GO:0005622)	2.37	2	IL1RN, KRAS
extracellular region (GO:0005576)	2.18	3	IL1RN, IL1B, CDH1

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NET-GE enrichment

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Term	New enriched term	IC	P value	Genes
T-tubule (GO:0030315)	NEW	6.09	0.031	IL1B, CDH1
external side of plasma membrane (GO:0009897)	NEW	4.46	0.033	KRAS, IL1B, CDH1
early endosome (GO:0005769)	NEW	4.34	0.013	KRAS, IL1B, CDH1
vacuolar membrane (GO:0005774)	NEW	3.45	0.041	KRAS, IL1B, CDH1

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