Gastric carcinoma

Summary

Gastric carcinoma (MONDO:0004950) is a cancer (an umbrella term covering 12 Mondo subtypes) with 36 cohort genes (138 GWAS associations across 28 studies; 18 CIViC-evidence somatic drivers) and 2,388 clinical trials. The dominant Reactome pathway is Developmental Lineage of Mammary Gland Luminal Epithelial Cells (4 cohort genes). Molecularly, ERBB2 Amplification confers sensitivity to Pembrolizumab + Trastuzumab + Chemotherapy in Stomach Cancer (CIViC Level A); 35 further subtype–drug associations are mapped below. Top therapeutic interventions include irinotecan, epirubicin, and ramucirumab.

At a glance

• Classification: Cancer
• Umbrella term: 12 Mondo subtypes
• Cohort genes: 36
• GWAS associations: 138
• Clinical trials: 2,388
• Precision-medicine evidence (CIViC): 36 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	gastric carcinoma
Mondo ID	MONDO:0004950
EFO	EFO:0000178
DOID	DOID:10538, DOID:5517
ICD-11	1503707183
NCIT	C4911
SNOMED CT	187741001
UMLS	C0699791
MedGen	147066
GARD	0027710
Anatomy (UBERON)	UBERON:0000945
Is cancer (heuristic)	yes

Also known as: Ca fundus - stomach · cancer of fundus of stomach · cancer of stomach · cancer of the stomach · carcinoma of stomach · carcinoma of the stomach · fundus of stomach cancer · gastric (stomach) cancer · gastric cancer · gastric cancer, NOS · gastric carcinoma · gastric fundus cancer · malignant fundus of stomach neoplasm · malignant neoplasm of fundus of stomach · malignant tumor of fundus of stomach · malignant tumour of fundus of stomach · stomach cancer · stomach carcinoma

Data availability: 138 GWAS associations (28 studies) · 1 GenCC gene-disease record · 47 cell lines.

Disease family

An umbrella term covering 12 Mondo subtypes.

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

Related subtypes (8): malignant gastric granular cell tumor, gastric lymphoma, pylorus cancer, cardia cancer, malignant gastric germ cell tumor, gastric leiomyosarcoma, gastric liposarcoma, diffuse gastric cancer

Subtypes (12): gastric cardia carcinoma, gastric fundus carcinoma, gastric pylorus carcinoma, gastric body carcinoma, stomach carcinoma in situ, gastric adenocarcinoma, gastric small cell neuroendocrine carcinoma, gastric squamous cell carcinoma, Epstein-Barr virus-associated gastric carcinoma, hereditary gastric cancer, carcinoma of stomach, salivary gland type, undifferentiated carcinoma of stomach

Genetics & variants

GWAS landscape

138 GWAS associations across 28 studies. Top hits map to 23 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2920280	4e-49	JRK, PSCA	C	0.23
chr8:143779622	4e-46		?	0.24
rs372173246	8e-46	JRK, PSCA	C	0.24
rs2294008	1e-44	JRK, PSCA	T	1.31
rs2978977	3e-43	PSCA, JRK	A	1.29
rs760077	2e-40	THBS3, MTX1	T	0.33
chr1:155184975	1e-39		?	0.32
rs7366775	1e-34	THBS3-AS1, THBS3	A	1.41
rs1057941	2e-33	GBA1LP, GBA1LP	A	1.33
rs2920293	3e-32	PSCA - LY6K	G	1.39
rs10074991	3e-30	PRKAA1	A	0.78
chr5:40726138	3e-29		?	0.18
rs13361707	8e-29	PRKAA1	?	1.41
rs57067284	3e-26	TTC33	TGAACAGAC	0.18
rs59585832	1e-25	TTC33	T	0.18
rs10509670	2e-22	PLCE1	A	0.78
rs3805495	9e-20	TTC33	T	0.85
rs80142782	2e-19	ASH1L	T	1.61
rs4072037	6e-17	MUC1	T	1.35
rs2285947	1e-16	DNAH11	A	1.17
rs72706172	1e-15	GON4L	A	1.29
rs138554234	4e-15	LMNA	A	0.64
rs1205527	9e-14	RNU6-309P - GAPDHP77	C	0.09
rs2976394	2e-13	PSCA	C	0.7
rs2585177	2e-13	PSCA - LY6K	A	0.8
rs7849280	3e-13	ABO	G	1.15
rs67579710	6e-13	THBS3-AS1, THBS3	G	1.21
rs2494938	1e-12	LRFN2	A	1.15
chr8:143703571	1e-12		?	0.14
chr1:156045662	2e-12		?	0.16

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90432138	Jiang Y	2023	116,382	213,325	A cross-disorder study to identify causal relationships, shared genetic variants, and genes across 21 digestive disorders.
GCST012016	Jin G	2020	10,254	10,914	Genetic risk, incident gastric cancer, and healthy lifestyle: a meta-analysis of genome-wide association studies and prospective cohort study.
GCST90018629	Sakaue S	2021	7,921	159,201	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90013700	Ishigaki K	2020	6,563	195,745	Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases.
GCST006707	Tanikawa C	2018	6,171	27,178	A GWAS identifies gastric cancer susceptibility loci at 12q24.11-12 and 20q11.21.
GCST90296724	Hess T	2023	5,815	10,999	Dissecting the genetic heterogeneity of gastric cancer.
GCST90013739	Ishigaki K	2020	4,885	97,655	Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases.
GCST008646	Yan C	2019	3,771	5,426	Meta-analysis of genome-wide association studies and functional assays decipher susceptibility genes for gastric cancer in Chinese populations.
GCST90296726	Hess T	2023	3,183	10,999	Dissecting the genetic heterogeneity of gastric cancer.
GCST002992	Helgason H	2015	2,500	205,652	Loss-of-function variants in ATM confer risk of gastric cancer.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	3
Tier 3: regulatory	1
Tier 4: intronic/intergenic	44

MAF distribution

Bucket	Variants
common (>=0.05)	40
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	10

Functional consequences

Consequence	Count
intron_variant	23
unknown	10
intergenic_variant	9
missense_variant	2
3_prime_UTR_variant	2
5_prime_UTR_variant	1
regulatory_region_variant	1
non_coding_transcript_exon_variant	1
synonymous_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2920280	8	142679726	G>A,C,T	0.05	intergenic_variant	JRK, PSCA	4e-49	Tier 4: intronic/intergenic
chr8:143779622							4e-46	Tier 4: intronic/intergenic
rs372173246	8	142678701	CACCACCACCCAGCCACTGGCAGCAGAGCTTGGGCCTGCTCTAGAGGGTCCTAGCCACTGCT>C	0.473	intergenic_variant	JRK, PSCA	8e-46	Tier 4: intronic/intergenic
rs2294008	8	142680513	C>T	0.05	5_prime_UTR_variant	JRK, PSCA	1e-44	Tier 2: splice/UTR
rs2978977	8	142674302	C>A,G,T	0.491	regulatory_region_variant	PSCA, JRK	3e-43	Tier 3: regulatory
rs760077	1	155208991	T>A,C,G	0.15	missense_variant	THBS3, MTX1	2e-40	Tier 1: coding
chr1:155184975							1e-39	Tier 4: intronic/intergenic
rs7366775	1	155199139	G>A,C	0.2	intron_variant	THBS3-AS1, THBS3	1e-34	Tier 4: intronic/intergenic
rs1057941	1	155216951	G>A,C,T	0.05	non_coding_transcript_exon_variant	GBA1LP, GBA1LP	2e-33	Tier 4: intronic/intergenic
rs2920293	8	142683996	C>A,G,T	0.05	intergenic_variant	PSCA - LY6K	3e-32	Tier 4: intronic/intergenic
rs10074991	5	40790449	G>A	0.49	intron_variant	PRKAA1	3e-30	Tier 4: intronic/intergenic
chr5:40726138							3e-29	Tier 4: intronic/intergenic
rs13361707	5	40791782	C>T	0.05	intron_variant	PRKAA1	8e-29	Tier 4: intronic/intergenic
rs57067284	5	40734315	T>TGAACAGAC,TGAACAGACGGAACAGAC,TGAACAGACTAACAGAC,TGAACAGACTG,TGAACAGACTGAACAGAC,TGAGCAGAC	0.05	intron_variant	TTC33	3e-26	Tier 4: intronic/intergenic
rs59585832	5	40743936	C>T	0.413	intron_variant	TTC33	1e-25	Tier 4: intronic/intergenic
rs10509670	10	94308190	A>G	0.21	intron_variant	PLCE1	2e-22	Tier 4: intronic/intergenic
rs3805495	5	40755466	C>T	0.42	intron_variant	TTC33	9e-20	Tier 4: intronic/intergenic
rs80142782	1	155515236	T>C	0.07	intron_variant	ASH1L	2e-19	Tier 4: intronic/intergenic
rs4072037	1	155192276	C>A,G,T	0.16	synonymous_variant	MUC1	6e-17	Tier 4: intronic/intergenic
rs2285947	7	21544470	G>A	0.27	intron_variant	DNAH11	1e-16	Tier 4: intronic/intergenic
rs72706172	1	155827701	A>C,G	0.18	intron_variant	GON4L	1e-15	Tier 4: intronic/intergenic
rs138554234	1	156119243	G>A,C,T	0.05	intron_variant	LMNA	4e-15	Tier 4: intronic/intergenic
rs1205527	X	109299580	G>A,C	0.05	intergenic_variant	RNU6-309P - GAPDHP77	9e-14	Tier 4: intronic/intergenic
rs2976394	8	142682204	C>A,T	0.48	3_prime_UTR_variant	PSCA	2e-13	Tier 2: splice/UTR
rs2585177	8	142695299	A>C,T	0.16	intergenic_variant	PSCA - LY6K	2e-13	Tier 4: intronic/intergenic
rs7849280	9	133251249	A>G	0.05	3_prime_UTR_variant	ABO	3e-13	Tier 2: splice/UTR
rs67579710	1	155203736	G>A	0.05	intron_variant	THBS3-AS1, THBS3	6e-13	Tier 4: intronic/intergenic
rs2494938	6	40568389	G>A	0.23	intron_variant	LRFN2	1e-12	Tier 4: intronic/intergenic
chr8:143703571							1e-12	Tier 4: intronic/intergenic
chr1:156045662							2e-12	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 95 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
ATM	ATM	GWAS, GenCC, Orphanet

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
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
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
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
CCND2	LoF	AML,CLLSLL	CIViC #9
CCNE1			CIViC #11
CD44			CIViC #855
CDH1	LoF	BLCA,BRCA,CSCC,DLBCLNOS,ESCA,STAD	CIViC #888
CD274	LoF	DLBCLNOS	CIViC #11335
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
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
RHOA	Act	BL,BLCA,DLBCLNOS,HNSC,MLYM,NHL,PLMESO,PRAD,SKCM,STAD	CIViC #399
MLH1			CIViC #3532
MTHFR			CIViC #3672
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
ZBTB20	LoF	LGGNOS

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
ATM	Limited	Autosomal dominant	gastric carcinoma	14

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
ARID1A	Orphanet:1465	Coffin-Siris syndrome
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
CCND2	Orphanet:83473	Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome
CDH1	Orphanet:1331	Familial prostate cancer
CDH1	Orphanet:199306	Cleft lip/palate
CDH1	Orphanet:1997	Blepharo-cheilo-odontic syndrome
CDH1	Orphanet:227535	Hereditary breast cancer
CDH1	Orphanet:26106	Hereditary diffuse gastric cancer
BCOR	Orphanet:2712	Oculofaciocardiodental syndrome
BCOR	Orphanet:457246	Clear cell sarcoma of kidney
BCOR	Orphanet:520	Acute promyelocytic leukemia
BCOR	Orphanet:568	Microphthalmia, Lenz type
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

Cohort genes → proteins

36 cohort genes, 36 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	19
civic_only	16
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	gwas,gencc,civic_evidence
ARID1A	HGNC:11110	ENSG00000117713	O14497	AT-rich interactive domain-containing protein 1A	civic_evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	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
CDH1	HGNC:1748	ENSG00000039068	P12830	Cadherin-1	civic_evidence
CD274	HGNC:17635	ENSG00000120217	Q9NZQ7	Programmed cell death 1 ligand 1	civic_evidence
SLTM	HGNC:20709	ENSG00000137776	Q9NWH9	SAFB-like transcription modulator	civic_evidence
BCOR	HGNC:20893	ENSG00000183337	Q6W2J9	BCL-6 corepressor	civic_evidence
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	civic_evidence
FGFR2	HGNC:3689	ENSG00000066468	P21802	Fibroblast growth factor receptor 2	civic_evidence
RHOA	HGNC:667	ENSG00000067560	P61586	Transforming protein RhoA	civic_evidence
MLH1	HGNC:7127	ENSG00000076242	P40692	DNA mismatch repair protein Mlh1	civic_evidence
MTHFR	HGNC:7436	ENSG00000177000	P42898	Methylenetetrahydrofolate reductase (NADPH)	civic_evidence
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	civic_evidence
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	civic_evidence
SP4	HGNC:11209	ENSG00000105866	Q02446	Transcription factor Sp4	gwas
ZBTB20	HGNC:13503	ENSG00000181722	Q9HC78	Zinc finger and BTB domain-containing protein 20	gwas
PLCE1	HGNC:17175	ENSG00000138193	Q9P212	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1	gwas
ASH1L	HGNC:19088	ENSG00000116539	Q9NR48	Histone-lysine N-methyltransferase ASH1L	gwas
HCN3	HGNC:19183	ENSG00000143630	Q9P1Z3	Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3	gwas
UNC5CL	HGNC:21203	ENSG00000124602	Q8IV45	UNC5C-like protein	gwas
LRFN2	HGNC:21226	ENSG00000156564	Q9ULH4	Leucine-rich repeat and fibronectin type-III domain-containing protein 2	gwas
TSPO2	HGNC:21256	ENSG00000112212	Q5TGU0	Translocator protein 2	gwas
NOC3L	HGNC:24034	ENSG00000173145	Q8WTT2	Nucleolar complex protein 3 homolog	gwas
NSUN3	HGNC:26208	ENSG00000178694	Q9H649	tRNA (cytosine(34)-C(5))-methyltransferase, mitochondrial	gwas
ANKRD50	HGNC:29223	ENSG00000151458	Q9ULJ7	Ankyrin repeat domain-containing protein 50	gwas
DNAH11	HGNC:2942	ENSG00000105877	Q96DT5	Dynein axonemal heavy chain 11	gwas
TTC33	HGNC:29959	ENSG00000113638	Q6PID6	Tetratricopeptide repeat protein 33	gwas
MTX1	HGNC:7504	ENSG00000173171	Q13505	Metaxin-1	gwas
MUC1	HGNC:7508	ENSG00000185499	P15941	Mucin-1	gwas
OPCML	HGNC:8143	ENSG00000183715	Q14982	Opioid-binding protein/cell adhesion molecule	gwas
PRKAA1	HGNC:9376	ENSG00000132356	Q13131	5’-AMP-activated protein kinase catalytic subunit alpha-1	gwas
PSCA	HGNC:9500	ENSG00000167653	O43653	Prostate stem cell antigen	gwas
PTGER4	HGNC:9596	ENSG00000171522	P35408	Prostaglandin E2 receptor EP4 subtype	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
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).
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
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.
CDH1	Cadherin-1	Cadherins are calcium-dependent cell adhesion proteins.
CD274	Programmed cell death 1 ligand 1	Plays a critical role in induction and maintenance of immune tolerance to self.
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.
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…
RHOA	Transforming protein RhoA	Small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state.
MLH1	DNA mismatch repair protein Mlh1	Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR).
MTHFR	Methylenetetrahydrofolate reductase (NADPH)	Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine.
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.
SP4	Transcription factor Sp4	Binds to GT and GC boxes promoters elements.
ZBTB20	Zinc finger and BTB domain-containing protein 20	May be a transcription factor that may be involved in hematopoiesis, oncogenesis, and immune responses.
PLCE1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1	The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes.
ASH1L	Histone-lysine N-methyltransferase ASH1L	Histone methyltransferase specifically trimethylating ‘Lys-36’ of histone H3 forming H3K36me3.
HCN3	Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3	Hyperpolarization-activated ion channel that are permeable to sodium and potassium ions, with an about 3:1 preference for potassium ions.
UNC5CL	UNC5C-like protein	Inhibits NF-kappa-B-dependent transcription by impairing NF-kappa-B binding to its targets.
LRFN2	Leucine-rich repeat and fibronectin type-III domain-containing protein 2	Promotes neurite outgrowth in hippocampal neurons.
TSPO2	Translocator protein 2	Cholesterol-binding protein involved in the redistribution of cholesterol from lipid droplets to the endoplasmic reticulum.
NOC3L	Nucleolar complex protein 3 homolog	May be required for adipogenesis.
NSUN3	tRNA (cytosine(34)-C(5))-methyltransferase, mitochondrial	Mitochondrial tRNA methyltransferase that mediates methylation of cytosine to 5-methylcytosine (m5C) at position 34 of mt-tRNA(Met). mt-tRNA(Met) methylation at cytosine(34) takes place at the wobble position of the anticodon and initiates…
ANKRD50	Ankyrin repeat domain-containing protein 50	Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1.
DNAH11	Dynein axonemal heavy chain 11	Force generating protein required for cilia beating in respiratory epithelia.
MTX1	Metaxin-1	Involved in transport of proteins into the mitochondrion.
MUC1	Mucin-1	The alpha subunit has cell adhesive properties.
OPCML	Opioid-binding protein/cell adhesion molecule	Binds opioids in the presence of acidic lipids; probably involved in cell contact.
PRKAA1	5’-AMP-activated protein kinase catalytic subunit alpha-1	Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism.
PSCA	Prostate stem cell antigen	May be involved in the regulation of cell proliferation.
PTGER4	Prostaglandin E2 receptor EP4 subtype	Receptor for prostaglandin E2 (PGE2).

Protein-family classification

Druggable: 15 · Difficult: 6 · Unknown: 15 · Druggable fraction: 0.42

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	5	3.9×	0.081
Antibody/Immunoglobulin	3	2.4×	0.561
Ion channel	1	3.1×	0.636
Phosphatase	1	2.3×	0.636
Enzyme (other)	4	1.3×	0.636
Scaffold/PPI	2	1.0×	0.835
Transcription factor	4	0.9×	0.835
GPCR	1	0.7×	0.883
Other/Unknown	15	0.8×	0.970

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
ARID1A	Other/Unknown	no		ARID_dom, ARM-like, ARM-type_fold
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
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
CDH1	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin_pro_dom
CD274	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
SLTM	Other/Unknown	no		RRM_dom, SAP_dom, Nucleotide-bd_a/b_plait_sf
BCOR	Scaffold/PPI	no		Ankyrin_rpt, BCOR, PUFD
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
RHOA	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTPase_Rho, Small_GTP-bd
MLH1	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
MTHFR	Enzyme (other)	yes	1.5.1.20	Mehydrof_redctse-like, Fadh2_euk, FAD-linked_oxidoreductase-like
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
SP4	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Sp4-like
ZBTB20	Transcription factor	no		BTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
PLCE1	Enzyme (other)	yes	3.1.4.11	C2_dom, RA_dom, PLipase_C_PInositol-sp_X_dom
ASH1L	Transcription factor	no	2.1.1.357	BAH_dom, SET_dom, Bromodomain
HCN3	Ion channel	yes		cNMP-bd_dom, K_chnl_volt-dep_EAG/ELK/ERG, Ion_trans_dom
UNC5CL	Other/Unknown	no		Death_dom, ZU5_dom, DEATH-like_dom_sf
LRFN2	Antibody/Immunoglobulin	yes		Cys-rich_flank_reg_C, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
TSPO2	Other/Unknown	no		TspO_MBR, TspO/MBR-related_sf
NOC3L	Other/Unknown	no		CCAAT-binding_factor, Noc3_N, ARM-type_fold
NSUN3	Enzyme (other)	yes	2.1.1.203	MeTrfase_RsmB-F_NOP2_dom, RCMT, SAM-dependent_MTases_sf
ANKRD50	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, NPHP3-like_N
DNAH11	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
TTC33	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, TPR-containing
MTX1	Other/Unknown	no		Sam37/metaxin_N, Metaxin_GST, Glutathione-S-Trfase_C_sf
MUC1	Other/Unknown	no		SEA_dom, SEA_dom_sf
OPCML	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
PRKAA1	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
PSCA	Other/Unknown	no		LY6_UPA_recep-like, Toxin/TOLIP, Snake_toxin-like_sf
PTGER4	GPCR	yes		GPCR_Rhodpsn, Prostglndn_DP_rcpt, Prost_EP4_rcpt

Expression context

Cohort genes with no expression data: 0.

33 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)	36
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	8
cortical plate	4
sperm	4
ventricular zone	3
adrenal tissue	3
sural nerve	3
colonic epithelium	2
corpus callosum	2
bone marrow cell	2
ganglionic eminence	2
cauda epididymis	2
secondary oocyte	2
jejunal mucosa	2
lower esophagus mucosa	2
right uterine tube	2
corpus epididymis	2
endothelial cell	2
renal glomerulus	2
Brodmann (1909) area 23	2
pylorus	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATM	286	ubiquitous	marker	calcaneal tendon, colonic epithelium, corpus callosum
ARID1A	286	ubiquitous	marker	bone marrow cell, ventricular zone, embryo
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
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
CDH1	245	broad	marker	jejunal mucosa, esophagus squamous epithelium, gingival epithelium
CD274	208	ubiquitous	marker	cartilage tissue, placenta, lower lobe of lung
SLTM	291	ubiquitous	marker	calcaneal tendon, sural nerve, tibia
BCOR	265	ubiquitous	marker	buccal mucosa cell, ganglionic eminence, cortical plate
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
RHOA	295	ubiquitous	marker	monocyte, leukocyte, mononuclear cell
MLH1	296	ubiquitous	marker	tibialis anterior, skeletal muscle tissue of rectus abdominis, deltoid
MTHFR	254	ubiquitous	marker	corpus epididymis, sural nerve, apex of heart
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon
SP4	265	ubiquitous	marker	cerebellar vermis, germinal epithelium of ovary, superficial temporal artery
ZBTB20	292	ubiquitous	marker	corpus epididymis, caput epididymis, cauda epididymis
PLCE1	271	broad	marker	renal glomerulus, metanephric glomerulus, ventricular zone
ASH1L	267	ubiquitous	marker	Brodmann (1909) area 23, pylorus, cardia of stomach
HCN3	132	ubiquitous	marker	cortical plate, right hemisphere of cerebellum, cerebellum
UNC5CL	180	tissue_specific	yes	epithelial cell of pancreas, pancreatic ductal cell, kidney epithelium
LRFN2	66	tissue_specific	yes	cortical plate, prefrontal cortex, right frontal lobe
TSPO2	140	tissue_specific	marker	trabecular bone tissue, bone marrow, bone marrow cell
NOC3L	276	ubiquitous	marker	secondary oocyte, calcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis
NSUN3	231	ubiquitous	marker	sperm, male germ cell, calcaneal tendon
ANKRD50	246	ubiquitous	marker	sperm, skin of hip, upper leg skin
DNAH11	163	broad	marker	right uterine tube, bronchial epithelial cell, bronchus
TTC33	270	ubiquitous	yes	calcaneal tendon, colonic epithelium, cortical plate

Protein interactions among cohort

Intra-cohort edges: 20.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
PTEN	11,626
ERBB2	9,659
CDH1	8,738
ATM	7,383
CD44	6,810
PIK3CA	5,157
CD274	5,012
MLH1	4,435
CCNE1	3,811

Intra-cohort edges

A	B	Sources
ATM	MLH1	string_interaction
ATM	TP53	biogrid_interaction, string_interaction
CCNE1	TP53	string_interaction
CD44	ERBB2	string_interaction
CDH1	ERBB2	string_interaction
CDH1	PTEN	string_interaction
ERBB2	MUC1	biogrid_interaction
ERBB2	OPCML	biogrid_interaction
ERBB2	PIK3CA	string_interaction
LRFN2	UNC5CL	string_interaction
NOC3L	PLCE1	string_interaction
PIK3CA	PTEN	string_interaction
PIK3CA	SLTM	intact
PLCE1	TP53	biogrid_interaction
PLCE1	UNC5CL	string_interaction
PRKAA1	TTC33	string_interaction
PRKAA1	UNC5CL	string_interaction
PSCA	UNC5CL	string_interaction
PTEN	TP53	string_interaction
UNC5CL	ZBTB20	string_interaction

Structural data

PDB: 26 · AlphaFold-only: 10 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TP53	P04637	313
PIK3CA	P42336	135
RHOA	P61586	131
CD274	Q9NZQ7	76
ERBB2	P04626	63
FGFR2	P21802	63
MUC1	P15941	23
CCNE1	P24864	22
CDH1	P12830	22
ASH1L	Q9NR48	16
ATM	Q13315	14
PTEN	P60484	12
PRKAA1	Q13131	12
PTGER4	P35408	10
ARID1A	O14497	7
MLH1	P40692	7
CD44	P16070	6
BCOR	Q6W2J9	5
MTHFR	P42898	4
NOC3L	Q8WTT2	4
PLCE1	Q9P212	3
HCN3	Q9P1Z3	3
ZBTB20	Q9HC78	2
CCND2	P30279	1
OPCML	Q14982	1
PSCA	O43653	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NSUN3	Q9H649	90.97
TTC33	Q6PID6	80.26
UNC5CL	Q8IV45	80.18
ANKRD50	Q9ULJ7	74.26
MTX1	Q13505	71.83
LRFN2	Q9ULH4	70.36
TSPO2	Q5TGU0	68.09
SLTM	Q9NWH9	52.38
SP4	Q02446	39.58
DNAH11	Q96DT5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 363. Enrichment computed across 36 evidence-associated genes (25 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 25 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	4	73.1×	8e-05	CD44, CDH1, ERBB2, MUC1
Developmental Lineage of Mammary Stem Cells	3	91.4×	8e-04	CD44, CDH1, ERBB2
Developmental Lineage of Mammary Gland Myoepithelial Cells	3	65.3×	0.001	CD44, CDH1, ERBB2
Ovarian tumor domain proteases	3	33.4×	0.008	TP53, RHOA, PTEN
PI3K/AKT activation	2	101.5×	0.012	RHOA, PIK3CA
TP53 Regulates Transcription of Caspase Activators and Caspases	2	76.1×	0.012	ATM, TP53
Positive Regulation of CDH1 Gene Transcription	2	76.1×	0.012	ARID1A, CDH1
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects	2	70.3×	0.012	CCND2, CCNE1
Stabilization of p53	2	60.9×	0.012	ATM, TP53
ERBB2 Regulates Cell Motility	2	57.1×	0.012	ERBB2, RHOA
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	2	57.1×	0.012	TP53, CCNE1
p53-Dependent G1 DNA Damage Response	2	57.1×	0.012	ATM, CCNE1
p53-Dependent G1/S DNA damage checkpoint	2	57.1×	0.012	ATM, CCNE1
PI3K events in ERBB2 signaling	2	53.7×	0.012	ERBB2, PIK3CA
G1/S DNA Damage Checkpoints	2	53.7×	0.012	ATM, CCNE1
Signaling by ERBB2 ECD mutants	2	53.7×	0.012	ERBB2, PIK3CA
TP53 Regulates Transcription of DNA Repair Genes	3	21.8×	0.012	ATM, TP53, MLH1
DNA Damage/Telomere Stress Induced Senescence	3	19.6×	0.012	ATM, TP53, CCNE1
Transcriptional Regulation by TP53	4	9.9×	0.012	ATM, CCNE1, MLH1, PRKAA1
RNA Polymerase II Transcription	6	5.4×	0.012	ATM, ARID1A, CCND2, CCNE1, MLH1, PRKAA1
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	2	50.8×	0.012	CCND2, CCNE1
Sema4D induced cell migration and growth-cone collapse	2	45.7×	0.013	ERBB2, RHOA
Diseases of DNA repair	2	45.7×	0.013	ATM, MLH1
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	2	43.5×	0.013	ATM, TP53
Regulation of TP53 Activity through Methylation	2	43.5×	0.013	ATM, TP53
TP53 Regulates Metabolic Genes	3	15.6×	0.013	TP53, PRKAA1, PTEN
Constitutive Signaling by Aberrant PI3K in Cancer	3	15.2×	0.013	ERBB2, FGFR2, PIK3CA
PI-3K cascade:FGFR2	2	39.7×	0.015	FGFR2, PIK3CA
Regulation of TP53 Activity through Phosphorylation	3	14.1×	0.015	ATM, TP53, PRKAA1
Synthesis of IP3 and IP4 in the cytosol	2	33.8×	0.018	PLCE1, PTEN

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 35 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of osteoblast proliferation	2	321.0×	0.009	FGFR2, RHOA
odontogenesis	3	45.1×	0.013	BCOR, FGFR2, RHOA
meiotic telomere clustering	2	107.0×	0.021	ATM, MLH1
negative regulation of cell size	2	96.3×	0.021	RHOA, PTEN
cellular response to X-ray	2	96.3×	0.021	ATM, CCND2
DNA damage response, signal transduction by p53 class mediator	3	30.7×	0.021	ATM, TP53, MUC1
positive regulation of protein localization	2	80.2×	0.023	CDH1, PRKAA1
cellular response to glucose stimulus	3	22.9×	0.023	ZBTB20, PIK3CA, PRKAA1
cell migration	5	8.8×	0.023	CD44, CDH1, RHOA, PIK3CA, PTEN
cardiac septum morphogenesis	2	68.8×	0.023	TP53, DNAH11
epidermal growth factor receptor signaling pathway	3	21.2×	0.023	PLCE1, ERBB2, PIK3CA
wound healing, spreading of cells	2	64.2×	0.024	CD44, RHOA
mitotic G1 DNA damage checkpoint signaling	2	60.2×	0.024	TP53, MUC1
negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	2	60.2×	0.024	CD44, MUC1
replicative senescence	2	56.6×	0.025	ATM, TP53
phosphatidylinositol 3-kinase/protein kinase B signal transduction	3	18.1×	0.026	ERBB2, PIK3CA, PTEN
post-embryonic development	3	17.6×	0.026	ATM, ASH1L, FGFR2
angiotensin-mediated vasoconstriction involved in regulation of systemic arterial blood pressure	1	481.5×	0.027	RHOA
tRNA wobble base cytosine methylation	1	481.5×	0.027	NSUN3
alpha-beta T cell lineage commitment	1	481.5×	0.027	RHOA
response to muscle inactivity	1	481.5×	0.027	PIK3CA
fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell	1	481.5×	0.027	FGFR2
fibroblast growth factor receptor signaling pathway involved in hemopoiesis	1	481.5×	0.027	FGFR2
fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow	1	481.5×	0.027	FGFR2
meiotic metaphase I homologous chromosome alignment	1	481.5×	0.027	MLH1
negative regulation of glucosylceramide biosynthetic process	1	481.5×	0.027	PRKAA1
negative regulation of helicase activity	1	481.5×	0.027	TP53
lateral sprouting from an epithelium	1	481.5×	0.027	FGFR2
specification of axis polarity	1	481.5×	0.027	BCOR
cellular response to actinomycin D	1	481.5×	0.027	TP53

Therapeutics

Drugs indicated for this disease

3 approved, 14 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Capecitabine	Approved (phase 4)
Ramucirumab	Approved (phase 4)
Trastuzumab	Approved (phase 4)
Bevacizumab	Phase 3 (in late-stage trials)
Camrelizumab	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Ferric Carboxymaltose	Phase 3 (in late-stage trials)
Fluorouracil	Phase 3 (in late-stage trials)
Gimeracil	Phase 3 (in late-stage trials)
Irinotecan	Phase 3 (in late-stage trials)
Oteracil	Phase 3 (in late-stage trials)
Oxaliplatin	Phase 3 (in late-stage trials)
Paclitaxel	Phase 3 (in late-stage trials)
Pemetrexed	Phase 3 (in late-stage trials)
Rivoceranib	Phase 3 (in late-stage trials)
Sintilimab	Phase 3 (in late-stage trials)
Tegafur	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): ANTINEOPLASTON A10, Gefitinib, Lenvatinib, Penpulimab, Tesetaxel.

Drug target analysis

Approved (phase 4): 11 · Phase ≥3: 11 · Phased (≥1): 11 · Undrugged: 25

Druggability breadth: 23 of 36 evidence-associated genes (64%) 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
ATM	AMIODARONE HYDROCHLORIDE
TP53	NITROFURANTOIN
CCND2	PALBOCICLIB
CCNE1	PALBOCICLIB
CD274	MOCLOBEMIDE
SLTM	CABOZANTINIB
ERBB2	CLOTRIMAZOLE
FGFR2	PONATINIB
PIK3CA	IDELALISIB
PRKAA1	ADENOSINE PHOSPHATE
PTGER4	DINOPROSTONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
ERBB2	83	4
PIK3CA	67	4
FGFR2	59	4
PRKAA1	46	4
CCNE1	38	4
ATM	35	4
PTGER4	9	4
CD274	4	4
CCND2	3	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
FURAZOLIDONE	4	ATM, TP53
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM, TP53
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM, TP53
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM, TP53
FENOFIBRATE	4	ATM
DIPYRIDAMOLE	4	ATM
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	ERBB2, TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMOXAPINE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 11.

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

Symbol	Assays	Type breakdown
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6
FGFR2	966	Binding:940, Functional:22, ADMET:4
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
PRKAA1	738	Binding:734, Functional:4
CCNE1	691	Binding:690, ADMET:1
CD274	525	Binding:520, Functional:5
PTGER4	288	Binding:207, Functional:80, ADMET:1
ATM	240	Binding:233, Functional:5, ADMET:2
ASH1L	65	Binding:63, ADMET:1, Functional:1
RHOA	48	Binding:48
CCND2	28	Binding:28
CDH1	18	Binding:18
SLTM	14	Binding:14
MUC1	13	Binding:13
CD44	9	Binding:9
PTEN	8	Binding:8
ARID1A	6	Binding:6
NSUN3	5	Binding:5
HCN3	3	Binding:1, ADMET:1, Functional:1
BCOR	2	Binding:2
MTX1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ATM	2.7.11.1	non-specific serine/threonine protein kinase
ERBB2	2.7.10.1	receptor protein-tyrosine kinase
FGFR2	2.7.10.1	receptor protein-tyrosine kinase
RHOA	3.6.5.2	small monomeric GTPase
MTHFR	1.5.1.20, 1.5.1.53	methylenetetrahydrofolate reductase [NAD(P)H], methylenetetrahydrofolate reductase (NADPH)
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
PLCE1	3.1.4.11	phosphoinositide phospholipase C
ASH1L	2.1.1.357	[histone H3]-lysine36 N-dimethyltransferase
NSUN3	2.1.1.203	tRNA (cytosine34-C5)-methyltransferase
PRKAA1	2.7.11.1, 2.7.11.31	non-specific serine/threonine protein kinase, [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ATM	240
TP53	869
CCNE1	691
CD274	525
ERBB2	1,221
FGFR2	966
PIK3CA	2,034
PRKAA1	738
PTGER4	288

Pharmacogenomics

Cohort genes with a PharmGKB record: 36; 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)
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM, TP53
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM, TP53
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM, TP53
FENOFIBRATE	4	ATM
DIPYRIDAMOLE	4	ATM
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	ERBB2, TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMOXAPINE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	11	ATM, TP53, CCND2, CCNE1, CD274, SLTM, ERBB2, FGFR2, PIK3CA, PRKAA1 (+1 more)
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	6	RHOA, MTHFR, PTEN, PLCE1, HCN3, OPCML
D	Druggable family + AlphaFold only, no drug	2	LRFN2, NSUN3
E	Difficult family or no structure, no drug	17	ARID1A, CD44, CDH1, BCOR, MLH1, SP4, ZBTB20, ASH1L, UNC5CL, TSPO2 (+7 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PTEN	8	TP53
ARID1A	6	—
CD44	9	—
CDH1	18	—
BCOR	2	—
RHOA	48	—
MLH1	0	—
MTHFR	0	—
SP4	0	—
ZBTB20	0	—
PLCE1	0	—
ASH1L	65	—
HCN3	3	—
UNC5CL	0	—
LRFN2	0	—
TSPO2	0	—
NOC3L	0	—
NSUN3	5	—
ANKRD50	0	—
DNAH11	0	—
TTC33	0	—
MTX1	1	—
MUC1	13	—
OPCML	0	—
PSCA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2,388.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	618
PHASE3	202
PHASE1/PHASE2	186
PHASE4	49
PHASE2/PHASE3	45

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
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
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
NCT04607057	PHASE4	UNKNOWN	Supplemental Parenteral Nutrition During Postgastrectomy in Nutritionally at Risk Patient
NCT04660123	PHASE4	COMPLETED	A Real World Study of Bismuth Colloidal Pectin Granules Quadruple Therapy for H. Pylori Eradication

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
IRINOTECAN	4	41
EPIRUBICIN	4	34
RAMUCIRUMAB	4	15
FRUQUINTINIB	4	11
INDOCYANINE GREEN ACID FORM	4	10
FLOXURIDINE	4	8
LEUCOVORIN	4	8
TISLELIZUMAB	4	6
TEGAFUR	4	5
ZOLBETUXIMAB	4	5
AFATINIB	4	4
FLUOROURACIL	4	4
NIVOLUMAB	4	4
OLAPARIB	4	4
OXALIPLATIN	4	4
RELATLIMAB	4	4
TORIPALIMAB	4	4
TRASTUZUMAB	4	4
TRASTUZUMAB EMTANSINE	4	4
CABAZITAXEL	4	3
CISPLATIN	4	3
CLARITHROMYCIN	4	3
FURAZOLIDONE	4	3
MITOMYCIN	4	3
PERTUZUMAB	4	3
TETRACYCLINE	4	3
BERBERINE	4	2
CAPIVASERTIB	4	2
CATUMAXOMAB	4	2
EFLORNITHINE	4	2

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 36 predictive associations from 38 curated evidence items; also 16 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
FGFR2 Amplification	Fexagratinib	Sensitivity/Response	CIViC B	EID1990
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
MET Overexpression	Rilotumumab	Sensitivity/Response	CIViC B	EID5835
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
MLH1 METHYLATION	Oxaliplatin	Resistance	CIViC B	EID1315
PTEN Loss	Chemotherapy	Resistance	CIViC B	EID1493
TP53 Mutation	Cisplatin + Etoposide + Doxorubicin	Sensitivity/Response	CIViC C	EID2820
TP53 R175H	EAP Protocol	Sensitivity/Response	CIViC C	EID2310
TP53 R213P	EAP Protocol	Sensitivity/Response	CIViC C	EID2819
TP53 R273C	Etoposide + Mitomycin + Cisplatin	Sensitivity/Response	CIViC C	EID2292
TP53 R282L	EAP Protocol	Sensitivity/Response	CIViC C	EID2818
TP53 Y220C	Mitomycin + Cisplatin + Etoposide	Sensitivity/Response	CIViC C	EID2306
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
NPTXR Overexpression	Cisplatin + Fluorouracil	Sensitivity/Response	CIViC D	EID12774

+6 more predictive associations (showing top 30 by evidence level).