Endometrial carcinoma

Summary

Endometrial carcinoma (MONDO:0002447) is a cancer (an umbrella term covering 7 Mondo subtypes) with 75 cohort genes (117 GWAS associations across 13 studies; 35 CIViC-evidence somatic drivers; 2,044 ClinVar predisposition records) and 1,033 clinical trials. The dominant Reactome pathway is Diseases of DNA repair (10 cohort genes). Molecularly, ERBB2 Amplification confers sensitivity to Trastuzumab in Endometrial Cancer (CIViC Level B); 19 further subtype–drug associations are mapped below. Top therapeutic interventions include lenvatinib, megestrol acetate, and dostarlimab.

At a glance

• Classification: Cancer
• Umbrella term: 7 Mondo subtypes
• Cohort genes: 75
• GWAS associations: 117
• ClinVar variants: 2,044
• Clinical trials: 1,033
• Precision-medicine evidence (CIViC): 20 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	endometrial carcinoma
Mondo ID	MONDO:0002447
EFO	EFO:1001512
DOID	DOID:2871
ICD-11	1123821211
NCIT	C7558
SNOMED CT	254878006
UMLS	C0476089
MedGen	96903
Anatomy (UBERON)	UBERON:0001295
Is cancer (heuristic)	yes

Also known as: carcinoma of endometrium · carcinoma of the endometrium · carcinoma, endometrial, malignant · endometrial cancer · endometrial carcinoma · endometrial carcinoma (disease) · endometrium carcinoma

Data availability: 2,044 ClinVar variants · 117 GWAS associations (13 studies) · 1 HPO phenotype · 21 cell lines · 71 intOGen driver records.

Disease family

An umbrella term covering 7 Mondo subtypes.

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

Related subtypes (8): uterus carcinoma in situ, cervical carcinoma, endometrial serous adenocarcinoma, squamous cell carcinoma of the corpus uteri, undifferentiated carcinoma of the corpus uteri, papillary carcinoma of the corpus uteri, adenoid cystic carcinoma of the corpus uteri, transitional cell carcinoma of the corpus uteri

Subtypes (7): uterine corpus endometrial carcinoma, endometrial transitional cell carcinoma, endometrium carcinoma in situ, endometrium adenocarcinoma, endometrial small cell carcinoma, endometrial squamous cell carcinoma, endometrial undifferentiated carcinoma

Genetics & variants

GWAS landscape

117 GWAS associations across 13 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
rs11263761	3e-20	HNF1B	A	1.15
rs11263763	3e-19	HNF1B	A	1.2
rs7981863	3e-17	RNY1P8 - MARK2P12	C	1.16
rs1740828	4e-16	BOLA2P3 - CASC15	G	1.15
rs17601876	3e-14	MIR4713HG, CYP19A1	G	1.12
rs4733613	8e-14	LINC00824 - CCDC26	C	1.18
rs2797160	4e-13	HEY2-AS1, LINC02523	?	1.21
rs2414098	5e-13	CYP19A1, MIR4713HG	C	1.17
rs9600103	4e-12	RNY1P8 - MARK2P12	?	1.23
rs11841589	5e-11	RNY1P8 - MARK2P12	G	1.15
rs3184504	1e-10	ATXN2, SH2B3	C	1.1
rs2747716	3e-10	LINC02523, HEY2-AS1	A	1.1
rs13328298	4e-10	HEY2-AS1, LINC02523	G	1.13
rs937213	7e-10	EIF2AK4	C	1.12
rs9668337	1e-09	SSPN-AS1, SSPN	A	1.11
rs6782972	3e-09	RARB	G	1.2
rs35286446	3e-09	LINC00824	GAT	1.1
rs10850382	3e-09	TBX3-AS1 - UBA52P7	T	1.1
rs882380	5e-09	SKAP1	A	1.1
rs1679014	6e-09	CDKN2B-AS1	T	1.18
rs11651052	1e-08	HNF1B	?	1.16
rs10835920	1e-08	WT1-AS	T	1.09
rs9639594	2e-08	CPVL	A	1.14
rs187798970	2e-08	NTM-AS2, NTM	T	3.45
rs148261157	3e-08	RN7SL361P - IFITM3P9	A	1.26
rs113998067	3e-08	GNL2 - RSPO1	C	1.27
rs2498796	4e-08	AKT1	A	1.12
rs2218868	4e-08	OR9Q1	T	1.15
rs1129506	4e-08	NF1, EVI2A	G	1.1
rs79024726	5e-08	CSMD2	T	1.11

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST006464	O’Mara TA	2018	12,906	108,979	Identification of nine new susceptibility loci for endometrial cancer.
GCST006465	O’Mara TA	2018	8,758	46,126	Identification of nine new susceptibility loci for endometrial cancer.
GCST003436	Chen MM	2016	4,907	11,945	GWAS meta-analysis of 16 852 women identifies new susceptibility locus for endometrial cancer.
GCST005906	Painter JN	2018	3,194	5,330	Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses.
GCST90018838	Sakaue S	2021	2,188	237,839	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST003524	Cheng TH	2016	2,082	9,544	Five endometrial cancer risk loci identified through genome-wide association analysis.
GCST90011820	Rashkin SR	2020	2,037	410,350	Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts.
GCST006466	O’Mara TA	2018	1,230	35,447	Identification of nine new susceptibility loci for endometrial cancer.
GCST90018618	Sakaue S	2021	1,200	60,614	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90013698	Ishigaki K	2020	999	89,731	Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	2
Tier 3: regulatory	0
Tier 4: intronic/intergenic	46

MAF distribution

Bucket	Variants
common (>=0.05)	41
low_freq (0.01-0.05)	8
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	34
intergenic_variant	11
missense_variant	2
non_coding_transcript_exon_variant	1
5_prime_UTR_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs11263761	17	37737784	A>G,T	0.48	intron_variant	HNF1B	3e-20	Tier 4: intronic/intergenic
rs11263763	17	37743574	A>C,G	0.46	intron_variant	HNF1B	3e-19	Tier 4: intronic/intergenic
rs7981863	13	73238004	C>T	0.28	intergenic_variant	RNY1P8 - MARK2P12	3e-17	Tier 4: intronic/intergenic
rs1740828	6	21648854	G>A	0.48	intergenic_variant	BOLA2P3 - CASC15	4e-16	Tier 4: intronic/intergenic
rs17601876	15	51261712	A>C,G	0.48	intron_variant	MIR4713HG, CYP19A1	3e-14	Tier 4: intronic/intergenic
rs4733613	8	128587032	C>A,G,T	0.12	intergenic_variant	LINC00824 - CCDC26	8e-14	Tier 4: intronic/intergenic
rs2797160	6	125688970	A>G	0.422	intron_variant	HEY2-AS1, LINC02523	4e-13	Tier 4: intronic/intergenic
rs2414098	15	51245609	T>A,C,G	0.38	intron_variant	CYP19A1, MIR4713HG	5e-13	Tier 4: intronic/intergenic
rs9600103	13	73237742	A>C,T	0.278	intergenic_variant	RNY1P8 - MARK2P12	4e-12	Tier 4: intronic/intergenic
rs11841589	13	73240754	G>T	0.26	intergenic_variant	RNY1P8 - MARK2P12	5e-11	Tier 4: intronic/intergenic
rs3184504	12	111446804	T>A,C,G	0.48	missense_variant	ATXN2, SH2B3	1e-10	Tier 1: coding
rs2747716	6	125687226	A>G,T	0.43	intron_variant	LINC02523, HEY2-AS1	3e-10	Tier 4: intronic/intergenic
rs13328298	6	125695434	G>A,C	0.42	intron_variant	HEY2-AS1, LINC02523	4e-10	Tier 4: intronic/intergenic
rs937213	15	40029923	T>A,C	0.422	intron_variant	EIF2AK4	7e-10	Tier 4: intronic/intergenic
rs9668337	12	26273405	G>A	0.26	non_coding_transcript_exon_variant	SSPN-AS1, SSPN	1e-09	Tier 4: intronic/intergenic
rs6782972	3	24922859	A>G	0.05	intron_variant	RARB	3e-09	Tier 4: intronic/intergenic
rs35286446	8	128433618	GATATAT>G,GATAT,GATATATAT,GATATATATAT	0.42	intron_variant	LINC00824	3e-09	Tier 4: intronic/intergenic
rs10850382	12	114776743	C>G,T	0.31	intergenic_variant	TBX3-AS1 - UBA52P7	3e-09	Tier 4: intronic/intergenic
rs882380	17	48216874	C>A,G	0.39	intron_variant	SKAP1	5e-09	Tier 4: intronic/intergenic
rs1679014	9	22207038	T>A,C,G	0.07	intron_variant	CDKN2B-AS1	6e-09	Tier 4: intronic/intergenic
rs11651052	17	37742390	G>A,C,T	0.465	intron_variant	HNF1B	1e-08	Tier 4: intronic/intergenic
rs10835920	11	32468118	C>G,T	0.38	intron_variant	WT1-AS	1e-08	Tier 4: intronic/intergenic
rs9639594	7	29139570	G>A,T	0.206	intron_variant	CPVL	2e-08	Tier 4: intronic/intergenic
rs187798970	11	131536940	G>A,C,T		intron_variant	NTM-AS2, NTM	2e-08	Tier 4: intronic/intergenic
rs148261157	2	60670444	G>A	0.03	intergenic_variant	RN7SL361P - IFITM3P9	3e-08	Tier 4: intronic/intergenic
rs113998067	1	37607755	T>C	0.043	intergenic_variant	GNL2 - RSPO1	3e-08	Tier 4: intronic/intergenic
rs2498796	14	104776883	G>A	0.3	intron_variant	AKT1	4e-08	Tier 4: intronic/intergenic
rs2218868	11	58158505	C>T	0.05	intron_variant	OR9Q1	4e-08	Tier 4: intronic/intergenic
rs1129506	17	31319014	G>A,C,T	0.38	5_prime_UTR_variant	NF1, EVI2A	4e-08	Tier 2: splice/UTR
rs79024726	1	33832760	T>A,G	0.19	intron_variant	CSMD2	5e-08	Tier 4: intronic/intergenic

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

216 conflicting classifications of pathogenicity, 208 uncertain significance, 72 pathogenic/likely pathogenic, 45 pathogenic, 24 benign/likely benign, 18 likely benign, 7 likely pathogenic, 7 benign, 3 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
141182	NM_000051.4(ATM):c.2921+1G>A	ATM	Pathogenic	criteria provided, multiple submitters, no conflicts
127720	NM_000465.4(BARD1):c.1690C>T (p.Gln564Ter)	BARD1	Pathogenic	criteria provided, multiple submitters, no conflicts
17662	NM_007294.4(BRCA1):c.68_69del (p.Glu23fs)	BRCA1	Pathogenic	reviewed by expert panel
17677	NM_007294.4(BRCA1):c.5266dup (p.Gln1756fs)	BRCA1	Pathogenic	reviewed by expert panel
132709	NM_004360.5(CDH1):c.715G>A (p.Gly239Arg)	CDH1	Pathogenic	reviewed by expert panel
136055	NM_004360.5(CDH1):c.1003C>T (p.Arg335Ter)	CDH1	Pathogenic	reviewed by expert panel
140781	NM_004360.5(CDH1):c.2064_2065del (p.Cys688_Glu689delinsTer)	CDH1	Pathogenic	reviewed by expert panel
142888	NM_004360.5(CDH1):c.1147C>T (p.Gln383Ter)	CDH1	Pathogenic	reviewed by expert panel
128075	NM_007194.4(CHEK2):c.444+1G>A	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
216652	NM_007194.4(CHEK2):c.846+4_846+7del	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070997	NM_002439.5(MSH3):c.76C>T (p.Arg26Ter)	DHFR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075635	NM_002439.5(MSH3):c.136C>T (p.Gln46Ter)	DHFR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1786093	NM_002439.5(MSH3):c.211_218dup (p.Gln74fs)	DHFR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1787741	NM_002439.5(MSH3):c.220C>T (p.Gln74Ter)	DHFR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13272	NM_000141.5(FGFR2):c.755C>G (p.Ser252Trp)	FGFR2	Pathogenic	criteria provided, multiple submitters, no conflicts
13277	NM_000141.5(FGFR2):c.1124A>G (p.Tyr375Cys)	FGFR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12589	NM_004985.5(KRAS):c.40G>A (p.Val14Ile)	KRAS	Pathogenic	reviewed by expert panel
1376058	NM_002439.5(MSH3):c.1022del (p.Gly341fs)	LOC126807437	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2020610	NM_002439.5(MSH3):c.1017_1018insC (p.Ile340fs)	LOC126807437	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1048910	NM_000249.4(MLH1):c.131_132delinsTT (p.Ser44Phe)	MLH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1050662	NM_000249.4(MLH1):c.1559-4_1667+63del	MLH1	Pathogenic	no assertion criteria provided
17094	NM_000249.4(MLH1):c.350C>T (p.Thr117Met)	MLH1	Pathogenic	reviewed by expert panel
1048814	NM_000251.3(MSH2):c.459del (p.Ala154fs)	MSH2	Pathogenic	criteria provided, single submitter
1049291	NM_000251.3(MSH2):c.1163dup (p.Asn388fs)	MSH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1049937	NM_000251.3(MSH2):c.367-2_645+742del	MSH2	Pathogenic	no assertion criteria provided
1068925	NM_002439.5(MSH3):c.724C>T (p.Gln242Ter)	MSH3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069054	NM_002439.5(MSH3):c.2835del (p.Tyr946fs)	MSH3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069310	NM_002439.5(MSH3):c.1828C>T (p.Gln610Ter)	MSH3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070175	NM_002439.5(MSH3):c.2620C>T (p.Gln874Ter)	MSH3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070750	NM_002439.5(MSH3):c.242del (p.Thr81fs)	MSH3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 243 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
TP53	LoF	ACC,ALL,AML,ANGS,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,EGC,ES,ESCA,ESCC,GB,GBC,GBM,GIST,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LNM,LUAD,LUSC,MBL,MEL,MLYM,MT,NBL,NETNOS,NHL,NPC,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PCM,PLMESO,PRAD,PRCC,PROSTATE,RCC,READ,SACA,SARCNOS,SCLC,SIC,SKCM,SKIN,SOFT_TISSUE,STAD,STOMACH,THYM,UCEC,UCS,UTUC,VULVA,WDTC,WT	CIViC #45
ERBB2	Act	BLCA,BRCA,CESC,CHOL,COADREAD,EGC,ESCA,ESCC,LMS,LUAD,NSCLC,OVT,PRCC,READ,STAD,UCEC	CIViC #20
FGFR2	Act	BRCA,CHOL,LUSC,SACA,UCEC	CIViC #22
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
MLH1			CIViC #3532
MSH2			CIViC #3628
MSH6			CIViC #2478
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
POLE	Act	ACC,BLCA	CIViC #4386
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
RIT1			CIViC #4875
CCNE1			CIViC #11
ANTXR1	LoF	LUNG,MEL,STAD,UTUC	CIViC #524
KIT	Act	AML,GIST,MEL,MGCT	CIViC #29
STMN1			CIViC #3255
MRE11			CIViC #3586
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
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
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
STK11	LoF	ANSC,CEAD,CESC,CHOL,LUAD,NSCLC,WDTC	CIViC #5534
WT1	LoF	AML,MEL,PAAD	CIViC #49
BCL11A	Act	NHL	CIViC #12133
FBXO11	LoF	BL,MLYM,NHL	CIViC #15318
CHEK2	Act	BRCA	CIViC #8950
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
CDKN2B			CIViC #916
PALB2	LoF	OVT	CIViC #15013

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma
ERBB2	Orphanet:213726	Serous carcinoma of the corpus uteri
ERBB2	Orphanet:2800	Extramammary Paget disease
ERBB2	Orphanet:388	Hirschsprung disease
ERBB2	Orphanet:99976	Adenocarcinoma of the oesophagus and oesophagogastric junction
FGFR2	Orphanet:1540	Jackson-Weiss syndrome
FGFR2	Orphanet:1555	Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome
FGFR2	Orphanet:168624	Familial scaphocephaly syndrome, McGillivray type
FGFR2	Orphanet:207	Crouzon syndrome
FGFR2	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGFR2	Orphanet:313855	FGFR2-related bent bone dysplasia
FGFR2	Orphanet:596008	Antley-Bixler syndrome without genital anomaly or disorder of steroidogenesis
FGFR2	Orphanet:794	Saethre-Chotzen syndrome
FGFR2	Orphanet:87	Apert syndrome
FGFR2	Orphanet:93258	Pfeiffer syndrome type 1
FGFR2	Orphanet:93259	Pfeiffer syndrome type 2
FGFR2	Orphanet:93260	Pfeiffer syndrome type 3
KRAS	Orphanet:1333	Familial pancreatic carcinoma
KRAS	Orphanet:1340	Cardiofaciocutaneous syndrome
KRAS	Orphanet:144	Lynch syndrome
KRAS	Orphanet:146	Differentiated thyroid carcinoma
KRAS	Orphanet:2396	Encephalocraniocutaneous lipomatosis
KRAS	Orphanet:251615	Pilomyxoid astrocytoma
KRAS	Orphanet:2612	Linear nevus sebaceus syndrome
KRAS	Orphanet:268114	RAS-associated autoimmune leukoproliferative disease
KRAS	Orphanet:3339	Oculoectodermal syndrome
KRAS	Orphanet:648	Noonan syndrome
KRAS	Orphanet:86834	Juvenile myelomonocytic leukemia
MLH1	Orphanet:144	Lynch syndrome
MLH1	Orphanet:252202	Constitutional mismatch repair deficiency syndrome
MSH2	Orphanet:144	Lynch syndrome

Cohort genes → proteins

75 cohort genes, 73 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	42
civic_only	6
multi_evidence	27

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar,civic_evidence
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	clinvar,civic_evidence
FGFR2	HGNC:3689	ENSG00000066468	P21802	Fibroblast growth factor receptor 2	clinvar,civic_evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	clinvar,civic_evidence
MLH1	HGNC:7127	ENSG00000076242	P40692	DNA mismatch repair protein Mlh1	clinvar,civic_evidence
MSH2	HGNC:7325	ENSG00000095002	P43246	DNA mismatch repair protein Msh2	clinvar,civic_evidence
MSH6	HGNC:7329	ENSG00000116062	P52701	DNA mismatch repair protein Msh6	clinvar,civic_evidence
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	clinvar,civic_evidence
PMS2	HGNC:9122	ENSG00000122512	P54278	Mismatch repair endonuclease PMS2	clinvar,civic_evidence
POLE	HGNC:9177	ENSG00000177084	Q07864	DNA polymerase epsilon catalytic subunit A	clinvar,civic_evidence
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	clinvar,civic_evidence
RIT1	HGNC:10023	ENSG00000143622	Q92963	GTP-binding protein Rit1	civic_evidence
CCNE1	HGNC:1589	ENSG00000105173	P24864	G1/S-specific cyclin-E1	civic_evidence
ANTXR1	HGNC:21014	ENSG00000169604	Q9H6X2	Anthrax toxin receptor 1	civic_evidence
KIT	HGNC:6342	ENSG00000157404	P10721	Mast/stem cell growth factor receptor Kit	civic_evidence
STMN1	HGNC:6510	ENSG00000117632	P16949	Stathmin	civic_evidence
MRE11	HGNC:7230	ENSG00000020922	P49959	Double-strand break repair protein MRE11	civic_evidence
RUVBL1	HGNC:10474	ENSG00000175792	Q9Y265	RuvB-like 1	gwas
BLM	HGNC:1058	ENSG00000197299	P54132	RecQ-like DNA helicase BLM	clinvar
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	clinvar
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar
ARID1A	HGNC:11110	ENSG00000117713	O14497	AT-rich interactive domain-containing protein 1A	clinvar
SOX4	HGNC:11200	ENSG00000124766	Q06945	Transcription factor SOX-4	gwas
SRP9	HGNC:11304	ENSG00000143742	P49458	Signal recognition particle 9 kDa protein	gwas
SSPN	HGNC:11322	ENSG00000123096	Q14714	Sarcospan	gwas
STK11	HGNC:11389	ENSG00000118046	Q15831	Serine/threonine-protein kinase STK11	clinvar
HNF1B	HGNC:11630	ENSG00000275410	P35680	Hepatocyte nuclear factor 1-beta	gwas
WT1	HGNC:12796	ENSG00000184937	P19544	Wilms tumor protein	gwas
BCL11A	HGNC:13221	ENSG00000119866	Q9H165	BCL11 transcription factor A	gwas
PCDH10	HGNC:13404	ENSG00000138650	Q9P2E7	Protocadherin-10	gwas
FBXO11	HGNC:13590	ENSG00000138081	Q86XK2	F-box only protein 11	clinvar
SGCZ	HGNC:14075	ENSG00000185053	Q96LD1	Zeta-sarcoglycan	gwas
CPVL	HGNC:14399	ENSG00000106066	Q9H3G5	Probable serine carboxypeptidase CPVL	gwas
PPP1R14C	HGNC:14952	ENSG00000198729	Q8TAE6	Protein phosphatase 1 regulatory subunit 14C	gwas
TFAP2D	HGNC:15581	ENSG00000008197	Q7Z6R9	Transcription factor AP-2-delta	gwas
SKAP1	HGNC:15605	ENSG00000141293	Q86WV1	Src kinase-associated phosphoprotein 1	gwas
TLR10	HGNC:15634	ENSG00000174123	Q9BXR5	Toll-like receptor 10	gwas
NAV3	HGNC:15998	ENSG00000067798	Q8IVL0	Neuron navigator 3	gwas
KLF3	HGNC:16516	ENSG00000109787	P57682	Krueppel-like factor 3	gwas
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	clinvar
PRICKLE1	HGNC:17019	ENSG00000139174	Q96MT3	Prickle-like protein 1	gwas
CDH1	HGNC:1748	ENSG00000039068	P12830	Cadherin-1	clinvar
SIVA1	HGNC:17712	ENSG00000184990	O15304	Apoptosis regulatory protein Siva	gwas
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	gwas
CDKN2B	HGNC:1788	ENSG00000147883	P42772	Cyclin-dependent kinase 4 inhibitor B	gwas
CDKN3	HGNC:1791	ENSG00000100526	Q16667	Cyclin-dependent kinase inhibitor 3	gwas
CSMD2	HGNC:19290	ENSG00000121904	Q7Z408	CUB and sushi domain-containing protein 2	gwas
AREL1	HGNC:20363	ENSG00000119682	O15033	Apoptosis-resistant E3 ubiquitin protein ligase 1	clinvar
CDKAL1	HGNC:21050	ENSG00000145996	Q5VV42	Threonylcarbamoyladenosine tRNA methylthiotransferase	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
ERBB2	Receptor tyrosine-protein kinase erbB-2	Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding.
FGFR2	Fibroblast growth factor receptor 2	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic de…
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
MLH1	DNA mismatch repair protein Mlh1	Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR).
MSH2	DNA mismatch repair protein Msh2	Component of the post-replicative DNA mismatch repair system (MMR).
MSH6	DNA mismatch repair protein Msh6	Component of the post-replicative DNA mismatch repair system (MMR).
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).
POLE	DNA polymerase epsilon catalytic subunit A	Catalytic component of the DNA polymerase epsilon complex.
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.
RIT1	GTP-binding protein Rit1	Plays a crucial role in coupling NGF stimulation to the activation of both EPHB2 and MAPK14 signaling pathways and in NGF-dependent neuronal differentiation.
CCNE1	G1/S-specific cyclin-E1	Essential for the control of the cell cycle at the G1/S (start) transition.
ANTXR1	Anthrax toxin receptor 1	Plays a role in cell attachment and migration.
KIT	Mast/stem cell growth factor receptor Kit	Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell develo…
STMN1	Stathmin	Involved in the regulation of the microtubule (MT) filament system by destabilizing microtubules.
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.
RUVBL1	RuvB-like 1	Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (3’ to 5’) activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activ…
BLM	RecQ-like DNA helicase BLM	ATP-dependent DNA helicase that unwinds double-stranded (ds)DNA in a 3’-5’ direction.
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
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.
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).
SOX4	Transcription factor SOX-4	Transcriptional activator that binds with high affinity to the T-cell enhancer motif 5’-AACAAAG-3’ motif.
SRP9	Signal recognition particle 9 kDa protein	Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER).
SSPN	Sarcospan	Component of the dystrophin-glycoprotein complex (DGC), a complex that spans the muscle plasma membrane and forms a link between the F-actin cytoskeleton and the extracellular matrix.
STK11	Serine/threonine-protein kinase STK11	Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage…
HNF1B	Hepatocyte nuclear factor 1-beta	Transcription factor that binds to the inverted palindrome 5’-GTTAATNATTAAC-3’.
WT1	Wilms tumor protein	Transcription factor that plays an important role in cellular development and cell survival.
BCL11A	BCL11 transcription factor A	Transcription factor.
PCDH10	Protocadherin-10	Potential calcium-dependent cell-adhesion protein.
FBXO11	F-box only protein 11	Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as DTL/CDT2, BCL6, SNAI1 and PRDM1/BLI…
SGCZ	Zeta-sarcoglycan	Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.
CPVL	Probable serine carboxypeptidase CPVL	May be involved in the digestion of phagocytosed particles in the lysosome, participation in an inflammatory protease cascade, and trimming of peptides for antigen presentation.
PPP1R14C	Protein phosphatase 1 regulatory subunit 14C	Inhibitor of the PP1 regulatory subunit PPP1CA.
TFAP2D	Transcription factor AP-2-delta	Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes.
SKAP1	Src kinase-associated phosphoprotein 1	Positively regulates T-cell receptor signaling by enhancing the MAP kinase pathway.
TLR10	Toll-like receptor 10	Participates in the innate immune response to microbial agents.
NAV3	Neuron navigator 3	Is involved in microtubule cytoskeleton organization and plays a role in cell migration.
KLF3	Krueppel-like factor 3	Binds to the CACCC box of erythroid cell-expressed genes.
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.
PRICKLE1	Prickle-like protein 1	Involved in the planar cell polarity pathway that controls convergent extension during gastrulation and neural tube closure.
CDH1	Cadherin-1	Cadherins are calcium-dependent cell adhesion proteins.
SIVA1	Apoptosis regulatory protein Siva	Induces CD27-mediated apoptosis.
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
CDKN2B	Cyclin-dependent kinase 4 inhibitor B	Interacts strongly with CDK4 and CDK6.
CDKN3	Cyclin-dependent kinase inhibitor 3	May play a role in cell cycle regulation.
AREL1	Apoptosis-resistant E3 ubiquitin protein ligase 1	E3 ubiquitin-protein ligase that catalyzes ‘Lys-11’- or ‘Lys-33’-linked polyubiquitin chains, with some preference for ‘Lys-33’ linkages.
CDKAL1	Threonylcarbamoyladenosine tRNA methylthiotransferase	Catalyzes the methylthiolation of N6-threonylcarbamoyladenosine (t(6)A), leading to the formation of 2-methylthio-N6-threonylcarbamoyladenosine (ms(2)t(6)A) at position 37 in tRNAs that read codons beginning with adenine.
NCOA7	Nuclear receptor coactivator 7	Enhances the transcriptional activities of several nuclear receptors.

Protein-family classification

Druggable: 24 · Difficult: 21 · Unknown: 30 · Druggable fraction: 0.32

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	11	4.1×	7e-04
Transcription factor	15	1.6×	0.168
Complement	1	3.6×	0.532
Phosphatase	2	2.2×	0.532
Scaffold/PPI	6	1.4×	0.532
Enzyme (other)	7	1.1×	0.727
Transporter	1	1.0×	0.888
Other/Unknown	30	0.7×	0.998
Protease	1	0.5×	0.998
Antibody/Immunoglobulin	1	0.4×	0.998

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
ERBB2	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
FGFR2	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
MLH1	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
MSH2	Other/Unknown	no		DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N, DNA_mismatch_repair_MutS_core
MSH6	Other/Unknown	no		PWWP_dom, DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N
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
POLE	Transcription factor	no	2.7.7.7	DNA-dir_DNA_pol_B_exonuc, DNA-dir_DNA_pol_B, RNaseH-like_sf
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom
RIT1	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
CCNE1	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
ANTXR1	Other/Unknown	no		VWF_A, Anthrax_toxin_rcpt_C, Anthrax_toxin_rcpt_extracel
KIT	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
STMN1	Other/Unknown	no		Stathmin_fam, Stathmin_CS, Stathmin_sf
MRE11	Other/Unknown	no		Mre11, Calcineurin-like_PHP, Mre11_DNA-bd
RUVBL1	Other/Unknown	no		AAA+_ATPase, TIP49_P-loop, RuvB-like
BLM	Enzyme (other)	yes	3.6.4.12	Helicase_C-like, HRDC_dom, DNA/RNA_helicase_DEAH_CS
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
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
ARID1A	Other/Unknown	no		ARID_dom, ARM-like, ARM-type_fold
SOX4	Transcription factor	no		HMG_box_dom, SOX-12/11/4, HMG_box_dom_sf
SRP9	Other/Unknown	no		SRP9, Signal_recog_particle_SRP9/14, SRP9_dom
SSPN	Other/Unknown	no		CD20-like_TM, Sarcospan
STK11	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
HNF1B	Transcription factor	no		HD, HNF1b_C, HNF-1_N
WT1	Transcription factor	no		Wilms_tumour_N, Znf_C2H2_type, Znf_C2H2_sf
BCL11A	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Dev/Hematopoietic_TF
PCDH10	Other/Unknown	no		Cadherin-like_dom, Cadherin_N, Cadherin-like_sf
FBXO11	Transcription factor	no		F-box_dom, Znf_UBR, PbH1
SGCZ	Other/Unknown	no		Sarcoglycan, Sarcoglycan_gamma/delta/zeta
CPVL	Protease	yes		Peptidase_S10, Ser_caboxypep_ser_AS, AB_hydrolase_fold
PPP1R14C	Other/Unknown	no		CPI-17, CPI-17_sf
TFAP2D	Transcription factor	no		TF_AP2, TF_AP2_C
SKAP1	Scaffold/PPI	no		SH3_domain, PH_domain, PH-like_dom_sf
TLR10	Other/Unknown	no		TIR_dom, Cys-rich_flank_reg_C, Leu-rich_rpt
NAV3	Other/Unknown	no		CH_dom, AAA+_ATPase, ATPase_AAA_core
KLF3	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
CHEK2	Kinase	yes	2.7.11.1	FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
PRICKLE1	Transcription factor	no		Znf_LIM, PET_domain, PET_prickle
CDH1	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin_pro_dom
SIVA1	Other/Unknown	no		Siva
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
CDKN2B	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor
CDKN3	Phosphatase	yes		Tyr_Pase_dom, Tyr_Pase_cat, CDK_inhib_3
CSMD2	Complement	yes		Sushi_SCR_CCP_dom, CUB_dom, Sperma_CUB_dom_sf
AREL1	Antibody/Immunoglobulin	yes	2.3.2.26	HECT_dom, Ig-like_fold, Ig_E-set
CDKAL1	Other/Unknown	no		TRAM_dom, Methylthiotransferase, MiaB-like_arc_euk

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	14
ganglionic eminence	11
secondary oocyte	9
male germ line stem cell (sensu Vertebrata) in testis	8
cortical plate	8
buccal mucosa cell	8
oocyte	7
primordial germ cell in gonad	6
calcaneal tendon	5
right testis	5
right uterine tube	4
embryo	4
sperm	4
leukocyte	4
monocyte	4
tendon of biceps brachii	3
lower esophagus mucosa	3
sural nerve	3
endothelial cell	3
mononuclear cell	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
ERBB2	276	ubiquitous	marker	lower esophagus mucosa, right uterine tube, sural nerve
FGFR2	272	broad	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
MLH1	296	ubiquitous	marker	tibialis anterior, skeletal muscle tissue of rectus abdominis, deltoid
MSH2	278	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
MSH6	293	ubiquitous	marker	ventricular zone, embryo, ganglionic eminence
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
POLE	221	ubiquitous	marker	right hemisphere of cerebellum, right testis, cerebellar hemisphere
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon
RIT1	268	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
CCNE1	201	ubiquitous	marker	secondary oocyte, oocyte, adrenal tissue
ANTXR1	270	ubiquitous	marker	stromal cell of endometrium, decidua, palpebral conjunctiva
KIT	263	broad	marker	lateral nuclear group of thalamus, secondary oocyte, oocyte
STMN1	266	ubiquitous	marker	cortical plate, ganglionic eminence, ventricular zone
MRE11	254	ubiquitous	marker	calcaneal tendon, oocyte, secondary oocyte
RUVBL1	134	ubiquitous	marker	right uterine tube, ventricular zone, primordial germ cell in gonad
BLM	199	ubiquitous	marker	parotid gland, primordial germ cell in gonad, secondary oocyte
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
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
ARID1A	286	ubiquitous	marker	bone marrow cell, ventricular zone, embryo
SOX4	295	ubiquitous	marker	cortical plate, ganglionic eminence, embryo
SRP9	149	ubiquitous	marker	embryo, ganglionic eminence, ventricular zone
SSPN	285	ubiquitous	marker	synovial joint, skeletal muscle tissue of rectus abdominis, body of tongue
STK11	238	ubiquitous	marker	left testis, right testis, hindlimb stylopod muscle
HNF1B	74	broad	marker	metanephros cortex, adult mammalian kidney, kidney
WT1	168	broad	marker	germinal epithelium of ovary, renal glomerulus, metanephric glomerulus
BCL11A	247	ubiquitous	marker	cortical plate, ganglionic eminence, primary visual cortex

Protein interactions among cohort

Intra-cohort edges: 107.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
EGFR	18,421
AKT1	16,601
KRAS	14,509
PTEN	11,626
ERBB2	9,659
CDKN2A	9,311
BRCA1	9,064
CDH1	8,738
BRAF	7,394

Intra-cohort edges

A	B	Sources
AKT1	CDKN2B	biogrid_interaction
AKT1	PIK3CA	biogrid_interaction, string_interaction
AKT1	PTEN	string_interaction
ALK	KRAS	string_interaction
ARID1A	BCL11A	string_interaction
ARID1A	MSH2	string_interaction
BCL11A	FGFR2	intact
BLM	MLH1	string_interaction
BLM	MSH6	string_interaction
BRAF	BRCA2	biogrid_interaction
BRAF	CDKN2A	string_interaction
BRAF	CPVL	intact
BRAF	EGFR	biogrid_interaction
BRAF	FGFR2	biogrid_interaction
BRAF	KRAS	biogrid_interaction, intact, string_interaction
BRAF	MLH1	string_interaction
BRAF	PIK3CA	biogrid_interaction, string_interaction
BRAF	PMS2	string_interaction
BRAF	POLE	intact
BRAF	PTEN	biogrid_interaction, string_interaction
BRAF	TP53	string_interaction
BRCA1	BRCA2	string_interaction
BRCA1	CHEK2	string_interaction
BRCA1	MLH1	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	TP53	string_interaction
BRCA2	CHEK2	string_interaction
BRCA2	MLH1	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	STK11	string_interaction
BRCA2	TP53	string_interaction
CCNE1	CDKN2A	string_interaction
CCNE1	TP53	string_interaction
CDH1	EGFR	intact, string_interaction
CDH1	ERBB2	string_interaction
CDH1	PTEN	string_interaction
CDKAL1	CDKN2B	string_interaction
CDKAL1	HNF1B	string_interaction
CDKAL1	MBOAT1	string_interaction
CDKN2A	CDKN2B	biogrid_interaction
CDKN2A	CDKN3	string_interaction
CDKN2A	KRAS	string_interaction

Structural data

PDB: 52 · AlphaFold-only: 21 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
EGFR	P00533	388
TP53	P04637	313
PIK3CA	P42336	135
BRAF	P15056	131
DHFR	P00374	89
ALK	Q9UM73	79
ERBB2	P04626	63
FGFR2	P21802	63
KIT	P10721	52
BPTF	Q12830	45
AKT1	P31749	43
CHEK2	O96017	38
RUVBL1	Q9Y265	36
BRCA1	P38398	33
MSH2	P43246	30
WT1	P19544	28
GNL2	Q13823	23
CCNE1	P24864	22
CDH1	P12830	22
POLE	Q07864	18
BCL11A	Q9H165	17
BLM	P54132	15
FGFR3	P22607	15
BRCA2	P51587	14
PTEN	P60484	12
CYP19A1	P11511	11
MRE11	P49959	10
PMS2	P54278	9
MSH6	P52701	8

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CPVL	Q9H3G5	93.55
CDKN2B	P42772	90.12
MBOAT1	Q6ZNC8	89.63
STMN1	P16949	88.59
CDKAL1	Q5VV42	82.72
SGCZ	Q96LD1	80.59
SIVA1	O15304	76.34
SSPN	Q14714	74.41
HEY2	Q9UBP5	65.56
PPP1R14C	Q8TAE6	64.37
SH2B3	Q9UQQ2	63.45
TFAP2D	Q7Z6R9	62.75
ZSCAN5A	Q9BUG6	58.50
EVI2A	P22794	56.81
PLPPR4	Q7Z2D5	56.09
SOX4	Q06945	55.71
PRICKLE1	Q96MT3	55.55
KLF3	P57682	54.04
GATA6	Q92908	53.48
NAV3	Q8IVL0	48.21
CSMD2	Q7Z408

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 656. Enrichment computed across 90 evidence-associated genes (71 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 71 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Diseases of DNA repair	10	80.4×	5e-15	MLH1, MSH2, MSH6, BLM, BRCA1, BRCA2, MRE11, MSH3 (+2 more)
Impaired BRCA2 binding to PALB2	8	51.5×	3e-10	BLM, BRCA1, BRCA2, PALB2, MRE11, ATM, BARD1, RAD51C
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	8	47.7×	3e-10	BLM, BRCA1, BRCA2, PALB2, MRE11, ATM, BARD1, RAD51C
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	8	47.7×	3e-10	BLM, BRCA1, BRCA2, PALB2, MRE11, ATM, BARD1, RAD51C
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	8	47.7×	3e-10	BLM, BRCA1, BRCA2, PALB2, MRE11, ATM, BARD1, RAD51C
HDR through Homologous Recombination (HRR)	10	26.8×	3e-10	POLE, BLM, BRCA1, BRCA2, PALB2, MRE11, ATM, POLD1 (+2 more)
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	8	44.4×	5e-10	BLM, BRCA1, BRCA2, PALB2, MRE11, ATM, BARD1, RAD51C
Homologous DNA Pairing and Strand Exchange	8	42.9×	6e-10	BLM, BRCA1, BRCA2, PALB2, MRE11, ATM, BARD1, RAD51C
Defective homologous recombination repair (HRR) due to PALB2 loss of function	6	80.4×	3e-09	BLM, BRCA1, BRCA2, MRE11, ATM, BARD1
Resolution of D-loop Structures through Holliday Junction Intermediates	8	33.9×	4e-09	BLM, BRCA1, BRCA2, PALB2, MRE11, ATM, BARD1, RAD51C
DNA Repair	11	15.2×	7e-09	MLH1, MSH2, MSH6, RUVBL1, BLM, BRCA1, BRCA2, MRE11 (+3 more)
Diseases of DNA Double-Strand Break Repair	6	68.9×	7e-09	BLM, BRCA1, BRCA2, MRE11, ATM, BARD1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	6	68.9×	7e-09	BLM, BRCA1, BRCA2, MRE11, ATM, BARD1
Resolution of D-Loop Structures	6	53.6×	4e-08	BLM, BRCA1, BRCA2, MRE11, ATM, BARD1
Mismatch Repair	4	160.8×	6e-08	MLH1, MSH2, MSH6, MSH3
Diseases of Mismatch Repair (MMR)	4	160.8×	6e-08	MLH1, MSH2, MSH6, MSH3
Meiosis	7	28.1×	2e-07	MLH1, BLM, BRCA1, BRCA2, MLH3, MRE11, ATM
Presynaptic phase of homologous DNA pairing and strand exchange	7	26.8×	2e-07	BLM, BRCA1, BRCA2, MRE11, ATM, BARD1, RAD51C
Cell Cycle	14	7.1×	2e-07	MLH1, RUVBL1, BLM, BRCA1, BRCA2, CCNE1, CDKN2A, CDKN2B (+6 more)
Disease	22	4.0×	2e-07	MLH1, MSH2, MSH6, BLM, BRAF, BRCA1, BRCA2, BCL11A (+14 more)
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	5	57.4×	4e-07	MLH1, MSH2, MSH6, PMS2, POLD1
Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)	5	57.4×	4e-07	MLH1, MSH2, PMS2, MSH3, POLD1
Transcriptional Regulation by TP53	11	9.6×	4e-07	MLH1, MSH2, BLM, BRCA1, STK11, CCNE1, CDKN2A, AKT1 (+3 more)
Regulation of TP53 Activity	8	15.0×	1e-06	BLM, BRCA1, STK11, CDKN2A, AKT1, MRE11, ATM, BARD1
RNA Polymerase II Transcription	16	5.1×	2e-06	MLH1, MSH2, BLM, BRCA1, ARID1A, STK11, TFAP2D, CCNE1 (+8 more)
Meiotic recombination	8	14.6×	2e-06	MLH1, BLM, BRCA1, BRCA2, MLH3, MRE11, ATM, RAD51C
Reproduction	7	18.8×	2e-06	MLH1, BLM, BRCA1, BRCA2, MLH3, MRE11, ATM
Homology Directed Repair	6	26.1×	2e-06	BLM, BRCA1, BRCA2, MRE11, ATM, BARD1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	6	26.1×	2e-06	BLM, BRCA1, BRCA2, MRE11, ATM, BARD1
Impaired BRCA2 binding to RAD51	6	26.1×	2e-06	BLM, BRCA1, BRCA2, 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 86 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mismatch repair	7	52.8×	6e-08	MLH1, MSH2, MSH6, PMS2, MLH3, MSH3, MUTYH
somatic recombination of immunoglobulin gene segments	4	195.9×	4e-07	MSH2, MSH6, PMS2, MSH3
positive regulation of DNA-templated transcription	16	5.2×	3e-05	TP53, RUVBL1, BLM, BRCA1, BRCA2, ARID1A, SOX4, HNF1B (+8 more)
DNA repair	11	8.2×	3e-05	MSH2, MSH6, RUVBL1, BLM, BRCA1, MRE11, MSH3, MUTYH (+3 more)
positive regulation of transcription by RNA polymerase II	21	3.6×	5e-05	TP53, FGFR2, PTEN, BRCA1, SOX4, WT1, BCL11A, TFAP2D (+13 more)
double-strand break repair	7	16.5×	5e-05	TP53, MSH2, BRCA1, BRCA2, CHEK2, MRE11, ATM
intrinsic apoptotic signaling pathway in response to DNA damage	6	22.6×	5e-05	MLH1, MSH6, BRCA1, CHEK2, MYC, ATM
anoikis	4	60.3×	7e-05	PIK3CA, STK11, BMF, AKT1
negative regulation of DNA recombination	4	52.2×	1e-04	MSH2, MSH6, BLM, MSH3
somatic hypermutation of immunoglobulin genes	4	49.0×	1e-04	MLH1, MSH2, MSH6, PMS2
epidermal growth factor receptor signaling pathway	6	17.3×	1e-04	ERBB2, PIK3CA, BRAF, PRICKLE1, EGFR, AKT1
double-strand break repair via homologous recombination	7	12.7×	1e-04	BLM, BRCA1, BRCA2, PALB2, MRE11, ATM, RAD51C
replicative senescence	4	46.1×	1e-04	TP53, CHEK2, CDKN2A, ATM
cellular response to ionizing radiation	5	23.9×	2e-04	TP53, BLM, BRCA1, BRCA2, BARD1
protein autophosphorylation	7	11.8×	2e-04	FGFR2, STK11, CHEK2, AKT1, ALK, KIT, ATM
response to X-ray	4	41.2×	2e-04	TP53, MSH2, BLM, BRCA2
positive regulation of isotype switching to IgA isotypes	3	98.0×	2e-04	MLH1, MSH2, PMS2
phosphatidylinositol 3-kinase/protein kinase B signal transduction	6	14.7×	2e-04	ERBB2, PIK3CA, PTEN, EGFR, AKT1, NF1
DNA damage response	10	6.2×	3e-04	TP53, BLM, BRCA1, STK11, CHEK2, APC, MRE11, MYC (+2 more)
negative regulation of apoptotic process	12	4.8×	4e-04	TP53, ERBB2, BRAF, WT1, AREL1, PALB2, EGFR, AKT1 (+4 more)
DNA strand resection involved in replication fork processing	3	73.5×	5e-04	BRCA1, MRE11, BARD1
cell fate commitment	5	17.2×	6e-04	FGFR2, EXT1, GATA6, HEY2, PPARG
cellular senescence	5	17.2×	6e-04	TP53, BRCA2, CDKN2A, CDKN2B, ATM
positive regulation of miRNA transcription	5	16.9×	6e-04	TP53, WT1, EGFR, MYC, PPARG
gene expression	8	7.4×	7e-04	KRAS, SOX4, HNF1B, PRICKLE1, EGFR, EXT1, AKT1, GATA6
positive regulation of gene expression	11	5.0×	7e-04	TP53, KRAS, BRAF, BRCA1, HNF1B, WT1, BCL11A, AKT1 (+3 more)
endochondral bone growth	3	58.8×	8e-04	FGFR2, EXT1, FGFR3
reciprocal meiotic recombination	4	26.1×	8e-04	MLH3, MRE11, ATM, RAD51C
telomere maintenance	5	15.6×	8e-04	RUVBL1, BLM, CCNE1, MRE11, ATM
DNA double-strand break processing	3	53.4×	8e-04	BLM, MRE11, ATM

Therapeutics

Drugs indicated for this disease

1 approved, 8 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Pembrolizumab	Approved (phase 4)
Carboplatin	Phase 3 (in late-stage trials)
Lenvatinib	Phase 3 (in late-stage trials)
Lerociclib	Phase 3 (in late-stage trials)
Letrozole	Phase 3 (in late-stage trials)
Megestrol Acetate	Phase 3 (in late-stage trials)
Olaparib	Phase 3 (in late-stage trials)
Paclitaxel	Phase 3 (in late-stage trials)
Sacituzumab Govitecan	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Aflibercept, Arsenic Trioxide, Bevacizumab, Camrelizumab, Catequentinib, Cridanimod, Epacadostat, Fluzoparib, Fulvestrant, Levonorgestrel, Niraparib, Nivolumab, Rosuvastatin, Temsirolimus, Trastuzumab.

Drug target analysis

Approved (phase 4): 19 · Phase ≥3: 19 · Phased (≥1): 22 · Undrugged: 53

Druggability breadth: 45 of 90 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

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

Symbol	Example approved molecule
TP53	NITROFURANTOIN
ERBB2	CLOTRIMAZOLE
FGFR2	PONATINIB
KRAS	VEMURAFENIB
PIK3CA	IDELALISIB
CCNE1	PALBOCICLIB
KIT	PONATINIB
BLM	AMIFOSTINE
BRAF	VEMURAFENIB
BRCA1	RIBOFLAVIN
STK11	FEDRATINIB
CHEK2	NERATINIB
CYP19A1	CLOTRIMAZOLE
CYP3A7	TELITHROMYCIN
DHFR	TRIMETREXATE
EGFR	LEVODOPA
FGFR3	PONATINIB
AKT1	CAPIVASERTIB
ALK	CERITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BLM	284	4
TP53	196	4
EGFR	175	4
KIT	99	4
ERBB2	83	4
PIK3CA	67	4
FGFR3	64	4
ALK	61	4
FGFR2	59	4
BRAF	48	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	BLM, CYP19A1, EGFR, ERBB2, TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	BLM, TP53
AMIODARONE HYDROCHLORIDE	4	BLM, TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	BLM, TP53
NICARDIPINE HYDROCHLORIDE	4	BLM, 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
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	BLM, TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	BLM, 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
KIT	2,305	Binding:2242, ADMET:32, Functional:22, Toxicity:9
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
AKT1	1,942	Binding:1900, Functional:34, ADMET:7, Toxicity:1
ALK	1,815	Binding:1801, Functional:13, ADMET:1
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6
FGFR3	975	Binding:948, Functional:18, ADMET:9
FGFR2	966	Binding:940, Functional:22, ADMET:4
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
CYP19A1	728	Binding:698, ADMET:17, Functional:13
CCNE1	691	Binding:690, ADMET:1
CHEK2	690	Binding:687, Functional:2, ADMET:1
DHFR	457	Binding:426, ADMET:16, Functional:12, Toxicity:3
CYP3A7	303	ADMET:301, Binding:2
STK11	244	Binding:244
BPTF	125	Binding:123, Functional:2
BLM	82	Binding:78, Functional:4
MRE11	36	Binding:36
CDH1	18	Binding:18
RUVBL1	15	Binding:15
BRCA1	13	Binding:9, Functional:4
MSH6	10	Binding:10
MSH2	9	Binding:9
PTEN	8	Binding:8
SRP9	7	Binding:7
ARID1A	6	Binding:6
STMN1	2	Binding:2
FBXO11	2	Binding:2
CDKN2A	2	Binding:2
PMS2	1	Binding:1
CDKAL1	1	Binding:1
MBOAT1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ERBB2	2.7.10.1	receptor protein-tyrosine kinase
FGFR2	2.7.10.1	receptor protein-tyrosine kinase
KRAS	3.6.5.2	small monomeric GTPase
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
POLE	2.7.7.7	DNA-directed DNA polymerase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase
KIT	2.7.10.1	receptor protein-tyrosine kinase
BLM	3.6.4.12	DNA helicase
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
STK11	2.7.11.1	non-specific serine/threonine protein kinase
CHEK2	2.7.11.1	non-specific serine/threonine protein kinase
AREL1	2.3.2.26	HECT-type E3 ubiquitin transferase
PLPPR4	3.1.3.4	phosphatidate phosphatase
CYP19A1	1.14.14.14	aromatase
CYP3A7	1.14.14.1	unspecific monooxygenase
DHFR	1.5.1.3	dihydrofolate reductase
EGFR	2.7.10.1	receptor protein-tyrosine kinase
EXT1	2.4.1.224, 2.4.1.225	glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase, N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase
FGFR3	2.7.10.1	receptor protein-tyrosine kinase
AKT1	2.7.11.1	non-specific serine/threonine protein kinase
ALK	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TP53	869
ERBB2	1,221
FGFR2	966
KRAS	861
PIK3CA	2,034
CCNE1	691
KIT	2,305
BRAF	1,442
STK11	244
CHEK2	690
CYP19A1	728
CYP3A7	303
DHFR	457
EGFR	6,531
BPTF	125
FGFR3	975
AKT1	1,942
ALK	1,815

Pharmacogenomics

Cohort genes with a PharmGKB record: 73; 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)
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	BLM, CYP19A1, EGFR, ERBB2, TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	BLM, TP53
AMIODARONE HYDROCHLORIDE	4	BLM, TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	BLM, TP53
NICARDIPINE HYDROCHLORIDE	4	BLM, 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
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	BLM, TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	BLM, TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	19	TP53, ERBB2, FGFR2, KRAS, PIK3CA, CCNE1, KIT, BLM, BRAF, BRCA1 (+9 more)
B	Phased (≥1) drug, not yet approved	3	MSH6, RUVBL1, BPTF
C	Druggable family + PDB, no drug	5	PTEN, CDKN3, AREL1, ABCA3, EXT1
D	Druggable family + AlphaFold only, no drug	3	CPVL, CSMD2, PLPPR4
E	Difficult family or no structure, no drug	45	MLH1, MSH2, PMS2, POLE, RIT1, ANTXR1, STMN1, MRE11, BRCA2, ARID1A (+35 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MLH1	0	MSH6
PMS2	1	MSH6
POLE	0	MSH6
PTEN	8	STK11, TP53, AKT1
MRE11	36	BRCA1
BRCA2	0	BRCA1
WT1	0	TP53
FBXO11	2	MSH6
CDH1	18	EGFR
CDKN2B	0	TP53
CDKN3	0	TP53
PALB2	0	BRCA1
MSH2	9	—
RIT1	0	—
ANTXR1	0	—
STMN1	2	—
ARID1A	6	—
SOX4	0	—
SRP9	7	—
SSPN	0	—
HNF1B	0	—
BCL11A	0	—
PCDH10	0	—
SGCZ	0	—
CPVL	0	—
PPP1R14C	0	—
TFAP2D	0	—
SKAP1	0	—
TLR10	0	—
NAV3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,033.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	462
PHASE2	246
PHASE1	145
PHASE1/PHASE2	79
PHASE3	58
EARLY_PHASE1	22
PHASE4	11
PHASE2/PHASE3	10

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02543710	PHASE4	RECRUITING	Biomarker Guided Treatment in Gynaecological Cancer
NCT06726291	PHASE4	RECRUITING	Akynzeo as Antiemetic Treatment in Patients With Endometrial Cancer
NCT06871787	PHASE4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT07281547	PHASE4	NOT_YET_RECRUITING	Low Dose Aspirin to Lower Inflammation and Prevent Endometrial Cancer in Postmenopausal Women With Non-atrophic Endometrial Changes and Pain
NCT07462663	PHASE4	NOT_YET_RECRUITING	SHAPE-ENDO: Multimodal Pre-Surgical Optimization in Patients With Obesity and Early-Stage Endometrial Cancer (Phase 1)
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00719017	PHASE4	UNKNOWN	Upper Vaginectomy Versus Brachytherapy in Patients With Early Stage Endometrial Cancer Treated With Laparoscopic Surgery
NCT03349463	PHASE4	UNKNOWN	Evaluation of Fluciclovine Uptake in Patients With Cervical, Ovarian Epithelial or Endometrial Cancers.
NCT03752606	PHASE4	COMPLETED	Application of Tachosil During Lymphadenectomy
NCT05949424	PHASE4	UNKNOWN	OPTI - DOSE: Optimal Dosing of Oral Anticancer Drugs in Older Adults
NCT06049693	PHASE4	COMPLETED	Iron Prehabilitation in Endometrial Cancer
NCT03463252	PHASE2/PHASE3	RECRUITING	Value of LNG-IUS as Fertility-preserving Treatment of EAH and EC
NCT03469674	PHASE3	ACTIVE_NOT_RECRUITING	PORTEC-4a: Molecular Profile-based Versus Standard Adjuvant Radiotherapy in Endometrial Cancer
NCT03785288	PHASE3	RECRUITING	Vaginal Cuff Brachytherapy Fractionation Study
NCT03914612	PHASE3	ACTIVE_NOT_RECRUITING	Testing the Addition of the Immunotherapy Drug Pembrolizumab to the Usual Chemotherapy Treatment (Paclitaxel and Carboplatin) in Stage III-IV or Recurrent Endometrial Cancer
NCT04073706	PHASE3	RECRUITING	Sentinel Node Biopsy in Endometrial Cancer
NCT04789694	PHASE3	RECRUITING	Prehabilitation in Gynaecological Cancer Patients
NCT05077215	PHASE3	NOT_YET_RECRUITING	Efficacy and Safety of a Repurposed Drug Added to the Combination of Len Plus Pem in Advanced Endometrial Cancer
NCT05078047	PHASE3	RECRUITING	Study Comparing the Standard Administration of IO Versus the Same IO Administered Each 3 Months in Patients in Response After 6 Months of Standard IO
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NCT05256225	PHASE3	RECRUITING	Testing the Addition of Herceptin Hylecta or Phesgo to the Usual Chemotherapy for HER2 Positive Endometrial Serous Carcinoma or Carcinosarcoma
NCT05316467	PHASE2/PHASE3	RECRUITING	Weight Management Plus Megestrol Acetate in Early-stage Endometrioid Carcinoma
NCT05489848	PHASE2/PHASE3	NOT_YET_RECRUITING	Chemotherapy vs Chemoradiotherapy for Post-operative Endometrial Cancer Patients With P53-mutation
NCT05524389	PHASE3	NOT_YET_RECRUITING	Study of Early Stage Endometrial Cancer Based on Molecular Classification and Traditional Risk Stratification to Guide Adjuvant Radiotherapy Decisions
NCT05611931	PHASE3	ACTIVE_NOT_RECRUITING	Selinexor in Maintenance Therapy After Systemic Therapy for Participants With p53 Wild-Type, Advanced or Recurrent Endometrial Carcinoma
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Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LENVATINIB	4	14
MEGESTROL ACETATE	4	14
DOSTARLIMAB	4	10
DOXORUBICIN	4	8
ATEZOLIZUMAB	4	7
MEDROXYPROGESTERONE ACETATE	4	7
ABEMACICLIB	4	5
COPANLISIB	4	5
NIRAPARIB	4	5
TIRZEPATIDE	4	5
FILGRASTIM	4	4
OLAPARIB	4	4
RUCAPARIB	4	4
CAPIVASERTIB	4	3
FRUQUINTINIB	4	3
LURBINECTEDIN	4	3
MIRVETUXIMAB SORAVTANSINE	4	3
PACLITAXEL	4	3
PALBOCICLIB	4	3
SACITUZUMAB GOVITECAN	4	3
SELINEXOR	4	3
TEMSIROLIMUS	4	3
TRASTUZUMAB DERUXTECAN	4	3
ALPELISIB	4	2
AMIFOSTINE	4	2
AVELUMAB	4	2
AXITINIB	4	2
BINIMETINIB	4	2
CABOZANTINIB S-MALATE	4	2
CEMIPLIMAB	4	2

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 20 predictive associations from 21 curated evidence items; also 8 oncogenic, 4 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
ERBB2 Amplification	Trastuzumab	Sensitivity/Response	CIViC B	EID1098
FGFR2 Mutation	Dovitinib + Fulvestrant	Sensitivity/Response	CIViC B	EID6457
KRAS Mutation	Ridaforolimus + Temsirolimus	Sensitivity/Response	CIViC B	EID894
MSI High	Carboplatin + Dostarlimab + Paclitaxel	Sensitivity/Response	CIViC B	EID12341
MSI High	Paclitaxel + Dostarlimab + Carboplatin	Sensitivity/Response	CIViC B	EID12343
MSI High	Pembrolizumab	Sensitivity/Response	CIViC B	EID12364
PIK3CA Mutation	Temsirolimus + Ridaforolimus	Sensitivity/Response	CIViC B	EID892
PTEN Mutation	Everolimus	Sensitivity/Response	CIViC B	EID1232
PTEN Loss	Temsirolimus + Ridaforolimus	Resistance	CIViC B	EID893
STMN1 EXPRESSION	Paclitaxel	Resistance	CIViC B	EID855
KIT EXPRESSION	Imatinib	Sensitivity/Response	CIViC C	EID1024 +1
AKT1 L52R	Capivasertib	Sensitivity/Response	CIViC C	EID10762
FGFR2::BICC1 Fusion	Erdafitinib	Sensitivity/Response	CIViC C	EID1920
POLE Mutation	Pembrolizumab	Sensitivity/Response	CIViC C	EID1862
CCNE1 Amplification	Lunresertib + Camonsertib	Sensitivity/Response	CIViC D	EID12762
FGFR2 Mutation	Ponatinib	Sensitivity/Response	CIViC D	EID1236
FGFR2 N550K	PD173074	Sensitivity/Response	CIViC D	EID1322
MRE11 Loss	Talazoparib	Sensitivity/Response	CIViC D	EID876
PIK3CA Mutation	Pictilisib	Sensitivity/Response	CIViC D	EID1616
PTEN Loss	Temsirolimus	Sensitivity/Response	CIViC D	EID1614