Ovarian neoplasm

Summary

Ovarian neoplasm (MONDO:0021068) is a cancer (an umbrella term covering 8 Mondo subtypes) with 32 cohort genes (1 GWAS associations across 7 studies; 29 CIViC-evidence somatic drivers; 538 ClinVar predisposition records) and 336 clinical trials. The dominant Reactome pathway is Impaired BRCA2 binding to PALB2 (9 cohort genes). Top therapeutic interventions include bevacizumab, niraparib, and topotecan.

At a glance

• Classification: Cancer
• Umbrella term: 8 Mondo subtypes
• Cohort genes: 32
• GWAS associations: 1
• ClinVar variants: 538
• Clinical trials: 336

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ovarian neoplasm
Mondo ID	MONDO:0021068
EFO	EFO:0003893
NCIT	C4984
SNOMED CT	123843001
UMLS	C0919267
MedGen	181539
Anatomy (UBERON)	UBERON:0000992
Is cancer (heuristic)	yes

Also known as: neoplasm of ovary · neoplasm of the ovary · ovarian neoplasm · ovarian tumor · ovarian tumors · ovarian tumour · ovarian tumours · ovary neoplasm · ovary neoplasm (disease) · ovary tumor · ovary tumour · tumor of ovary · tumor of the ovary · tumour of ovary · tumour of the ovary

Data availability: 538 ClinVar variants · 1 GWAS association (7 studies).

Disease family

An umbrella term covering 8 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › gonadal disorder › ovarian disorder › ovarian neoplasm

Related subtypes (10): ovarian dysfunction, anovulation, ovarian cyst, ovarian stromal hyperthecosis, luteoma of pregnancy, ovarian endometriosis, oophoritis, ovarian hyperstimulation syndrome, ovarian remnant syndrome, ovarian ectopic pregnancy

Subtypes (8): ovarian melanoma, ovarian benign neoplasm, ovarian epithelial tumor, rete ovarii neoplasm, ovarian endometrioid stromal and related neoplasms, ovarian cancer, ovarian germ cell tumor, ovarian sex cord-stromal tumor

Genetics & variants

GWAS landscape

1 GWAS associations across 7 studies. Top hits map to 1 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs146344777	1e-08	NPAS3	G	0.27

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90454203	Pujol Gualdo N	2025	1,797	293,494	Atlas of genetic and phenotypic associations across 42 female reproductive health diagnoses.
GCST90079609	Backman JD	2021	1,188	210,464	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083595	Backman JD	2021	1,188	210,464	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90079111	Backman JD	2021	1,106	39,899	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083097	Backman JD	2021	1,106	39,899	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90043893	Jiang L	2021	1,079	246,461	A generalized linear mixed model association tool for biobank-scale data.
GCST90041850	Jiang L	2021	952	246,588	A generalized linear mixed model association tool for biobank-scale data.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

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

MAF distribution

Bucket	Variants
common (>=0.05)	0
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs146344777	14	33115000	G>A		intron_variant	NPAS3	1e-08	Tier 4: intronic/intergenic

ClinVar germline variants

538 retrieved; paginated sample, class counts are floors:

281 pathogenic, 86 pathogenic/likely pathogenic, 53 conflicting classifications of pathogenicity, 38 uncertain significance, 24 likely pathogenic, 21 benign, 18 benign/likely benign, 14 likely benign, 3 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
13983	NM_001382430.1(AKT1):c.49G>A (p.Glu17Lys)	AKT1	Pathogenic	criteria provided, multiple submitters, no conflicts
1174013	Single allele	ATM	Pathogenic	no assertion criteria provided
1174015	NM_007294.4(BRCA1):c.1195_1196del (p.Ser398_His399insTer)	BRCA1	Pathogenic	no assertion criteria provided
17661	NM_007294.4(BRCA1):c.181T>G (p.Cys61Gly)	BRCA1	Pathogenic	reviewed by expert panel
17662	NM_007294.4(BRCA1):c.68_69del (p.Glu23fs)	BRCA1	Pathogenic	reviewed by expert panel
17671	NM_007294.4(BRCA1):c.3607C>T (p.Arg1203Ter)	BRCA1	Pathogenic	reviewed by expert panel
17673	NM_007294.4(BRCA1):c.3756_3759del (p.Ser1253fs)	BRCA1	Pathogenic	reviewed by expert panel
17677	NM_007294.4(BRCA1):c.5266dup (p.Gln1756fs)	BRCA1	Pathogenic	reviewed by expert panel
17684	NM_007294.4(BRCA1):c.3481_3491del (p.Glu1161fs)	BRCA1	Pathogenic	reviewed by expert panel
254374	NM_007294.4(BRCA1):c.397del (p.Arg133fs)	BRCA1	Pathogenic	reviewed by expert panel
254459	NM_007294.4(BRCA1):c.4932_4933dup (p.Arg1645fs)	BRCA1	Pathogenic	reviewed by expert panel
266370	NM_007294.4(BRCA1):c.342del (p.Pro115fs)	BRCA1	Pathogenic	reviewed by expert panel
267512	NM_007294.4(BRCA1):c.212G>C (p.Arg71Thr)	BRCA1	Pathogenic	criteria provided, multiple submitters, no conflicts
267600	NM_007294.4(BRCA1):c.5333-1G>T	BRCA1	Pathogenic	criteria provided, multiple submitters, no conflicts
37426	NM_007294.4(BRCA1):c.1687C>T (p.Gln563Ter)	BRCA1	Pathogenic	reviewed by expert panel
37435	NM_007294.4(BRCA1):c.1953_1956del (p.Lys653fs)	BRCA1	Pathogenic	reviewed by expert panel
37450	NM_007294.4(BRCA1):c.213-12A>G	BRCA1	Pathogenic	reviewed by expert panel
37472	NM_007294.4(BRCA1):c.2475del (p.Asp825fs)	BRCA1	Pathogenic	reviewed by expert panel
37474	NM_007294.4(BRCA1):c.2515del (p.His839fs)	BRCA1	Pathogenic	reviewed by expert panel
37524	NM_007294.4(BRCA1):c.3352C>T (p.Gln1118Ter)	BRCA1	Pathogenic	reviewed by expert panel
37542	NM_007294.4(BRCA1):c.3700_3704del (p.Val1234fs)	BRCA1	Pathogenic	reviewed by expert panel
37546	NM_007294.4(BRCA1):c.3770_3771del (p.Glu1257fs)	BRCA1	Pathogenic	reviewed by expert panel
37607	NM_007294.4(BRCA1):c.4689C>G (p.Tyr1563Ter)	BRCA1	Pathogenic	reviewed by expert panel
37616	NM_007294.4(BRCA1):c.4964_4982del (p.Ser1655fs)	BRCA1	Pathogenic	reviewed by expert panel
37633	NM_007294.4(BRCA1):c.5074G>C (p.Asp1692His)	BRCA1	Pathogenic	reviewed by expert panel
37636	NM_007294.4(BRCA1):c.5096G>A (p.Arg1699Gln)	BRCA1	Pathogenic	reviewed by expert panel
37644	NM_007294.4(BRCA1):c.5177_5180del (p.Arg1726fs)	BRCA1	Pathogenic	reviewed by expert panel
37691	NM_007294.4(BRCA1):c.66dup (p.Glu23fs)	BRCA1	Pathogenic	reviewed by expert panel
409310	NM_007294.4(BRCA1):c.2209del (p.Thr737fs)	BRCA1	Pathogenic	reviewed by expert panel
54102	NM_007294.4(BRCA1):c.1016dup (p.Val340fs)	BRCA1	Pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 179 · 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
SMARCA4	Act	BL,BLADDER,BLCA,CCRCC,CHOL,COAD,COADREAD,EGC,ESCA,ESCC,HCC,HNSC,LGGNOS,LUAD,MBL,MLYM,NHL,NSCLC,OVT,PAAD,PANCREAS,PAST,PRCC,SACA,STAD,THYM	CIViC #78
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
CHEK2	Act	BRCA	CIViC #8950
RRAS2	Act	UCEC	CIViC #9054
CDH1	LoF	BLCA,BRCA,CSCC,DLBCLNOS,ESCA,STAD	CIViC #888
CDKN2A	LoF	ACYC,BLCA,BRCA,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,GBM,HCC,HNSC,LGGNOS,LUAD,LUSC,MEL,MLYM,NPC,NSCLC,OS,PAAD,PANCREAS,RCC,SKCM,SKIN,STAD,STOMACH,WDTC	CIViC #14
BRIP1			CIViC #15955
CTNNB1	Act	ACC,COAD,COADREAD,ESCA,HCC,LIHB,LUAD,MBL,MEL,NSCLC,OVT,PAST,PRAD,PROSTATE,RMS,SKIN,SOFT_TISSUE,STAD,UCEC,WT	CIViC #1290
PALB2	LoF	OVT	CIViC #15013
ERBB2	Act	BLCA,BRCA,CESC,CHOL,COADREAD,EGC,ESCA,ESCC,LMS,LUAD,NSCLC,OVT,PRCC,READ,STAD,UCEC	CIViC #20
FGFR3	Act	BLADDER,BLCA,HNSC,LUSC,PCM,PLMESO,UTUC	CIViC #23
AKT1	Act	ALL,BRCA,CESC,COADREAD,PRAD,PROSTATE,SARCNOS,UCEC,WDTC	CIViC #2
GATA3	Act	ALL,BRCA	CIViC #2189
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
MAP3K1	LoF	BRCA,CCRCC,CEAD,COAD,COADREAD,GBM,HCC,PCM,UCEC,WDTC	CIViC #3480
MRE11			CIViC #3586
MSH2			CIViC #3628
MSH6			CIViC #2478
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
PRKN			CIViC #4103
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
PMS2	ambiguous	HCC	CIViC #4371
BARD1	Act	PRAD	CIViC #549
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
RAD51C			CIViC #4762
RAD51D			CIViC #4765
RB1	LoF	ACC,BLADDER,BLCA,BRCA,CESC,ESCA,GB,GBM,GIST,HCC,HNSC,LGGNOS,LIPO,LMS,LUAD,LUSC,MEL,MT,NSCLC,OS,OVT,PANCREAS,PCM,PRAD,PROSTATE,RBL,SCLC,SKCM,SOFT_TISSUE,STAD,STOMACH,UCEC,UCS	CIViC #4795

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
SMARCA4	Orphanet:1465	Coffin-Siris syndrome
SMARCA4	Orphanet:231108	Rhabdoid tumor predisposition syndrome
SMARCA4	Orphanet:370396	Small cell carcinoma of the ovary
SMARCA4	Orphanet:466962	SMARCA4-deficient sarcoma of thorax
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
CHEK2	Orphanet:1331	Familial prostate cancer
CHEK2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
CHEK2	Orphanet:440437	Familial colorectal cancer Type X
CHEK2	Orphanet:524	Li-Fraumeni syndrome
CHEK2	Orphanet:668	Osteosarcoma

Cohort genes → proteins

32 cohort genes, 31 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	32

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar
SMARCA4	HGNC:11100	ENSG00000127616	P51532	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	clinvar
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	clinvar
RRAS2	HGNC:17271	ENSG00000133818	P62070	Ras-related protein R-Ras2	clinvar
CDH1	HGNC:1748	ENSG00000039068	P12830	Cadherin-1	clinvar
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	clinvar
BRIP1	HGNC:20473	ENSG00000136492	Q9BX63	Fanconi anemia group J protein	clinvar
CTNNB1	HGNC:2514	ENSG00000168036	P35222	Catenin beta-1	clinvar
PALB2	HGNC:26144	ENSG00000083093	Q86YC2	Partner and localizer of BRCA2	clinvar
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	clinvar
FGFR3	HGNC:3690	ENSG00000068078	P22607	Fibroblast growth factor receptor 3	clinvar
AKT1	HGNC:391	ENSG00000142208	P31749	RAC-alpha serine/threonine-protein kinase	clinvar
GATA3	HGNC:4172	ENSG00000107485	P23771	Trans-acting T-cell-specific transcription factor GATA-3	clinvar
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	clinvar
MAP3K1	HGNC:6848	ENSG00000095015	Q13233	Mitogen-activated protein kinase kinase kinase 1	clinvar
MRE11	HGNC:7230	ENSG00000020922	P49959	Double-strand break repair protein MRE11	clinvar
MSH2	HGNC:7325	ENSG00000095002	P43246	DNA mismatch repair protein Msh2	clinvar
MSH6	HGNC:7329	ENSG00000116062	P52701	DNA mismatch repair protein Msh6	clinvar
MT-CYB	HGNC:7427	ENSG00000198727	P00156	Cytochrome b	clinvar
MT-TT	HGNC:7499	ENSG00000210195		mitochondrially encoded tRNA-Thr (ACN)	clinvar
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	clinvar
OPCML	HGNC:8143	ENSG00000183715	Q14982	Opioid-binding protein/cell adhesion molecule	clinvar
PRKN	HGNC:8607	ENSG00000185345	O60260	E3 ubiquitin-protein ligase parkin	clinvar
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	clinvar
PMS2	HGNC:9122	ENSG00000122512	P54278	Mismatch repair endonuclease PMS2	clinvar
BARD1	HGNC:952	ENSG00000138376	Q99728	BRCA1-associated RING domain protein 1	clinvar
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	clinvar
RAD51C	HGNC:9820	ENSG00000108384	O43502	DNA repair protein RAD51 homolog 3	clinvar
RAD51D	HGNC:9823	ENSG00000185379	O75771	DNA repair protein RAD51 homolog 4	clinvar
RB1	HGNC:9884	ENSG00000139687	P06400	Retinoblastoma-associated protein	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.
SMARCA4	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	ATPase 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.
CHEK2	Serine/threonine-protein kinase Chk2	Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks.
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.
CDH1	Cadherin-1	Cadherins are calcium-dependent cell adhesion proteins.
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
BRIP1	Fanconi anemia group J protein	DNA-dependent ATPase and 5’-3’ DNA helicase required for the maintenance of chromosomal stability.
CTNNB1	Catenin beta-1	Key downstream component of the canonical Wnt signaling pathway.
PALB2	Partner and localizer of BRCA2	Plays a critical role in homologous recombination repair (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks.
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.
FGFR3	Fibroblast growth factor receptor 3	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 and apoptosis.
AKT1	RAC-alpha serine/threonine-protein kinase	AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis.
GATA3	Trans-acting T-cell-specific transcription factor GATA-3	Transcriptional activator which binds to the enhancer of the T-cell receptor alpha and delta genes.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
MAP3K1	Mitogen-activated protein kinase kinase kinase 1	Component of a protein kinase signal transduction cascade.
MRE11	Double-strand break repair protein MRE11	Core component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.
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).
MT-CYB	Cytochrome b	Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex) that is part of the mitochondrial respiratory chain.
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.
OPCML	Opioid-binding protein/cell adhesion molecule	Binds opioids in the presence of acidic lipids; probably involved in cell contact.
PRKN	E3 ubiquitin-protein ligase parkin	Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins.
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.
PMS2	Mismatch repair endonuclease PMS2	Component of the post-replicative DNA mismatch repair system (MMR).
BARD1	BRCA1-associated RING domain protein 1	E3 ubiquitin-protein ligase.
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.
RAD51C	DNA repair protein RAD51 homolog 3	Essential for the homologous recombination (HR) pathway of DNA repair.
RAD51D	DNA repair protein RAD51 homolog 4	Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents.
RB1	Retinoblastoma-associated protein	Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle.

Protein-family classification

Druggable: 11 · Difficult: 7 · Unknown: 14 · Druggable fraction: 0.34

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	7	6.1×	8e-04
Phosphatase	1	2.6×	0.805
Transcription factor	5	1.3×	0.805
Scaffold/PPI	2	1.1×	0.886
Antibody/Immunoglobulin	1	0.9×	0.886
Enzyme (other)	2	0.8×	0.886
Other/Unknown	14	0.8×	0.939

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
SMARCA4	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
CHEK2	Kinase	yes	2.7.11.1	FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
RRAS2	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
CDH1	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin_pro_dom
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
BRIP1	Enzyme (other)	yes	3.6.4.12	Helicase-like_DEXD_c2, ATP-dep_Helicase_C, RAD3-like_helicase_DEAD
CTNNB1	Other/Unknown	no		Armadillo, ARM-like, Beta-catenin
PALB2	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, PALB2_WD40, WD40_repeat_dom_sf
ERBB2	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
FGFR3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
AKT1	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, PH_domain
GATA3	Transcription factor	no		Znf_GATA, Znf_NHR/GATA, TF_GATA-2/3
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
MAP3K1	Kinase	yes	2.7.11.25	Prot_kinase_dom, Znf_RING, Znf_SWIM
MRE11	Other/Unknown	no		Mre11, Calcineurin-like_PHP, Mre11_DNA-bd
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
MT-CYB	Other/Unknown	no		Cyt_b/b6_N, Cyt_b/b6_C, Di-haem_cyt_TM
MT-TT	Other/Unknown	no
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
OPCML	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
PRKN	Transcription factor	no	2.3.2.27	Ubiquitin-like_dom, IBR_dom, Parkin
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom
PMS2	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
BARD1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, Ankyrin_rpt
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom
RAD51C	Other/Unknown	no		Rad51_C, DNA_recomb/repair_RecA-like, RecA_ATP-bd
RAD51D	Other/Unknown	no		AAA+_ATPase, Rad51_C, DNA_recomb/repair_RecA-like
RB1	Other/Unknown	no		RB_B, RB_A, Cyclin-like_dom

Expression context

Cohort genes with no expression data: 0.

29 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)	32
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	7
ventricular zone	7
secondary oocyte	6
oocyte	6
primordial germ cell in gonad	4
ganglionic eminence	4
calcaneal tendon	4
sural nerve	3
skin of hip	3
upper leg skin	3
cervix squamous epithelium	2
lower esophagus mucosa	2
pituitary gland	2
adrenal tissue	2
buccal mucosa cell	2
endometrium epithelium	2
endothelial cell	2
sperm	2
cortical plate	1
tendon of biceps brachii	1

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
SMARCA4	295	ubiquitous	marker	ganglionic eminence, cortical plate, cervix squamous epithelium
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
CHEK2	183	ubiquitous	marker	primordial germ cell in gonad, lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis
RRAS2	287	ubiquitous	marker	secondary oocyte, oocyte, skeletal muscle tissue of rectus abdominis
CDH1	245	broad	marker	jejunal mucosa, esophagus squamous epithelium, gingival epithelium
CDKN2A	220	ubiquitous	marker	parotid gland, cervix squamous epithelium, pituitary gland
BRIP1	181	ubiquitous	marker	ventricular zone, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
CTNNB1	295	ubiquitous	marker	adrenal tissue, ventricular zone, periodontal ligament
PALB2	232	ubiquitous	yes	secondary oocyte, buccal mucosa cell, oocyte
ERBB2	276	ubiquitous	marker	lower esophagus mucosa, right uterine tube, sural nerve
FGFR3	262	broad	marker	upper leg skin, skin of hip, upper arm skin
AKT1	273	ubiquitous	marker	stromal cell of endometrium, ganglionic eminence, endometrium epithelium
GATA3	220	broad	marker	upper leg skin, skin of hip, endometrium epithelium
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
MAP3K1	264	ubiquitous	marker	buccal mucosa cell, upper leg skin, skin of hip
MRE11	254	ubiquitous	marker	calcaneal tendon, oocyte, secondary oocyte
MSH2	278	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
MSH6	293	ubiquitous	marker	ventricular zone, embryo, ganglionic eminence
MT-CYB	134	ubiquitous	marker	apex of heart, pituitary gland, zone of skin
MT-TT	118	broad	yes	skeletal muscle tissue, sural nerve, substantia nigra
ATM	286	ubiquitous	marker	calcaneal tendon, colonic epithelium, corpus callosum
OPCML	189	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, endothelial cell
PRKN	174	ubiquitous	marker	sural nerve, male germ line stem cell (sensu Vertebrata) in testis, hindlimb stylopod muscle
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon
PMS2	143	ubiquitous	marker	thymus, prefrontal cortex, male germ line stem cell (sensu Vertebrata) in testis
BARD1	271	ubiquitous	marker	secondary oocyte, oocyte, tongue squamous epithelium
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon
RAD51C	281	ubiquitous	marker	primordial germ cell in gonad, right testis, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 80.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
AKT1	16,601
CTNNB1	15,668
KRAS	14,509
PTEN	11,626
PRKN	10,281
ERBB2	9,659
CDKN2A	9,311
BRCA1	9,064
CDH1	8,738

Intra-cohort edges

A	B	Sources
AKT1	ATM	intact
AKT1	PIK3CA	biogrid_interaction, string_interaction
AKT1	PTEN	string_interaction
ATM	BARD1	string_interaction
ATM	BRCA1	string_interaction
ATM	BRCA2	string_interaction
ATM	CHEK2	string_interaction
ATM	MRE11	string_interaction
ATM	MSH2	string_interaction
ATM	MSH6	string_interaction
ATM	RAD51D	string_interaction
ATM	TP53	biogrid_interaction, string_interaction
BARD1	BRCA1	biogrid_interaction, intact, string_interaction
BARD1	BRCA2	string_interaction
BARD1	BRIP1	biogrid_interaction
BARD1	CHEK2	string_interaction
BARD1	PALB2	string_interaction
BARD1	RAD51C	string_interaction
BARD1	RAD51D	string_interaction
BRCA1	BRCA2	string_interaction
BRCA1	BRIP1	biogrid_interaction, intact, string_interaction
BRCA1	CHEK2	string_interaction
BRCA1	MAP3K1	string_interaction
BRCA1	MRE11	string_interaction
BRCA1	MSH2	string_interaction
BRCA1	MSH6	string_interaction
BRCA1	PALB2	biogrid_interaction, intact, string_interaction
BRCA1	PMS2	string_interaction
BRCA1	RAD51C	string_interaction
BRCA1	RAD51D	string_interaction
BRCA1	TP53	string_interaction
BRCA2	BRIP1	string_interaction
BRCA2	CHEK2	string_interaction
BRCA2	MRE11	string_interaction
BRCA2	MSH2	string_interaction
BRCA2	MSH6	string_interaction
BRCA2	PALB2	biogrid_interaction, intact, string_interaction
BRCA2	PMS2	string_interaction
BRCA2	RAD51C	biogrid_interaction, string_interaction
BRCA2	RAD51D	string_interaction
BRCA2	TP53	string_interaction
BRIP1	PALB2	string_interaction
BRIP1	PMS2	biogrid_interaction, intact
CDH1	CTNNB1	biogrid_interaction, intact, string_interaction
CDH1	ERBB2	string_interaction
CDH1	PTEN	string_interaction
CDKN2A	KRAS	string_interaction
CDKN2A	RB1	string_interaction
CDKN2A	TP53	string_interaction
CHEK2	MRE11	string_interaction

Structural data

PDB: 31 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
TP53	P04637	313
PIK3CA	P42336	135
ERBB2	P04626	63
CTNNB1	P35222	50
AKT1	P31749	43
CHEK2	O96017	38
BRCA1	P38398	33
SMARCA4	P51532	31
MSH2	P43246	30
CDH1	P12830	22
PRKN	O60260	21
RB1	P06400	19
RAD51C	O43502	17
RAD51D	O75771	17
FGFR3	P22607	15
BRCA2	P51587	14
ATM	Q13315	14
PTEN	P60484	12
BARD1	Q99728	11
MRE11	P49959	10
PMS2	P54278	9
MSH6	P52701	8
CDKN2A	P42771	5
MT-CYB	P00156	5
PALB2	Q86YC2	4
RRAS2	P62070	3
BRIP1	Q9BX63	3
GATA3	P23771	3
MAP3K1	Q13233	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 501. Enrichment computed across 32 evidence-associated genes (31 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 31 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Impaired BRCA2 binding to PALB2	9	132.6×	1e-15	BRCA1, BRCA2, BRIP1, PALB2, MRE11, ATM, BARD1, RAD51C (+1 more)
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	9	122.8×	1e-15	BRCA1, BRCA2, BRIP1, PALB2, MRE11, ATM, BARD1, RAD51C (+1 more)
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	9	122.8×	1e-15	BRCA1, BRCA2, BRIP1, PALB2, MRE11, ATM, BARD1, RAD51C (+1 more)
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	9	122.8×	1e-15	BRCA1, BRCA2, BRIP1, PALB2, MRE11, ATM, BARD1, RAD51C (+1 more)
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	9	114.3×	2e-15	BRCA1, BRCA2, BRIP1, PALB2, MRE11, ATM, BARD1, RAD51C (+1 more)
Homologous DNA Pairing and Strand Exchange	9	110.5×	3e-15	BRCA1, BRCA2, BRIP1, PALB2, MRE11, ATM, BARD1, RAD51C (+1 more)
Resolution of D-loop Structures through Holliday Junction Intermediates	9	87.2×	2e-14	BRCA1, BRCA2, BRIP1, PALB2, MRE11, ATM, BARD1, RAD51C (+1 more)
HDR through Homologous Recombination (HRR)	9	55.3×	2e-12	BRCA1, BRCA2, BRIP1, PALB2, MRE11, ATM, BARD1, RAD51C (+1 more)
Diseases of DNA repair	7	128.9×	2e-12	BRCA1, BRCA2, MRE11, MSH2, MSH6, ATM, BARD1
Presynaptic phase of homologous DNA pairing and strand exchange	8	70.2×	6e-12	BRCA1, BRCA2, BRIP1, MRE11, ATM, BARD1, RAD51C, RAD51D
Defective homologous recombination repair (HRR) due to PALB2 loss of function	5	153.5×	4e-09	BRCA1, BRCA2, MRE11, ATM, BARD1
Diseases of DNA Double-Strand Break Repair	5	131.6×	8e-09	BRCA1, BRCA2, MRE11, ATM, BARD1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	5	131.6×	8e-09	BRCA1, BRCA2, MRE11, ATM, BARD1
Impaired BRCA2 binding to RAD51	6	59.7×	2e-08	BRCA1, BRCA2, BRIP1, MRE11, ATM, BARD1
Resolution of D-Loop Structures	5	102.3×	3e-08	BRCA1, BRCA2, MRE11, ATM, BARD1
G2/M DNA damage checkpoint	7	27.1×	2e-07	BRCA1, TP53, CHEK2, BRIP1, MRE11, ATM, BARD1
Regulation of TP53 Activity through Phosphorylation	7	26.6×	2e-07	BRCA1, TP53, CHEK2, BRIP1, MRE11, ATM, BARD1
TP53 Regulates Transcription of DNA Repair Genes	6	35.1×	4e-07	BRCA1, TP53, MSH2, ATM, PMS2, RAD51D
DNA Repair	7	22.2×	5e-07	BRCA1, BRCA2, MRE11, MSH2, MSH6, ATM, BARD1
Homology Directed Repair	5	49.8×	1e-06	BRCA1, BRCA2, MRE11, ATM, BARD1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	5	49.8×	1e-06	BRCA1, BRCA2, MRE11, ATM, BARD1
HDR through Single Strand Annealing (SSA)	5	47.2×	1e-06	BRCA1, BRIP1, MRE11, ATM, BARD1
Regulation of TP53 Degradation	5	47.2×	1e-06	TP53, CHEK2, CDKN2A, AKT1, ATM
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	6	28.3×	1e-06	BRCA1, TP53, CHEK2, MRE11, ATM, BARD1
Stabilization of p53	4	98.2×	1e-06	TP53, CHEK2, CDKN2A, ATM
Regulation of TP53 Activity	6	25.7×	2e-06	BRCA1, CDKN2A, AKT1, MRE11, ATM, BARD1
DNA Double-Strand Break Repair	5	40.0×	2e-06	BRCA1, BRCA2, MRE11, ATM, BARD1
DNA Double Strand Break Response	4	61.4×	8e-06	BRCA1, MRE11, ATM, BARD1
Transcriptional Regulation by TP53	7	14.0×	8e-06	BRCA1, CDKN2A, AKT1, MRE11, MSH2, ATM, BARD1
G2/M Checkpoints	5	21.7×	5e-05	BRCA1, TP53, MRE11, ATM, BARD1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 31 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
double-strand break repair	8	52.4×	2e-09	BRCA1, BRCA2, TP53, CHEK2, BRIP1, MRE11, MSH2, ATM
double-strand break repair via homologous recombination	7	35.2×	4e-07	BRCA1, BRCA2, PALB2, MRE11, ATM, RAD51C, RAD51D
homologous recombination	4	181.2×	1e-06	BRCA1, BRIP1, MRE11, BARD1
somatic recombination of immunoglobulin gene segments	3	407.7×	4e-06	MSH2, MSH6, PMS2
replicative senescence	4	127.9×	4e-06	TP53, CHEK2, CDKN2A, ATM
DNA repair	8	16.5×	4e-06	BRCA1, BRIP1, MRE11, MSH2, MSH6, BARD1, RAD51C, RAD51D
negative regulation of mammary gland epithelial cell proliferation	3	326.2×	7e-06	BRCA2, CDKN2A, GATA3
cellular response to indole-3-methanol	3	326.2×	7e-06	BRCA1, CDH1, CTNNB1
regulation of cell cycle	7	16.8×	1e-05	BRCA1, TP53, CDKN2A, ATM, BARD1, RAD51D, RB1
reciprocal meiotic recombination	4	72.5×	2e-05	MRE11, ATM, RAD51C, RAD51D
DNA strand resection involved in replication fork processing	3	203.8×	3e-05	BRCA1, MRE11, BARD1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	34.0×	3e-05	ERBB2, AKT1, GATA3, PIK3CA, PTEN
Ras protein signal transduction	5	33.1×	3e-05	TP53, RRAS2, CDKN2A, KRAS, RB1
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	4	64.0×	3e-05	BRCA2, TP53, CHEK2, MSH2
determination of adult lifespan	4	55.8×	5e-05	TP53, MSH2, MSH6, ATM
telomere maintenance via recombination	3	148.3×	5e-05	BRCA2, RAD51C, RAD51D
cellular response to ionizing radiation	4	53.0×	5e-05	BRCA1, BRCA2, TP53, BARD1
positive regulation of DNA-templated transcription	9	8.1×	5e-05	BRCA1, BRCA2, SMARCA4, TP53, CHEK2, CDH1, CDKN2A, CTNNB1 (+1 more)
DNA damage response, signal transduction by p53 class mediator	4	46.3×	8e-05	BRCA2, TP53, CHEK2, ATM
negative regulation of cell growth	5	23.2×	1e-04	BRCA1, SMARCA4, TP53, CDKN2A, RB1
intrinsic apoptotic signaling pathway in response to DNA damage	4	41.8×	1e-04	BRCA1, CHEK2, MSH6, ATM
regulation of DNA damage checkpoint	3	108.7×	1e-04	BRCA1, BRCA2, BARD1
positive regulation of transcription by RNA polymerase II	11	5.3×	1e-04	BRCA1, SMARCA4, TP53, CDKN2A, CTNNB1, AKT1, GATA3, ATM (+3 more)
somatic hypermutation of immunoglobulin genes	3	101.9×	1e-04	MSH2, MSH6, PMS2
regulation of nephron tubule epithelial cell differentiation	2	543.6×	1e-04	CTNNB1, GATA3
striated muscle cell differentiation	3	95.9×	1e-04	AKT1, KRAS, RB1
protein K6-linked ubiquitination	3	95.9×	1e-04	BRCA1, PRKN, BARD1
cellular senescence	4	38.1×	1e-04	BRCA2, TP53, CDKN2A, ATM
negative regulation of cell cycle	4	37.5×	1e-04	BRCA1, GATA3, BARD1, RB1
mitotic intra-S DNA damage checkpoint signaling	3	90.6×	1e-04	CHEK2, MRE11, MSH2

Therapeutics

Drugs indicated for this disease

6 approved, 17 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Bevacizumab	Approved (phase 4)
Carboplatin	Approved (phase 4)
Igovomab	Approved (phase 4)
Olaparib	Approved (phase 4)
Paclitaxel	Approved (phase 4)
Trabectedin	Approved (phase 4)
Atezolizumab	Phase 3 (in late-stage trials)
Batiraxcept	Phase 3 (in late-stage trials)
Cediranib	Phase 3 (in late-stage trials)
Cisplatin	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)
Filgrastim	Phase 3 (in late-stage trials)
Fluzoparib	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Niraparib	Phase 3 (in late-stage trials)
Oregovomab	Phase 3 (in late-stage trials)
Pazopanib	Phase 3 (in late-stage trials)
Progesterone	Phase 3 (in late-stage trials)
Rivoceranib	Phase 3 (in late-stage trials)
Topotecan	Phase 3 (in late-stage trials)
Veliparib	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Adebrelimab, Aldesleukin, Alectinib, Aspirin, Celecoxib, Erlotinib, Ganitumab, Incomplete Freund’S Adjuvant, Ipatasertib, Irinotecan, Nintedanib, Olaratumab, Pembrolizumab, Regorafenib, Sargramostim, Sorafenib, Volasertib, Vorinostat.

Drug target analysis

Approved (phase 4): 11 · Phase ≥3: 11 · Phased (≥1): 14 · Undrugged: 18

Druggability breadth: 21 of 32 evidence-associated genes (66%) 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
CHEK2	NERATINIB
CTNNB1	DITHIAZANINE IODIDE
ERBB2	CLOTRIMAZOLE
FGFR3	PONATINIB
AKT1	CAPIVASERTIB
KRAS	VEMURAFENIB
MAP3K1	PONATINIB
ATM	AMIODARONE HYDROCHLORIDE
PIK3CA	IDELALISIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
ERBB2	83	4
PIK3CA	67	4
FGFR3	64	4
ATM	35	4
MAP3K1	31	4
CHEK2	30	4
AKT1	30	4
BRCA1	12	4
KRAS	11	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1, TP53
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	ATM, BRCA1
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
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
FURAZOLIDONE	4	ATM, TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 13.

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
AKT1	1,942	Binding:1900, Functional:34, ADMET:7, Toxicity:1
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6
FGFR3	975	Binding:948, Functional:18, ADMET:9
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
CHEK2	690	Binding:687, Functional:2, ADMET:1
CTNNB1	361	Binding:358, Functional:3
ATM	240	Binding:233, Functional:5, ADMET:2
SMARCA4	230	Binding:207, ADMET:12, Functional:11
MAP3K1	167	Binding:165, ADMET:1, Functional:1
RB1	59	Binding:59
MRE11	36	Binding:36
CDH1	18	Binding:18
BRCA1	13	Binding:9, Functional:4
MSH6	10	Binding:10
MSH2	9	Binding:9
PTEN	8	Binding:8
RRAS2	3	Binding:3
CDKN2A	2	Binding:2
PMS2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
CHEK2	2.7.11.1	non-specific serine/threonine protein kinase
BRIP1	3.6.4.12	DNA helicase
ERBB2	2.7.10.1	receptor protein-tyrosine kinase
FGFR3	2.7.10.1	receptor protein-tyrosine kinase
AKT1	2.7.11.1	non-specific serine/threonine protein kinase
KRAS	3.6.5.2	small monomeric GTPase
MAP3K1	2.7.11.25	mitogen-activated protein kinase kinase kinase
ATM	2.7.11.1	non-specific serine/threonine protein kinase
PRKN	2.3.2.27, 2.3.2.31	RING-type E3 ubiquitin transferase, RBR-type E3 ubiquitin transferase
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
BARD1	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

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SMARCA4	230
TP53	869
CHEK2	690
CTNNB1	361
ERBB2	1,221
FGFR3	975
AKT1	1,942
KRAS	861
MAP3K1	167
ATM	240
PIK3CA	2,034

Pharmacogenomics

Cohort genes with a PharmGKB record: 32; with CPIC/DPWG dosing guidelines: 0.

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

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	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1, TP53
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	ATM, BRCA1
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
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
FURAZOLIDONE	4	ATM, TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	11	BRCA1, TP53, CHEK2, CTNNB1, ERBB2, FGFR3, AKT1, KRAS, MAP3K1, ATM (+1 more)
B	Phased (≥1) drug, not yet approved	3	SMARCA4, MSH6, RB1
C	Druggable family + PDB, no drug	3	BRIP1, OPCML, PTEN
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	15	BRCA2, RRAS2, CDH1, CDKN2A, PALB2, GATA3, MRE11, MSH2, MT-CYB, MT-TT (+5 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BRCA2	0	BRCA1
CDH1	18	CTNNB1
BRIP1	0	BRCA1
PALB2	0	BRCA1
MRE11	36	BRCA1, ATM
PMS2	1	MSH6
PTEN	8	TP53, AKT1
RAD51D	0	BRCA1
RRAS2	3	—
CDKN2A	2	—
GATA3	0	—
MSH2	9	—
MT-CYB	0	—
MT-TT	0	—
OPCML	0	—
PRKN	0	—
BARD1	0	—
RAD51C	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 336.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	132
PHASE2	80
PHASE1	57
PHASE3	27
PHASE1/PHASE2	26
PHASE2/PHASE3	7
PHASE4	5
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
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
NCT00727961	PHASE4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT01932125	PHASE4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT02243059	PHASE4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
NCT03858166	PHASE4	TERMINATED	Efficacy and Safety of PEG-rhG-CSF Secondary Prophylaxis vs. Therapeutic Administration in Patients With Ovarian Cancer
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
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
NCT03842982	PHASE3	ACTIVE_NOT_RECRUITING	Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Ovarian Cancer (CHIPPI)
NCT04498117	PHASE3	ACTIVE_NOT_RECRUITING	Oregovomab Plus Chemo in Newly Diagnosed Patients With Advanced Epithelial Ovarian Cancer Following Optimal Debulking Surgery
NCT05257408	PHASE3	ACTIVE_NOT_RECRUITING	Relacorilant in Combination With Nab-Paclitaxel in Advanced, Platinum-Resistant, High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian-Tube Cancer
NCT05768178	PHASE2/PHASE3	RECRUITING	DETERMINE Trial Treatment Arm 05: Vemurafenib in Combination With Cobimetinib in Adult Patients With BRAF Positive Cancers.
NCT05786716	PHASE2/PHASE3	RECRUITING	DETERMINE Trial Treatment Arm 04: Trastuzumab in Combination With Pertuzumab in Adult, Paediatric and Teenage/Young Adult Patients With Cancers With HER2 Amplification or Activating Mutations
NCT06963268	PHASE3	RECRUITING	Validation of the Sentinel Lymph Node Technique in Early-stage Ovarian Cancer (SENTOV II)
NCT07213804	PHASE3	RECRUITING	A Two-Part Phase 3 Study of Sofetabart Mipitecan (LY4170156) in Participants With Platinum-Resistant (Part A) and Platinum-Sensitive (Part B) Ovarian Cancer
NCT07286266	PHASE3	NOT_YET_RECRUITING	A Study to Investigate Mocertatug Rezetecan Compared With Standard of Care in Participants With Platinum-resistant Ovarian Cancer (BEHOLD-Ovarian01)
NCT07318558	PHASE3	RECRUITING	A Clinical Trial of Sac-TMT in People With Non-HRD Positive Advanced Ovarian Cancer (MK-2870-021)
NCT07440290	PHASE2/PHASE3	NOT_YET_RECRUITING	DETERMINE Trial Treatment Arm 07: Dabrafenib in Combination With Trametinib in Adult, Paediatric and Teenage/Young Adult Patients With BRAF V600 Mutation-Positive Cancers.
NCT00057720	PHASE3	COMPLETED	TLK286 (Telcyta) vs. Doxil/Caelyx or Hycamtin in Platinum Refractory or Resistant Ovarian Cancer
NCT00102973	PHASE3	COMPLETED	TLK286 (Telcyta) in Combination With Carboplatin (Paraplatin) Versus Doxil in Platinum Refractory or Resistant Ovarian Cancer
NCT00191607	PHASE3	COMPLETED	A Randomized Trial for Patients With Platinum Resistant Ovarian, Fallopian or Primary Peritoneal Cancer.
NCT00191646	PHASE3	COMPLETED	An Ovarian, Primary Peritoneal or Fallopian Tube Cancer Study for Patients That Have Not Received Prior Chemotherapy
NCT00243685	PHASE2/PHASE3	COMPLETED	Chemotherapy Drug Sensitivity Microculture (MiCK) Assay for Apoptosis
NCT00327444	PHASE2/PHASE3	COMPLETED	Study of the Effect of Intravenous AVE0005 (VEGF Trap) in Advanced Ovarian Cancer Patients With Recurrent Symptomatic Malignant Ascites
NCT00350948	PHASE3	TERMINATED	Phase 3 Randomized Study of Telcyta + Doxorubicin Versus Doxorubicin in Platinum Refractory or Resistant Ovarian Cancer
NCT00443196	PHASE2/PHASE3	COMPLETED	Testing Drug Sensitivity of Ovarian, Fallopian and Primary Peritoneal Adenocarcinomas
NCT00653952	PHASE3	TERMINATED	CAELYX Versus Paclitaxel HCl in Patients With Epithelial Ovarian Carcinoma Following Failure of First-Line, Platinum-Based Chemotherapy
NCT01015118	PHASE3	COMPLETED	LUME-Ovar 1: Nintedanib (BIBF 1120) or Placebo in Combination With Paclitaxel and Carboplatin in First Line Treatment of Ovarian Cancer
NCT01462890	PHASE3	COMPLETED	Evaluation of Optimal Treatment Duration of Bevacizumab Combination With Standard Chemotherapy in Patients With Ovarian Cancer
NCT01628380	PHASE3	UNKNOWN	Phase 3 Trial Evaluating Hyperthermic Intraperitoneal Chemotherapy in Upfront Treatment of Stage IIIC Epithelial Ovarian Cancer
NCT01846611	PHASE3	COMPLETED	A Study Comparing the Combination of Trabectedin (YONDELIS) and DOXIL/CAELYX With DOXIL/CAELYX for the Treatment of Advanced-Relapsed Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
NCT01847274	PHASE3	COMPLETED	A Maintenance Study With Niraparib Versus Placebo in Patients With Platinum Sensitive Ovarian Cancer
NCT01905592	PHASE3	TERMINATED	A Phase III Trial of Niraparib Versus Physician’s Choice in HER2 Negative, Germline BRCA Mutation-positive Breast Cancer Patients
NCT02470585	PHASE3	TERMINATED	Veliparib With Carboplatin and Paclitaxel and as Continuation Maintenance Therapy in Adults With Newly Diagnosed Stage III or IV, High-grade Serous, Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
NCT02903004	PHASE3	COMPLETED	Trial on Trabectedin (ET-743) vs Clinician’s Choice Chemotherapy in Recurrent Ovarian, Primary Peritoneal or Fallopian Tube Cancers of BRCA Mutated or BRCAness Phenotype Patients
NCT03371693	PHASE3	UNKNOWN	Cytoreductive Surgery(CRS) Plus Hyperthermic Intraperitoneal Chemotherapy(HIPEC) With Lobaplatin in Advanced and Recurrent Epithelial Ovarian Cancer
NCT04055038	PHASE2/PHASE3	UNKNOWN	Efficacy of Platinum-based Chemotherapy in Platinum-resistant Ovarian Cancer) (EPITOC)
NCT05244811	PHASE3	UNKNOWN	Treat of Functional Ovarian Cysts by Compare Between Cocs and Progesterone Only Pills
NCT02346747	PHASE2	ACTIVE_NOT_RECRUITING	A Trial of Vigil for Participants With Ovarian Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BEVACIZUMAB	4	17
NIRAPARIB	4	10
TOPOTECAN	4	9
DOXORUBICIN	4	8
DOSTARLIMAB	4	5
TRABECTEDIN	4	3
BLEOMYCIN	4	2
GEMCITABINE	4	2
NINTEDANIB	4	2
OLAPARIB	4	2
AFLIBERCEPT	4	1
ALDESLEUKIN	4	1
ALECTINIB	4	1
ASPARAGINASE	4	1
COBIMETINIB	4	1
DABRAFENIB	4	1
ERLOTINIB	4	1
OLARATUMAB	4	1
PAZOPANIB	4	1
PERTUZUMAB	4	1
REGORAFENIB	4	1
SARGRAMOSTIM	4	1
TEMSIROLIMUS	4	1
TRAMETINIB	4	1
VANDETANIB	4	1
VEMURAFENIB	4	1
VORINOSTAT	4	1
CANFOSFAMIDE HYDROCHLORIDE	3	5
OREGOVOMAB	3	4
FOSBRETABULIN	3	2