Gastric cancer

Summary

Gastric cancer (MONDO:0001056) is a cancer (an umbrella term covering 9 Mondo subtypes) with 54 cohort genes (138 GWAS associations across 24 studies; 40 CIViC-evidence somatic drivers; 1,033 ClinVar predisposition records) and 2,317 clinical trials. The dominant Reactome pathway is Impaired BRCA2 binding to PALB2 (10 cohort genes). Molecularly, ERBB2 Amplification confers sensitivity to Pembrolizumab + Trastuzumab + Chemotherapy in Stomach Cancer (CIViC Level A); 23 further subtype–drug associations are mapped below. Top therapeutic interventions include cisplatin, irinotecan, and epirubicin.

At a glance

• Classification: Cancer
• Umbrella term: 9 Mondo subtypes
• Cohort genes: 54
• GWAS associations: 138
• ClinVar variants: 1,033
• Clinical trials: 2,317
• Precision-medicine evidence (CIViC): 24 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	gastric cancer
Mondo ID	MONDO:0001056
OMIM	613659
DOID	DOID:10534
ICD-10-CM	C16
ICD-11	1397617262
NCIT	C9331
UMLS	C0024623
MedGen	44264
GARD	0007704
Anatomy (UBERON)	UBERON:0000945
Is cancer (heuristic)	yes

Also known as: Ca body - stomach · ca greater curvature of stomach · Ca lesser curvature - stomach · cancer of stomach · gastric cancer · gastric cancer risk after h. pylori infection · gastric cancer, somatic · gastric neoplasm · GC · malignant gastric neoplasm · malignant gastric tumor · malignant gastric tumour · malignant neoplasm of body of stomach · malignant neoplasm of lesser curve of stomach · malignant neoplasm of stomach · malignant neoplasm of the stomach · malignant stomach neoplasm · malignant tumor of body of stomach · malignant tumor of greater curve of stomach · malignant tumor of lesser curve of stomach (+8 more)

Data availability: 1,033 ClinVar variants · 138 GWAS associations (24 studies) · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 9 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › digestive system cancer › gastric cancer

Related subtypes (14): jaw cancer, liver cancer, gastrointestinal lymphoma, gallbladder cancer, oral cavity cancer, pharynx cancer, intestinal cancer, spleen cancer, digestive system carcinoma, esophageal cancer, malignant pancreatic neoplasm, malignant tumor of floor of mouth, digestive system melanoma, gastroesophageal cancer

Subtypes (9): malignant gastric granular cell tumor, gastric lymphoma, pylorus cancer, cardia cancer, malignant gastric germ cell tumor, gastric leiomyosarcoma, gastric liposarcoma, gastric carcinoma, diffuse gastric cancer

Genetics & variants

GWAS landscape

138 GWAS associations across 24 studies. Top hits map to 24 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2303771	1e-83	KLHDC4	?
rs9940714	5e-83	KLHDC4	?
rs66767559	5e-82	KLHDC4	?
rs7120658	2e-56	XNDC1N-ZNF705EP-ALG1L9P, DEFB108B	?
rs4309179	5e-55	ENPP7P8, ALG1L9P	?
chr11:71548492	4e-54		?
chr11:71498465	4e-53		?
chr11:71544105	3e-51		?
chr11:71462469	1e-49		?
rs606799	2e-47	XNDC1N, XNDC1N-ZNF705EP-ALG1L9P	?
chr11:71507385	5e-47		?
chr11:71494680	5e-45		?
chr16:87794371	5e-44		?
chr16:87795580	5e-44		?
chr16:87783383	9e-44		?
chr16:87801691	1e-43		?
rs59585832	8e-43	TTC33	?	0.27
rs2920280	9e-43	JRK, PSCA	C	1.3
chr16:87792272	3e-36		?
rs760077	8e-33	THBS3, MTX1	T	1.4
rs12682374	9e-29	PCAT1, CASC8, POU5F1B	?	0.93
chr16:87778574	2e-27		?
chr16:87780823	2e-27		?
rs1219651	1e-25	FGFR2	?	1.09
rs73544781	6e-23	PRXL2C - MKRN10P	?
rs3765524	7e-22	PLCE1	T	1.45
rs2981584	1e-21	FGFR2	?	0.94
rs10908278	3e-21	HNF1B	?	1.06
rs10509670	2e-18	PLCE1	G	1.76
chr16:88096203	5e-18		?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90651054	Sato G	2023	43,098	334,343	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90308764	Sato G	2023	29,753	150,462	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90651069	Sato G	2023	29,753	150,462	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90308756	Sato G	2023	5,775	150,462	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90651061	Sato G	2023	5,775	150,462	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90319844	Pyun H	2023	1,253	4,827	Functional Annotation and Gene Set Analysis of Gastric Cancer Risk Loci in a Korean Population.
GCST90477175	Verma A	2024	1,152	449,540	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651046	Sato G	2023	1,023	334,343	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90841198	He F	2026	1,015	4,541	Genome wide association analysis and association of genetic risk and lifestyle with upper gastrointestinal cancer among an endoscopy-screened cohort in China.
GCST90651360	Liu TY	2025	740	211,360	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	4
Tier 2: splice/UTR	0
Tier 3: regulatory	1
Tier 4: intronic/intergenic	45

MAF distribution

Bucket	Variants
common (>=0.05)	31
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	19

Functional consequences

Consequence	Count
unknown	19
intron_variant	18
intergenic_variant	6
missense_variant	4
non_coding_transcript_exon_variant	2
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2303771	16	87755258	G>A,C,T	0.05	missense_variant	KLHDC4	1e-83	Tier 1: coding
rs9940714	16	87749984	A>G	0.05	intron_variant	KLHDC4	5e-83	Tier 4: intronic/intergenic
rs66767559	16	87755985	T>C	0.05	intron_variant	KLHDC4	5e-82	Tier 4: intronic/intergenic
rs7120658	11	71837498	A>C,G	0.05	missense_variant	XNDC1N-ZNF705EP-ALG1L9P, DEFB108B	2e-56	Tier 1: coding
rs4309179	11	71758292	C>A	0.05	intron_variant	ENPP7P8, ALG1L9P	5e-55	Tier 4: intronic/intergenic
chr11:71548492							4e-54	Tier 4: intronic/intergenic
chr11:71498465							4e-53	Tier 4: intronic/intergenic
chr11:71544105							3e-51	Tier 4: intronic/intergenic
chr11:71462469							1e-49	Tier 4: intronic/intergenic
rs606799	11	71897536	G>A,C,T	0.05	intron_variant	XNDC1N, XNDC1N-ZNF705EP-ALG1L9P	2e-47	Tier 4: intronic/intergenic
chr11:71507385							5e-47	Tier 4: intronic/intergenic
chr11:71494680							5e-45	Tier 4: intronic/intergenic
chr16:87794371							5e-44	Tier 4: intronic/intergenic
chr16:87795580							5e-44	Tier 4: intronic/intergenic
chr16:87783383							9e-44	Tier 4: intronic/intergenic
chr16:87801691							1e-43	Tier 4: intronic/intergenic
rs59585832	5	40743936	C>T	0.05	intron_variant	TTC33	8e-43	Tier 4: intronic/intergenic
rs2920280	8	142679726	G>A,C,T	0.05	intergenic_variant	JRK, PSCA	9e-43	Tier 4: intronic/intergenic
chr16:87792272							3e-36	Tier 4: intronic/intergenic
rs760077	1	155208991	T>A,C,G	0.05	missense_variant	THBS3, MTX1	8e-33	Tier 1: coding
rs12682374	8	127398703	C>A,G,T	0.05	intron_variant	PCAT1, CASC8, POU5F1B	9e-29	Tier 4: intronic/intergenic
chr16:87778574							2e-27	Tier 4: intronic/intergenic
chr16:87780823							2e-27	Tier 4: intronic/intergenic
rs1219651	10	121584987	G>A,C,T	0.05	intron_variant	FGFR2	1e-25	Tier 4: intronic/intergenic
rs73544781	9	96682499	A>C,T	0.05	intergenic_variant	PRXL2C - MKRN10P	6e-23	Tier 4: intronic/intergenic
rs3765524	10	94298541	C>A,T	0.05	missense_variant	PLCE1	7e-22	Tier 1: coding
rs2981584	10	121590702	A>C,G,T	0.05	intron_variant	FGFR2	1e-21	Tier 4: intronic/intergenic
rs10908278	17	37739961	A>C,G,T	0.05	intron_variant	HNF1B	3e-21	Tier 4: intronic/intergenic
rs10509670	10	94308190	A>G	0.05	intron_variant	PLCE1	2e-18	Tier 4: intronic/intergenic
chr16:88096203							5e-18	Tier 4: intronic/intergenic

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

224 pathogenic, 173 uncertain significance, 81 conflicting classifications of pathogenicity, 61 pathogenic/likely pathogenic, 26 likely pathogenic, 17 likely benign, 9 benign/likely benign, 7 benign, 1 pathogenic/likely pathogenic/pathogenic, low penetrance, 1 benign; association

ClinVar	Variant (HGVS)	Gene	Classification	Review
127312	NM_000038.6(APC):c.646C>T (p.Arg216Ter)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
141368	NM_000038.6(APC):c.147_150del (p.Lys49fs)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
1801523	NM_000038.6(APC):c.1612G>T (p.Glu538Ter)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
1801524	NM_000038.6(APC):c.8246C>G (p.Ser2749Ter)	APC	Pathogenic	no assertion criteria provided
1801562	NM_000038.6(APC):c.1809dup (p.Ala604fs)	APC	Pathogenic	no assertion criteria provided
1801580	NM_000038.6(APC):c.4dup (p.Ala2fs)	APC	Pathogenic	no assertion criteria provided
1801581	NM_000038.6(APC):c.6503dup (p.Pro2170fs)	APC	Pathogenic	no assertion criteria provided
1801625	NM_000038.6(APC):c.5818del (p.Ile1940fs)	APC	Pathogenic	no assertion criteria provided
183078	NM_000038.6(APC):c.3149del (p.Ala1050fs)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
184937	NM_000038.6(APC):c.994C>T (p.Arg332Ter)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
184999	NM_000038.6(APC):c.847C>T (p.Arg283Ter)	APC	Pathogenic	reviewed by expert panel
2583948	NM_000038.6(APC):c.423-12A>G	APC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2584112	NM_000038.6(APC):c.6634dup (p.Gln2212fs)	APC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3232245	NM_000038.6(APC):c.1380del (p.Glu461fs)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
1066028	NM_000051.4(ATM):c.2638+1G>T	ATM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1209849	NM_000051.4(ATM):c.6951_6952del (p.Lys2318fs)	ATM	Pathogenic/Likely pathogenic	no assertion criteria provided
127337	NM_000051.4(ATM):c.1339C>T (p.Arg447Ter)	ATM	Pathogenic	criteria provided, multiple submitters, no conflicts
127445	NM_000051.4(ATM):c.7456C>T (p.Arg2486Ter)	ATM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
141409	NM_000051.4(ATM):c.5893_5897del (p.Lys1965fs)	ATM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
141416	NM_000051.4(ATM):c.5712dup (p.Ser1905fs)	ATM	Pathogenic	criteria provided, multiple submitters, no conflicts
142575	NM_000051.4(ATM):c.8432del (p.Lys2811fs)	ATM	Pathogenic	criteria provided, multiple submitters, no conflicts
142791	NM_000051.4(ATM):c.8122G>A (p.Asp2708Asn)	ATM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1786233	NM_000051.4(ATM):c.211G>T (p.Glu71Ter)	ATM	Pathogenic	criteria provided, multiple submitters, no conflicts
1801530	NM_000051.4(ATM):c.550A>T (p.Arg184Ter)	ATM	Pathogenic	no assertion criteria provided
1801531	NM_000051.4(ATM):c.2187C>G (p.Tyr729Ter)	ATM	Pathogenic	no assertion criteria provided
1801532	NM_000051.4(ATM):c.2530G>T (p.Gly844Ter)	ATM	Pathogenic	no assertion criteria provided
1801533	NM_000051.4(ATM):c.3394A>T (p.Arg1132Ter)	ATM	Pathogenic	no assertion criteria provided
1801534	NM_000051.4(ATM):c.4772T>A (p.Leu1591Ter)	ATM	Pathogenic	no assertion criteria provided
1801535	NM_000051.4(ATM):c.5125C>T (p.Gln1709Ter)	ATM	Pathogenic	no assertion criteria provided
1801536	NM_000051.4(ATM):c.5170G>T (p.Glu1724Ter)	ATM	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 193 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
TP53	LoF	ACC,ALL,AML,ANGS,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,EGC,ES,ESCA,ESCC,GB,GBC,GBM,GIST,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LNM,LUAD,LUSC,MBL,MEL,MLYM,MT,NBL,NETNOS,NHL,NPC,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PCM,PLMESO,PRAD,PRCC,PROSTATE,RCC,READ,SACA,SARCNOS,SCLC,SIC,SKCM,SKIN,SOFT_TISSUE,STAD,STOMACH,THYM,UCEC,UCS,UTUC,VULVA,WDTC,WT	CIViC #45
ERBB2	Act	BLCA,BRCA,CESC,CHOL,COADREAD,EGC,ESCA,ESCC,LMS,LUAD,NSCLC,OVT,PRCC,READ,STAD,UCEC	CIViC #20
FGFR2	Act	BRCA,CHOL,LUSC,SACA,UCEC	CIViC #22
ATM	LoF	BLCA,BRCA,CCRCC,CHOL,CLLSLL,COAD,COADREAD,ESCA,HCC,LUAD,LUSC,MEL,NSCLC,PAAD,PANCREAS,PANET,PCM,PLMESO,PRAD,PROSTATE,STAD,UCEC,UTUC,WDTC	CIViC #69
PIK3CA	Act	ACYC,ANGS,ANSC,BCC,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,COAD,COADREAD,EPM,ESCA,ESCC,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LUAD,LUSC,MBL,MGCT,NPC,NSCLC,OVT,PAAD,PAST,PLMESO,PRAD,PRCC,PROSTATE,RCC,SACA,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,UTUC,VULVA,WDTC	CIViC #37
PTEN	LoF	ANGS,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,COADREAD,CSCC,ESCA,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LUAD,LUSC,MBL,MEL,MT,NSCLC,OVT,PANET,PAST,PRAD,PRCC,PROSTATE,RCC,SCLC,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,WDTC	CIViC #41
ARID1A	LoF	BL,BLCA,BRCA,CCRCC,CESC,CHOL,CLLSLL,COAD,COADREAD,DLBCLNOS,EGC,ESCA,ESCC,GBC,GBM,HCC,LGGNOS,LUAD,LUNG,LUSC,MBL,MLYM,MT,NHL,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PRAD,RCC,SCLC,SKIN,STAD,UCEC,UCS,UTUC	CIViC #6559
CCND2	LoF	AML,CLLSLL	CIViC #9
CCNE1			CIViC #11
CD44			CIViC #855
SLTM	Act	CCRCC,LGGNOS,LUAD,NSCLC,OS,PRCC,RCC	CIViC #52
BCOR	LoF	ACC,AML,CHOL,CLLSLL,COADREAD,GBM,LGGNOS,LUAD,MBL,PAAD,PAST,PGNG,PLMESO,SIC,STAD,THYM,UCEC,UCS	CIViC #12555
MTHFR			CIViC #3672
BRCA1	LoF	BLCA,BRCA,MEL,OVT	CIViC #6
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7
STK11	LoF	ANSC,CEAD,CESC,CHOL,LUAD,NSCLC,WDTC	CIViC #5534
EPCAM			CIViC #3364
CHEK2	Act	BRCA	CIViC #8950
CDH1	LoF	BLCA,BRCA,CSCC,DLBCLNOS,ESCA,STAD	CIViC #888
CDH11	Act	CHOL,COAD,ESCA,HCC,LUSC,STAD
CDK4	LoF	MEL	CIViC #13
CDKN2A	LoF	ACYC,BLCA,BRCA,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,GBM,HCC,HNSC,LGGNOS,LUAD,LUSC,MEL,MLYM,NPC,NSCLC,OS,PAAD,PANCREAS,RCC,SKCM,SKIN,STAD,STOMACH,WDTC	CIViC #14
BRIP1			CIViC #15955
KLF6	LoF	MEL
PALB2	LoF	OVT	CIViC #15013
NQO1			CIViC #1463
ABCB1			CIViC #4244
HOXB13			CIViC #8351
APC	LoF	AML,ANSC,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,HCC,LUAD,MEL,MT,NETNOS,NSCLC,PRAD,PROSTATE,READ,STAD,STOMACH,UM,VULVA	CIViC #66
IRF1	LoF	PCM

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
MAP3K6	Supportive	Autosomal dominant	hereditary diffuse gastric adenocarcinoma	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma
ERBB2	Orphanet:213726	Serous carcinoma of the corpus uteri
ERBB2	Orphanet:2800	Extramammary Paget disease
ERBB2	Orphanet:388	Hirschsprung disease
ERBB2	Orphanet:99976	Adenocarcinoma of the oesophagus and oesophagogastric junction
FGFR2	Orphanet:1540	Jackson-Weiss syndrome
FGFR2	Orphanet:1555	Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome
FGFR2	Orphanet:168624	Familial scaphocephaly syndrome, McGillivray type
FGFR2	Orphanet:207	Crouzon syndrome
FGFR2	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGFR2	Orphanet:313855	FGFR2-related bent bone dysplasia
FGFR2	Orphanet:596008	Antley-Bixler syndrome without genital anomaly or disorder of steroidogenesis
FGFR2	Orphanet:794	Saethre-Chotzen syndrome
FGFR2	Orphanet:87	Apert syndrome
FGFR2	Orphanet:93258	Pfeiffer syndrome type 1
FGFR2	Orphanet:93259	Pfeiffer syndrome type 2
FGFR2	Orphanet:93260	Pfeiffer syndrome type 3
ATM	Orphanet:100	Ataxia-telangiectasia
ATM	Orphanet:1331	Familial prostate cancer
ATM	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
ATM	Orphanet:227535	Hereditary breast cancer
ATM	Orphanet:370109	Ataxia-telangiectasia variant
ATM	Orphanet:440437	Familial colorectal cancer Type X
ATM	Orphanet:52416	Mantle cell lymphoma
ATM	Orphanet:67038	B-cell chronic lymphocytic leukemia
PIK3CA	Orphanet:140944	CLOVES syndrome
PIK3CA	Orphanet:144	Lynch syndrome
PIK3CA	Orphanet:168984	CLAPO syndrome
PIK3CA	Orphanet:201	Cowden syndrome
PIK3CA	Orphanet:210159	Adult hepatocellular carcinoma
PIK3CA	Orphanet:221061	Familial cerebral cavernous malformation

Cohort genes → proteins

54 cohort genes, 54 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	7
multi_evidence	47

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar,civic_evidence
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	clinvar,civic_evidence
FGFR2	HGNC:3689	ENSG00000066468	P21802	Fibroblast growth factor receptor 2	clinvar,civic_evidence
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	clinvar,civic_evidence
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	clinvar,civic_evidence
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	clinvar,civic_evidence
ARID1A	HGNC:11110	ENSG00000117713	O14497	AT-rich interactive domain-containing protein 1A	civic_evidence
CCND2	HGNC:1583	ENSG00000118971	P30279	G1/S-specific cyclin-D2	civic_evidence
CCNE1	HGNC:1589	ENSG00000105173	P24864	G1/S-specific cyclin-E1	civic_evidence
CD44	HGNC:1681	ENSG00000026508	P16070	CD44 antigen	civic_evidence
SLTM	HGNC:20709	ENSG00000137776	Q9NWH9	SAFB-like transcription modulator	civic_evidence
BCOR	HGNC:20893	ENSG00000183337	Q6W2J9	BCL-6 corepressor	civic_evidence
MAP3K6	HGNC:6858	ENSG00000142733	O95382	Mitogen-activated protein kinase kinase kinase 6	gencc
MTHFR	HGNC:7436	ENSG00000177000	P42898	Methylenetetrahydrofolate reductase (NADPH)	civic_evidence
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar
STK11	HGNC:11389	ENSG00000118046	Q15831	Serine/threonine-protein kinase STK11	clinvar
EPCAM	HGNC:11529	ENSG00000119888	P16422	Epithelial cell adhesion molecule	clinvar
EGLN1	HGNC:1232	ENSG00000135766	Q9GZT9	Egl nine homolog 1	clinvar
SLC2A9	HGNC:13446	ENSG00000109667	Q9NRM0	Solute carrier family 2, facilitated glucose transporter member 9	clinvar
CA9	HGNC:1383	ENSG00000107159	Q16790	Carbonic anhydrase 9	clinvar
CASP10	HGNC:1500	ENSG00000003400	Q92851	Caspase-10	clinvar
TOE1	HGNC:15954	ENSG00000132773	Q96GM8	Target of EGR1 protein 1	clinvar
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	clinvar
CDH1	HGNC:1748	ENSG00000039068	P12830	Cadherin-1	clinvar
CDH11	HGNC:1750	ENSG00000140937	P55287	Cadherin-11	clinvar
CDK4	HGNC:1773	ENSG00000135446	P11802	Cyclin-dependent kinase 4	clinvar
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	clinvar
BRIP1	HGNC:20473	ENSG00000136492	Q9BX63	Fanconi anemia group J protein	clinvar
KLF6	HGNC:2235	ENSG00000067082	Q99612	Krueppel-like factor 6	clinvar
CDC20B	HGNC:24222	ENSG00000164287	Q86Y33	Cell division cycle protein 20 homolog B	clinvar
FANCI	HGNC:25568	ENSG00000140525	Q9NVI1	Fanconi anemia group I protein	clinvar
PALB2	HGNC:26144	ENSG00000083093	Q86YC2	Partner and localizer of BRCA2	clinvar
LOXHD1	HGNC:26521	ENSG00000167210	Q8IVV2	Lipoxygenase homology domain-containing protein 1	clinvar
C11orf65	HGNC:28519	ENSG00000166323	Q8NCR3	Protein MFI	clinvar
NQO1	HGNC:2874	ENSG00000181019	P15559	NAD(P)H dehydrogenase [quinone] 1	clinvar
EXO1	HGNC:3511	ENSG00000174371	Q9UQ84	Exonuclease 1	clinvar
ABCB1	HGNC:40	ENSG00000085563	P08183	ATP-dependent translocase ABCB1	clinvar
HOXB13	HGNC:5112	ENSG00000159184	Q92826	Homeobox protein Hox-B13	clinvar
APC	HGNC:583	ENSG00000134982	P25054	Adenomatous polyposis coli protein	clinvar
IL1RN	HGNC:6000	ENSG00000136689	P18510	Interleukin-1 receptor antagonist protein	clinvar
IRF1	HGNC:6116	ENSG00000125347	P10914	Interferon regulatory factor 1	clinvar
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	clinvar
SMAD4	HGNC:6770	ENSG00000141646	Q13485	SMAD family member 4	clinvar
MLH1	HGNC:7127	ENSG00000076242	P40692	DNA mismatch repair protein Mlh1	clinvar
MSH2	HGNC:7325	ENSG00000095002	P43246	DNA mismatch repair protein Msh2	clinvar
MSH6	HGNC:7329	ENSG00000116062	P52701	DNA mismatch repair protein Msh6	clinvar
MUTYH	HGNC:7527	ENSG00000132781	Q9UIF7	Adenine DNA glycosylase	clinvar
NBN	HGNC:7652	ENSG00000104320	O60934	Nibrin	clinvar
NF1	HGNC:7765	ENSG00000196712	P21359	Neurofibromin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
ERBB2	Receptor tyrosine-protein kinase erbB-2	Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding.
FGFR2	Fibroblast growth factor receptor 2	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic de…
ATM	Serine-protein kinase ATM	Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor.
PIK3CA	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.
PTEN	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.
ARID1A	AT-rich interactive domain-containing protein 1A	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
CCND2	G1/S-specific cyclin-D2	Regulatory component of the cyclin D2-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition.
CCNE1	G1/S-specific cyclin-E1	Essential for the control of the cell cycle at the G1/S (start) transition.
CD44	CD44 antigen	Cell-surface receptor that plays a role in cell-cell interactions, cell adhesion and migration, helping them to sense and respond to changes in the tissue microenvironment.
SLTM	SAFB-like transcription modulator	When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis.
BCOR	BCL-6 corepressor	Transcriptional corepressor.
MAP3K6	Mitogen-activated protein kinase kinase kinase 6	Component of a protein kinase signal transduction cascade.
MTHFR	Methylenetetrahydrofolate reductase (NADPH)	Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine.
BRCA1	Breast cancer type 1 susceptibility protein	E3 ubiquitin-protein ligase that specifically mediates the formation of ‘Lys-6’-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
STK11	Serine/threonine-protein kinase STK11	Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage…
EPCAM	Epithelial cell adhesion molecule	May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as a first line of defense against mucosa…
EGLN1	Egl nine homolog 1	Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins.
SLC2A9	Solute carrier family 2, facilitated glucose transporter member 9	High-capacity urate transporter, which may play a role in the urate reabsorption by proximal tubules.
CA9	Carbonic anhydrase 9	Catalyzes the interconversion between carbon dioxide and water and the dissociated ions of carbonic acid (i.e. bicarbonate and hydrogen ions).
CASP10	Caspase-10	Involved in the activation cascade of caspases responsible for apoptosis execution.
TOE1	Target of EGR1 protein 1	Inhibits cell growth rate and cell cycle.
CHEK2	Serine/threonine-protein kinase Chk2	Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks.
CDH1	Cadherin-1	Cadherins are calcium-dependent cell adhesion proteins.
CDH11	Cadherin-11	Cadherins are calcium-dependent cell adhesion proteins.
CDK4	Cyclin-dependent kinase 4	Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition.
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
BRIP1	Fanconi anemia group J protein	DNA-dependent ATPase and 5’-3’ DNA helicase required for the maintenance of chromosomal stability.
KLF6	Krueppel-like factor 6	Transcriptional activator.
CDC20B	Cell division cycle protein 20 homolog B	Protein regulator of centriole-deuterosome disengagement and subsequently participates in the ciliogenesis in multiciliated cells (MCCs).
FANCI	Fanconi anemia group I protein	Plays an essential role in the repair of DNA double-strand breaks by homologous recombination and in the repair of interstrand DNA cross-links (ICLs) by promoting FANCD2 monoubiquitination by FANCL and participating in recruitment to DNA r…
PALB2	Partner and localizer of BRCA2	Plays a critical role in homologous recombination repair (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks.
LOXHD1	Lipoxygenase homology domain-containing protein 1	Involved in hearing.
C11orf65	Protein MFI	Acts as an inhibitor of mitochondrial fission.
NQO1	NAD(P)H dehydrogenase [quinone] 1	Flavin-containing quinone reductase that catalyzes two-electron reduction of quinones to hydroquinones using either NADH or NADPH as electron donors.
EXO1	Exonuclease 1	5’->3’ double-stranded DNA exonuclease which may also possess a cryptic 3’->5’ double-stranded DNA exonuclease activity.
ABCB1	ATP-dependent translocase ABCB1	Translocates drugs and phospholipids across the membrane.
HOXB13	Homeobox protein Hox-B13	Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.
APC	Adenomatous polyposis coli protein	Tumor suppressor.
IL1RN	Interleukin-1 receptor antagonist protein	Anti-inflammatory antagonist of interleukin-1 family of proinflammatory cytokines such as interleukin-1beta/IL1B and interleukin-1alpha/IL1A.
IRF1	Interferon regulatory factor 1	Transcriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
SMAD4	SMAD family member 4	In muscle physiology, plays a central role in the balance between atrophy and hypertrophy.
MLH1	DNA mismatch repair protein Mlh1	Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR).
MSH2	DNA mismatch repair protein Msh2	Component of the post-replicative DNA mismatch repair system (MMR).
MSH6	DNA mismatch repair protein Msh6	Component of the post-replicative DNA mismatch repair system (MMR).
MUTYH	Adenine DNA glycosylase	Involved in oxidative DNA damage repair.
NBN	Nibrin	Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.
NF1	Neurofibromin	Stimulates the GTPase activity of Ras.

Protein-family classification

Druggable: 19 · Difficult: 11 · Unknown: 24 · Druggable fraction: 0.35

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	8	4.1×	0.005
Enzyme (other)	8	1.8×	0.271
Transporter	2	2.9×	0.357
Phosphatase	1	1.6×	0.566
Scaffold/PPI	4	1.3×	0.566
Transcription factor	7	1.1×	0.566
Other/Unknown	24	0.8×	0.965

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
ERBB2	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
FGFR2	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom
ARID1A	Other/Unknown	no		ARID_dom, ARM-like, ARM-type_fold
CCND2	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
CCNE1	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
CD44	Other/Unknown	no		Link_dom, CD44_antigen, C-type_lectin-like/link_sf
SLTM	Other/Unknown	no		RRM_dom, SAP_dom, Nucleotide-bd_a/b_plait_sf
BCOR	Scaffold/PPI	no		Ankyrin_rpt, BCOR, PUFD
MAP3K6	Kinase	yes	2.7.11.25	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
MTHFR	Enzyme (other)	yes	1.5.1.20	Mehydrof_redctse-like, Fadh2_euk, FAD-linked_oxidoreductase-like
BRCA1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, BRCA1
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
STK11	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
EPCAM	Enzyme (other)	yes	2.4.1.37	Thyroglobulin_1, Thyroglobulin_1_sf, EpCAM_N
EGLN1	Transcription factor	no	1.14.11.2	Znf_MYND, Oxoglu/Fe-dep_dioxygenase_dom, Pro_4_hyd_alph
SLC2A9	Transporter	yes		Sugar/inositol_transpt, MFS_sugar_transport-like, Sugar_transporter_CS
CA9	Enzyme (other)	yes	4.2.1.1	CA_dom, Carbonic_anhydrase_a-class_CS, Carbonic_anhydrase_a-class
CASP10	Enzyme (other)	yes	3.4.22.63	Pept_C14_p20, DED_dom, Pept_C14_p10
TOE1	Transcription factor	no		Znf_CCCH, RNase_CAF1, RNaseH-like_sf
CHEK2	Kinase	yes	2.7.11.1	FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
CDH1	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin_pro_dom
CDH11	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin-like_sf
CDK4	Kinase	yes	2.7.11.22	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
BRIP1	Enzyme (other)	yes	3.6.4.12	Helicase-like_DEXD_c2, ATP-dep_Helicase_C, RAD3-like_helicase_DEAD
KLF6	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
CDC20B	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
FANCI	Other/Unknown	no		FANCI, FANCI_S1-cap, FANCI_S1
PALB2	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, PALB2_WD40, WD40_repeat_dom_sf
LOXHD1	Other/Unknown	no		PLAT/LH2_dom, PLAT/LH2_dom_sf, Inner_ear_hair_cell_LOXHD
C11orf65	Other/Unknown	no
NQO1	Enzyme (other)	yes	1.6.5.2	Flavodoxin_fold, Flavoprotein-like_sf, NAD(P)H_dehydrogenase_qn
EXO1	Enzyme (other)	yes	3.1.11.1	XPG/Rad2, XPG_DNA_repair_N, XPG-I_dom
ABCB1	Transporter	yes	7.6.2.2	ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom
HOXB13	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
APC	Other/Unknown	no		Armadillo, APC_rpt, SAMP
IL1RN	Other/Unknown	no		IL-1_fam, IL-1RA/IL-36, IL1/FGF
IRF1	Other/Unknown	no		Interferon_reg_fact_DNA-bd_dom, IRF1/IRF2, Interferon_reg_fac_CS
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
SMAD4	Other/Unknown	no		SMAD_dom, MAD_homology1_Dwarfin-type, SMAD_FHA_dom_sf
MLH1	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
MSH2	Other/Unknown	no		DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N, DNA_mismatch_repair_MutS_core
MSH6	Other/Unknown	no		PWWP_dom, DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N
MUTYH	Other/Unknown	no		NUDIX_hydrolase_dom, HhH_motif, HhH-GPD_domain
NBN	Other/Unknown	no		FHA_dom, BRCT_dom, SMAD_FHA_dom_sf
NF1	Other/Unknown	no		CRAL-TRIO_dom, RasGAP_dom, Rho_GTPase_activation_prot

Expression context

Cohort genes with no expression data: 0.

51 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	54
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	11
secondary oocyte	7
male germ line stem cell (sensu Vertebrata) in testis	7
calcaneal tendon	6
primordial germ cell in gonad	6
ganglionic eminence	5
adrenal tissue	5
oocyte	5
buccal mucosa cell	5
lower esophagus mucosa	4
right testis	4
sural nerve	3
colonic epithelium	3
sperm	3
embryo	3
stromal cell of endometrium	3
left testis	3
monocyte	3
corpus callosum	2
cauda epididymis	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
ERBB2	276	ubiquitous	marker	lower esophagus mucosa, right uterine tube, sural nerve
FGFR2	272	broad	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum
ATM	286	ubiquitous	marker	calcaneal tendon, colonic epithelium, corpus callosum
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon
ARID1A	286	ubiquitous	marker	bone marrow cell, ventricular zone, embryo
CCND2	293	ubiquitous	marker	adrenal tissue, seminal vesicle, cauda epididymis
CCNE1	201	ubiquitous	marker	secondary oocyte, oocyte, adrenal tissue
CD44	294	ubiquitous	marker	parotid gland, stromal cell of endometrium, mammalian vulva
SLTM	291	ubiquitous	marker	calcaneal tendon, sural nerve, tibia
BCOR	265	ubiquitous	marker	buccal mucosa cell, ganglionic eminence, cortical plate
MAP3K6	227	ubiquitous	marker	lower esophagus mucosa, right lung, skin of abdomen
MTHFR	254	ubiquitous	marker	corpus epididymis, sural nerve, apex of heart
BRCA1	208	ubiquitous	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
STK11	238	ubiquitous	marker	left testis, right testis, hindlimb stylopod muscle
EPCAM	253	broad	marker	jejunal mucosa, colonic mucosa, mucosa of sigmoid colon
EGLN1	214	ubiquitous	marker	gastrocnemius, muscle of leg, adrenal tissue
SLC2A9	182	broad	marker	buccal mucosa cell, monocyte, mononuclear cell
CA9	176	broad	marker	body of stomach, gall bladder, fundus of stomach
CASP10	206	ubiquitous	marker	colonic epithelium, granulocyte, monocyte
TOE1	268	ubiquitous	yes	type B pancreatic cell, olfactory bulb, primordial germ cell in gonad
CHEK2	183	ubiquitous	marker	primordial germ cell in gonad, lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis
CDH1	245	broad	marker	jejunal mucosa, esophagus squamous epithelium, gingival epithelium
CDH11	277	ubiquitous	marker	periodontal ligament, stromal cell of endometrium, tibia
CDK4	138	ubiquitous	marker	embryo, ganglionic eminence, ventricular zone
CDKN2A	220	ubiquitous	marker	parotid gland, cervix squamous epithelium, pituitary gland
BRIP1	181	ubiquitous	marker	ventricular zone, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
KLF6	301	ubiquitous	marker	nipple, lower lobe of lung, upper leg skin

Protein interactions among cohort

Intra-cohort edges: 129.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
KRAS	14,509
PTEN	11,626
ERBB2	9,659
CDKN2A	9,311
BRCA1	9,064
CDH1	8,738
CDK4	8,412
ATM	7,383
SMAD4	7,320

Intra-cohort edges

A	B	Sources
ARID1A	MSH2	string_interaction
ATM	BARD1	string_interaction
ATM	BRCA1	string_interaction
ATM	BRCA2	string_interaction
ATM	CHEK2	string_interaction
ATM	MLH1	string_interaction
ATM	MSH2	string_interaction
ATM	MSH6	string_interaction
ATM	NBN	biogrid_interaction, string_interaction
ATM	RAD51D	string_interaction
ATM	STK11	string_interaction
ATM	TP53	biogrid_interaction, string_interaction
BARD1	BRCA1	biogrid_interaction, intact, string_interaction
BARD1	BRCA2	string_interaction
BARD1	BRIP1	biogrid_interaction
BARD1	CHEK2	string_interaction
BARD1	PALB2	string_interaction
BARD1	RAD51C	string_interaction
BARD1	RAD51D	string_interaction
BRCA1	BRCA2	string_interaction
BRCA1	BRIP1	biogrid_interaction, intact, string_interaction
BRCA1	CHEK2	string_interaction
BRCA1	EXO1	biogrid_interaction, string_interaction
BRCA1	FANCI	string_interaction
BRCA1	HOXB13	string_interaction
BRCA1	MLH1	string_interaction
BRCA1	MSH2	string_interaction
BRCA1	MSH6	string_interaction
BRCA1	NBN	string_interaction
BRCA1	NF1	string_interaction
BRCA1	PALB2	biogrid_interaction, intact, string_interaction
BRCA1	PMS2	string_interaction
BRCA1	RAD51C	string_interaction
BRCA1	RAD51D	string_interaction
BRCA1	TP53	string_interaction
BRCA2	BRIP1	string_interaction
BRCA2	CHEK2	string_interaction
BRCA2	FANCI	string_interaction
BRCA2	HOXB13	string_interaction
BRCA2	MLH1	string_interaction
BRCA2	MSH2	string_interaction
BRCA2	MSH6	string_interaction
BRCA2	NBN	string_interaction
BRCA2	PALB2	biogrid_interaction, intact, string_interaction
BRCA2	PMS2	string_interaction
BRCA2	RAD51C	biogrid_interaction, string_interaction
BRCA2	RAD51D	string_interaction
BRCA2	STK11	string_interaction
BRCA2	TP53	string_interaction
BRIP1	FANCI	string_interaction

Structural data

PDB: 45 · AlphaFold-only: 9 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
TP53	P04637	313
PIK3CA	P42336	135
EGLN1	Q9GZT9	64
ERBB2	P04626	63
FGFR2	P21802	63
CHEK2	O96017	38
BRCA1	P38398	33
CA9	Q16790	32
APC	P25054	31
MSH2	P43246	30
NQO1	P15559	28
NF1	P21359	26
EXO1	Q9UQ84	25
ABCB1	P08183	24
CCNE1	P24864	22
CDH1	P12830	22
RAD51C	O43502	17
RAD51D	O75771	17
CDK4	P11802	15
ATM	Q13315	14
BRCA2	P51587	14
PTEN	P60484	12
SMAD4	Q13485	12
BARD1	Q99728	11
HOXB13	Q92826	10
PMS2	P54278	9
FANCI	Q9NVI1	8
MSH6	P52701	8
ARID1A	O14497	7

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LOXHD1	Q8IVV2	84.00
CDH11	P55287	77.65
MAP3K6	O95382	75.36
C11orf65	Q8NCR3	74.69
CDC20B	Q86Y33	69.60
CASP10	Q92851	69.54
IRF1	P10914	66.65
KLF6	Q99612	59.24
SLTM	Q9NWH9	52.38

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 497. Enrichment computed across 54 evidence-associated genes (45 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 45 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Impaired BRCA2 binding to PALB2	10	101.5×	3e-16	ATM, BRCA1, BRCA2, BRIP1, PALB2, EXO1, NBN, BARD1 (+2 more)
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	10	94.0×	3e-16	ATM, BRCA1, BRCA2, BRIP1, PALB2, EXO1, NBN, BARD1 (+2 more)
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	10	94.0×	3e-16	ATM, BRCA1, BRCA2, BRIP1, PALB2, EXO1, NBN, BARD1 (+2 more)
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	10	94.0×	3e-16	ATM, BRCA1, BRCA2, BRIP1, PALB2, EXO1, NBN, BARD1 (+2 more)
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	10	87.5×	6e-16	ATM, BRCA1, BRCA2, BRIP1, PALB2, EXO1, NBN, BARD1 (+2 more)
Homologous DNA Pairing and Strand Exchange	10	84.6×	7e-16	ATM, BRCA1, BRCA2, BRIP1, PALB2, EXO1, NBN, BARD1 (+2 more)
Resolution of D-loop Structures through Holliday Junction Intermediates	10	66.8×	1e-14	ATM, BRCA1, BRCA2, BRIP1, PALB2, EXO1, NBN, BARD1 (+2 more)
Diseases of DNA repair	8	101.5×	2e-13	ATM, BRCA1, BRCA2, MLH1, MSH2, MSH6, NBN, BARD1
HDR through Homologous Recombination (HRR)	10	42.3×	1e-12	ATM, BRCA1, BRCA2, BRIP1, PALB2, EXO1, NBN, BARD1 (+2 more)
Presynaptic phase of homologous DNA pairing and strand exchange	9	54.4×	2e-12	ATM, BRCA1, BRCA2, BRIP1, EXO1, NBN, BARD1, RAD51C (+1 more)
Impaired BRCA2 binding to RAD51	7	48.0×	4e-09	ATM, BRCA1, BRCA2, BRIP1, EXO1, NBN, BARD1
TP53 Regulates Transcription of DNA Repair Genes	8	32.2×	4e-09	TP53, ATM, BRCA1, FANCI, MLH1, MSH2, PMS2, RAD51D
Regulation of TP53 Activity through Phosphorylation	9	23.6×	4e-09	TP53, ATM, BRCA1, STK11, CHEK2, BRIP1, EXO1, NBN (+1 more)
Defective homologous recombination repair (HRR) due to PALB2 loss of function	5	105.7×	2e-08	ATM, BRCA1, BRCA2, NBN, BARD1
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	5	90.6×	4e-08	EXO1, MLH1, MSH2, MSH6, PMS2
Diseases of DNA Double-Strand Break Repair	5	90.6×	4e-08	ATM, BRCA1, BRCA2, NBN, BARD1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	5	90.6×	4e-08	ATM, BRCA1, BRCA2, NBN, BARD1
Transcriptional Regulation by TP53	10	13.8×	5e-08	ATM, BRCA1, STK11, CASP10, CCNE1, CDKN2A, MLH1, MSH2 (+2 more)
G2/M DNA damage checkpoint	8	21.4×	7e-08	TP53, ATM, BRCA1, CHEK2, BRIP1, EXO1, NBN, BARD1
RNA Polymerase II Transcription	14	7.0×	1e-07	ATM, BRCA1, ARID1A, STK11, CASP10, CCND2, CCNE1, CDK4 (+6 more)
Resolution of D-Loop Structures	5	70.5×	1e-07	ATM, BRCA1, BRCA2, NBN, BARD1
HDR through Single Strand Annealing (SSA)	6	39.0×	2e-07	ATM, BRCA1, BRIP1, EXO1, NBN, BARD1
Meiosis	6	38.1×	2e-07	ATM, BRCA1, BRCA2, CDK4, MLH1, NBN
DNA Repair	8	17.5×	3e-07	ATM, BRCA1, BRCA2, MLH1, MSH2, MSH6, NBN, BARD1
Meiotic recombination	7	20.2×	9e-07	ATM, BRCA1, BRCA2, CDK4, MLH1, NBN, RAD51C
Gene expression (Transcription)	14	5.5×	2e-06	ATM, BRCA1, ARID1A, STK11, CASP10, CCND2, CCNE1, CDK4 (+6 more)
Disease	16	4.7×	2e-06	ATM, BRCA1, BRCA2, CCND2, CCNE1, CDH1, CDK4, CDKN2A (+8 more)
Reproduction	6	25.4×	2e-06	ATM, BRCA1, BRCA2, CDK4, MLH1, NBN
Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)	4	72.5×	4e-06	EXO1, MLH1, MSH2, PMS2
Mismatch Repair	3	190.3×	4e-06	MLH1, MSH2, MSH6

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 54 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mismatch repair	6	72.0×	1e-07	EXO1, MLH1, MSH2, MSH6, MUTYH, PMS2
double-strand break repair	8	30.1×	1e-07	TP53, ATM, BRCA1, BRCA2, CHEK2, BRIP1, MSH2, NBN
somatic hypermutation of immunoglobulin genes	5	97.5×	4e-07	EXO1, MLH1, MSH2, MSH6, PMS2
regulation of cell cycle	10	13.8×	5e-07	TP53, ATM, BRCA1, STK11, CDK4, CDKN2A, IRF1, NBN (+2 more)
isotype switching	5	78.0×	8e-07	EXO1, MLH1, MSH2, MSH6, NBN
DNA strand resection involved in replication fork processing	4	156.0×	1e-06	BRCA1, EXO1, NBN, BARD1
homologous recombination	4	104.0×	6e-06	BRCA1, BRIP1, NBN, BARD1
double-strand break repair via homologous recombination	7	20.2×	6e-06	ATM, BRCA1, BRCA2, PALB2, NBN, RAD51C, RAD51D
somatic recombination of immunoglobulin gene segments	3	234.1×	1e-05	MSH2, MSH6, PMS2
DNA repair	9	10.6×	1e-05	BRCA1, BRIP1, EXO1, MSH2, MSH6, MUTYH, BARD1, RAD51C (+1 more)
replicative senescence	4	73.4×	2e-05	TP53, ATM, CHEK2, CDKN2A
DNA damage response, signal transduction by p53 class mediator	5	33.2×	3e-05	TP53, ATM, BRCA2, CHEK2, NBN
positive regulation of isotype switching to IgA isotypes	3	156.0×	4e-05	MLH1, MSH2, PMS2
intrinsic apoptotic signaling pathway in response to DNA damage	5	30.0×	4e-05	ATM, BRCA1, CHEK2, MLH1, MSH6
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	4	36.7×	2e-04	TP53, BRCA2, CHEK2, MSH2
telomere maintenance via recombination	3	85.1×	3e-04	BRCA2, RAD51C, RAD51D
positive regulation of isotype switching to IgG isotypes	3	85.1×	3e-04	MLH1, MSH2, PMS2
determination of adult lifespan	4	32.0×	4e-04	TP53, ATM, MSH2, MSH6
cellular response to ionizing radiation	4	30.4×	4e-04	TP53, BRCA1, BRCA2, BARD1
DNA damage checkpoint signaling	4	29.0×	5e-04	ATM, CHEK2, BRIP1, NBN
regulation of DNA damage checkpoint	3	62.4×	6e-04	BRCA1, BRCA2, BARD1
positive regulation of DNA-templated transcription	10	5.2×	8e-04	TP53, BRCA1, BRCA2, ARID1A, CHEK2, CDH1, CDKN2A, KLF6 (+2 more)
response to hypoxia	6	10.6×	8e-04	EGLN1, CA9, ABCB1, SMAD4, MTHFR, NF1
forebrain astrocyte development	2	208.1×	0.001	KRAS, NF1
response to X-ray	3	49.3×	0.001	TP53, BRCA2, MSH2
cellular senescence	4	21.9×	0.001	TP53, ATM, BRCA2, CDKN2A
negative regulation of cell growth	5	13.3×	0.001	TP53, BRCA1, STK11, CDKN2A, SMAD4
mitotic G2/M transition checkpoint	3	44.6×	0.001	BRCA1, NBN, BARD1
positive regulation of neuron apoptotic process	4	20.1×	0.001	TP53, ATM, CASP10, NF1
telomere maintenance	4	19.8×	0.001	ATM, CCNE1, NBN, RAD51D

Therapeutics

Drug target analysis

Approved (phase 4): 18 · Phase ≥3: 19 · Phased (≥1): 21 · Undrugged: 33

Druggability breadth: 38 of 54 evidence-associated genes (70%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
TP53	NITROFURANTOIN
ERBB2	CLOTRIMAZOLE
FGFR2	PONATINIB
ATM	AMIODARONE HYDROCHLORIDE
PIK3CA	IDELALISIB
CCND2	PALBOCICLIB
CCNE1	PALBOCICLIB
SLTM	CABOZANTINIB
MAP3K6	LENVATINIB
BRCA1	RIBOFLAVIN
STK11	FEDRATINIB
EGLN1	ROXADUSTAT
CA9	METHAZOLAMIDE
CHEK2	NERATINIB
CDK4	PALBOCICLIB
NQO1	DICUMAROL
ABCB1	PROGESTERONE
KRAS	VEMURAFENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
ABCB1	119	4
ERBB2	83	4
CA9	68	4
PIK3CA	67	4
FGFR2	59	4
CDK4	56	4
CCNE1	38	4
ATM	35	4
CHEK2	30	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	ABCB1, ERBB2, TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
FURAZOLIDONE	4	ATM, TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	CA9, TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	ATM, TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 21.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ABCB1	3,063	Binding:2135, Functional:746, ADMET:182
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6
CDK4	1,142	Binding:1086, Functional:53, ADMET:2, Toxicity:1
FGFR2	966	Binding:940, Functional:22, ADMET:4
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
CA9	791	Binding:785, ADMET:5, Functional:1
CCNE1	691	Binding:690, ADMET:1
CHEK2	690	Binding:687, Functional:2, ADMET:1
NQO1	279	Binding:227, ADMET:48, Functional:4
STK11	244	Binding:244
ATM	240	Binding:233, Functional:5, ADMET:2
EGLN1	211	Binding:211
MAP3K6	103	Binding:103
CCND2	28	Binding:28
IL1RN	26	Binding:26
APC	24	Binding:24
CASP10	22	Binding:21, Functional:1
CDH1	18	Binding:18
SLTM	14	Binding:14
BRCA1	13	Binding:9, Functional:4
SLC2A9	13	Binding:11, Functional:2
MSH6	10	Binding:10
CD44	9	Binding:9
MSH2	9	Binding:9
PTEN	8	Binding:8
ARID1A	6	Binding:6
TOE1	6	Binding:6
SMAD4	6	Binding:6
BCOR	2	Binding:2
CDKN2A	2	Binding:2
EXO1	2	Binding:2
NBN	2	Binding:2
EPCAM	1	Binding:1
FANCI	1	Binding:1
MUTYH	1	Functional:1
PMS2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ERBB2	2.7.10.1	receptor protein-tyrosine kinase
FGFR2	2.7.10.1	receptor protein-tyrosine kinase
ATM	2.7.11.1	non-specific serine/threonine protein kinase
PIK3CA	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase
MAP3K6	2.7.11.25	mitogen-activated protein kinase kinase kinase
MTHFR	1.5.1.20, 1.5.1.53	methylenetetrahydrofolate reductase [NAD(P)H], methylenetetrahydrofolate reductase (NADPH)
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
STK11	2.7.11.1	non-specific serine/threonine protein kinase
EPCAM	2.4.1.37, 2.4.1.40	fucosylgalactoside 3-alpha-galactosyltransferase, glycoprotein-fucosylgalactoside alpha-N-acetylgalactosaminyltransferase
EGLN1	1.14.11.2, 1.14.11.29	procollagen-proline 4-dioxygenase, hypoxia-inducible factor-proline dioxygenase
CA9	4.2.1.1	carbonic anhydrase
CASP10	3.4.22.63	caspase-10
CHEK2	2.7.11.1	non-specific serine/threonine protein kinase
CDK4	2.7.11.22	cyclin-dependent kinase
BRIP1	3.6.4.12	DNA helicase
NQO1	1.6.5.2	NAD(P)H dehydrogenase (quinone)
EXO1	3.1.11.1	exodeoxyribonuclease I
ABCB1	7.6.2.2, 7.6.2.3	ABC-type xenobiotic transporter, ABC-type glutathione-S-conjugate transporter
KRAS	3.6.5.2	small monomeric GTPase
BARD1	2.3.2.27	RING-type E3 ubiquitin transferase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
TP53	869
ERBB2	1,221
FGFR2	966
ATM	240
PIK3CA	2,034
CCNE1	691
MAP3K6	103
STK11	244
EGLN1	211
CA9	791
CHEK2	690
CDK4	1,142
NQO1	279
ABCB1	3,063
KRAS	861

Pharmacogenomics

Cohort genes with a PharmGKB record: 54; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

29 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	ABCB1, ERBB2, TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	CA9, TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	ATM, TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	18	TP53, ERBB2, FGFR2, ATM, PIK3CA, CCND2, CCNE1, SLTM, MAP3K6, BRCA1 (+8 more)
B	Phased (≥1) drug, not yet approved	3	SLC2A9, TOE1, MSH6
C	Druggable family + PDB, no drug	5	PTEN, MTHFR, EPCAM, BRIP1, EXO1
D	Druggable family + AlphaFold only, no drug	1	CASP10
E	Difficult family or no structure, no drug	27	ARID1A, CD44, BCOR, BRCA2, CDH1, CDH11, CDKN2A, KLF6, CDC20B, FANCI (+17 more)

Undrugged target profiles

33 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PTEN	8	STK11, TP53
BRCA2	0	BRCA1
EPCAM	1	ERBB2
CDKN2A	2	CDK4
BRIP1	0	BRCA1
KLF6	0	TP53
PALB2	0	BRCA1
MLH1	0	MSH6
MUTYH	1	MSH6
NBN	2	ATM, BRCA1
NF1	0	KRAS
PMS2	1	MSH6
RAD51D	0	BRCA1
ARID1A	6	—
CD44	9	—
BCOR	2	—
MTHFR	0	—
CASP10	22	—
CDH1	18	—
CDH11	0	—
CDC20B	0	—
FANCI	1	—
LOXHD1	0	—
C11orf65	0	—
EXO1	2	—
HOXB13	0	—
APC	24	—
IL1RN	26	—
IRF1	0	—
SMAD4	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2,317.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	622
PHASE3	205
PHASE1/PHASE2	178
PHASE4	51
PHASE2/PHASE3	44

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02047994	PHASE4	RECRUITING	Multicentric Randomized Study of H. Pylori Eradication and Pepsinogen Testing for Prevention of Gastric Cancer Mortality
NCT04168346	PHASE4	NOT_YET_RECRUITING	Preoperative Intravenous Iron Therapy in Patients With Gastric Cancer
NCT05183126	PHASE4	RECRUITING	Pharmacokinetic Study of Skeletal Muscle Area-based Paclitaxel Infusion in Patients With Cancer
NCT05498766	PHASE4	NOT_YET_RECRUITING	Effect and Safety of Huaier Granule Versus SOX Regimen in Gastric Cancer Patients
NCT06499610	PHASE4	NOT_YET_RECRUITING	Clinical Study of Irinotecan Liposome Combination Therapy for Advanced Gastric Cancer
NCT07124351	PHASE4	RECRUITING	Intraoperative Imaging of Gastrointestinal Malignancies Using Pafolacianine (CYTALUX™)
NCT07139366	PHASE4	RECRUITING	Saccharomyces Boulardii Combined With Bismuth Quadruple Therapy for Helicobacter Pylori Rescue Treatment
NCT07224035	PHASE4	ACTIVE_NOT_RECRUITING	Helicobacter Pylori Screening and Treatment in the At-risk South Florida Community- AIM 1
NCT07224048	PHASE4	ACTIVE_NOT_RECRUITING	Helicobacter Pylori Screening and Treatment in the At-risk South Florida Community-AIM 2
NCT07312370	PHASE4	NOT_YET_RECRUITING	Esomeprazole Plus Sucralfate for Post-ESD Ulcer Healing
NCT07467174	PHASE4	NOT_YET_RECRUITING	RCT Comparing Reduced-port Robotic and Conventional Laparoscopic Subtotal Gastrectomy
NCT07502027	PHASE4	NOT_YET_RECRUITING	A Clinical Study of Iparomlimab and Tuvonralimab Combined With SOX Following Heterogeneous Radiotherapy as First-line Treatment for Unresectable Locally Advanced or Metastatic HER2-negative Gastric or Gastroesophageal Junction Adenocarcinoma
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00558155	PHASE4	COMPLETED	The Impact of Immunostimulating Nutrition on the Outcome of Surgery
NCT00576940	PHASE4	COMPLETED	Standard and Immunostimulating Enteral Nutrition in Surgical Patients
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT01038154	PHASE4	UNKNOWN	Study to Evaluate the Efficacy of Pravastatin on Survival and Recurrence of Advanced Gastroesophageal Cancer
NCT01234272	PHASE4	COMPLETED	Comparison of the Analgesic Effect Between Intrathecal Morphine and IV-fentanyl Patient Controlled Analgesia (ITM-IVPCA) and Epidural PCA (PCEA) in Patients Undergoing Gastrectomy -Randomized Allocation Study-
NCT01260194	PHASE4	TERMINATED	A Study of Herceptin (Trastuzumab) in Combination With Standard Chemotherapy in Patients With HER Positive Metastatic Gastric Cancer
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01401075	PHASE4	COMPLETED	RCT With Adjuvant Mistletoe Treatment in Gastric Cancer Patients
NCT01471756	PHASE4	COMPLETED	Improving Complete Endoscopic Mucosal Resection (EMR) of Colorectal Neoplasia
NCT01766765	PHASE4	UNKNOWN	Early Jejunostomy Nutrition Minimizes Time to Chemotherapy
NCT01910948	PHASE4	UNKNOWN	Perioperative Application of Omega-3 Polyunsaturated Fatty Acids in Gastric Cancer Patients
NCT01927328	PHASE4	UNKNOWN	Iron Replacement in Oesophagogastric Neoplasia
NCT01962272	PHASE4	COMPLETED	The Effect of Nutritional Counseling for Cancer Patients
NCT01962376	PHASE4	UNKNOWN	Preoperative Chemotherapy With Bevacizumab For Potentially Resectable Gastric Cancer With Liver Metastasis
NCT02235246	PHASE4	COMPLETED	The Effect of Perioperative Intravenous Magnesium on Pain After Endoscopic Submucosal Dissection for Gastric Neoplasm: Prospective Randomized Double-blind Placebo Controlled Study
NCT02366819	PHASE4	SUSPENDED	Genetic Analysis-Guided Irinotecan Hydrochloride Dosing of mFOLFIRINOX in Treating Patients With Locally Advanced Gastroesophageal or Stomach Cancer
NCT02401971	PHASE4	UNKNOWN	Irinotecan Plus Thalidomide in Second Line Advanced Gastric Cancer
NCT02458573	PHASE4	COMPLETED	Comparison of the Effects of Continuous Epidural Analgesia and Continuous Intravenous Analgesia on Postoperative Bowel Movement in Patients Undergoing Laparoscopic Gastrectomy
NCT02638584	PHASE4	COMPLETED	Effects of Ilaprazole on Ulcer Healing Rate and Prevention of Gastrointestinal Bleeding in the Patients Undergone ESD.
NCT02776527	PHASE4	UNKNOWN	A Clinical Trial of Maintenance Treatment of Apatinib in Advanced Gastric Cancer Patients Have Completed Postoprative Adjuvant Chemotherapy
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03550482	PHASE4	COMPLETED	Oncoxin® and Quality of Life in Cancer Patients
NCT03609892	PHASE4	COMPLETED	Helicobacter Rescue Therapy With Berberine Plus Amoxicillin Quadruple Therapy Versus Tetracycline Plus Furazolidone Quadruple Therapy
NCT03642093	PHASE4	UNKNOWN	HOPE - A Study to Evaluate the Effect of a Prehabilitation Program on GI Cancer Patients Planning to Undergo Surgery
NCT03733639	PHASE4	UNKNOWN	Tisseel® as a Reinforcement of Esophagojejunal Anastomoses
NCT04209933	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Different Bismuth Quadruple Therapies
NCT04591028	PHASE4	WITHDRAWN	A Study to Evaluate Indocyanine Green Lymphangiography to Improve Lymphadenectomy in Gastric Cancer Patients

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CISPLATIN	4	111
IRINOTECAN	4	41
EPIRUBICIN	4	24
RAMUCIRUMAB	4	15
INDOCYANINE GREEN ACID FORM	4	10
LEUCOVORIN	4	7
BERBERINE	4	6
TEGAFUR	4	5
FLUOROURACIL	4	4
NIVOLUMAB	4	4
OLAPARIB	4	4
OXALIPLATIN	4	4
TRASTUZUMAB	4	4
CLARITHROMYCIN	4	3
FURAZOLIDONE	4	3
MITOMYCIN	4	3
PERTUZUMAB	4	3
TETRACYCLINE	4	3
TRASTUZUMAB EMTANSINE	4	3
FISH OIL TRIGLYCERIDES	4	2
MENTHOL	4	2
RABEPRAZOLE	4	2
ROFECOXIB	4	2
AMOXICILLIN	4	1
BUPROPION HYDROCHLORIDE	4	1
CAPECITABINE	4	1
CETUXIMAB	4	1
CHLORAMBUCIL	4	1
CITALOPRAM	4	1
DOCETAXEL	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 24 predictive associations from 26 curated evidence items; also 12 prognostic, 1 oncogenic, 1 diagnostic.

Molecular subtype	Therapy	Effect	Level	CIViC
ERBB2 Amplification	Pembrolizumab + Trastuzumab + Chemotherapy	Sensitivity/Response	CIViC A	EID11251
ERBB2 Amplification	Trastuzumab	Sensitivity/Response	CIViC A	EID11253
ERBB2 Amplification OR ERBB2 Overexpression	Trastuzumab + Chemotherapy	Sensitivity/Response	CIViC A	EID11255
ATM Underexpression	Paclitaxel + Olaparib	Sensitivity/Response	CIViC B	EID5215 +1
ERBB2 Amplification	Trastuzumab Deruxtecan	Sensitivity/Response	CIViC B	EID7647
ERBB2 Overexpression	Trastuzumab	Sensitivity/Response	CIViC B	EID7063
MET Amplification	Savolitinib	Sensitivity/Response	CIViC B	EID7729
MET Exon 14 Skipping Mutation	Crizotinib	Sensitivity/Response	CIViC B	EID11377
MET Exon 14 Skipping Mutation	SAIT301	Sensitivity/Response	CIViC B	EID11378
MTHFR A222V	Fluorouracil	Sensitivity/Response	CIViC B	EID669
TP53 Overexpression	Cisplatin + Mitomycin + Etoposide	Sensitivity/Response	CIViC B	EID2799
VEGFA Overexpression	Bevacizumab	Sensitivity/Response	CIViC B	EID7216
VEGFA Overexpression of VEGF121 and VEGF110	Bevacizumab	Sensitivity/Response	CIViC B	EID9298
CRKL Amplification	Dasatinib	Sensitivity/Response	CIViC D	EID6398
DDR2 High expression	Dasatinib	Sensitivity/Response	CIViC D	EID9853
ERBB2 Amplification	Afatinib	Sensitivity/Response	CIViC D	EID7808
FGFR2 Amplification	Erdafitinib	Sensitivity/Response	CIViC D	EID7953
FGFR2 Amplification	Ponatinib	Sensitivity/Response	CIViC D	EID8062
FGFR4 G636C	FGFR Inhibitor ASP5878	Sensitivity/Response	CIViC D	EID8905
PIK3CA E542K AND PTEN Loss	Capivasertib	Sensitivity/Response	CIViC D	EID11063
PIK3CA Mutation	Capivasertib	Sensitivity/Response	CIViC D	EID1501
PTEN Loss	Capivasertib + Docetaxel	Sensitivity/Response	CIViC D	EID1500
CD44 CD44v6	Cisplatin	Resistance	CIViC D	EID9430 +1
PTEN Loss	Docetaxel	Resistance	CIViC D	EID11064