Ovarian cancer

Summary

Ovarian cancer (MONDO:0008170) is a cancer (an umbrella term covering 11 Mondo subtypes) caused by variants in MLH1, MSH2, and MSH6, with 75 cohort genes (79 GWAS associations across 22 studies; 56 CIViC-evidence somatic drivers; 1,056 ClinVar predisposition records) and 2,577 clinical trials. The dominant Reactome pathway is Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) (14 cohort genes). Molecularly, BRCA1 Mutation confers sensitivity to Rucaparib in Ovarian Cancer (CIViC Level A); 61 further subtype–drug associations are mapped below. Top therapeutic interventions include topotecan, niraparib, and olaparib.

At a glance

• Classification: Cancer
• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Causal genes: MLH1 (GenCC Strong), MSH2 (GenCC Strong), MSH6 (GenCC Strong)
• Umbrella term: 11 Mondo subtypes
• Cohort genes: 75
• GWAS associations: 79
• ClinVar variants: 1,056
• Clinical trials: 2,577
• Precision-medicine evidence (CIViC): 62 subtype–drug associations

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	49	Europe	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	ovarian cancer
Mondo ID	MONDO:0008170
MeSH	D010051
OMIM	167000
Orphanet	213500
DOID	DOID:2394
ICD-10-CM	C56
ICD-11	685124533
NCIT	C7431
SNOMED CT	363443007
UMLS	C1140680
MedGen	216027
Anatomy (UBERON)	UBERON:0000992
Is cancer (heuristic)	yes

Also known as: cancer of ovary · cancer of the ovary · malignant neoplasm of ovary · malignant neoplasm of the ovary · malignant ovarian neoplasm · malignant ovarian tumor · malignant ovarian tumour · malignant ovary neoplasm · malignant tumor of ovary · malignant tumor of the ovary · malignant tumour of ovary · malignant tumour of the ovary · ovarian cancer · ovarian cancer, somatic · ovarian malignant tumor · ovarian malignant tumour · ovarian neoplasm · ovary cancer · ovary neoplasm · tumor of the ovary (+1 more)

Data availability: 1,056 ClinVar variants · 79 GWAS associations (22 studies) · 6 GenCC gene-disease records.

Disease family

An umbrella term covering 11 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › reproductive system cancer › female reproductive organ cancer › ovarian cancer

Related subtypes (8): vaginal cancer, vulva cancer, fallopian tube cancer, uterine cancer, adenocarcinofibroma, endometrioid adenocarcinoma, adenosarcoma, gestational choriocarcinoma

Subtypes (11): ovarian malignant mesothelioma, malignant ovarian cyst, ovarian sarcoma, ovarian lymphoma, ovarian Wilms tumor, ovarian neuroendocrine neoplasm, ovarian adenosarcoma, ovarian endometrioid adenocarcinofibroma, familial ovarian cancer, malignant epithelial tumor of ovary, malignant non-epithelial tumor of ovary

Genetics & variants

GWAS landscape

79 GWAS associations across 22 studies. Top hits map to 35 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs12682374	9e-29	PCAT1, CASC8, POU5F1B	?	0.93
rs1219651	1e-25	FGFR2	?	1.09
rs2981584	1e-21	FGFR2	?	0.94
rs10908278	3e-21	HNF1B	?	1.06
rs17688434	2e-20	LINC02210-CRHR1	?
rs7098100	8e-18	MLLT10	?
rs112149573	2e-17	TOX3	?	1.08
rs12551733	4e-16	BNC2 - RN7SL720P	?
rs78540526	1e-15	LINC01488 - PNCRNA-D	?	1.13
rs35409710	2e-15	HLA-DQB1	?	1.09
rs7463708	2e-15	PCAT1, PRNCR1, CASC19	?	1.08
rs11651755	1e-14	HNF1B	?	1.06
rs1485995	8e-14	LINC01488	?	0.95
rs9273736	2e-13	HLA-DQB1	?	1.12
rs372745970	2e-13	MAPK8IP1P1 - ARL17B	?
rs2976384	3e-13	PSCA, JRK	?	1.07
rs2585181	3e-12	PSCA - LY6K	?	1.05
rs11926561	6e-12	TIPARP-AS1	?
rs2532395	6e-12	KANSL1 - MAPK8IP1P1	?
rs6512302	4e-11	TCEA2	?
rs7894565	5e-11	MLLT10	?
rs4007642	6e-11	CDKN2B-AS1	?	0.96
rs75637630	7e-11	ATAD5	?
rs10786774	1e-10	STN1	?	0.92
rs2990223	1e-10	GBA1LP, GBA1LP	?	1.09
rs7209484	1e-10	NFE2L1 - CBX1	?
rs4442975	2e-10	TESHL	?	0.96
rs4630240	2e-10	RPL23AP61	?	0.96
rs10171315	4e-10	DNMT3A - ARNILA	?
rs6062344	5e-10	TCEA2	?

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.
GCST90435610	Zhou W	2018	2,127	389,695	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90435611	Zhou W	2018	2,103	389,695	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90651050	Sato G	2023	1,997	334,343	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90503276	Wilcox N	2025	1,372	226,021	The contribution of coding variants to the heritability of multiple cancer types using UK Biobank whole-exome sequencing data.
GCST90077632	Backman JD	2021	769	38,845	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081618	Backman JD	2021	769	38,845	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90652081	Liu TY	2025	740	112,967	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	0
Tier 2: splice/UTR	1
Tier 3: regulatory	1
Tier 4: intronic/intergenic	48

MAF distribution

Bucket	Variants
common (>=0.05)	48
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	2

Functional consequences

Consequence	Count
intron_variant	32
intergenic_variant	13
non_coding_transcript_exon_variant	3
regulatory_region_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs12682374	8	127398703	C>A,G,T	0.05	intron_variant	PCAT1, CASC8, POU5F1B	9e-29	Tier 4: intronic/intergenic
rs1219651	10	121584987	G>A,C,T	0.05	intron_variant	FGFR2	1e-25	Tier 4: intronic/intergenic
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
rs17688434	17	45695174	G>A	0.05	intron_variant	LINC02210-CRHR1	2e-20	Tier 4: intronic/intergenic
rs7098100	10	21545607	G>A	0.05	intron_variant	MLLT10	8e-18	Tier 4: intronic/intergenic
rs112149573	16	52547333	G>C,T	0.05	intron_variant	TOX3	2e-17	Tier 4: intronic/intergenic
rs12551733	9	16895580	C>G	0.05	intergenic_variant	BNC2 - RN7SL720P	4e-16	Tier 4: intronic/intergenic
rs78540526	11	69516650	C>T	0.05	regulatory_region_variant	LINC01488 - PNCRNA-D	1e-15	Tier 3: regulatory
rs35409710	6	32661126	G>A	0.05	intron_variant	HLA-DQB1	2e-15	Tier 4: intronic/intergenic
rs7463708	8	127091810	G>A,C,T	0.05	non_coding_transcript_exon_variant	PCAT1, PRNCR1, CASC19	2e-15	Tier 4: intronic/intergenic
rs11651755	17	37739849	T>C	0.05	intron_variant	HNF1B	1e-14	Tier 4: intronic/intergenic
rs1485995	11	69492939	G>A,C	0.05	non_coding_transcript_exon_variant	LINC01488	8e-14	Tier 4: intronic/intergenic
rs9273736	6	32661595	G>A,C	0.05	intron_variant	HLA-DQB1	2e-13	Tier 4: intronic/intergenic
rs372745970	17	46245211	G>A,C	0.05	intron_variant	MAPK8IP1P1 - ARL17B	2e-13	Tier 4: intronic/intergenic
rs2976384	8	142671576	T>A,C	0.05	intergenic_variant	PSCA, JRK	3e-13	Tier 4: intronic/intergenic
rs2585181	8	142690296	C>A	0.05	intergenic_variant	PSCA - LY6K	3e-12	Tier 4: intronic/intergenic
rs11926561	3	156639539	T>A,C,G	0.05	intergenic_variant	TIPARP-AS1	6e-12	Tier 4: intronic/intergenic
rs2532395	17	46229827	C>T	0.05	intron_variant	KANSL1 - MAPK8IP1P1	6e-12	Tier 4: intronic/intergenic
rs6512302	20	64060197	G>C,T	0.05	intron_variant	TCEA2	4e-11	Tier 4: intronic/intergenic
rs7894565	10	21583984	T>C,G	0.05	intron_variant	MLLT10	5e-11	Tier 4: intronic/intergenic
rs4007642	9	22093300	A>C,T	0.05	intron_variant	CDKN2B-AS1	6e-11	Tier 4: intronic/intergenic
rs75637630	17	30841060	A>C	0.05	intron_variant	ATAD5	7e-11	Tier 4: intronic/intergenic
rs10786774	10	103884565	G>A,C,T	0.05	intron_variant	STN1	1e-10	Tier 4: intronic/intergenic
rs2990223	1	155215184	G>A,T	0.05	intron_variant	GBA1LP, GBA1LP	1e-10	Tier 4: intronic/intergenic
rs7209484	17	48065680	T>C,G	0.05	intergenic_variant	NFE2L1 - CBX1	1e-10	Tier 4: intronic/intergenic
rs4442975	2	217056046	G>A,C,T	0.05	intron_variant	TESHL	2e-10	Tier 4: intronic/intergenic
rs4630240	10	46063294	C>A,T	0.05	non_coding_transcript_exon_variant	RPL23AP61	2e-10	Tier 4: intronic/intergenic
rs10171315	2	25359922	G>A	0.05	intergenic_variant	DNMT3A - ARNILA	4e-10	Tier 4: intronic/intergenic
rs6062344	20	64064671	C>G,T	0.05	intron_variant	TCEA2	5e-10	Tier 4: intronic/intergenic

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

284 conflicting classifications of pathogenicity, 86 benign, 77 uncertain significance, 52 benign/likely benign, 39 likely pathogenic, 25 likely benign, 20 pathogenic, 16 pathogenic/likely pathogenic, 1 pathogenic/likely pathogenic/pathogenic, low penetrance

ClinVar	Variant (HGVS)	Gene	Classification	Review
17671	NM_007294.4(BRCA1):c.3607C>T (p.Arg1203Ter)	BRCA1	Pathogenic	reviewed by expert panel
225756	NM_000059.4(BRCA2):c.9053_9057del (p.Ser3018fs)	BRCA2	Pathogenic	reviewed by expert panel
128151	NM_032043.3(BRIP1):c.1126_1127del (p.Gln376fs)	BRIP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
128154	NM_032043.3(BRIP1):c.1315C>T (p.Arg439Ter)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
128156	NM_032043.3(BRIP1):c.1372G>T (p.Glu458Ter)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
128166	NM_032043.3(BRIP1):c.2038_2039dup (p.Leu680fs)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
128170	NM_032043.3(BRIP1):c.2273dup (p.Ala759fs)	BRIP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
140808	NM_032043.3(BRIP1):c.133G>T (p.Glu45Ter)	BRIP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
140852	NM_032043.3(BRIP1):c.1871C>A (p.Ser624Ter)	BRIP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
141382	NM_032043.3(BRIP1):c.1240C>T (p.Gln414Ter)	BRIP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
141753	NM_032043.3(BRIP1):c.1853_1854insG (p.Pro619fs)	BRIP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
142343	NM_032043.3(BRIP1):c.2400C>G (p.Tyr800Ter)	BRIP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
142366	NM_032043.3(BRIP1):c.2765T>G (p.Leu922Ter)	BRIP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
142595	NM_032043.3(BRIP1):c.2377C>T (p.Gln793Ter)	BRIP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1713216	NM_032043.3(BRIP1):c.1223_1224insT (p.Ser409fs)	BRIP1	Pathogenic	no assertion criteria provided
1713217	NM_032043.3(BRIP1):c.2109_2110insCC (p.Leu704fs)	BRIP1	Pathogenic	no assertion criteria provided
1713218	NM_032043.3(BRIP1):c.2839_2840del (p.Gln947fs)	BRIP1	Pathogenic	criteria provided, single submitter
1713220	NM_032043.3(BRIP1):c.3527dup (p.Glu1178fs)	BRIP1	Pathogenic	no assertion criteria provided
182372	NM_032043.3(BRIP1):c.2255_2256del (p.Lys752fs)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
185848	NM_032043.3(BRIP1):c.751C>T (p.Arg251Cys)	BRIP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
185987	NM_032043.3(BRIP1):c.890del (p.Lys297fs)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
187379	NM_032043.3(BRIP1):c.290_293del (p.Asn97fs)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
219850	NM_032043.3(BRIP1):c.508-1G>C	BRIP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
220629	NM_032043.3(BRIP1):c.2114_2118del (p.Lys705fs)	BRIP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
221621	NM_032043.3(BRIP1):c.1702_1703del (p.Asn568fs)	BRIP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
230237	NM_032043.3(BRIP1):c.1510dup (p.Ile504fs)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
232067	NM_032043.3(BRIP1):c.2053C>T (p.Gln685Ter)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
232527	NM_032043.3(BRIP1):c.633del (p.Gly212fs)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
12237	NM_004360.5(CDH1):c.2095C>T (p.Gln699Ter)	CDH1	Pathogenic	reviewed by expert panel
127915	NM_004360.5(CDH1):c.1565+1G>A	CDH1	Pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 87 · Orphanet: 240 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
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
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
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
FANCC			CIViC #1811
MLH1			CIViC #3532
MSH2			CIViC #3628
MSH6			CIViC #2478
PMS2	ambiguous	HCC	CIViC #4371
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
BRAF	Act	BLCA,BRCA,CHOL,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,GBM,GIST,HGGNOS,LGGNOS,LUAD,MEL,MLYM,NSCLC,OVT,PAST,PCM,PRAD,PRCC,PROSTATE,READ,SACA,SKCM,STAD,UCEC,WDTC	CIViC #5
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
SYK			CIViC #5572
TOP1	Act	BCC,HCC	CIViC #5845
CCND1	Act	HNSC,PCM,UCEC	CIViC #8
CCNE1			CIViC #11
CD44			CIViC #855
RRAS2	Act	UCEC	CIViC #9054
VPS37A			CIViC #18353
DNMT1			CIViC #1510
FGF19			CIViC #7909
FNTB			CIViC #1950
ABCB1			CIViC #4244
GADD45A			CIViC #1411
IGF2			CIViC #60
KRAS	Act	ALL,AML,ANSC,BLADDER,BLCA,BRCA,CEAD,CESC,CHOL,CLLSLL,COAD,COADREAD,DLBCLNOS,EGC,ESCA,ESCC,HCC,LUAD,LUSC,MEL,MGCT,MT,NSCLC,OVT,PAAD,PANCREAS,PAST,PCM,PRAD,PRCC,READ,STAD,STOMACH,UCEC,UCS,WDTC	CIViC #30
LRP1B	Act	AML,BCC,BRCA,CCRCC,CHOL,CLLSLL,COAD,COADREAD,CSCC,ESCA,GB,GBM,GIST,HCC,HNSC,LUAD,LUSC,MBL,MEL,MGCT,MT,NBL,NETNOS,NPC,NSCLC,OS,OVT,PAAD,PANCREAS,PCM,PLMESO,PRAD,READ,RMS,SCLC,SKIN,STAD,UCS,UM,WDTC	CIViC #12146
MDM2	Act	LMS	CIViC #3465
ABCG2			CIViC #7451
ASNS			CIViC #446

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
MLH1	Strong	Autosomal dominant	ovarian cancer	19
MSH2	Strong	Autosomal dominant	ovarian cancer	17
MSH6	Strong	Autosomal dominant	ovarian cancer	17
PMS2	Moderate	Autosomal dominant	ovarian cancer	15
FANCC	Limited	Autosomal dominant	ovarian cancer	11
RRAS2	No Known Disease Relationship	Unknown	ovarian cancer	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BRCA1	Orphanet:1331	Familial prostate cancer
BRCA1	Orphanet:1333	Familial pancreatic carcinoma
BRCA1	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA1	Orphanet:168829	Primary peritoneal carcinoma
BRCA1	Orphanet:227535	Hereditary breast cancer
BRCA1	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA1	Orphanet:694963	Inflammatory breast cancer
BRCA1	Orphanet:70567	Cholangiocarcinoma
BRCA1	Orphanet:84	Fanconi anemia
BRCA2	Orphanet:1331	Familial prostate cancer
BRCA2	Orphanet:1333	Familial pancreatic carcinoma
BRCA2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA2	Orphanet:178	Chordoma
BRCA2	Orphanet:227535	Hereditary breast cancer
BRCA2	Orphanet:319462	Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations
BRCA2	Orphanet:440437	Familial colorectal cancer Type X
BRCA2	Orphanet:654	Nephroblastoma
BRCA2	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA2	Orphanet:694963	Inflammatory breast cancer
BRCA2	Orphanet:70567	Cholangiocarcinoma
BRCA2	Orphanet:84	Fanconi anemia
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
CDKN2A	Orphanet:1333	Familial pancreatic carcinoma
CDKN2A	Orphanet:1501	Adrenocortical carcinoma
CDKN2A	Orphanet:252206	Melanoma and neural system tumor syndrome
CDKN2A	Orphanet:404560	Familial atypical multiple mole melanoma syndrome
CDKN2A	Orphanet:524	Li-Fraumeni syndrome
CDKN2A	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
CDKN2A	Orphanet:618	Familial melanoma
CDKN2A	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
FANCC	Orphanet:84	Fanconi anemia

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	21
multi_evidence	54

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar,civic_evidence
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar,civic_evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar,civic_evidence
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	clinvar,civic_evidence
FANCC	HGNC:3584	ENSG00000158169	Q00597	Fanconi anemia group C protein	gencc,clinvar
MLH1	HGNC:7127	ENSG00000076242	P40692	DNA mismatch repair protein Mlh1	gencc,clinvar
MSH2	HGNC:7325	ENSG00000095002	P43246	DNA mismatch repair protein Msh2	gencc,clinvar
MSH6	HGNC:7329	ENSG00000116062	P52701	DNA mismatch repair protein Msh6	gencc,clinvar
PMS2	HGNC:9122	ENSG00000122512	P54278	Mismatch repair endonuclease PMS2	gencc,clinvar
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	clinvar,civic_evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	civic_evidence
ARID1A	HGNC:11110	ENSG00000117713	O14497	AT-rich interactive domain-containing protein 1A	civic_evidence
SYK	HGNC:11491	ENSG00000165025	P43405	Tyrosine-protein kinase SYK	civic_evidence
TOP1	HGNC:11986	ENSG00000198900	P11387	DNA topoisomerase 1	civic_evidence
CCND1	HGNC:1582	ENSG00000110092	P24385	G1/S-specific cyclin-D1	civic_evidence
CCNE1	HGNC:1589	ENSG00000105173	P24864	G1/S-specific cyclin-E1	civic_evidence
CD44	HGNC:1681	ENSG00000026508	P16070	CD44 antigen	civic_evidence
RRAS2	HGNC:17271	ENSG00000133818	P62070	Ras-related protein R-Ras2	gencc
VPS37A	HGNC:24928	ENSG00000155975	Q8NEZ2	Vacuolar protein sorting-associated protein 37A	civic_evidence
DNMT1	HGNC:2976	ENSG00000130816	P26358	DNA (cytosine-5)-methyltransferase 1	civic_evidence
FGF19	HGNC:3675	ENSG00000162344	O95750	Fibroblast growth factor 19	civic_evidence
FNTB	HGNC:3785	ENSG00000257365	P49356	Protein farnesyltransferase subunit beta	civic_evidence
ABCB1	HGNC:40	ENSG00000085563	P08183	ATP-dependent translocase ABCB1	civic_evidence
GADD45A	HGNC:4095	ENSG00000116717	P24522	Growth arrest and DNA damage-inducible protein GADD45 alpha	civic_evidence
IGF2	HGNC:5466	ENSG00000167244	P01344	Insulin-like growth factor 2	civic_evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	civic_evidence
LRP1B	HGNC:6693	ENSG00000168702	Q9NZR2	Low-density lipoprotein receptor-related protein 1B	civic_evidence
MDM2	HGNC:6973	ENSG00000135679	Q00987	E3 ubiquitin-protein ligase Mdm2	civic_evidence
ABCG2	HGNC:74	ENSG00000118777	Q9UNQ0	Broad substrate specificity ATP-binding cassette transporter ABCG2	civic_evidence
ASNS	HGNC:753	ENSG00000070669	P08243	Asparagine synthetase [glutamine-hydrolyzing]	civic_evidence
ASS1	HGNC:758	ENSG00000130707	P00966	Argininosuccinate synthase	civic_evidence
NRG1	HGNC:7997	ENSG00000157168	Q02297	Pro-neuregulin-1, membrane-bound isoform	civic_evidence
RNASEL	HGNC:10050	ENSG00000135828	Q05823	2-5A-dependent ribonuclease	clinvar
TSPAN31	HGNC:10539	ENSG00000135452	Q12999	Tetraspanin-31	clinvar
BLM	HGNC:1058	ENSG00000197299	P54132	RecQ-like DNA helicase BLM	clinvar
SDHB	HGNC:10681	ENSG00000117118	P21912	Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial	clinvar
SDHC	HGNC:10682	ENSG00000143252	Q99643	Succinate dehydrogenase cytochrome b560 subunit, mitochondrial	clinvar
BMPR1A	HGNC:1076	ENSG00000107779	P36894	Bone morphogenetic protein receptor type-1A	clinvar
SMARCB1	HGNC:11103	ENSG00000099956	Q12824	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1	clinvar
STK11	HGNC:11389	ENSG00000118046	Q15831	Serine/threonine-protein kinase STK11	clinvar
BUB1B	HGNC:1149	ENSG00000156970	O60566	Mitotic checkpoint serine/threonine-protein kinase BUB1 beta	clinvar
EPCAM	HGNC:11529	ENSG00000119888	P16422	Epithelial cell adhesion molecule	clinvar
HNF1A	HGNC:11621	ENSG00000135100	P20823	Hepatocyte nuclear factor 1-alpha	clinvar
HNF1B	HGNC:11630	ENSG00000275410	P35680	Hepatocyte nuclear factor 1-beta	clinvar
TRIM24	HGNC:11812	ENSG00000122779	O15164	Transcription intermediary factor 1-alpha	clinvar
TSC1	HGNC:12362	ENSG00000165699	Q92574	Hamartin	clinvar
TSC2	HGNC:12363	ENSG00000103197	P49815	Tuberin	clinvar
TSHR	HGNC:12373	ENSG00000165409	P16473	Thyrotropin receptor	clinvar
VHL	HGNC:12687	ENSG00000134086	P40337	von Hippel-Lindau disease tumor suppressor	clinvar
WRN	HGNC:12791	ENSG00000165392	Q14191	Bifunctional 3’-5’ exonuclease/ATP-dependent helicase WRN	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
FANCC	Fanconi anemia group C protein	DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function.
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).
PMS2	Mismatch repair endonuclease PMS2	Component of the post-replicative DNA mismatch repair system (MMR).
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.
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
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).
SYK	Tyrosine-protein kinase SYK	Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR).
TOP1	DNA topoisomerase 1	Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex.
CCND1	G1/S-specific cyclin-D1	Regulatory component of the cyclin D1-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.
RRAS2	Ras-related protein R-Ras2	GTP-binding protein with GTPase activity, involved in the regulation of MAPK signaling pathway and thereby controlling multiple cellular processes.
VPS37A	Vacuolar protein sorting-associated protein 37A	Component of the ESCRT-I complex, a regulator of vesicular trafficking process.
DNMT1	DNA (cytosine-5)-methyltransferase 1	DNA methyltransferase that methylates CpG residues.
FGF19	Fibroblast growth factor 19	Involved in the suppression of bile acid biosynthesis through down-regulation of CYP7A1 expression, following positive regulation of the JNK and ERK1/2 cascades.
FNTB	Protein farnesyltransferase subunit beta	Essential subunit of the farnesyltransferase complex.
ABCB1	ATP-dependent translocase ABCB1	Translocates drugs and phospholipids across the membrane.
GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	In T-cells, functions as a regulator of p38 MAPKs by inhibiting p88 phosphorylation and activity.
IGF2	Insulin-like growth factor 2	The insulin-like growth factors possess growth-promoting activity.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
LRP1B	Low-density lipoprotein receptor-related protein 1B	Potential cell surface proteins that bind and internalize ligands in the process of receptor-mediated endocytosis.
MDM2	E3 ubiquitin-protein ligase Mdm2	E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome.
ABCG2	Broad substrate specificity ATP-binding cassette transporter ABCG2	Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells.
ASS1	Argininosuccinate synthase	One of the enzymes of the urea cycle, the metabolic pathway transforming neurotoxic amonia produced by protein catabolism into inocuous urea in the liver of ureotelic animals.
NRG1	Pro-neuregulin-1, membrane-bound isoform	Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors.
RNASEL	2-5A-dependent ribonuclease	Endoribonuclease that functions in the interferon (IFN) antiviral response.
BLM	RecQ-like DNA helicase BLM	ATP-dependent DNA helicase that unwinds double-stranded (ds)DNA in a 3’-5’ direction.
SDHB	Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial	Iron-sulfur protein (IP) subunit of the succinate dehydrogenase complex (mitochondrial respiratory chain complex II), responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
SDHC	Succinate dehydrogenase cytochrome b560 subunit, mitochondrial	Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
BMPR1A	Bone morphogenetic protein receptor type-1A	On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases.
SMARCB1	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1	Core component of the BAF (hSWI/SNF) complex.
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…
BUB1B	Mitotic checkpoint serine/threonine-protein kinase BUB1 beta	Essential component of the mitotic checkpoint.
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…
HNF1A	Hepatocyte nuclear factor 1-alpha	Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver.
HNF1B	Hepatocyte nuclear factor 1-beta	Transcription factor that binds to the inverted palindrome 5’-GTTAATNATTAAC-3’.
TRIM24	Transcription intermediary factor 1-alpha	Transcriptional coactivator that interacts with numerous nuclear receptors and coactivators and modulates the transcription of target genes.
TSC1	Hamartin	Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolec…
TSC2	Tuberin	Catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule…
TSHR	Thyrotropin receptor	Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin.
VHL	von Hippel-Lindau disease tumor suppressor	Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex.
WRN	Bifunctional 3’-5’ exonuclease/ATP-dependent helicase WRN	Multifunctional enzyme that has magnesium and ATP-dependent 3’-5’ DNA-helicase activity on partially duplex substrates.
WT1	Wilms tumor protein	Transcription factor that plays an important role in cellular development and cell survival.
XPA	DNA repair protein complementing XP-A cells	Involved in DNA nucleotide excision repair (NER).

Protein-family classification

Druggable: 28 · Difficult: 15 · Unknown: 32 · Druggable fraction: 0.37

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
Enzyme (other)	14	2.2×	0.033
Transporter	3	3.1×	0.241
Kinase	6	2.2×	0.241
Transcription factor	11	1.2×	0.741
Phosphatase	1	1.1×	0.910
Protease	2	1.0×	0.910
Scaffold/PPI	4	0.9×	0.910
Other/Unknown	32	0.8×	0.992
Antibody/Immunoglobulin	1	0.4×	0.992
GPCR	1	0.3×	0.992

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
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
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
FANCC	Other/Unknown	no		FANCC
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
PMS2	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
ARID1A	Other/Unknown	no		ARID_dom, ARM-like, ARM-type_fold
SYK	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
TOP1	Enzyme (other)	yes	5.6.2.1	TopoI, TopoI_DNA-bd_euk, DNA_brk_join_enz
CCND1	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
RRAS2	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
VPS37A	Other/Unknown	no		Mod_r, UBQ-conjugating_enzyme/RWD, Helix_hairpin_bin_sf
DNMT1	Transcription factor	no	2.1.1.37	BAH_dom, C5_MeTfrase, Znf_CXXC
FGF19	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF, FGF15/19/21
FNTB	Enzyme (other)	yes	2.5.1.58	Prenyltrans, Terpenoid_cyclase/PrenylTrfase, FTB
ABCB1	Transporter	yes	7.6.2.2	ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom
GADD45A	Other/Unknown	no		Ribosomal_eL8/eL30/eS12/Gad45, GADD45, Ribosomal_eL30-like_sf
IGF2	Other/Unknown	no		IGF2_C, Insulin-like, IGF2
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
LRP1B	Other/Unknown	no		LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, EGF
MDM2	Transcription factor	no	2.3.2.27	Znf_RING, Znf_RanBP2, SWIB_MDM2_domain
ABCG2	Transporter	yes	7.6.2.2	ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM
ASNS	Enzyme (other)	yes	6.3.5.4	Asn_synthase, Asn_synth_AEB, Rossmann-like_a/b/a_fold
ASS1	Enzyme (other)	yes	6.3.4.5	Arginosuc_synth, Rossmann-like_a/b/a_fold, Arginosuc_synth_CS
NRG1	Antibody/Immunoglobulin	yes		EGF, Neuregulin_C, Ig_sub2
RNASEL	Kinase	yes	4.6.1.19	Prot_kinase_dom, Ankyrin_rpt, KEN_dom
TSPAN31	Other/Unknown	no		Tetraspanin_animals, Tetraspanin/Peripherin
BLM	Enzyme (other)	yes	3.6.4.12	Helicase_C-like, HRDC_dom, DNA/RNA_helicase_DEAH_CS
SDHB	Enzyme (other)	yes	1.3.5.1	2Fe-2S_ferredoxin-type, Succ_DH/fum_Rdtase_Fe-S, 2Fe2S_fd_BS
SDHC	Enzyme (other)	yes	1.3.5.1	SuccDH_FuR_B_TM-su, Succ_DH_cytb556, Succ_DH_cyt_bsu_CS
BMPR1A	Kinase	yes	2.7.10.2	TGFB_receptor, Activin_recp, Prot_kinase_dom
SMARCB1	Other/Unknown	no		SNF5, Sfh1/SNF5, INI1_DNA-bd
STK11	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
BUB1B	Kinase	yes	2.7.11.1	Kinase-like_dom_sf, Mad3/Bub1_I, Bub1/Mad3
EPCAM	Enzyme (other)	yes	2.4.1.37	Thyroglobulin_1, Thyroglobulin_1_sf, EpCAM_N
HNF1A	Transcription factor	no		HD, HNF1b_C, HNF1a_C
HNF1B	Transcription factor	no		HD, HNF1b_C, HNF-1_N
TRIM24	Transcription factor	no		Znf_B-box, Bromodomain, Znf_RING
TSC1	Other/Unknown	no		Hamartin
TSC2	Other/Unknown	no		Rap/Ran_GAP_dom, Tuberin, ARM-like
TSHR	GPCR	yes		GPCR_Rhodpsn, Gphrmn_rcpt_fam, TSH_rcpt
VHL	Enzyme (other)	yes	2.3.2.B13	VHL_tumour_suppress_b/a_dom, VHL_alpha_dom, VHL_beta_dom
WRN	Enzyme (other)	yes	3.6.4.12	Helicase_C-like, HRDC_dom, 3’-5’_exonuclease_dom

Expression context

Cohort genes with no expression data: 0.

72 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)	75
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	13
secondary oocyte	13
oocyte	11
calcaneal tendon	9
adrenal tissue	7
male germ line stem cell (sensu Vertebrata) in testis	5
sural nerve	5
primordial germ cell in gonad	4
ganglionic eminence	4
sperm	4
islet of Langerhans	4
parotid gland	3
right lobe of liver	3
skeletal muscle tissue of rectus abdominis	3
embryo	3
endothelial cell	3
buccal mucosa cell	3
monocyte	3
cortical plate	3
jejunal mucosa	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
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
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
CDKN2A	220	ubiquitous	marker	parotid gland, cervix squamous epithelium, pituitary gland
FANCC	195	ubiquitous	marker	pancreatic ductal cell, right lobe of liver, male germ line stem cell (sensu Vertebrata) in testis
MLH1	296	ubiquitous	marker	tibialis anterior, skeletal muscle tissue of rectus abdominis, deltoid
MSH2	278	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
MSH6	293	ubiquitous	marker	ventricular zone, embryo, ganglionic eminence
PMS2	143	ubiquitous	marker	thymus, prefrontal cortex, male germ line stem cell (sensu Vertebrata) in testis
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
ARID1A	286	ubiquitous	marker	bone marrow cell, ventricular zone, embryo
SYK	239	broad	marker	monocyte, mononuclear cell, leukocyte
TOP1	278	ubiquitous	marker	oocyte, ventricular zone, secondary oocyte
CCND1	280	ubiquitous	marker	endometrium epithelium, stromal cell of endometrium, upper arm skin
CCNE1	201	ubiquitous	marker	secondary oocyte, oocyte, adrenal tissue
CD44	294	ubiquitous	marker	parotid gland, stromal cell of endometrium, mammalian vulva
RRAS2	287	ubiquitous	marker	secondary oocyte, oocyte, skeletal muscle tissue of rectus abdominis
VPS37A	255	ubiquitous	marker	islet of Langerhans, gastrocnemius, adrenal tissue
DNMT1	266	ubiquitous	marker	oocyte, secondary oocyte, sural nerve
FGF19	28	tissue_specific	marker	gall bladder, epithelial cell of pancreas, primordial germ cell in gonad
FNTB	139	ubiquitous	marker	C1 segment of cervical spinal cord, corpus callosum, substantia nigra
ABCB1	232	broad	marker	right adrenal gland, right adrenal gland cortex, left adrenal gland cortex
GADD45A	294	ubiquitous	marker	descending thoracic aorta, vena cava, ascending aorta
IGF2	135	ubiquitous	marker	adrenal tissue, placenta, sural nerve
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
LRP1B	194	broad	marker	endothelial cell, Brodmann (1909) area 23, cortical plate
MDM2	274	ubiquitous	marker	calcaneal tendon, adrenal tissue, ventricular zone
ABCG2	245	broad	marker	jejunal mucosa, ileal mucosa, endothelial cell
ASNS	143	ubiquitous	marker	cerebellar hemisphere, cerebellar cortex, cerebellum

Protein interactions among cohort

Intra-cohort edges: 130.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
CTNNB1	15,668
KRAS	14,509
PTEN	11,626
MDM2	9,892
CDKN2A	9,311
BRCA1	9,064
CDH1	8,738
CCND1	8,328
DICER1	8,268

Intra-cohort edges

A	B	Sources
AOPEP	BMPR1A	intact
AOPEP	CDH1	intact
AOPEP	CDKN2A	intact
ARID1A	LRP1B	string_interaction
ARID1A	MSH2	string_interaction
ARID1A	SMARCB1	biogrid_interaction, intact, string_interaction
ASNS	ASS1	biogrid_interaction
BLM	BRIP1	intact
BLM	FANCC	string_interaction
BLM	MLH1	string_interaction
BLM	MSH6	string_interaction
BRAF	BRCA2	biogrid_interaction
BRAF	CDKN2A	string_interaction
BRAF	FGF19	intact
BRAF	KRAS	biogrid_interaction, intact, string_interaction
BRAF	MLH1	string_interaction
BRAF	PMS2	string_interaction
BRAF	PTEN	biogrid_interaction, string_interaction
BRAF	SDHC	intact
BRAF	TP53	string_interaction
BRAF	VHL	biogrid_interaction
BRCA1	BRCA2	string_interaction
BRCA1	BRIP1	biogrid_interaction, intact, string_interaction
BRCA1	GADD45A	string_interaction
BRCA1	MLH1	string_interaction
BRCA1	MSH2	string_interaction
BRCA1	MSH6	string_interaction
BRCA1	PALB2	biogrid_interaction, intact, string_interaction
BRCA1	PMS2	string_interaction
BRCA1	TP53	string_interaction
BRCA1	WRN	string_interaction
BRCA1	XRCC3	string_interaction
BRCA2	BRIP1	string_interaction
BRCA2	CCND1	intact
BRCA2	FANCC	string_interaction
BRCA2	MLH1	string_interaction
BRCA2	MSH2	string_interaction
BRCA2	MSH6	string_interaction
BRCA2	PALB2	biogrid_interaction, intact, string_interaction
BRCA2	PMS2	string_interaction
BRCA2	STK11	string_interaction
BRCA2	TP53	string_interaction
BRCA2	XRCC3	biogrid_interaction, string_interaction
BRIP1	FANCC	string_interaction
BRIP1	MLH1	intact, string_interaction
BRIP1	PALB2	string_interaction
BRIP1	PMS2	biogrid_interaction, intact
CCND1	CDKN1B	biogrid_interaction, intact, string_interaction
CCND1	CDKN2A	biogrid_interaction, string_interaction
CCND1	CTNNB1	string_interaction

Structural data

PDB: 67 · AlphaFold-only: 8 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
TP53	P04637	313
MDM2	Q00987	147
VHL	P40337	142
BRAF	P15056	131
SYK	P43405	93
WRN	Q14191	51
CTNNB1	P35222	50
BRCA1	P38398	33
MSH2	P43246	30
ABCG2	Q9UNQ0	29
WT1	P19544	28
DNMT1	P26358	27
ABCB1	P08183	24
CCNE1	P24864	22
TRIM24	O15164	22
CDH1	P12830	22
DICER1	Q9UPY3	21
CDC73	Q6P1J9	20
CDKN1B	P46527	19
XPA	P23025	18
XPC	Q01831	18
SMARCB1	Q12824	17
IGF2	P01344	16
TOP1	P11387	15
BLM	P54132	15
BRCA2	P51587	14
FNTB	P49356	14
XRCC3	O43542	13
PTEN	P60484	12

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TSPAN31	Q12999	89.29
SLC49A4	Q96SL1	84.53
AOPEP	Q8N6M6	83.36
TMEM127	O75204	77.38
C11orf65	Q8NCR3	74.69
C12orf43	Q96C57	64.08
ZNF276	Q8N554	56.21
LRP1B	Q9NZR2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 859. Enrichment computed across 131 evidence-associated genes (116 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 116 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	14	47.5×	3e-18	BRCA1, BRCA2, BLM, WRN, XRCC3, BRIP1, PALB2, MRE11 (+6 more)
Homologous DNA Pairing and Strand Exchange	14	45.9×	3e-18	BRCA1, BRCA2, BLM, WRN, XRCC3, BRIP1, PALB2, MRE11 (+6 more)
Impaired BRCA2 binding to PALB2	13	51.2×	8e-18	BRCA1, BRCA2, BLM, WRN, BRIP1, PALB2, MRE11, NBN (+5 more)
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	13	47.4×	2e-17	BRCA1, BRCA2, BLM, WRN, BRIP1, PALB2, MRE11, NBN (+5 more)
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	13	47.4×	2e-17	BRCA1, BRCA2, BLM, WRN, BRIP1, PALB2, MRE11, NBN (+5 more)
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	13	47.4×	2e-17	BRCA1, BRCA2, BLM, WRN, BRIP1, PALB2, MRE11, NBN (+5 more)
Resolution of D-loop Structures through Holliday Junction Intermediates	14	36.3×	5e-17	BRCA1, BRCA2, BLM, WRN, XRCC3, BRIP1, PALB2, MRE11 (+6 more)
HDR through Homologous Recombination (HRR)	14	23.0×	7e-14	BRCA1, BRCA2, BLM, WRN, XRCC3, BRIP1, PALB2, MRE11 (+6 more)
Diseases of DNA repair	10	49.2×	1e-13	BRCA1, BRCA2, MLH1, MSH2, MSH6, BLM, MRE11, NBN (+2 more)
Presynaptic phase of homologous DNA pairing and strand exchange	12	28.1×	5e-13	BRCA1, BRCA2, BLM, WRN, BRIP1, MRE11, NBN, ATM (+4 more)
Impaired BRCA2 binding to RAD51	11	29.3×	4e-12	BRCA1, BRCA2, BLM, WRN, BRIP1, MRE11, NBN, ATM (+3 more)
HDR through Single Strand Annealing (SSA)	11	27.8×	7e-12	BRCA1, BLM, WRN, BRIP1, ERCC4, MRE11, NBN, ATM (+3 more)
Defective homologous recombination repair (HRR) due to PALB2 loss of function	7	57.4×	5e-10	BRCA1, BRCA2, BLM, MRE11, NBN, ATM, BARD1
Diseases of DNA Double-Strand Break Repair	7	49.2×	2e-09	BRCA1, BRCA2, BLM, MRE11, NBN, ATM, BARD1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	7	49.2×	2e-09	BRCA1, BRCA2, BLM, MRE11, NBN, ATM, BARD1
TP53 Regulates Transcription of DNA Repair Genes	11	17.2×	2e-09	BRCA1, TP53, FANCC, MLH1, MSH2, PMS2, DDB2, ERCC2 (+3 more)
Regulation of TP53 Activity through Phosphorylation	12	12.2×	1e-08	BRCA1, TP53, BLM, STK11, WRN, BRIP1, MDM2, MRE11 (+4 more)
Resolution of D-Loop Structures	7	38.3×	1e-08	BRCA1, BRCA2, BLM, MRE11, NBN, ATM, BARD1
Meiotic recombination	11	12.3×	6e-08	BRCA1, BRCA2, MLH1, BLM, MLH3, MRE11, NBN, ATM (+3 more)
Transcriptional Regulation by TP53	14	7.5×	2e-07	BRCA1, CDKN2A, MLH1, MSH2, BLM, STK11, CCNE1, CDKN1B (+6 more)
Meiosis	8	19.7×	2e-07	BRCA1, BRCA2, MLH1, BLM, MLH3, MRE11, NBN, ATM
RAF/MAP kinase cascade	14	7.4×	2e-07	BRAF, EGFR, ERBB2, FGF19, HRAS, KIT, KRAS, AREG (+6 more)
RNA Polymerase II Transcription	22	4.3×	2e-07	BRCA1, CDKN2A, MLH1, MSH2, BLM, SMARCB1, ARID1A, STK11 (+14 more)
Regulation of TP53 Activity	10	11.4×	5e-07	BRCA1, CDKN2A, BLM, STK11, AKT1, MDM2, MRE11, NBN (+2 more)
Disease	28	3.2×	1e-06	BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, BLM, BRAF (+20 more)
G2/M DNA damage checkpoint	10	10.4×	1e-06	BRCA1, TP53, BLM, WRN, BRIP1, MRE11, NBN, ATM (+2 more)
Developmental Lineage of Mammary Gland Myoepithelial Cells	6	28.1×	1e-06	EPCAM, CD44, CDH1, EGFR, ERBB2, AREG
Homology Directed Repair	7	18.6×	2e-06	BRCA1, BRCA2, BLM, MRE11, NBN, ATM, BARD1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	7	18.6×	2e-06	BRCA1, BRCA2, BLM, MRE11, NBN, ATM, BARD1
Cell Cycle Checkpoints	11	8.4×	2e-06	BRCA1, CDKN2A, BLM, BUB1B, CCNE1, CDKN1B, MDM2, MRE11 (+3 more)

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 128 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
DNA repair	24	12.0×	4e-16	BRCA1, FANCC, MSH2, MSH6, BLM, XPA, XPC, XRCC3 (+16 more)
double-strand break repair via homologous recombination	14	17.1×	7e-11	BRCA1, BRCA2, BLM, WRN, XRCC3, PALB2, ERCC4, MRE11 (+6 more)
mismatch repair	9	45.6×	1e-10	MLH1, MSH2, MSH6, PMS2, WRN, XPC, MLH3, MUTYH (+1 more)
nucleotide-excision repair	10	29.9×	4e-10	BRCA2, TP53, FANCC, XPA, XPC, BRIP1, DDB2, ERCC2 (+2 more)
negative regulation of cell population proliferation	20	6.6×	9e-09	TP53, CDKN2A, PTEN, SMARCB1, STK11, TSC1, TSC2, VHL (+12 more)
DNA damage response	18	7.5×	9e-09	BRCA1, TP53, BLM, STK11, WRN, XRCC3, CCND1, DDB2 (+10 more)
homologous recombination	6	65.8×	4e-08	BRCA1, BRIP1, MRE11, NBN, BARD1, RAD50
regulation of cell cycle	15	8.7×	4e-08	BRCA1, TP53, CDKN2A, STK11, TSC1, TSC2, CDKN1B, GADD45A (+7 more)
epithelial cell proliferation	9	21.9×	5e-08	BMPR1A, HNF1B, TRIM24, FLCN, EGFR, GPC3, KIT, AR (+1 more)
interstrand cross-link repair	8	27.0×	8e-08	FANCC, XRCC3, FANCA, FANCD2, FANCE, FANCF, FANCG, RAD51
double-strand break repair	10	15.9×	1e-07	BRCA1, BRCA2, TP53, MSH2, WRN, BRIP1, MRE11, NBN (+2 more)
telomere maintenance	9	18.8×	2e-07	BLM, WRN, CCNE1, ERCC4, MRE11, NBN, ATM, RAD50 (+1 more)
DNA strand resection involved in replication fork processing	5	82.3×	2e-07	BRCA1, MRE11, NBN, BARD1, RAD50
response to X-ray	6	41.6×	6e-07	BRCA2, TP53, MSH2, BLM, CCND1, RAD51
response to xenobiotic stimulus	14	7.5×	6e-07	PMS2, TOP1, XPC, CCND1, CDH1, CTNNB1, ABCB1, MDM2 (+6 more)
positive regulation of gene expression	18	5.5×	6e-07	BRCA1, TP53, BMPR1A, BRAF, HNF1B, TRIM24, WT1, CTNNB1 (+10 more)
telomere maintenance via recombination	5	59.8×	1e-06	BRCA2, XRCC3, RAD50, RAD51, RAD51C
DNA double-strand break processing	5	59.8×	1e-06	BLM, MRE11, NBN, ATM, RAD50
cellular response to ionizing radiation	7	22.5×	2e-06	BRCA1, BRCA2, TP53, BLM, GADD45A, BARD1, RAD51
cellular response to gamma radiation	6	28.2×	5e-06	TP53, WRN, HRAS, MDM2, ATM, RAD51
DNA damage response, signal transduction by p53 class mediator	7	19.6×	5e-06	BRCA2, TP53, CDKN1B, MDM2, NBN, ATM, PPM1D
reciprocal meiotic recombination	6	26.3×	7e-06	MLH3, MRE11, ATM, RAD50, RAD51, RAD51C
MAPK cascade	9	10.8×	1e-05	BMPR1A, BRAF, CTNNB1, HRAS, KRAS, AR, MEN1, NF1 (+1 more)
embryonic organ development	6	22.6×	2e-05	TP53, BMPR1A, PALB2, ERCC2, ERCC3, PTCH1
cellular senescence	7	16.2×	2e-05	BRCA2, TP53, CDKN2A, WRN, CDKN1B, HRAS, ATM
positive regulation of cell population proliferation	17	4.5×	2e-05	PTEN, TSPAN31, EPCAM, TSHR, CDKN1B, CTNNB1, EGFR, FGF19 (+9 more)
negative regulation of epithelial cell proliferation	7	15.9×	2e-05	TRIM24, CDC73, CDKN1B, FLCN, GPC3, AR, RB1
mitotic G2/M transition checkpoint	5	31.4×	3e-05	BRCA1, MRE11, NBN, BARD1, RAD50
determination of adult lifespan	6	20.2×	3e-05	TP53, MSH2, MSH6, WRN, ERCC2, ATM
negative regulation of transcription by RNA polymerase II	23	3.2×	4e-05	TP53, CDKN2A, HNF1B, VHL, WT1, CCND1, CCNE1, TRIM33 (+15 more)

Therapeutics

Drugs indicated for this disease

6 approved, 49 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Amifostine	Approved (phase 4)
Bevacizumab	Approved (phase 4)
Carboplatin	Approved (phase 4)
Olaparib	Approved (phase 4)
Paclitaxel	Approved (phase 4)
Trabectedin	Approved (phase 4)
Alvimopan	Phase 3 (in late-stage trials)
Anastrozole	Phase 3 (in late-stage trials)
Atezolizumab	Phase 3 (in late-stage trials)
Avelumab	Phase 3 (in late-stage trials)
Avutometinib	Phase 3 (in late-stage trials)
Batiraxcept	Phase 3 (in late-stage trials)
Benmelstobart	Phase 3 (in late-stage trials)
Binimetinib	Phase 3 (in late-stage trials)
Bleomycin	Phase 3 (in late-stage trials)
Catequentinib	Phase 3 (in late-stage trials)
Cediranib	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Defactinib	Phase 3 (in late-stage trials)
Dexamethasone	Phase 3 (in late-stage trials)
Dostarlimab	Phase 3 (in late-stage trials)
Doxorubicin	Phase 3 (in late-stage trials)
Durvalumab	Phase 3 (in late-stage trials)
Epoetin Alfa	Phase 3 (in late-stage trials)
Etoposide	Phase 3 (in late-stage trials)
Exemestane	Phase 3 (in late-stage trials)
Farletuzumab	Phase 3 (in late-stage trials)
Filgrastim	Phase 3 (in late-stage trials)
Fluzoparib	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Hydralazine	Phase 3 (in late-stage trials)
Ifosfamide	Phase 3 (in late-stage trials)
Isophenoxodiol	Phase 3 (in late-stage trials)
Karenitecin	Phase 3 (in late-stage trials)
Letrozole	Phase 3 (in late-stage trials)
Lurbinectedin	Phase 3 (in late-stage trials)
Melphalan	Phase 3 (in late-stage trials)
Niraparib	Phase 3 (in late-stage trials)
Ofranergene Obadenovec	Phase 3 (in late-stage trials)
Oregovomab	Phase 3 (in late-stage trials)
Pafolacianine	Phase 3 (in late-stage trials)
Patupilone	Phase 3 (in late-stage trials)
Pazopanib	Phase 3 (in late-stage trials)
Pertuzumab	Phase 3 (in late-stage trials)
Rivoceranib	Phase 3 (in late-stage trials)
Ropivacaine	Phase 3 (in late-stage trials)
Rucaparib	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Talazoparib	Phase 3 (in late-stage trials)
Tamoxifen	Phase 3 (in late-stage trials)
Topotecan	Phase 3 (in late-stage trials)
Trebananib	Phase 3 (in late-stage trials)
Treosulfan	Phase 3 (in late-stage trials)
Veliparib	Phase 3 (in late-stage trials)
Vintafolide	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): ANTINEOPLASTON A10, Abagovomab, Acalabrutinib, Adagloxad Simolenin, Afuresertib, Aldesleukin, Alendronic Acid, Allopurinol, Ascorbic Acid, Aspirin, Azacitidine, Bcg Vaccine, Becatecarin, Belotecan, Bendamustine, Bicalutamide, Bortezomib, Cabazitaxel, Cadonilimab, Camrelizumab, Capecitabine, Carboxyamidotriazole, Carmustine, Catumaxomab, Celecoxib, Ceralasertib, Cetuximab, Cholecalciferol, Cirmtuzumab, Cyclosporine, Cytarabine, Dalteparin Sodium, Decitabine, Denileukin Diftitox, Dipyridamole, Enoxaparin Sodium, Envafolimab, Enzalutamide, Enzastaurin, Epacadostat, Epirubicin, Epoetin Beta, Eprenetapopt, Erlotinib, Etirinotecan Pegol, Everolimus, Floxuridine, Fludarabine, Fludarabine Phosphate, Fluorouracil, Flutamide, Fosgemcitabine Palabenamide, Fulvestrant, Ganciclovir, Gefitinib, Glufosfamide, Guadecitabine, INTERFERON GAMMA-1B, Ibcasertib, Incomplete Freund’S Adjuvant, Iniparib, Ipilimumab, Irinotecan, Irofulven, Itraconazole, Ixabepilone, Lapatinib, Lenvatinib, Lonafarnib, Lovastatin, Masitinib, Methotrexate, Methylprednisolone, Mifepristone, Minoxidil, Navitoclax, Nintedanib, Nivolumab, Nogapendekin Alfa, Ombrabulin, Oxaliplatin, Oxiglutatione, Palbociclib, Pamiparib, Panitumumab, Pegfilgrastim, Pembrolizumab, Pemetrexed, Pexastimogene Devacirepvec, Regorafenib, Regramostim, Relacorilant, Ribociclib, Romidepsin, Romiplostim, Rosuvastatin, Rubitecan, Saracatinib, Sargramostim, Selinexor, Sintilimab, Sirolimus, Sorafenib, Sunitinib, Tasisulam, Temozolomide, Temsirolimus, Tetanus Toxoid, Thalidomide, Tigatuzumab, Tirapazamine, Tislelizumab, Tisotumab Vedotin, Tivozanib, Tocotrienol, Toremifene, Trastuzumab, Tremelimumab, Vandetanib, Vinorelbine, Vismodegib, Volociximab, Vorinostat, Zafirlukast, Zibotentan.

Drug target analysis

Approved (phase 4): 21 · Phase ≥3: 21 · Phased (≥1): 24 · Undrugged: 51

Druggability breadth: 89 of 131 evidence-associated genes (68%) 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
BRCA1	RIBOFLAVIN
TP53	NITROFURANTOIN
BRAF	VEMURAFENIB
SYK	FEDRATINIB
TOP1	TOPOTECAN HYDROCHLORIDE
CCND1	PALBOCICLIB
CCNE1	PALBOCICLIB
DNMT1	DECITABINE
FNTB	CORTISONE ACETATE
ABCB1	PROGESTERONE
KRAS	VEMURAFENIB
MDM2	NITROFURANTOIN
ABCG2	CANDESARTAN CILEXETIL
BLM	AMIFOSTINE
BMPR1A	MOMELOTINIB
STK11	FEDRATINIB
BUB1B	CERITINIB
TSHR	LEVOSALBUTAMOL
VHL	OSIMERTINIB
WRN	INDIGOTINDISULFONATE
CTNNB1	DITHIAZANINE IODIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TSHR	354	4
BLM	284	4
TP53	196	4
ABCB1	119	4
ABCG2	92	4
SYK	54	4
BRAF	48	4
CCNE1	38	4
CCND1	35	4
STK11	17	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BLM, BRCA1, TSHR
TOPOTECAN HYDROCHLORIDE	4	BRCA1, TOP1
DAUNORUBICIN	4	ABCB1, BLM, BRCA1, TP53
DOXORUBICIN HYDROCHLORIDE	4	ABCB1, BLM, BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	ABCB1, ABCG2, BLM, BRCA1, TSHR
NITROFURANTOIN	4	MDM2, TP53, TSHR
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	ABCG2, TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	ABCB1, BLM, TP53, TSHR
COLCHICINE	4	TP53, TSHR
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	BLM, TP53
AMIODARONE HYDROCHLORIDE	4	BLM, TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53, TSHR
RALOXIFENE HYDROCHLORIDE	4	BLM, TP53
NICARDIPINE HYDROCHLORIDE	4	BLM, TP53, TSHR
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53, TSHR
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53, TSHR
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 26.

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

Symbol	Assays	Type breakdown
VHL	3,575	Binding:3482, Functional:54, ADMET:39
ABCB1	3,063	Binding:2135, Functional:746, ADMET:182
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
TOP1	1,200	Binding:1161, Functional:38, ADMET:1
MDM2	1,007	Binding:979, Functional:28
ABCG2	878	Binding:651, ADMET:115, Functional:111, Toxicity:1
SYK	873	Binding:863, Functional:10
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
CCNE1	691	Binding:690, ADMET:1
CCND1	576	Binding:574, Functional:1, ADMET:1
FNTB	425	Binding:366, Functional:59
CTNNB1	361	Binding:358, Functional:3
STK11	244	Binding:244
DNMT1	233	Binding:229, Functional:3, ADMET:1
BMPR1A	169	Binding:166, ADMET:3
TRIM24	115	Binding:113, Functional:2
BLM	82	Binding:78, Functional:4
TRIM33	47	Binding:47
RNASEL	43	Binding:42, Functional:1
TSHR	33	Functional:24, Binding:9
WRN	32	Binding:30, Functional:2
ASNS	27	Binding:27
CDH1	18	Binding:18
BRCA1	13	Binding:9, Functional:4
BUB1B	12	Binding:12
MSH6	10	Binding:10
MSH2	9	Binding:9
CD44	9	Binding:9
PTEN	8	Binding:8
CDC73	8	Binding:8
DICER1	8	Binding:8
SMARCB1	7	Binding:7
ARID1A	6	Binding:6
XPA	6	Binding:6
CDKN1B	5	Binding:5
SDHB	4	Binding:4
RRAS2	3	Binding:3
CYLD	3	Binding:3
CDKN2A	2	Binding:2
PMS2	1	Binding:1
ASS1	1	Binding:1
EPCAM	1	Binding:1
HNF1A	1	Binding:1
TSC2	1	Binding:1
AOPEP	1	ADMET:1
KIF1B	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
SYK	2.7.10.2, 2.7.12.1	non-specific protein-tyrosine kinase, dual-specificity kinase
TOP1	5.6.2.1, 5.99.1.2	DNA topoisomerase, DNA topoisomerase
DNMT1	2.1.1.37	DNA (cytosine-5-)-methyltransferase
FNTB	2.5.1.58, 2.5.1.59	protein farnesyltransferase, protein geranylgeranyltransferase type 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
MDM2	2.3.2.27	RING-type E3 ubiquitin transferase
ABCG2	7.6.2.2, 7.6.2.3	ABC-type xenobiotic transporter, ABC-type glutathione-S-conjugate transporter
ASNS	6.3.5.4	asparagine synthase (glutamine-hydrolysing)
ASS1	6.3.4.5	argininosuccinate synthase
RNASEL	4.6.1.19	ribonuclease T2
BLM	3.6.4.12	DNA helicase
SDHB	1.3.5.1	succinate dehydrogenase
SDHC	1.3.5.1	succinate dehydrogenase
BMPR1A	2.7.10.2	non-specific protein-tyrosine kinase
STK11	2.7.11.1	non-specific serine/threonine protein kinase
BUB1B	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
VHL	2.3.2.B13
WRN	3.6.4.12	DNA helicase
ELAC2	3.1.26.11	tRNase Z
DICER1	3.1.26.3	ribonuclease III
BRIP1	3.6.4.12	DNA helicase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TP53	869
BRAF	1,442
SYK	873
TOP1	1,200
CCND1	576
CCNE1	691
DNMT1	233
FNTB	425
ABCB1	3,063
KRAS	861
MDM2	1,007
ABCG2	878
BMPR1A	169
STK11	244
TRIM24	115
VHL	3,575
CTNNB1	361

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
ABCG2	1

Drug repurposing candidates

30 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)
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BLM, BRCA1, TSHR
TOPOTECAN HYDROCHLORIDE	4	BRCA1, TOP1
DAUNORUBICIN	4	ABCB1, BLM, BRCA1, TP53
DOXORUBICIN HYDROCHLORIDE	4	ABCB1, BLM, BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	ABCB1, ABCG2, BLM, BRCA1, TSHR
NITROFURANTOIN	4	MDM2, TP53, TSHR
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	ABCG2, TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	ABCB1, BLM, TP53, TSHR
COLCHICINE	4	TP53, TSHR
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	BLM, TP53
AMIODARONE HYDROCHLORIDE	4	BLM, TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53, TSHR
RALOXIFENE HYDROCHLORIDE	4	BLM, TP53
NICARDIPINE HYDROCHLORIDE	4	BLM, TP53, TSHR
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53, TSHR
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53, TSHR
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	21	BRCA1, TP53, BRAF, SYK, TOP1, CCND1, CCNE1, DNMT1, FNTB, ABCB1 (+11 more)
B	Phased (≥1) drug, not yet approved	3	MSH6, TRIM33, CDC73
C	Druggable family + PDB, no drug	12	PTEN, ASNS, ASS1, NRG1, RNASEL, SDHB, SDHC, EPCAM, ELAC2, DICER1 (+2 more)
D	Druggable family + AlphaFold only, no drug	2	AOPEP, SLC49A4
E	Difficult family or no structure, no drug	37	BRCA2, CDKN2A, FANCC, MLH1, MSH2, PMS2, ARID1A, CD44, RRAS2, VPS37A (+27 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BRCA2	0	BRCA1
CDKN2A	2	MDM2
MLH1	0	MSH6
PMS2	1	MSH6
PTEN	8	STK11, TP53
WT1	0	TP53
SLC49A4	0	VHL
CDH1	18	CTNNB1
BRIP1	0	BRCA1
PALB2	0	BRCA1
TRIM24	115	—
FANCC	0	—
MSH2	9	—
ARID1A	6	—
CD44	9	—
RRAS2	3	—
VPS37A	0	—
FGF19	0	—
GADD45A	0	—
IGF2	0	—
LRP1B	0	—
ASNS	27	—
ASS1	1	—
NRG1	0	—
RNASEL	43	—
TSPAN31	0	—
SDHB	4	—
SDHC	0	—
SMARCB1	7	—
EPCAM	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2,577.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	636
PHASE1/PHASE2	227
PHASE3	187
PHASE4	26
PHASE2/PHASE3	24

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05606692	PHASE4	RECRUITING	Influences of Propofol and Sevoflurane Anesthesia in Ovarian Cancer (Anesthetics)
NCT05926336	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06412120	PHASE4	RECRUITING	Study Evaluating Safety, Tolerability, and Metabolism of Niraparib
NCT06871787	PHASE4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT06887933	PHASE4	NOT_YET_RECRUITING	A Trial to Evaluate the Safety of Niraparib Tablets in Adult Female Participants With Advanced or Relapsed Epithelial Ovarian Cancer
NCT07469202	PHASE4	NOT_YET_RECRUITING	CYTALUX Dose Extension Study
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00727961	PHASE4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT00740116	PHASE4	COMPLETED	Tranexamic Acid in Surgery of Advanced Ovarian Cancer
NCT00817479	PHASE4	COMPLETED	Tumor Gene Expression in Women With Ovarian Cancer
NCT01432015	PHASE4	COMPLETED	Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting
NCT01706120	PHASE4	UNKNOWN	Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
NCT01932125	PHASE4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT01953107	PHASE4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02035345	PHASE4	TERMINATED	Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment
NCT02243059	PHASE4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
NCT03164980	PHASE4	TERMINATED	QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03543462	PHASE4	COMPLETED	Diaphragmatic Resection And Gynecological Ovarian Neoplasm
NCT03752216	PHASE4	COMPLETED	NIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib.
NCT03858166	PHASE4	TERMINATED	Efficacy and Safety of PEG-rhG-CSF Secondary Prophylaxis vs. Therapeutic Administration in Patients With Ovarian Cancer
NCT04024254	PHASE4	COMPLETED	A Study of Serum Folate Levels in Patients Treated With Olaparib
NCT04330040	PHASE4	COMPLETED	Prospective Multicentre Phase-IV Clinical Trial of Olaparib in Indian Patients With Ovarian and Metastatic Breast Cancer
NCT04352439	PHASE4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
NCT05187208	PHASE4	UNKNOWN	PARP Inhibitor Oral Maintenance in Low-Risk Ovarian Cancer
NCT01223248	PHASE3	ACTIVE_NOT_RECRUITING	Randomized Study Comparing Two Dosing Schedules for Hypofractionated Image-Guided Radiation Therapy
NCT01844986	PHASE3	ACTIVE_NOT_RECRUITING	Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Ovarian Cancer Following First Line Platinum Based Chemotherapy.
NCT02429687	PHASE3	RECRUITING	TC or BEP in Treating Patients With Malignant Ovarian Germ Cell Tumors
NCT02429700	PHASE3	RECRUITING	TC or BEP in Treating Patients With Ovarian Malignant Sex Cord-Stromal Tumors
NCT02655016	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Niraparib (GSK3985771) Maintenance Treatment in Participants With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy
NCT03458221	PHASE2/PHASE3	RECRUITING	Signal TrAnsduction Pathway Activity Analysis in OVarian cancER
NCT03519230	PHASE3	ACTIVE_NOT_RECRUITING	Maintenance Treatment With BGB-290 Versus Placebo in Participants With Platinum-sensitive Recurrent Ovarian Cancer
NCT03602859	PHASE3	ACTIVE_NOT_RECRUITING	A Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care (SOC) Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer
NCT03737643	PHASE3	ACTIVE_NOT_RECRUITING	Durvalumab Treatment in Combination With Chemotherapy and Bevacizumab, Followed by Maintenance Durvalumab, Bevacizumab and Olaparib Treatment in Advanced Ovarian Cancer Patients
NCT03755739	PHASE2/PHASE3	RECRUITING	Trans-Artery/Intra-Tumor Infusion of Checkpoint Inhibitors Plus Chemodrug for Immunotherapy of Advanced Solid Tumors
NCT03772028	PHASE3	ACTIVE_NOT_RECRUITING	Primary Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
NCT03842982	PHASE3	ACTIVE_NOT_RECRUITING	Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Ovarian Cancer (CHIPPI)
NCT04065009	PHASE3	ACTIVE_NOT_RECRUITING	The IPLA-OVCA Trial, Intra-Peritoneal Local Anaesthetics in Ovarian Cancer
NCT04095364	PHASE3	ACTIVE_NOT_RECRUITING	Letrozole With or Without Paclitaxel and Carboplatin in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TOPOTECAN	4	73
NIRAPARIB	4	33
OLAPARIB	4	21
DOXORUBICIN	4	20
CARBOPLATIN	4	19
PACLITAXEL	4	16
GEMCITABINE	4	15
RUCAPARIB	4	10
AMIFOSTINE	4	9
DOSTARLIMAB	4	9
PEGFILGRASTIM	4	9
INDOCYANINE GREEN ACID FORM	4	8
PAZOPANIB	4	8
CISPLATIN	4	7
TRABECTEDIN	4	7
NINTEDANIB	4	6
THIOTEPA	4	6
GEFITINIB	4	5
TALAZOPARIB	4	5
AVELUMAB	4	4
CEMIPLIMAB	4	4
IFOSFAMIDE	4	4
MIRVETUXIMAB SORAVTANSINE	4	4
SARGRAMOSTIM	4	4
TEMSIROLIMUS	4	4
APREPITANT	4	3
BEVACIZUMAB	4	3
CATUMAXOMAB	4	3
COBIMETINIB	4	3
EPIRUBICIN HYDROCHLORIDE	4	3

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 62 predictive associations from 72 curated evidence items; also 10 prognostic, 2 predisposing.

Molecular subtype	Therapy	Effect	Level	CIViC
BRCA1 Mutation	Rucaparib	Sensitivity/Response	CIViC A	EID11136 +3
BRCA2 Mutation	Rucaparib	Sensitivity/Response	CIViC A	EID11137 +3
BRCA1 Mutation	Olaparib	Sensitivity/Response	CIViC A	EID7274 +2
BRCA2 Mutation	Olaparib	Sensitivity/Response	CIViC A	EID7276 +2
ABCB1 S893T	Paclitaxel	Sensitivity/Response	CIViC B	EID674
BRAF V600E	Vemurafenib	Sensitivity/Response	CIViC B	EID5959
BRAF V600E	Trametinib + Dabrafenib	Sensitivity/Response	CIViC B	EID7454
BRAF Wildtype	Cetuximab	Sensitivity/Response	CIViC B	EID11663
BRCA1 Loss-of-function	Olaparib	Sensitivity/Response	CIViC B	EID211
BRCA1 Loss-of-function	Talazoparib	Sensitivity/Response	CIViC B	EID4876
BRCA1 Mutation	Cediranib + Olaparib	Sensitivity/Response	CIViC B	EID1677
BRCA1 Underexpression	Taxane Compound + Platinum Compound	Sensitivity/Response	CIViC B	EID942
BRCA2 Loss-of-function	Olaparib	Sensitivity/Response	CIViC B	EID212
BRCA2 Loss-of-function	Talazoparib	Sensitivity/Response	CIViC B	EID4875
BRCA2 Mutation	Cediranib + Olaparib	Sensitivity/Response	CIViC B	EID1678
KRAS Wildtype	Cetuximab	Sensitivity/Response	CIViC B	EID11661
NRAS Wildtype	Cetuximab	Sensitivity/Response	CIViC B	EID11662
TOP1 EXPRESSION	Carboplatin + Cyclophosphamide + Topotecan	Sensitivity/Response	CIViC B	EID910
FNTB RS11623866	Lonafarnib	Resistance	CIViC B	EID815
TP53 ALTERATION	Carboplatin + Cisplatin	Resistance	CIViC B	EID2771
TP53 Overexpression	Carboplatin + Cisplatin	Resistance	CIViC B	EID3013
VEGFA Overexpression	Bevacizumab + Erlotinib	Resistance	CIViC B	EID7237
BRCA1 Q1467*	Rucaparib	Sensitivity/Response	CIViC C	EID2878
BRCA2 M1I	Rucaparib	Sensitivity/Response	CIViC C	EID2880
BRCA2 M1R	Rucaparib	Sensitivity/Response	CIViC C	EID2879
BRCA2 R2336P	Rucaparib	Sensitivity/Response	CIViC C	EID2884
BRCA2 V159M	Rucaparib	Sensitivity/Response	CIViC C	EID2881
BRCA2 V211I	Rucaparib	Sensitivity/Response	CIViC C	EID2883
BRCA2 V211L	Rucaparib	Sensitivity/Response	CIViC C	EID2882
TP53 R273L	Carboplatin + Cisplatin	Resistance	CIViC C	EID2286

+32 more predictive associations (showing top 30 by evidence level).