Ovarian carcinoma

Summary

Ovarian carcinoma (MONDO:0005140) is a cancer (an umbrella term covering 9 Mondo subtypes) with 75 cohort genes (519 GWAS associations across 46 studies; 38 CIViC-evidence somatic drivers; 19 ClinVar predisposition records) and 2,834 clinical trials. The dominant Reactome pathway is Impaired BRCA2 binding to PALB2 (8 cohort genes). Molecularly, BRCA1 Mutation confers sensitivity to Rucaparib in Ovarian Cancer (CIViC Level A); 71 further subtype–drug associations are mapped below. Top therapeutic interventions include topotecan, olaparib, and niraparib.

At a glance

• Classification: Cancer
• Umbrella term: 9 Mondo subtypes
• Cohort genes: 75
• GWAS associations: 519
• ClinVar variants: 19
• Clinical trials: 2,834
• Precision-medicine evidence (CIViC): 72 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ovarian carcinoma
Mondo ID	MONDO:0005140
EFO	EFO:0001075
DOID	DOID:4001
NCIT	C4908
UMLS	C4721610
MedGen	1648335
GARD	0024154
Is cancer (heuristic)	yes

Also known as: carcinoma of ovary · carcinoma of the ovary · epithelial ovarian cancer · ovarian cancer · ovarian carcinoma · ovarian epithelial cancer · ovary carcinoma

Data availability: 19 ClinVar variants · 519 GWAS associations (46 studies) · 87 cell lines.

Disease family

An umbrella term covering 9 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › epithelial neoplasm › ovarian epithelial tumor › malignant epithelial tumor of ovary › ovarian carcinoma

Related subtypes (5): ovarian clear cell cancer, malignant ovarian Brenner tumor, ovarian endometrial cancer, mucinous ovarian cancer, malignant ovarian serous tumor

Subtypes (9): ovarian adenocarcinoma, ovarian large-cell neuroendocrine carcinoma, ovarian squamous cell carcinoma, ovarian carcinosarcoma, ovarian small cell carcinoma, ovarian seromucinous carcinoma, ovarian transitional cell carcinoma, undifferentiated ovarian carcinoma, familial ovarian carcinoma

Genetics & variants

GWAS landscape

519 GWAS associations across 46 studies. Top hits map to 34 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1219648	4e-254	FGFR2	A
rs554833	1e-88	ABO	T
rs10962692	5e-64	BNC2 - RN7SL720P	G	1.34
rs630965	1e-63	CHCHD4P2 - RPL36P14	C
rs62274041	2e-57	TIPARP-AS1	G	1.57
chr3:156406997	4e-55		T	0.36
chr9:16914716	8e-51		A	0.81
rs3814113	2e-43	BNC2 - RN7SL720P	T
rs11200014	8e-35	FGFR2	A
rs7651446	2e-34	TIPARP, TIPARP-AS1	?	1.59
rs244353	1e-31	STXBP4	G
chr8:129541931	2e-28		A	0.83
rs6826366	3e-28	ADAM29	G
rs12601991	7e-28	HNF1B	T
rs7098100	4e-27	MLLT10	G
chr19:17390291	6e-26		C	0.12
rs1400482	7e-26	LINC00824	G	1.23
rs657152	6e-25	ABO	A
chr17:46472432	1e-24		C	1.13
rs4277389	1e-23	MAPT-AS1, LINC02210-CRHR1, CRHR1	A
rs4808616	2e-23	ABHD8	C
rs10069690	5e-23	TERT	C
rs56343119	1e-22	SURF4	A
rs9411395	3e-22	LCN1P2	G
rs2290202	4e-20	PRC1-AS1, PRC1	G
chr2:177039578	5e-20		T	0.9
rs851980	9e-20	ESR1	T
rs1879586	2e-19	PLEKHM1	G	1.16
rs4808075	2e-19	BABAM1, USHBP1	C	1.14
chr5:1285974	1e-18		A	0.1

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90270342	Guo H	2023	122,977	146,915	A genome-wide cross-cancer meta-analysis highlights the shared genetic links of five solid cancers.
GCST010797	Kar SP	2016	62,533	60,976	Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types.
GCST90016665	Dareng EO	2022	23,564	40,138	Polygenic risk modeling for prediction of epithelial ovarian cancer risk.
GCST90244167	Dareng EO	2024	23,394	105,724	Integrative multi-omics analyses to identify the genetic and functional mechanisms underlying ovarian cancer risk regions.
GCST90296490	Zhao X	2023	22,406	2,516,181	A large-scale genome-wide cross-trait analysis for the effect of COVID-19 on female-specific cancers.
GCST90296491	Zhao X	2023	22,406	2,103,746	A large-scale genome-wide cross-trait analysis for the effect of COVID-19 on female-specific cancers.
GCST90296492	Zhao X	2023	22,406	1,113,383	A large-scale genome-wide cross-trait analysis for the effect of COVID-19 on female-specific cancers.
GCST004415	Phelan CM	2017	22,406	40,941	Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.
GCST004462	Phelan CM	2017	16,924	68,502	Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.
GCST003587	Fehringer G	2016	5,020	61,820	Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	4
Tier 3: regulatory	0
Tier 4: intronic/intergenic	44

MAF distribution

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

Functional consequences

Consequence	Count
intron_variant	30
unknown	7
intergenic_variant	4
3_prime_UTR_variant	4
missense_variant	2
non_coding_transcript_exon_variant	2
synonymous_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1219648	10	121586676	A>G,T	0.05	intron_variant	FGFR2	4e-254	Tier 4: intronic/intergenic
rs554833	9	133271745	T>A,C,G	0.05	intron_variant	ABO	1e-88	Tier 4: intronic/intergenic
rs10962692	9	16915876	G>A,C,T	0.2	intergenic_variant	BNC2 - RN7SL720P	5e-64	Tier 4: intronic/intergenic
rs630965	9	108123199	C>A,G,T	0.05	intergenic_variant	CHCHD4P2 - RPL36P14	1e-63	Tier 4: intronic/intergenic
rs62274041	3	156717851	G>A,T	0.048	intron_variant	TIPARP-AS1	2e-57	Tier 4: intronic/intergenic
chr3:156406997				0.05			4e-55	Tier 4: intronic/intergenic
chr9:16914716				0.205			8e-51	Tier 4: intronic/intergenic
rs3814113	9	16915023	T>C	0.05	intergenic_variant	BNC2 - RN7SL720P	2e-43	Tier 4: intronic/intergenic
rs11200014	10	121575416	G>A,T	0.05	intron_variant	FGFR2	8e-35	Tier 4: intronic/intergenic
rs7651446	3	156689208	G>T	0.05	intron_variant	TIPARP, TIPARP-AS1	2e-34	Tier 4: intronic/intergenic
rs244353	17	55117408	G>A	0.05	intron_variant	STXBP4	1e-31	Tier 4: intronic/intergenic
chr8:129541931				0.13			2e-28	Tier 4: intronic/intergenic
rs6826366	4	174924959	G>A	0.05	intron_variant	ADAM29	3e-28	Tier 4: intronic/intergenic
rs12601991	17	37741642	T>A,G	0.05	intron_variant	HNF1B	7e-28	Tier 4: intronic/intergenic
rs7098100	10	21545607	G>A	0.05	intron_variant	MLLT10	4e-27	Tier 4: intronic/intergenic
chr19:17390291				0.297			6e-26	Tier 4: intronic/intergenic
rs1400482	8	128529685	G>A	0.132	intron_variant	LINC00824	7e-26	Tier 4: intronic/intergenic
rs657152	9	133263862	A>C,G,T	0.05	intron_variant	ABO	6e-25	Tier 4: intronic/intergenic
chr17:46472432				0.273			1e-24	Tier 4: intronic/intergenic
rs4277389	17	45818287	A>C,G	0.05	intron_variant	MAPT-AS1, LINC02210-CRHR1, CRHR1	1e-23	Tier 4: intronic/intergenic
rs4808616	19	17292224	C>A	0.05	3_prime_UTR_variant	ABHD8	2e-23	Tier 2: splice/UTR
rs10069690	5	1279675	C>T	0.05	intron_variant	TERT	5e-23	Tier 4: intronic/intergenic
rs56343119	9	133370796	C>A,G,T	0.05	intron_variant	SURF4	1e-22	Tier 4: intronic/intergenic
rs9411395	9	133317947	G>A	0.05	intron_variant	LCN1P2	3e-22	Tier 4: intronic/intergenic
rs2290202	15	90969037	G>A,C,T	0.05	3_prime_UTR_variant	PRC1-AS1, PRC1	4e-20	Tier 2: splice/UTR
chr2:177039578				0.32			5e-20	Tier 4: intronic/intergenic
rs851980	6	151706820	T>C	0.05	intron_variant	ESR1	9e-20	Tier 4: intronic/intergenic
rs1879586	17	45489971	C>G	0.181	intron_variant	PLEKHM1	2e-19	Tier 4: intronic/intergenic
rs4808075	19	17279482	T>C	0.296	intron_variant	BABAM1, USHBP1	2e-19	Tier 4: intronic/intergenic
chr5:1285974				0.33			1e-18	Tier 4: intronic/intergenic

ClinVar germline variants

19 retrieved; paginated sample, class counts are floors:

12 pathogenic, 4 pathogenic/likely pathogenic, 2 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
187552	NM_000051.4(ATM):c.3626_3627del (p.Phe1209fs)	ATM	Pathogenic	criteria provided, multiple submitters, no conflicts
17671	NM_007294.4(BRCA1):c.3607C>T (p.Arg1203Ter)	BRCA1	Pathogenic	reviewed by expert panel
266478	NM_007294.4(BRCA1):c.4503C>A (p.Cys1501Ter)	BRCA1	Pathogenic	reviewed by expert panel
37428	NM_007294.4(BRCA1):c.1728dup (p.Glu577fs)	BRCA1	Pathogenic	reviewed by expert panel
37542	NM_007294.4(BRCA1):c.3700_3704del (p.Val1234fs)	BRCA1	Pathogenic	reviewed by expert panel
417828	NM_007294.4(BRCA1):c.445G>T (p.Glu149Ter)	BRCA1	Pathogenic	reviewed by expert panel
54423	NM_007294.4(BRCA1):c.1969C>T (p.Gln657Ter)	BRCA1	Pathogenic	reviewed by expert panel
54683	NM_007294.4(BRCA1):c.2800C>T (p.Gln934Ter)	BRCA1	Pathogenic	reviewed by expert panel
55049	NM_007294.4(BRCA1):c.3916_3917del (p.Leu1306fs)	BRCA1	Pathogenic	reviewed by expert panel
89290	NM_000179.3(MSH6):c.2569_2572del (p.Asp857fs)	MSH6	Pathogenic	reviewed by expert panel
5294	NM_001048174.2(MUTYH):c.1103G>A (p.Gly368Asp)	MUTYH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1244220	NM_002485.5(NBN):c.1147G>T (p.Glu383Ter)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1244221	NM_002485.5(NBN):c.1071dup (p.Val358fs)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1255697	NM_024675.4(PALB2):c.3483del (p.Phe1161fs)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1098883	NM_002878.4(RAD51D):c.24_27del (p.Cys9fs)	RAD51D	Pathogenic	criteria provided, single submitter
30288	NM_002878.4(RAD51D):c.757C>T (p.Arg253Ter)	RAD51D	Pathogenic	criteria provided, multiple submitters, no conflicts
1251977	NM_007294.4(BRCA1):c.2640_2643dup (p.Cys882fs)	BRCA1	Likely pathogenic	no assertion criteria provided
944881	NM_007194.4(CHEK2):c.792+2T>A	CHEK2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
30286	NM_002878.4(RAD51D):c.480+1G>A	RAD51L3-RFFL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 167 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 3

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

Gene	HGNC	Evidence routes
BRCA1	BRCA1	GWAS, Orphanet
BRCA2	BRCA2	GWAS, Orphanet
BRIP1	BRIP1	GWAS, Orphanet

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
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
AURKA			CIViC #61
SYK			CIViC #5572
TOP1	Act	BCC,HCC	CIViC #5845
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
CCND1	Act	HNSC,PCM,UCEC	CIViC #8
CCNE1			CIViC #11
CD44			CIViC #855
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
VPS37A			CIViC #18353
DNMT1			CIViC #1510
EGFR	Act	BRCA,COADREAD,GB,GBM,HGGNOS,LGGNOS,LUAD,LUSC,NSCLC,PAST,PCM,READ,SIC	CIViC #19
ERCC1			CIViC #1735
FGF19			CIViC #7909
FNTB			CIViC #1950
ABCB1			CIViC #4244
GADD45A			CIViC #1411
GSTP1			CIViC #2473
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
ASS1			CIViC #450
NRG1	Act	ESCA,PRCC,STAD	CIViC #2593
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

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
BRAF	Orphanet:1340	Cardiofaciocutaneous syndrome
BRAF	Orphanet:146	Differentiated thyroid carcinoma
BRAF	Orphanet:251615	Pilomyxoid astrocytoma
BRAF	Orphanet:389	Langerhans cell histiocytosis
BRAF	Orphanet:500	Noonan syndrome with multiple lentigines
BRAF	Orphanet:54595	Craniopharyngioma
BRAF	Orphanet:58017	Classic hairy cell leukemia
BRAF	Orphanet:626	Large/giant congenital melanocytic nevus
BRAF	Orphanet:648	Noonan syndrome
BRAF	Orphanet:840	Syringocystadenoma papilliferum
BRAF	Orphanet:96253	Cushing disease
ARID1A	Orphanet:1465	Coffin-Siris syndrome
SYK	Orphanet:695807	Immunodeficiency-systemic inflammation-lymphoma predisposition syndrome
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	43
civic_only	29
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	gwas,clinvar,civic_evidence
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	gwas,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
AURKA	HGNC:11393	ENSG00000087586	O14965	Aurora kinase A	civic_evidence
SYK	HGNC:11491	ENSG00000165025	P43405	Tyrosine-protein kinase SYK	civic_evidence
TOP1	HGNC:11986	ENSG00000198900	P11387	DNA topoisomerase 1	civic_evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	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
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	civic_evidence
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
EGFR	HGNC:3236	ENSG00000146648	P00533	Epidermal growth factor receptor	civic_evidence
ERCC1	HGNC:3433	ENSG00000012061	P07992	DNA excision repair protein ERCC-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
GSTP1	HGNC:4638	ENSG00000084207	P09211	Glutathione S-transferase P	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
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	civic_evidence
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	civic_evidence
SYNGR1	HGNC:11498	ENSG00000100321	O43759	Synaptogyrin-1	gwas
TADA2A	HGNC:11531	ENSG00000276234	O75478	Transcriptional adapter 2-alpha	gwas
HNF1B	HGNC:11630	ENSG00000275410	P35680	Hepatocyte nuclear factor 1-beta	gwas
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	gwas
TFAP2A	HGNC:11742	ENSG00000137203	P05549	Transcription factor AP-2-alpha	gwas
TFAP2C	HGNC:11744	ENSG00000087510	Q92754	Transcription factor AP-2 gamma	gwas
ZNF274	HGNC:13068	ENSG00000171606	Q96GC6	Neurotrophin receptor-interacting factor homolog	gwas
ARHGEF5	HGNC:13209	ENSG00000050327	Q12774	Rho guanine nucleotide exchange factor 5	gwas
CNOT6	HGNC:14099	ENSG00000113300	Q9ULM6	CCR4-NOT transcription complex subunit 6	gwas
IRX3	HGNC:14360	ENSG00000177508	P78415	Iroquois-class homeodomain protein IRX-3	gwas
SNX16	HGNC:14980	ENSG00000104497	P57768	Sorting nexin-16	gwas
SKAP1	HGNC:15605	ENSG00000141293	Q86WV1	Src kinase-associated phosphoprotein 1	gwas
RALY	HGNC:15921	ENSG00000125970	Q9UKM9	RNA-binding protein Raly	gwas
MLLT10	HGNC:16063	ENSG00000078403	P55197	Protein AF-10	gwas
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	clinvar
MRPL45	HGNC:16651	ENSG00000278845	Q9BRJ2	Large ribosomal subunit protein mL45	gwas
NEBL	HGNC:16932	ENSG00000078114	O76041	Nebulette	gwas
DUSP14	HGNC:17007	ENSG00000276023	O95147	Dual specificity protein phosphatase 14	gwas
ADAMTS16	HGNC:17108	ENSG00000145536	Q8TE57	A disintegrin and metalloproteinase with thrombospondin motifs 16	gwas

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.
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).
AURKA	Aurora kinase A	Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression.
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.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
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.
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
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.
EGFR	Epidermal growth factor receptor	Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses.
ERCC1	DNA excision repair protein ERCC-1	Non-catalytic component of a structure-specific DNA repair endonuclease responsible for the 5’-incision during DNA repair.
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.
GSTP1	Glutathione S-transferase P	Catalyzes conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
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.
PIK3CA	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.
PTEN	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.
SYNGR1	Synaptogyrin-1	May play a role in regulated exocytosis.
TADA2A	Transcriptional adapter 2-alpha	Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4.
HNF1B	Hepatocyte nuclear factor 1-beta	Transcription factor that binds to the inverted palindrome 5’-GTTAATNATTAAC-3’.
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
TFAP2A	Transcription factor AP-2-alpha	Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes.
TFAP2C	Transcription factor AP-2 gamma	Sequence-specific DNA-binding transcription factor that interacts with cellular enhancer elements to regulate transcription of selected genes, and which plays a key role in early embryonic development.
ZNF274	Neurotrophin receptor-interacting factor homolog	Probable transcription repressor.
ARHGEF5	Rho guanine nucleotide exchange factor 5	Guanine nucleotide exchange factor which activates Rho GTPases.
CNOT6	CCR4-NOT transcription complex subunit 6	Poly(A) nuclease with 3’-5’ RNase activity.
IRX3	Iroquois-class homeodomain protein IRX-3	Transcription factor involved in SHH-dependent neural patterning.
SNX16	Sorting nexin-16	May be involved in several stages of intracellular trafficking.
SKAP1	Src kinase-associated phosphoprotein 1	Positively regulates T-cell receptor signaling by enhancing the MAP kinase pathway.
RALY	RNA-binding protein Raly	RNA-binding protein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the liver.
MLLT10	Protein AF-10	Probably involved in transcriptional regulation.
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.
MRPL45	Large ribosomal subunit protein mL45	Component of the mitochondrial large ribosomal subunit (mt-LSU).
NEBL	Nebulette	Binds to actin and plays an important role in the assembly of the Z-disk.
DUSP14	Dual specificity protein phosphatase 14	Involved in the inactivation of MAP kinases.
PDSS1	All trans-polyprenyl-diphosphate synthase PDSS1	Heterotetrameric enzyme that catalyzes the condensation of farnesyl diphosphate (FPP), which acts as a primer, and isopentenyl diphosphate (IPP) to produce prenyl diphosphates of varying chain lengths and participates in the determination…
CDKN2B	Cyclin-dependent kinase 4 inhibitor B	Interacts strongly with CDK4 and CDK6.

Protein-family classification

Druggable: 25 · Difficult: 23 · Unknown: 27 · Druggable fraction: 0.33

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	2.6×	0.092
Transcription factor	16	1.8×	0.092
Phosphatase	3	3.4×	0.201
Scaffold/PPI	7	1.6×	0.342
Enzyme (other)	9	1.4×	0.342
Transporter	2	2.1×	0.418
Ion channel	1	1.5×	0.703
Protease	2	1.0×	0.764
Other/Unknown	27	0.6×	1.000
Antibody/Immunoglobulin	1	0.4×	1.000

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
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
AURKA	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
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
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
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
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
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
EGFR	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ERCC1	Other/Unknown	no		ERCC1/RAD10/SWI10, RuvA_2-like, Restrct_endonuc-II-like
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
GSTP1	Enzyme (other)	yes	2.5.1.18	GST_pi, Glutathione_S-Trfase_N, GST_C
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
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom
SYNGR1	Other/Unknown	no		Marvel, Synaptogyrin
TADA2A	Transcription factor	no		Znf_ZZ, SANT/Myb, SWIRM
HNF1B	Transcription factor	no		HD, HNF1b_C, HNF-1_N
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
TFAP2A	Transcription factor	no		TF_AP2, TF_AP2_alpha_N, TF_AP2_C
TFAP2C	Transcription factor	no		TF_AP2, TF_AP2_gamma, TF_AP2_C
ZNF274	Transcription factor	no		KRAB, SCAN_dom, Znf_C2H2_type
ARHGEF5	Scaffold/PPI	no		DH_dom, GDS_CDC24_CS, SH3_domain
CNOT6	Phosphatase	yes		Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, Endo/exonuclease/phosphatase
IRX3	Transcription factor	no		HD, Iroquois_homeo, KN_HD
SNX16	Other/Unknown	no		PX_dom, PX_dom_sf, SNX16_PX
SKAP1	Scaffold/PPI	no		SH3_domain, PH_domain, PH-like_dom_sf
RALY	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, hnRNP_C
MLLT10	Transcription factor	no		Znf_PHD, Znf_FYVE_PHD, Znf_RING/FYVE/PHD
CHEK2	Kinase	yes	2.7.11.1	FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
MRPL45	Other/Unknown	no		Tim44-like_dom, NTF2-like_dom_sf, mtLSU_mL45
NEBL	Scaffold/PPI	no		Nebulin_repeat, SH3_domain, Nebulette_SH3
DUSP14	Phosphatase	yes		Dual-sp_phosphatase_cat-dom, Tyr_Pase_dom, Tyr_Pase_AS
ADAMTS16	Protease	yes		TSP1_rpt, Peptidase_M12B, Peptidase_M12B_N

Expression context

Cohort genes with no expression data: 0.

70 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	12
secondary oocyte	12
male germ line stem cell (sensu Vertebrata) in testis	11
oocyte	10
calcaneal tendon	8
buccal mucosa cell	6
lower esophagus mucosa	6
primordial germ cell in gonad	5
adrenal tissue	5
right uterine tube	5
sural nerve	4
olfactory segment of nasal mucosa	4
ganglionic eminence	3
stromal cell of endometrium	3
parotid gland	3
nipple	3
endothelial cell	3
jejunal mucosa	3
granulocyte	3
colonic epithelium	2

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
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
ARID1A	286	ubiquitous	marker	bone marrow cell, ventricular zone, embryo
AURKA	236	ubiquitous	marker	oocyte, secondary oocyte, ventricular zone
SYK	239	broad	marker	monocyte, mononuclear cell, leukocyte
TOP1	278	ubiquitous	marker	oocyte, ventricular zone, secondary oocyte
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
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
CDKN2A	220	ubiquitous	marker	parotid gland, cervix squamous epithelium, pituitary gland
VPS37A	255	ubiquitous	marker	islet of Langerhans, gastrocnemius, adrenal tissue
DNMT1	266	ubiquitous	marker	oocyte, secondary oocyte, sural nerve
EGFR	285	ubiquitous	marker	nipple, gingiva, gingival epithelium
ERCC1	285	ubiquitous	marker	apex of heart, parotid gland, right atrium auricular region
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
GSTP1	293	ubiquitous	marker	lower esophagus mucosa, right uterine tube, olfactory segment of nasal mucosa
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
ASS1	292	ubiquitous	marker	right lobe of liver, palpebral conjunctiva, liver
NRG1	209	ubiquitous	marker	ventricular zone, ganglionic eminence, oocyte
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon

Protein interactions among cohort

Intra-cohort edges: 74.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
EGFR	18,421
KRAS	14,509
PTEN	11,626
MDM2	9,892
CDKN2A	9,311
BRCA1	9,064
CCND1	8,328
BRAF	7,394
DNMT1	7,179

Intra-cohort edges

A	B	Sources
ADAMTS16	IRX3	string_interaction
ADAMTS16	TOP1	intact
ARID1A	LRP1B	string_interaction
ASNS	ASS1	biogrid_interaction
AURKA	BRCA1	string_interaction
AURKA	EGFR	intact
AURKA	GADD45A	biogrid_interaction
AURKA	TP53	string_interaction
BABAM1	BRCA1	intact, string_interaction
BABAM1	BRCA2	string_interaction
BRAF	BRCA2	biogrid_interaction
BRAF	CDKN2A	string_interaction
BRAF	EGFR	biogrid_interaction
BRAF	FGF19	intact
BRAF	KRAS	biogrid_interaction, intact, string_interaction
BRAF	PIK3CA	biogrid_interaction, string_interaction
BRAF	PTEN	biogrid_interaction, string_interaction
BRAF	TP53	string_interaction
BRCA1	BRCA2	string_interaction
BRCA1	BRIP1	biogrid_interaction, intact, string_interaction
BRCA1	CHEK2	string_interaction
BRCA1	GADD45A	string_interaction
BRCA1	TP53	string_interaction
BRCA2	BRIP1	string_interaction
BRCA2	CCND1	intact
BRCA2	CHEK2	string_interaction
BRCA2	TP53	string_interaction
CCDC88C	KRAS	intact
CCND1	CDKN2A	biogrid_interaction, string_interaction
CCND1	CDKN2B	string_interaction
CCND1	TP53	string_interaction
CCNE1	CDKN2A	string_interaction
CCNE1	TP53	string_interaction
CD44	EGFR	biogrid_interaction, string_interaction
CDKN2A	CDKN2B	biogrid_interaction
CDKN2A	KRAS	string_interaction
CDKN2A	MDM2	biogrid_interaction, string_interaction
CDKN2A	TP53	string_interaction
CDKN2B	TP53	string_interaction
CHEK2	MDM2	intact
CHEK2	TP53	intact, string_interaction
DDX52	DUSP14	string_interaction
DDX52	TADA2A	string_interaction
DNMT1	TET2	string_interaction
DNMT1	TP53	string_interaction
DUSP14	TADA2A	string_interaction
EGFR	FGF19	intact
EGFR	NRG1	intact
EGFR	PIK3CA	string_interaction
EGFR	PTEN	string_interaction

Structural data

PDB: 53 · AlphaFold-only: 22 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
EGFR	P00533	388
TP53	P04637	313
AURKA	O14965	193
MDM2	Q00987	147
PIK3CA	P42336	135
BRAF	P15056	131
SYK	P43405	93
MRPL45	Q9BRJ2	85
GSTP1	P09211	68
CHEK2	O96017	38
BRCA1	P38398	33
ABCG2	Q9UNQ0	29
DNMT1	P26358	27
ABCB1	P08183	24
TERT	O14746	23
CCNE1	P24864	22
IGF2	P01344	16
TOP1	P11387	15
BRCA2	P51587	14
ERCC1	P07992	14
FNTB	P49356	14
PTEN	P60484	12
CCND1	P24385	11
NRG1	Q02297	11
ARID1A	O14497	7
CD44	P16070	6
MLLT10	P55197	6
TET2	Q6N021	6
CDKN2A	P42771	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TUBA1C	Q9BQE3	91.70
CDKN2B	P42772	90.12
SLC10A5	Q5PT55	79.89
PDSS1	Q5T2R2	78.45
ADAMTS16	Q8TE57	72.07
CNTLN	Q9NXG0	71.14
NEK10	Q6ZWH5	70.23
TIPARP	Q7Z3E1	70.00
BTBD10	Q9BSF8	69.79
KDM3A	Q9Y4C1	69.06
ADGB	Q8N7X0	67.79
TFAP2C	Q92754	66.37
CCDC88C	Q9P219	65.69
TBC1D3	Q8IZP1	60.64
TBC1D3F	A6NER0	60.58
ZNF274	Q96GC6	59.79
ZBTB7B	O15156	56.36
IRX3	P78415	54.98
ARHGEF5	Q12774	48.84
ZNF804B	A4D1E1	43.04
LRP1B	Q9NZR2
FRY	Q5TBA9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 715. Enrichment computed across 130 evidence-associated genes (88 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 88 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	8	41.5×	3e-09	BRCA1, BRCA2, BRIP1, PALB2, NBN, ATM, RAD51B, RAD51D
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	8	38.5×	3e-09	BRCA1, BRCA2, BRIP1, PALB2, NBN, ATM, RAD51B, RAD51D
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	8	38.5×	3e-09	BRCA1, BRCA2, BRIP1, PALB2, NBN, ATM, RAD51B, RAD51D
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	8	38.5×	3e-09	BRCA1, BRCA2, BRIP1, PALB2, NBN, ATM, RAD51B, RAD51D
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	8	35.8×	5e-09	BRCA1, BRCA2, BRIP1, PALB2, NBN, ATM, RAD51B, RAD51D
Homologous DNA Pairing and Strand Exchange	8	34.6×	5e-09	BRCA1, BRCA2, BRIP1, PALB2, NBN, ATM, RAD51B, RAD51D
Resolution of D-loop Structures through Holliday Junction Intermediates	8	27.3×	4e-08	BRCA1, BRCA2, BRIP1, PALB2, NBN, ATM, RAD51B, RAD51D
HDR through Homologous Recombination (HRR)	8	17.3×	1e-06	BRCA1, BRCA2, BRIP1, PALB2, NBN, ATM, RAD51B, RAD51D
Cell Cycle	15	6.1×	1e-06	BRCA1, BRCA2, AURKA, TERT, CCND1, CCNE1, CDKN2A, CDKN2B (+7 more)
Presynaptic phase of homologous DNA pairing and strand exchange	7	21.6×	2e-06	BRCA1, BRCA2, BRIP1, NBN, ATM, RAD51B, RAD51D
Stabilization of p53	5	43.3×	4e-06	TP53, CHEK2, CDKN2A, MDM2, ATM
SUMOylation of transcription factors	5	32.4×	2e-05	TFAP2A, TFAP2C, TP53, CDKN2A, MDM2
Diseases of DNA repair	5	32.4×	2e-05	BRCA1, BRCA2, MSH6, NBN, ATM
Regulation of TP53 Activity through Phosphorylation	8	10.7×	4e-05	BRCA1, AURKA, TP53, CHEK2, BRIP1, MDM2, NBN, ATM
Defective homologous recombination repair (HRR) due to PALB2 loss of function	4	43.3×	7e-05	BRCA1, BRCA2, NBN, ATM
Diseases of DNA Double-Strand Break Repair	4	37.1×	1e-04	BRCA1, BRCA2, NBN, ATM
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	4	37.1×	1e-04	BRCA1, BRCA2, NBN, ATM
TFAP2 (AP-2) family regulates transcription of cell cycle factors	3	77.9×	2e-04	TFAP2A, TFAP2C, MYC
Cellular responses to stress	12	5.0×	2e-04	BRCA1, CCNE1, CDKN2A, CDKN2B, TUBA1C, LMNA, MDM2, ABCG2 (+4 more)
FLT3 Signaling	5	19.7×	2e-04	SYK, SH2B3, KRAS, PIK3CA, BCL2L11
p53-Dependent G1 DNA Damage Response	4	32.4×	2e-04	CCNE1, CDKN2A, MDM2, ATM
p53-Dependent G1/S DNA damage checkpoint	4	32.4×	2e-04	CCNE1, CDKN2A, MDM2, ATM
Reproduction	6	13.0×	2e-04	BRCA1, BRCA2, TFAP2C, TET2, NBN, ATM
Cell Cycle Checkpoints	8	8.1×	2e-04	BRCA1, CCNE1, CDKN2A, BABAM1, INCENP, MDM2, NBN, ATM
RNA Polymerase II Transcription	15	3.8×	2e-04	BRCA1, ARID1A, AURKA, TFAP2A, TFAP2C, CCND1, CCNE1, CDKN2A (+7 more)
G1/S DNA Damage Checkpoints	4	30.5×	2e-04	CCNE1, CDKN2A, MDM2, ATM
Homology Directed Repair	5	17.5×	2e-04	BRCA1, BRCA2, BABAM1, NBN, ATM
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	5	17.5×	2e-04	BRCA1, BRCA2, BABAM1, NBN, ATM
Impaired BRCA2 binding to RAD51	5	17.5×	2e-04	BRCA1, BRCA2, BRIP1, NBN, ATM
MITF-M-dependent gene expression	6	12.4×	2e-04	BRCA1, ARID1A, TERT, TFAP2A, CCND1, CDKN2A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 117 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
replicative senescence	6	50.8×	2e-06	TERT, TP53, CHEK2, CDKN2A, ERCC1, ATM
double-strand break repair	8	13.9×	7e-05	BRCA1, BRCA2, TP53, CHEK2, BRIP1, BABAM1, NBN, ATM
DNA damage response, signal transduction by p53 class mediator	6	18.4×	3e-04	BRCA2, TP53, CHEK2, MDM2, NBN, ATM
double-strand break repair via homologous recombination	8	10.7×	3e-04	BRCA1, BRCA2, PALB2, ANKLE1, NBN, ATM, RAD51B, RAD51D
intrinsic apoptotic signaling pathway in response to DNA damage	6	16.6×	4e-04	BRCA1, CHEK2, MSH6, MYC, ATM, BCL2L11
positive regulation of gene expression	14	4.6×	4e-04	BRCA1, BRAF, HNF1B, TFAP2A, TP53, ZBTB7B, DNMT1, HOXD3 (+6 more)
negative regulation of transcription by RNA polymerase II	21	3.2×	4e-04	HNF1B, TFAP2A, TP53, ZNF274, IRX3, CCND1, CCNE1, RALY (+13 more)
cellular senescence	6	15.2×	4e-04	BRCA2, TP53, CDKN2A, CDKN2B, LMNA, ATM
response to X-ray	4	30.3×	0.001	BRCA2, TP53, CCND1, ERCC1
regulation of cell cycle	9	5.7×	0.004	BRCA1, TADA2A, TP53, CDKN2A, GADD45A, MDM2, NBN, ATM (+1 more)
cellular response to gamma radiation	4	20.6×	0.005	TP53, CHEK2, MDM2, ATM
telomere maintenance via recombination	3	39.3×	0.005	BRCA2, TERT, RAD51D
regulation of ERK1 and ERK2 cascade	4	19.9×	0.005	SYK, NEK10, FGFR2, GSTP1
cellular response to hypoxia	7	7.2×	0.005	TERT, TP53, CCND1, FGFR2, LMNA, MDM2, MYC
homologous recombination	3	36.0×	0.006	BRCA1, BRIP1, NBN
thymocyte apoptotic process	3	36.0×	0.006	TP53, CHEK2, BCL2L11
telomere maintenance	5	11.4×	0.006	TERT, CCNE1, NBN, ATM, RAD51D
positive regulation of mitotic cell cycle	4	16.0×	0.008	BRCA2, AURKA, MDM2, ASNS
mitotic G2 DNA damage checkpoint signaling	4	15.2×	0.009	BRCA1, BABAM1, NBN, ATM
determination of adult lifespan	4	14.8×	0.009	TP53, ERCC1, MSH6, ATM
positive regulation of vascular associated smooth muscle cell proliferation	4	14.8×	0.009	TERT, DNMT1, FGFR2, MDM2
negative regulation of apoptotic process	12	3.6×	0.009	BRAF, AURKA, TFAP2A, TP53, CD44, PALB2, DAPK1, EGFR (+4 more)
negative regulation of gene expression via chromosomal CpG island methylation	3	27.0×	0.010	BRCA1, DNMT1, MYC
lactation	4	14.4×	0.010	CCND1, ZBTB7B, ABCB1, MTX1
cellular response to ionizing radiation	4	14.1×	0.010	BRCA1, BRCA2, TP53, GADD45A
rRNA transcription	3	25.4×	0.010	TOP1, TP53, CDKN2A
positive regulation of G1/S transition of mitotic cell cycle	4	13.7×	0.010	TERT, CCND1, CCNE1, EGFR
DNA damage checkpoint signaling	4	13.4×	0.011	CHEK2, BRIP1, NBN, ATM
negative regulation of reactive oxygen species metabolic process	3	24.0×	0.011	BRCA1, TFAP2A, TP53
nucleotide-excision repair	4	13.1×	0.011	BRCA2, TP53, BRIP1, ERCC1

Therapeutics

Drugs indicated for this disease

5 approved, 14 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)
Olaparib	Approved (phase 4)
Paclitaxel	Approved (phase 4)
Trabectedin	Approved (phase 4)
Atezolizumab	Phase 3 (in late-stage trials)
Binimetinib	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Dexamethasone	Phase 3 (in late-stage trials)
Doxorubicin	Phase 3 (in late-stage trials)
Durvalumab	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Letrozole	Phase 3 (in late-stage trials)
Lurbinectedin	Phase 3 (in late-stage trials)
Niraparib	Phase 3 (in late-stage trials)
Oregovomab	Phase 3 (in late-stage trials)
Tamoxifen	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): Aldesleukin, Alisertib, Alpelisib, Auranofin, Capecitabine, Celecoxib, Dalpiciclib, Decitabine, Denileukin Diftitox, Epacadostat, Fludarabine, Fluorouracil, Fulvestrant, Ipatasertib, Ipilimumab, Irinotecan, Lenvatinib, Levonorgestrel, Metformin, Methotrexate, Milademetan, Modafinil, Nivolumab, Oxaliplatin, Palbociclib, Panitumumab, Pembrolizumab, Pemetrexed, Regorafenib, Ribociclib, Sacituzumab Govitecan, Sargramostim, Selinexor, Sirolimus, Sotorasib, Toripalimab, Tremelimumab.

Drug target analysis

Approved (phase 4): 22 · Phase ≥3: 23 · Phased (≥1): 23 · Undrugged: 52

Druggability breadth: 58 of 130 evidence-associated genes (45%) 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
BRAF	VEMURAFENIB
AURKA	INAMRINONE
SYK	FEDRATINIB
TOP1	TOPOTECAN HYDROCHLORIDE
TP53	NITROFURANTOIN
CCND1	PALBOCICLIB
CCNE1	PALBOCICLIB
DNMT1	DECITABINE
EGFR	LEVODOPA
FNTB	CORTISONE ACETATE
ABCB1	PROGESTERONE
GSTP1	ETHACRYNIC ACID
KRAS	VEMURAFENIB
MDM2	NITROFURANTOIN
ABCG2	CANDESARTAN CILEXETIL
PIK3CA	IDELALISIB
TERT	BERBERINE
CHEK2	NERATINIB
TUBA1C	COLCHICINE
TIPARP	OLAPARIB
TET2	VADADUSTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
EGFR	175	4
ABCB1	119	4
ABCG2	92	4
PIK3CA	67	4
AURKA	65	4
SYK	54	4
BRAF	48	4
CCNE1	38	4
CCND1	35	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1, TOP1
DAUNORUBICIN	4	ABCB1, BRCA1, TP53
DOXORUBICIN HYDROCHLORIDE	4	ABCB1, BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	ABCB1, ABCG2, BRCA1
VEMURAFENIB	4	BRAF, EGFR, KRAS
PONATINIB	4	ABCG2, BRAF, EGFR
FEDRATINIB	4	AURKA, BRAF, EGFR, PIK3CA, SYK
SORAFENIB	4	ABCG2, AURKA, BRAF, EGFR
DASATINIB ANHYDROUS	4	BRAF, EGFR
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF, SYK
INFIGRATINIB	4	BRAF, SYK
REGORAFENIB	4	ABCG2, BRAF
DABRAFENIB	4	BRAF, KRAS
COBIMETINIB	4	BRAF
NILOTINIB	4	ABCG2, BRAF
ABEMACICLIB	4	BRAF, CCND1, CCNE1, EGFR
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	AURKA, BRAF, SYK
DASATINIB	4	ABCG2, AURKA, BRAF, EGFR, PIK3CA, SYK
ERLOTINIB	4	ABCB1, ABCG2, AURKA, BRAF, EGFR, SYK
GEFITINIB	4	ABCB1, ABCG2, BRAF, CHEK2, EGFR
IMATINIB	4	ABCB1, ABCG2, BRAF, EGFR, SYK
INAMRINONE	4	AURKA
AXITINIB	4	AURKA, EGFR
NICLOSAMIDE	4	AURKA, EGFR, TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 22.

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

Symbol	Assays	Type breakdown
EGFR	6,531	Binding:6211, Functional:173, ADMET:138, Toxicity:9
ABCB1	3,063	Binding:2135, Functional:746, ADMET:182
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
TUBA1C	1,689	Binding:1648, Functional:35, ADMET:6
AURKA	1,500	Binding:1483, Functional:10, ADMET:7
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
CHEK2	690	Binding:687, Functional:2, ADMET:1
CCND1	576	Binding:574, Functional:1, ADMET:1
FNTB	425	Binding:366, Functional:59
TERT	391	Binding:389, Functional:2
DNMT1	233	Binding:229, Functional:3, ADMET:1
GSTP1	126	Binding:107, ADMET:19
TIPARP	48	Binding:48
NEK10	40	Binding:40
ERCC1	28	Binding:28
ASNS	27	Binding:27
KDM3A	25	Binding:25
TET2	24	Binding:24
BRCA1	13	Binding:9, Functional:4
CD44	9	Binding:9
PTEN	8	Binding:8
ARID1A	6	Binding:6
CNOT6	3	Binding:3
CDKN2A	2	Binding:2
ASS1	1	Binding:1
DUSP14	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
AURKA	2.7.11.1	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
EGFR	2.7.10.1	receptor protein-tyrosine kinase
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
GSTP1	2.5.1.18	glutathione transferase
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
PIK3CA	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase
CHEK2	2.7.11.1	non-specific serine/threonine protein kinase
PDSS1	2.5.1.91	all-trans-decaprenyl-diphosphate synthase
BRIP1	3.6.4.12	DNA helicase
KDM3A	1.14.11.65	[histone H3]-dimethyl-L-lysine9 demethylase
TIPARP	2.4.2.30	NAD+ ADP-ribosyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BRAF	1,442
AURKA	1,500
SYK	873
TOP1	1,200
TP53	869
CCND1	576
CCNE1	691
DNMT1	233
EGFR	6,531
FNTB	425
ABCB1	3,063
GSTP1	126
KRAS	861
MDM2	1,007
ABCG2	878
PIK3CA	2,034
TERT	391
CHEK2	690
TUBA1C	1,689

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

28 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, TOP1
DAUNORUBICIN	4	ABCB1, BRCA1, TP53
DOXORUBICIN HYDROCHLORIDE	4	ABCB1, BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	ABCB1, ABCG2, BRCA1
VEMURAFENIB	4	BRAF, EGFR, KRAS
PONATINIB	4	ABCG2, BRAF, EGFR
FEDRATINIB	4	AURKA, BRAF, EGFR, PIK3CA, SYK
SORAFENIB	4	ABCG2, AURKA, BRAF, EGFR
DASATINIB ANHYDROUS	4	BRAF, EGFR
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF, SYK
INFIGRATINIB	4	BRAF, SYK
REGORAFENIB	4	ABCG2, BRAF
DABRAFENIB	4	BRAF, KRAS
COBIMETINIB	4	BRAF
NILOTINIB	4	ABCG2, BRAF
ABEMACICLIB	4	BRAF, CCND1, CCNE1, EGFR
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
DASATINIB	4	ABCG2, AURKA, BRAF, EGFR, PIK3CA, SYK
ERLOTINIB	4	ABCB1, ABCG2, AURKA, BRAF, EGFR, SYK
IMATINIB	4	ABCB1, ABCG2, BRAF, EGFR, SYK
INAMRINONE	4	AURKA
AXITINIB	4	AURKA, EGFR
NICLOSAMIDE	4	AURKA, EGFR, TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	22	BRCA1, BRAF, AURKA, SYK, TOP1, TP53, CCND1, CCNE1, DNMT1, EGFR (+12 more)
B	Phased (≥1) drug, not yet approved	1	NEK10
C	Druggable family + PDB, no drug	8	ASNS, ASS1, NRG1, PTEN, CNOT6, DUSP14, BRIP1, TPCN2
D	Druggable family + AlphaFold only, no drug	4	ADAMTS16, PDSS1, KDM3A, ADGB
E	Difficult family or no structure, no drug	40	BRCA2, ARID1A, CD44, CDKN2A, VPS37A, ERCC1, FGF19, GADD45A, IGF2, LRP1B (+30 more)

Undrugged target profiles

52 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
NRG1	0	EGFR
PTEN	8	TP53
TFAP2A	0	TP53
CDKN2B	0	TP53
BRIP1	0	BRCA1
ARID1A	6	—
CD44	9	—
VPS37A	0	—
ERCC1	28	—
FGF19	0	—
GADD45A	0	—
IGF2	0	—
LRP1B	0	—
ASNS	27	—
ASS1	1	—
SYNGR1	0	—
TADA2A	0	—
HNF1B	0	—
TFAP2C	0	—
ZNF274	0	—
ARHGEF5	0	—
CNOT6	3	—
IRX3	0	—
SNX16	0	—
SKAP1	0	—
RALY	0	—
MLLT10	0	—
MRPL45	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2,834.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	641
PHASE1/PHASE2	208
PHASE3	205
PHASE4	24
PHASE2/PHASE3	22

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
NCT06972693	PHASE4	ACTIVE_NOT_RECRUITING	NGS-based Germline and Somatic Genetic Test in Ovarian Carcinoma
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
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
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
NCT03164980	PHASE4	TERMINATED	QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer
NCT03349463	PHASE4	UNKNOWN	Evaluation of Fluciclovine Uptake in Patients With Cervical, Ovarian Epithelial or Endometrial Cancers.
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
NCT05949424	PHASE4	UNKNOWN	OPTI - DOSE: Optimal Dosing of Oral Anticancer Drugs in Older Adults
NCT00565851	PHASE3	ACTIVE_NOT_RECRUITING	Carboplatin, Paclitaxel and Gemcitabine Hydrochloride With or Without Bevacizumab After Surgery in Treating Patients With Recurrent Ovarian, Epithelial, Primary Peritoneal, or Fallopian Tube Cancer
NCT01081262	PHASE3	ACTIVE_NOT_RECRUITING	Carboplatin and Paclitaxel or Oxaliplatin and Capecitabine With or Without Bevacizumab as First-Line Therapy in Treating Patients With Newly Diagnosed Stage II-IV or Recurrent Stage I Epithelial Ovarian or Fallopian Tube Cancer
NCT01223248	PHASE3	ACTIVE_NOT_RECRUITING	Randomized Study Comparing Two Dosing Schedules for Hypofractionated Image-Guided Radiation Therapy
NCT01376752	PHASE3	ACTIVE_NOT_RECRUITING	Hyperthermic Intra-Peritoneal Chemotherapy (HIPEC) in Relapse Ovarian Cancer Treatment
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
NCT02446600	PHASE3	ACTIVE_NOT_RECRUITING	Testing the Use of A Single Drug (Olaparib) or the Combination of Two Drugs (Cediranib and Olaparib) Compared to the Usual Chemotherapy for Women With Platinum Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
NCT02502266	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Testing the Combination of Cediranib and Olaparib in Comparison to Each Drug Alone or Other Chemotherapy in Recurrent Platinum-Resistant Ovarian Cancer
NCT02839707	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Pegylated Liposomal Doxorubicin Hydrochloride With Atezolizumab and/or Bevacizumab in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
NCT02859038	PHASE3	ACTIVE_NOT_RECRUITING	Study of Upfront Surgery Versus Neoadjuvant Chemotherapy in Patients With Advanced Ovarian Cancer (SUNNY)
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
NCT03522246	PHASE3	ACTIVE_NOT_RECRUITING	A Study in Ovarian Cancer Patients Evaluating Rucaparib and Nivolumab as Maintenance Treatment Following Response to Front-Line Platinum-Based Chemotherapy
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

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TOPOTECAN	4	82
OLAPARIB	4	27
NIRAPARIB	4	25
CARBOPLATIN	4	19
PACLITAXEL	4	16
GEMCITABINE	4	13
DOXORUBICIN	4	12
PAZOPANIB	4	12
RUCAPARIB	4	12
AMIFOSTINE	4	9
PEGFILGRASTIM	4	9
CISPLATIN	4	7
INDOCYANINE GREEN ACID FORM	4	6
MIRVETUXIMAB SORAVTANSINE	4	6
THIOTEPA	4	6
TRABECTEDIN	4	6
ATEZOLIZUMAB	4	5
AVELUMAB	4	5
ERLOTINIB HYDROCHLORIDE	4	5
GEFITINIB	4	5
IFOSFAMIDE	4	5
IXABEPILONE	4	5
SUNITINIB MALATE	4	5
TALAZOPARIB	4	5
CATUMAXOMAB	4	4
DOSTARLIMAB	4	4
IMATINIB MESYLATE	4	4
SORAFENIB TOSYLATE	4	4
TEMSIROLIMUS	4	4
TREMELIMUMAB	4	4

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 72 predictive associations from 84 curated evidence items; also 14 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
BRCA1 Mutation OR BRCA2 Mutation	Niraparib	Sensitivity/Response	CIViC A	EID11243
BRCA1 Mutation	Platinum Compound	Sensitivity/Response	CIViC B	EID1529 +1
BRCA2 Mutation	Platinum Compound	Sensitivity/Response	CIViC B	EID1530 +1
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 V600E AND BRAF Amplification	Atezolizumab + Bevacizumab	Sensitivity/Response	CIViC B	EID9885
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
ERCC1 Underexpression	Platinum Compound	Sensitivity/Response	CIViC B	EID10146
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
KRAS RS61764370	Paclitaxel + Carboplatin	Resistance	CIViC B	EID664
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

+42 more predictive associations (showing top 30 by evidence level).