Hereditary breast ovarian cancer syndrome

Summary

Hereditary breast ovarian cancer syndrome (MONDO:0003582) is a cancer with 75 cohort genes (27 CIViC-evidence somatic drivers; 24,312 ClinVar predisposition records) and 51 clinical trials. The dominant Reactome pathway is Homologous DNA Pairing and Strand Exchange (16 cohort genes). Top therapeutic interventions include letrozole, veliparib, and arzoxifene hydrochloride.

At a glance

• Classification: Cancer
• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 75
• ClinVar variants: 24,312
• Phenotypes (HPO): 7
• Clinical trials: 51

Clinical features

Signs & symptoms

Clinical features (HPO)

7 HPO clinical features (Orphanet curated; top 7 by frequency):

HPO ID	Term	Frequency
HP:0011027	Abnormality of the fallopian tube	Very frequent (80-99%)
HP:0030406	Primary peritoneal carcinoma	Very frequent (80-99%)
HP:0100615	Ovarian neoplasm	Very frequent (80-99%)
HP:0003002	Breast carcinoma	Frequent (30-79%)
HP:0002861	Melanoma	Occasional (5-29%)
HP:0002894	Neoplasm of the pancreas	Occasional (5-29%)
HP:0012125	Prostate cancer	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	hereditary breast ovarian cancer syndrome
Mondo ID	MONDO:0003582
MeSH	D061325
Orphanet	145
DOID	DOID:5683
ICD-11	1258896144
NCIT	C8493
SNOMED CT	718220008
UMLS	C0677776
MedGen	151793
GARD	0015010
NORD	1936
Is cancer (heuristic)	yes

Also known as: BRCA1- and BRCA2-associated hereditary breast and ovarian cancer (HBOC) · familial breast and ovarian cancer syndrome · familial breast/ovarian cancer (BRCA1, BRCA2) · HBOC syndrome · HBOC syndromes · hereditary breast and ovarian cancer · Hereditary Breast and Ovarian Cancer Syndrome · hereditary breast and ovarian cancer syndrome · hereditary breast ovarian cancer syndrome · hereditary breast/ovarian cancer (BRCA1, BRCA2) · syndrome, HBOC · syndromes, HBOC

Data availability: 24,312 ClinVar variants · 4 GenCC gene-disease records · 90 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › hereditary breast ovarian cancer syndrome

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

Subtypes (2): breast-ovarian cancer, familial, susceptibility to, 1, breast-ovarian cancer, familial, susceptibility to, 2

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

303 conflicting classifications of pathogenicity, 200 uncertain significance, 50 pathogenic, 23 likely benign, 12 likely pathogenic, 11 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1027595	NC_000017.10:g.(?41196311)(41203135_41209068)del	BRCA1	Pathogenic	criteria provided, single submitter
1027624	NC_000017.10:g.(41203135_41209068)_(41209153_41215349)del	BRCA1	Pathogenic	criteria provided, single submitter
1049208	NM_007294.4(BRCA1):c.672del (p.Ala225fs)	BRCA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1050371	NM_007294.4(BRCA1):c.709G>T (p.Glu237Ter)	BRCA1	Pathogenic	criteria provided, single submitter
1065138	NC_000017.10:g.(41197820_41199659)_(41199721_41201137)del	BRCA1	Pathogenic	criteria provided, single submitter
1066372	NC_000017.10:g.(?41258453)(41258570_?)del	BRCA1	Pathogenic	criteria provided, single submitter
1066373	NC_000017.10:g.(?41219605)(41228651_?)del	BRCA1	Pathogenic	criteria provided, single submitter
1066374	NC_000017.10:g.(?41228485)(41258570_?)del	BRCA1	Pathogenic	criteria provided, single submitter
1066580	NC_000017.10:g.(?41234401)(41249326_?)del	BRCA1	Pathogenic	criteria provided, single submitter
1068565	NM_007294.4(BRCA1):c.2479_2480del (p.Glu827fs)	BRCA1	Pathogenic	criteria provided, single submitter
1068881	NC_000017.10:g.(?41196977)(41277500_?)del	BRCA1	Pathogenic	criteria provided, single submitter
1068882	NC_000017.10:g.(?41242941)(41243069_?)del	BRCA1	Pathogenic	criteria provided, single submitter
1068883	NC_000017.10:g.(?41228485)(41228651_?)del	BRCA1	Pathogenic	criteria provided, single submitter
1068884	NC_000017.10:g.(?41226328)(41226558_?)del	BRCA1	Pathogenic	criteria provided, single submitter
1068885	NC_000017.10:g.(?41222925)(41223340_?)del	BRCA1	Pathogenic	criteria provided, single submitter
1068886	NC_000017.10:g.(?41219605)(41219732_?)del	BRCA1	Pathogenic	criteria provided, single submitter
1068970	NM_007294.4(BRCA1):c.166_169del (p.Lys56fs)	BRCA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069112	NM_007294.4(BRCA1):c.1095del (p.Asp366fs)	BRCA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069116	NM_007294.4(BRCA1):c.4475_4476insGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGGATCATGAGGTCAGGAGATCGAGACCATCCTGGCTAACAAGGTGAAACCNNNNNNNNNNAAAAAAAAAAAAAAAAAAAATAAAGAACCAGG (p.Gly1492_Val1493insAlaGlyArgGlyGlySerArgLeuTer)	BRCA1	Pathogenic	criteria provided, single submitter
1069175	NC_000017.10:g.(?41215330)(41223340_?)del	BRCA1	Pathogenic	criteria provided, single submitter
1069176	NC_000017.10:g.(?41215330)(41219732_?)del	BRCA1	Pathogenic	criteria provided, single submitter
1069177	NC_000017.10:g.(?41209048)(41219732_?)del	BRCA1	Pathogenic	criteria provided, single submitter
1069178	NC_000017.10:g.(?41215330)(41215988_?)del	BRCA1	Pathogenic	criteria provided, single submitter
1069179	NC_000017.10:g.(?41209048)(41215988_?)del	BRCA1	Pathogenic	criteria provided, single submitter
1069180	NC_000017.10:g.(?41197689)(41209158_?)del	BRCA1	Pathogenic	criteria provided, single submitter
1069350	NC_000017.10:g.(?41201118)(41203154_?)del	BRCA1	Pathogenic	criteria provided, single submitter
1069351	NC_000017.10:g.(?41199640)(41203154_?)del	BRCA1	Pathogenic	criteria provided, single submitter
1069352	NC_000017.10:g.(?41242941)(41267816_?)del	BRCA1	Pathogenic	criteria provided, single submitter
1069353	NC_000017.10:g.(?41222925)(41267816_?)del	BRCA1	Pathogenic	criteria provided, single submitter
1069423	NM_007294.4(BRCA1):c.1997_1998del (p.Leu666fs)	BRCA1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 39 · Orphanet: 146 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
BRCA1	LoF	BLCA,BRCA,MEL,OVT	CIViC #6
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7
RAD51C			CIViC #4762
RAD51D			CIViC #4765
RIPK1	LoF	CLLSLL
SLC25A15			CIViC #4046
SLC34A2	Act	AML,COADREAD,LUAD
STK11	LoF	ANSC,CEAD,CESC,CHOL,LUAD,NSCLC,WDTC	CIViC #5534
EPCAM			CIViC #3364
HNF1A	LoF	HCC,PRCC
TERT	Act	PRCC	CIViC #79
TFRC	Act	NSCLC,PRAD
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
TSHR	Act	COAD,WDTC
BIRC6	LoF	ANSC,BLCA,BRCA,CCRCC,CHOL,COADREAD,DLBCLNOS,HCC,HNSC,LUAD,MGCT,MT,NHL,PGNG,UCEC	CIViC #13783
CHEK2	Act	BRCA	CIViC #8950
CDH1	LoF	BLCA,BRCA,CSCC,DLBCLNOS,ESCA,STAD	CIViC #888
DROSHA	LoF	LUSC,PAAD,WT	CIViC #11314
CSMD3	Act	BLCA,BRCA,COAD,COADREAD,ESCA,GBM,HCC,HNSC,LUAD,LUSC,MEL,OVT,PAAD,PLMESO,PRAD,SOFT_TISSUE,STAD,UCEC
BRIP1			CIViC #15955
ANTXR1	LoF	LUNG,MEL,STAD,UTUC	CIViC #524
COL2A1	LoF	WDTC
CDK12	LoF	BLCA,CCRCC,CESC,DLBCLNOS,MEL,OVT,PRAD,PROSTATE,STAD	CIViC #12112
CTNNA1	Act	CEAD,COADREAD
CTNNA2	Act	CHOL,HCC,HNSC,LUAD,MEL,PAAD,PRAD
PALB2	LoF	OVT	CIViC #15013
FLCN	LoF	LUAD	CIViC #19959

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
BRCA1	Definitive	Autosomal dominant	breast-ovarian cancer, familial, susceptibility to, 1	11
BRCA2	Definitive	Autosomal dominant	breast-ovarian cancer, familial, susceptibility to, 2	13
RAD51C	Strong	Autosomal dominant	breast-ovarian cancer, familial, susceptibility to, 3	10
RAD51D	Strong	Autosomal dominant	breast-ovarian cancer, familial, susceptibility to, 4	5

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
RAD51C	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
RAD51C	Orphanet:84	Fanconi anemia
RAD51D	Orphanet:1331	Familial prostate cancer
RAD51D	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
RIPK1	Orphanet:529977	Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome
RPN1	Orphanet:402020	Acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2)
BLM	Orphanet:125	Bloom syndrome
NEMF	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability
SLC25A15	Orphanet:415	Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome
SLC34A2	Orphanet:60025	Pulmonary alveolar microlithiasis
STK11	Orphanet:2869	Peutz-Jeghers syndrome
TACC3	Orphanet:251576	Gliosarcoma
TACC3	Orphanet:251579	Giant cell glioblastoma
EPCAM	Orphanet:144	Lynch syndrome
EPCAM	Orphanet:92050	Congenital tufting enteropathy
HNF1A	Orphanet:319303	Chromophobe renal cell carcinoma
HNF1A	Orphanet:324575	Hyperinsulinism due to HNF1A deficiency
HNF1A	Orphanet:404511	Clear cell papillary renal cell carcinoma
HNF1A	Orphanet:552	MODY
TERT	Orphanet:146	Differentiated thyroid carcinoma
TERT	Orphanet:1501	Adrenocortical carcinoma
TERT	Orphanet:1775	Dyskeratosis congenita
TERT	Orphanet:2032	Idiopathic pulmonary fibrosis
TERT	Orphanet:2495	Meningioma
TERT	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
TERT	Orphanet:457246	Clear cell sarcoma of kidney
TERT	Orphanet:618	Familial melanoma
TERT	Orphanet:88	Idiopathic aplastic anemia
TFRC	Orphanet:476113	Combined immunodeficiency due to TFRC deficiency

Cohort genes → proteins

75 cohort genes, 74 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	75

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	gencc,clinvar
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	gencc,clinvar
RAD51C	HGNC:9820	ENSG00000108384	O43502	DNA repair protein RAD51 homolog 3	gencc,clinvar
RAD51D	HGNC:9823	ENSG00000185379	O75771	DNA repair protein RAD51 homolog 4	gencc,clinvar
RIPK1	HGNC:10019	ENSG00000137275	Q13546	Receptor-interacting serine/threonine-protein kinase 1	clinvar
RPN1	HGNC:10381	ENSG00000163902	P04843	Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit 1	clinvar
BLM	HGNC:1058	ENSG00000197299	P54132	RecQ-like DNA helicase BLM	clinvar
NEMF	HGNC:10663	ENSG00000165525	O60524	Ribosome quality control complex subunit NEMF	clinvar
SLC25A15	HGNC:10985	ENSG00000102743	Q9Y619	Mitochondrial ornithine transporter 1	clinvar
SLC34A2	HGNC:11020	ENSG00000157765	O95436	Sodium-dependent phosphate transport protein 2B	clinvar
SP100	HGNC:11206	ENSG00000067066	P23497	Nuclear autoantigen Sp-100	clinvar
STK11	HGNC:11389	ENSG00000118046	Q15831	Serine/threonine-protein kinase STK11	clinvar
TACC3	HGNC:11524	ENSG00000013810	Q9Y6A5	Transforming acidic coiled-coil-containing protein 3	clinvar
EPCAM	HGNC:11529	ENSG00000119888	P16422	Epithelial cell adhesion molecule	clinvar
HNF1A	HGNC:11621	ENSG00000135100	P20823	Hepatocyte nuclear factor 1-alpha	clinvar
TDG	HGNC:11700	ENSG00000139372	Q13569	G/T mismatch-specific thymine DNA glycosylase	clinvar
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	clinvar
TFRC	HGNC:11763	ENSG00000072274	P02786	Transferrin receptor protein 1	clinvar
TG	HGNC:11764	ENSG00000042832	P01266	Thyroglobulin	clinvar
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar
TPM4	HGNC:12013	ENSG00000167460	P67936	Tropomyosin alpha-4 chain	clinvar
TSHR	HGNC:12373	ENSG00000165409	P16473	Thyrotropin receptor	clinvar
TYRO3	HGNC:12446	ENSG00000092445	Q06418	Tyrosine-protein kinase receptor TYRO3	clinvar
UNG	HGNC:12572	ENSG00000076248	P13051	Uracil-DNA glycosylase	clinvar
VRK1	HGNC:12718	ENSG00000100749	Q99986	Serine/threonine-protein kinase VRK1	clinvar
WWOX	HGNC:12799	ENSG00000186153	Q9NZC7	WW domain-containing oxidoreductase	clinvar
XRCC2	HGNC:12829	ENSG00000196584	O43543	DNA repair protein XRCC2	clinvar
BIRC6	HGNC:13516	ENSG00000115760	Q9NR09	Dual E2 ubiquitin-conjugating enzyme/E3 ubiquitin-protein ligase BIRC6	clinvar
TLX3	HGNC:13532	ENSG00000164438	O43711	T-cell leukemia homeobox protein 3	clinvar
AOPEP	HGNC:1361	ENSG00000148120	Q8N6M6	Aminopeptidase O	clinvar
HERPUD1	HGNC:13744	ENSG00000051108	Q15011	Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein	clinvar
WDR11	HGNC:13831	ENSG00000120008	Q9BZH6	WD repeat-containing protein 11	clinvar
TES	HGNC:14620	ENSG00000135269	Q9UGI8	Testin	clinvar
PUM1	HGNC:14957	ENSG00000134644	Q14671	Pumilio homolog 1	clinvar
GPHN	HGNC:15465	ENSG00000171723	Q9NQX3	Gephyrin	clinvar
PHIP	HGNC:15673	ENSG00000146247	Q8WWQ0	PH-interacting protein	clinvar
CCNG1	HGNC:1592	ENSG00000113328	P51959	Cyclin-G1	clinvar
PAK4	HGNC:16059	ENSG00000130669	O96013	Serine/threonine-protein kinase PAK 4	clinvar
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	clinvar
MELK	HGNC:16870	ENSG00000165304	Q14680	Maternal embryonic leucine zipper kinase	clinvar
CDH1	HGNC:1748	ENSG00000039068	P12830	Cadherin-1	clinvar
VTI1A	HGNC:17792	ENSG00000151532	Q96AJ9	Vesicle transport through interaction with t-SNAREs homolog 1A	clinvar
SAV1	HGNC:17795	ENSG00000151748	Q9H4B6	Protein salvador homolog 1	clinvar
DROSHA	HGNC:17904	ENSG00000113360	Q9NRR4	Ribonuclease 3	clinvar
WIF1	HGNC:18081	ENSG00000156076	Q9Y5W5	Wnt inhibitory factor 1	clinvar
CHD1L	HGNC:1916	ENSG00000131778	Q86WJ1	ATP-dependent chromatin remodeler CHD1L	clinvar
CSMD3	HGNC:19291	ENSG00000164796	Q7Z407	CUB and sushi domain-containing protein 3	clinvar
TOX4	HGNC:20161	ENSG00000092203	O94842	TOX high mobility group box family member 4	clinvar
BRIP1	HGNC:20473	ENSG00000136492	Q9BX63	Fanconi anemia group J protein	clinvar
NBR2	HGNC:20691	ENSG00000198496		neighbor of BRCA1 lncRNA 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRCA1	Breast cancer type 1 susceptibility protein	E3 ubiquitin-protein ligase that specifically mediates the formation of ‘Lys-6’-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
RAD51C	DNA repair protein RAD51 homolog 3	Essential for the homologous recombination (HR) pathway of DNA repair.
RAD51D	DNA repair protein RAD51 homolog 4	Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents.
RIPK1	Receptor-interacting serine/threonine-protein kinase 1	Serine-threonine kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways.
RPN1	Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit 1	Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Se…
BLM	RecQ-like DNA helicase BLM	ATP-dependent DNA helicase that unwinds double-stranded (ds)DNA in a 3’-5’ direction.
NEMF	Ribosome quality control complex subunit NEMF	Key component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates the extraction of incompletely synthesized nascent chains from stalled ribosomes as well as their ubiquitin-mediated proteasomal degra…
SLC25A15	Mitochondrial ornithine transporter 1	Mitochondrial ornithine-citrulline antiporter.
SLC34A2	Sodium-dependent phosphate transport protein 2B	Involved in actively transporting phosphate into cells via Na(+) cotransport.
SP100	Nuclear autoantigen Sp-100	Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation and apoptosis.
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…
TACC3	Transforming acidic coiled-coil-containing protein 3	Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome.
EPCAM	Epithelial cell adhesion molecule	May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as a first line of defense against mucosa…
HNF1A	Hepatocyte nuclear factor 1-alpha	Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver.
TDG	G/T mismatch-specific thymine DNA glycosylase	DNA glycosylase that plays a key role in active DNA demethylation: specifically recognizes and binds 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) in the context of CpG sites and mediates their excision through base-excision repair…
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
TFRC	Transferrin receptor protein 1	Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes.
TG	Thyroglobulin	Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3).
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
TPM4	Tropomyosin alpha-4 chain	Binds to actin filaments in muscle and non-muscle cells.
TSHR	Thyrotropin receptor	Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin.
TYRO3	Tyrosine-protein kinase receptor TYRO3	Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including TULP1 or GAS6.
UNG	Uracil-DNA glycosylase	Uracil-DNA glycosylase that hydrolyzes the N-glycosidic bond between uracil and deoxyribose in single- and double-stranded DNA (ssDNA and dsDNA) to release a free uracil residue and form an abasic (apurinic/apyrimidinic; AP) site.
VRK1	Serine/threonine-protein kinase VRK1	Serine/threonine kinase involved in the regulation of key cellular processes including the cell cycle, nuclear condensation, transcription regulation, and DNA damage response.
WWOX	WW domain-containing oxidoreductase	Putative oxidoreductase.
XRCC2	DNA repair protein XRCC2	Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA, thought to repair chromosomal fragmentation, translocations and deletions.
BIRC6	Dual E2 ubiquitin-conjugating enzyme/E3 ubiquitin-protein ligase BIRC6	Anti-apoptotic protein known as inhibitor of apoptosis (IAP) which can regulate cell death by controlling caspases and by acting as an E3 ubiquitin-protein ligase.
AOPEP	Aminopeptidase O	Aminopeptidase which catalyzes the hydrolysis of amino acid residues from the N-terminus of peptide or protein substrates.
HERPUD1	Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein	Component of the endoplasmic reticulum quality control (ERQC) system also called ER-associated degradation (ERAD) involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins.
WDR11	WD repeat-containing protein 11	Involved in the Hedgehog (Hh) signaling pathway, is essential for normal ciliogenesis.
TES	Testin	Scaffold protein that may play a role in cell adhesion, cell spreading and in the reorganization of the actin cytoskeleton.
PUM1	Pumilio homolog 1	Sequence-specific RNA-binding protein that acts as a post-transcriptional repressor by binding the 3’-UTR of mRNA targets.
GPHN	Gephyrin	Microtubule-associated protein involved in membrane protein-cytoskeleton interactions.
PHIP	PH-interacting protein	Probable regulator of the insulin and insulin-like growth factor signaling pathways.
CCNG1	Cyclin-G1	May play a role in growth regulation.
PAK4	Serine/threonine-protein kinase PAK 4	Serine/threonine-protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell adhesion turnover, cell migration, growth, proliferation or cell survival.
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.
MELK	Maternal embryonic leucine zipper kinase	Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation.
CDH1	Cadherin-1	Cadherins are calcium-dependent cell adhesion proteins.
VTI1A	Vesicle transport through interaction with t-SNAREs homolog 1A	V-SNARE that mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane.
SAV1	Protein salvador homolog 1	Regulator of STK3/MST2 and STK4/MST1 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis.
DROSHA	Ribonuclease 3	Ribonuclease III double-stranded (ds) RNA-specific endoribonuclease that is involved in the initial step of microRNA (miRNA) biogenesis.
WIF1	Wnt inhibitory factor 1	Binds to WNT proteins and inhibits their activities.
CHD1L	ATP-dependent chromatin remodeler CHD1L	ATP-dependent chromatin remodeler that mediates chromatin-remodeling following DNA damage.
CSMD3	CUB and sushi domain-containing protein 3	Involved in dendrite development.
TOX4	TOX high mobility group box family member 4	Transcription factor that modulates cell fate reprogramming from the somatic state to the pluripotent and neuronal fate.
BRIP1	Fanconi anemia group J protein	DNA-dependent ATPase and 5’-3’ DNA helicase required for the maintenance of chromosomal stability.
ANTXR1	Anthrax toxin receptor 1	Plays a role in cell attachment and migration.
CDK20	Cyclin-dependent kinase 20	Required for high-level Shh responses in the developing neural tube.

Protein-family classification

Druggable: 23 · Difficult: 12 · Unknown: 40 · Druggable fraction: 0.31

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	9	3.3×	0.013
Complement	1	3.6×	0.757
Protease	3	1.5×	0.757
Enzyme (other)	8	1.3×	0.757
Scaffold/PPI	5	1.1×	0.790
Phosphatase	1	1.1×	0.891
Other/Unknown	40	1.0×	0.913
Transcription factor	7	0.8×	0.921
GPCR	1	0.3×	0.960

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
RAD51C	Other/Unknown	no		Rad51_C, DNA_recomb/repair_RecA-like, RecA_ATP-bd
RAD51D	Other/Unknown	no		AAA+_ATPase, Rad51_C, DNA_recomb/repair_RecA-like
RIPK1	Kinase	yes	2.7.10.2	Death_dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
RPN1	Enzyme (other)	yes	2.4.99.18	Ribophorin_I
BLM	Enzyme (other)	yes	3.6.4.12	Helicase_C-like, HRDC_dom, DNA/RNA_helicase_DEAH_CS
NEMF	Other/Unknown	no		NFACT_RNA-bd, NFACT-C, RQC_Subunit_NEMF
SLC25A15	Other/Unknown	no		MCP_transmembrane, MCP_dom_sf, Mitochondrial_Carrier
SLC34A2	Other/Unknown	no		Na/Pi_transpt
SP100	Other/Unknown	no		SAND_dom, HSR_dom, HMG_box_dom
STK11	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TACC3	Other/Unknown	no		TACC_C, TACC, TACC3_Aurora-A_bind
EPCAM	Enzyme (other)	yes	2.4.1.37	Thyroglobulin_1, Thyroglobulin_1_sf, EpCAM_N
HNF1A	Transcription factor	no		HD, HNF1b_C, HNF1a_C
TDG	Enzyme (other)	yes	3.2.2.29	TDG-like_euk, Uracil-DNA_glycosylase-like, MUG/TDG
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
TFRC	Protease	yes		PA_domain, TFR-like_dimer_dom, Peptidase_M28
TG	Other/Unknown	no		Thyroglobulin_1, CarbesteraseB, Tyr-kin_ephrin_A/B_rcpt-like
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
TPM4	Other/Unknown	no		Tropomyosin, XRCC4-like_C
TSHR	GPCR	yes		GPCR_Rhodpsn, Gphrmn_rcpt_fam, TSH_rcpt
TYRO3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
UNG	Enzyme (other)	yes	3.2.2.27	UDG_fam1, Uracil-DNA_glycosylase-like, Ura-DNA_Glyclase_AS
VRK1	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
WWOX	Scaffold/PPI	no		WW_dom, SDR_fam, WW_dom_sf
XRCC2	Other/Unknown	no		Rad51_C, RecA_ATP-bd, P-loop_NTPase
BIRC6	Other/Unknown	no		UBC, BIR_rpt, UBQ-conjugating_enzyme/RWD
TLX3	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
AOPEP	Protease	yes		Peptidase_M1_dom, Peptidase_M1_C, ARM-type_fold
HERPUD1	Other/Unknown	no		Ubiquitin-like_dom, Ubiquitin-like_domsf, HERPUD1/2
WDR11	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
TES	Transcription factor	no		Znf_LIM, PET_domain, PET_testin
PUM1	Transcription factor	no		Pumilio_RNA-bd_rpt, ARM-like, ARM-type_fold
GPHN	Other/Unknown	no		MoaB/Mog_dom, MoeA_linker/N, MoeA_C_domain_IV
PHIP	Scaffold/PPI	no		Bromodomain, WD40_rpt, WD40/YVTN_repeat-like_dom_sf
CCNG1	Other/Unknown	no		Cyclin_N, Cyclin-like_dom, Cyclin-like_sf
PAK4	Kinase	yes	2.7.11.1	CRIB_dom, Prot_kinase_dom, Kinase-like_dom_sf
CHEK2	Kinase	yes	2.7.11.1	FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
MELK	Kinase	yes		Prot_kinase_dom, KA1_dom, Ser/Thr_kinase_AS
CDH1	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin_pro_dom
VTI1A	Other/Unknown	no		T_SNARE_dom, Vesicle_trsprt_v-SNARE_N, SNARE
SAV1	Scaffold/PPI	no		WW_dom, SARAH_dom, Sav
DROSHA	Enzyme (other)	yes	3.1.26.3	RNase_III_dom, RNase_III, dsRBD_dom
WIF1	Other/Unknown	no		EGF, WIF, EGF-like_CS
CHD1L	Other/Unknown	no		SNF2_N, Helicase_C-like, DNA/RNA_helicase_DEAH_CS
CSMD3	Complement	yes		Sushi_SCR_CCP_dom, CUB_dom, Sperma_CUB_dom_sf
TOX4	Other/Unknown	no		HMG_box_dom, HMG_box_dom_sf, TOX_HMG-box_domain
BRIP1	Enzyme (other)	yes	3.6.4.12	Helicase-like_DEXD_c2, ATP-dep_Helicase_C, RAD3-like_helicase_DEAD
NBR2	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

69 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
secondary oocyte	10
male germ line stem cell (sensu Vertebrata) in testis	9
oocyte	9
primordial germ cell in gonad	8
ventricular zone	8
calcaneal tendon	8
buccal mucosa cell	7
stromal cell of endometrium	6
jejunal mucosa	6
cerebellar hemisphere	5
right hemisphere of cerebellum	5
right testis	4
right lobe of liver	4
corpus epididymis	4
liver	4
tibia	4
sperm	3
sural nerve	3
parotid gland	3
palpebral conjunctiva	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRCA1	208	ubiquitous	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
RAD51C	281	ubiquitous	marker	primordial germ cell in gonad, right testis, male germ line stem cell (sensu Vertebrata) in testis
RAD51D	187	ubiquitous	yes	sperm, male germ cell, oocyte
RIPK1	238	ubiquitous	marker	granulocyte, sural nerve, right lobe of liver
RPN1	294	ubiquitous	marker	stromal cell of endometrium, corpus epididymis, rectum
BLM	199	ubiquitous	marker	parotid gland, primordial germ cell in gonad, secondary oocyte
NEMF	292	ubiquitous	marker	calcaneal tendon, tendon, medial globus pallidus
SLC25A15	198	ubiquitous	marker	liver, right lobe of liver, duodenum
SLC34A2	171	broad	marker	lower lobe of lung, palpebral conjunctiva, upper lobe of lung
SP100	286	ubiquitous	marker	calcaneal tendon, lymph node, right lung
STK11	238	ubiquitous	marker	left testis, right testis, hindlimb stylopod muscle
TACC3	197	ubiquitous	marker	oocyte, ventricular zone, secondary oocyte
EPCAM	253	broad	marker	jejunal mucosa, colonic mucosa, mucosa of sigmoid colon
HNF1A	81	tissue_specific	yes	right lobe of liver, mucosa of transverse colon, liver
TDG	294	ubiquitous	marker	buccal mucosa cell, esophagus squamous epithelium, visceral pleura
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
TFRC	295	ubiquitous	marker	endothelial cell, trabecular bone tissue, tibia
TG	169	tissue_specific	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
TPM4	281	ubiquitous	marker	tendon of biceps brachii, stromal cell of endometrium, right coronary artery
TSHR	169	broad	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
TYRO3	252	ubiquitous	marker	frontal pole, Brodmann (1909) area 10, paraflocculus
UNG	293	ubiquitous	marker	secondary oocyte, oocyte, right adrenal gland cortex
VRK1	286	ubiquitous	marker	oocyte, bone marrow, secondary oocyte
WWOX	286	ubiquitous	marker	parotid gland, cervix squamous epithelium, cranial nerve II
XRCC2	283	ubiquitous	marker	buccal mucosa cell, tendon of biceps brachii, lateral globus pallidus
BIRC6	256	ubiquitous	marker	epithelial cell of pancreas, oviduct epithelium, calcaneal tendon
TLX3	26	tissue_specific	marker	right hemisphere of cerebellum, cerebellar cortex, cerebellar hemisphere
AOPEP	224	ubiquitous	marker	apex of heart, right coronary artery, ascending aorta

Protein interactions among cohort

Intra-cohort edges: 68.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
BRCA1	9,064
CDH1	8,738
DROSHA	6,846
TFRC	6,725
BIRC6	5,905
WWOX	5,892
PUM1	5,826
TERT	5,717
PALB2	5,641

Intra-cohort edges

A	B	Sources
ABRAXAS1	BRCA1	intact, string_interaction
ABRAXAS1	BRCA2	string_interaction
ABRAXAS1	PALB2	string_interaction
ABRAXAS1	RAD51C	string_interaction
ABRAXAS1	RAD51D	string_interaction
AOPEP	CDH1	intact
BIRC6	TP53	biogrid_interaction
BLM	BRIP1	intact
BLM	FAN1	biogrid_interaction
BLM	FANCM	string_interaction
BLM	XRCC2	biogrid_interaction
BRCA1	BRCA2	string_interaction
BRCA1	BRIP1	biogrid_interaction, intact, string_interaction
BRCA1	CDK12	string_interaction
BRCA1	CHEK2	string_interaction
BRCA1	DROSHA	string_interaction
BRCA1	PALB2	biogrid_interaction, intact, string_interaction
BRCA1	RAD51C	string_interaction
BRCA1	RAD51D	string_interaction
BRCA1	TP53	string_interaction
BRCA1	XRCC2	string_interaction
BRCA2	BRIP1	string_interaction
BRCA2	CDK12	string_interaction
BRCA2	CHEK2	string_interaction
BRCA2	PALB2	biogrid_interaction, intact, string_interaction
BRCA2	RAD51C	biogrid_interaction, string_interaction
BRCA2	RAD51D	string_interaction
BRCA2	STK11	string_interaction
BRCA2	TP53	string_interaction
BRCA2	XRCC2	string_interaction
BRIP1	FANCM	string_interaction
BRIP1	PALB2	string_interaction
CCNG1	TP53	string_interaction
CDH1	CTNNA1	intact, string_interaction
CDH1	CTNNA2	string_interaction
CDH1	EPCAM	intact, string_interaction
CDK12	PALB2	string_interaction
CDK12	RAD51C	string_interaction
CDK12	RAD51D	string_interaction
CDK20	PALB2	string_interaction
CHEK2	PALB2	string_interaction
CHEK2	RAD51D	string_interaction
CHEK2	TP53	intact, string_interaction
CHEK2	XRCC2	string_interaction
CPS1	SLC25A15	string_interaction
CTNNA1	CTNNA2	intact
CTNNA1	TES	intact
DROSHA	TP53	intact, string_interaction
FAN1	FANCM	string_interaction
FAN1	MTMR10	string_interaction

Structural data

PDB: 58 · AlphaFold-only: 16 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TP53	P04637	313
PHIP	Q8WWQ0	146
SP100	P23497	122
PAK4	O96013	49
RIPK1	Q13546	39
CDK12	Q9NYV4	39
CHEK2	O96017	38
BRCA1	P38398	33
MELK	Q14680	32
VRK1	Q99986	26
TFRC	P02786	24
UNG	P13051	24
TERT	O14746	23
BIRC6	Q9NR09	22
CDH1	P12830	22
TDG	Q13569	21
FAN1	Q9Y2M0	18
RAD51C	O43502	17
RAD51D	O75771	17
XRCC2	O43543	16
BLM	P54132	15
PUM1	Q14671	15
BRCA2	P51587	14
CPS1	P31327	14
DROSHA	Q9NRR4	12
COL2A1	P02458	11
CTNNA1	P35221	10
TSHR	P16473	9
UFL1	O94874	9
CHD1L	Q86WJ1	7

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TPM4	P67936	93.33
PM20D1	Q6GTS8	89.55
SLC25A15	Q9Y619	87.43
CDK20	Q8IZL9	86.08
RINT1	Q6NUQ1	85.97
CCNG1	P51959	85.69
VTI1A	Q96AJ9	85.00
AOPEP	Q8N6M6	83.36
MTMR10	Q9NXD2	79.94
C11orf65	Q8NCR3	74.69
SLC34A2	O95436	73.27
TLX3	O43711	68.52
FANCD2OS	Q96PS1	61.31
ESCO2	Q56NI9	58.81
NBPF3	Q9H094	47.16
CSMD3	Q7Z407

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 780. Enrichment computed across 151 evidence-associated genes (125 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 125 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Homologous DNA Pairing and Strand Exchange	16	48.7×	2e-21	BRCA1, BRCA2, RAD51C, RAD51D, BLM, XRCC2, BRIP1, PALB2 (+8 more)
Impaired BRCA2 binding to PALB2	15	54.8×	2e-21	BRCA1, BRCA2, RAD51C, RAD51D, BLM, XRCC2, BRIP1, PALB2 (+7 more)
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	15	50.8×	4e-21	BRCA1, BRCA2, RAD51C, RAD51D, BLM, XRCC2, BRIP1, PALB2 (+7 more)
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	15	50.8×	4e-21	BRCA1, BRCA2, RAD51C, RAD51D, BLM, XRCC2, BRIP1, PALB2 (+7 more)
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	15	50.8×	4e-21	BRCA1, BRCA2, RAD51C, RAD51D, BLM, XRCC2, BRIP1, PALB2 (+7 more)
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	15	47.3×	1e-20	BRCA1, BRCA2, RAD51C, RAD51D, BLM, XRCC2, BRIP1, PALB2 (+7 more)
Resolution of D-loop Structures through Holliday Junction Intermediates	16	38.5×	3e-20	BRCA1, BRCA2, RAD51C, RAD51D, BLM, XRCC2, BRIP1, SLX4 (+8 more)
HDR through Homologous Recombination (HRR)	18	27.4×	9e-20	BRCA1, BRCA2, RAD51C, RAD51D, BLM, XRCC2, BRIP1, SLX4 (+10 more)
Presynaptic phase of homologous DNA pairing and strand exchange	15	32.6×	1e-17	BRCA1, BRCA2, RAD51C, RAD51D, BLM, XRCC2, BRIP1, EXO1 (+7 more)
Diseases of DNA repair	11	50.2×	2e-15	BRCA1, BRCA2, BLM, MLH1, MRE11, MSH2, MSH6, NBN (+3 more)
Impaired BRCA2 binding to RAD51	11	27.2×	8e-12	BRCA1, BRCA2, BLM, BRIP1, EXO1, MRE11, NBN, ATM (+3 more)
Diseases of DNA Double-Strand Break Repair	8	52.2×	3e-11	BRCA1, BRCA2, BLM, MRE11, NBN, ATM, ATR, BARD1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	8	52.2×	3e-11	BRCA1, BRCA2, BLM, MRE11, NBN, ATM, ATR, BARD1
Homology Directed Repair	10	24.7×	2e-10	BRCA1, BRCA2, BLM, SLX4, ABRAXAS1, MRE11, NBN, ATM (+2 more)
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	10	24.7×	2e-10	BRCA1, BRCA2, BLM, SLX4, ABRAXAS1, MRE11, NBN, ATM (+2 more)
Resolution of D-Loop Structures	8	40.6×	3e-10	BRCA1, BRCA2, BLM, SLX4, MRE11, NBN, ATM, BARD1
HDR through Single Strand Annealing (SSA)	10	23.4×	4e-10	BRCA1, BLM, BRIP1, EXO1, MRE11, NBN, ATM, ATR (+2 more)
Defective homologous recombination repair (HRR) due to PALB2 loss of function	7	53.3×	5e-10	BRCA1, BRCA2, BLM, MRE11, NBN, ATM, BARD1
G2/M DNA damage checkpoint	13	12.5×	1e-09	BRCA1, BLM, TP53, CHEK2, BRIP1, ABRAXAS1, EXO1, MRE11 (+5 more)
DNA Repair	14	11.0×	1e-09	BRCA1, BRCA2, BLM, TDG, SLX4, ABRAXAS1, MLH1, MRE11 (+6 more)
Regulation of TP53 Activity through Phosphorylation	13	12.2×	1e-09	BRCA1, BLM, STK11, TP53, CHEK2, BRIP1, EXO1, MRE11 (+5 more)
DNA Double-Strand Break Repair	10	19.9×	2e-09	BRCA1, BRCA2, BLM, SLX4, ABRAXAS1, MRE11, NBN, ATM (+2 more)
TP53 Regulates Transcription of DNA Repair Genes	11	15.9×	2e-09	BRCA1, RAD51D, TP53, CDK12, FANCC, FANCD2, MLH1, MSH2 (+3 more)
HDR through MMEJ (alt-NHEJ)	6	42.2×	8e-08	BRCA2, FEN1, MRE11, NBN, POLQ, RAD50
Meiosis	8	18.3×	3e-07	BRCA1, BRCA2, BLM, MLH1, MRE11, NBN, ATM, ATR
Processing of DNA double-strand break ends	11	10.1×	3e-07	BRCA1, BLM, BRIP1, ABRAXAS1, EXO1, MRE11, NBN, ATM (+3 more)
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	10	11.7×	3e-07	BRCA1, TP53, CHEK2, ABRAXAS1, EYA2, MRE11, NBN, ATM (+2 more)
G2/M Checkpoints	10	10.8×	7e-07	BRCA1, BLM, TP53, ABRAXAS1, MRE11, NBN, ATM, ATR (+2 more)
DNA Double Strand Break Response	6	22.8×	5e-06	BRCA1, ABRAXAS1, MRE11, NBN, ATM, BARD1
Sensing of DNA Double Strand Breaks	4	60.9×	5e-06	MRE11, NBN, ATM, RAD50

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 146 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
DNA repair	28	12.2×	2e-19	BRCA1, RAD51C, RAD51D, BLM, XRCC2, CHD1L, BRIP1, UFL1 (+20 more)
double-strand break repair via homologous recombination	17	18.2×	4e-14	BRCA1, BRCA2, RAD51C, RAD51D, BLM, XRCC2, SLX4, PALB2 (+9 more)
double-strand break repair	15	20.9×	2e-13	BRCA1, BRCA2, TP53, CHEK2, BRIP1, ABRAXAS1, ESCO2, FEN1 (+7 more)
DNA strand resection involved in replication fork processing	6	86.6×	4e-09	BRCA1, EXO1, MRE11, NBN, BARD1, RAD50
somatic hypermutation of immunoglobulin genes	7	50.5×	1e-08	UNG, EXO1, MLH1, MSH2, MSH6, PMS2, POLQ
response to X-ray	7	42.5×	4e-08	BRCA2, BLM, TP53, XRCC2, ERCC6, ERCC8, MSH2
DNA damage response	18	6.6×	6e-08	BRCA1, BLM, STK11, TP53, VRK1, CHEK2, CHD1L, UFL1 (+10 more)
homologous recombination	6	57.7×	6e-08	BRCA1, BRIP1, MRE11, NBN, BARD1, RAD50
mitotic G2/M transition checkpoint	7	38.5×	6e-08	BRCA1, ABRAXAS1, MRE11, NBN, ATR, BARD1, RAD50
mismatch repair	7	31.1×	3e-07	EXO1, MLH1, MSH2, MSH6, MUTYH, PMS1, PMS2
telomere maintenance	9	16.5×	5e-07	RAD51D, BLM, SP100, TERT, MRE11, NBN, ATM, ATR (+1 more)
replicative senescence	6	40.7×	5e-07	TERT, TP53, CHEK2, MME, ATM, ATR
reciprocal meiotic recombination	7	26.9×	6e-07	RAD51C, RAD51D, MRE11, ATM, RAD50, RAD51B, RAD54L
isotype switching	6	34.6×	1e-06	UNG, EXO1, MLH1, MSH2, MSH6, NBN
telomere maintenance via recombination	5	52.5×	2e-06	BRCA2, RAD51C, RAD51D, TERT, RAD50
DNA double-strand break processing	5	52.5×	2e-06	BLM, MRE11, NBN, ATM, RAD50
mitotic G2 DNA damage checkpoint signaling	7	21.3×	3e-06	BRCA1, BLM, RINT1, ABRAXAS1, MRE11, NBN, ATM
interstrand cross-link repair	7	20.7×	3e-06	RAD51D, FANCM, FAN1, FANCC, FANCD2, FANCE, ATR
DNA damage checkpoint signaling	7	18.8×	6e-06	CHEK2, BRIP1, UFL1, ERCC6, NBN, ATM, ATR
response to gamma radiation	6	23.9×	1e-05	BRCA2, TP53, XRCC2, ERCC6, FANCD2, MEN1
DNA recombination	7	16.2×	2e-05	RAD51C, BLM, EXO1, MRE11, RAD50, RAD51B, RAD54L
intrinsic apoptotic signaling pathway in response to DNA damage	7	15.5×	2e-05	BRCA1, CHEK2, ERCC6, MLH1, MSH6, ATM, BCL2L1
multicellular organism growth	9	8.4×	8e-05	TP53, XRCC2, WDR11, PALB2, EP300, ERCC6, MME, NOTCH2 (+1 more)
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	6	16.9×	8e-05	RIPK1, TERT, COL2A1, CTNNA1, EYA2, BCL2L1
ovarian follicle development	6	16.1×	1e-04	CTNNA1, EIF2B5, FANCE, KIT, ATM, BCL2L1
positive regulation of apoptotic process	13	5.0×	1e-04	RIPK1, TP53, MELK, SAV1, FLCN, EIF2B5, ID3, APC (+5 more)
nucleotide-excision repair	6	15.7×	1e-04	BRCA2, TP53, BRIP1, SLX4, FAN1, FANCC
somatic recombination of immunoglobulin gene segments	3	86.6×	1e-04	MSH2, MSH6, PMS2
telomeric 3’ overhang formation	3	86.6×	1e-04	MRE11, NBN, RAD50
t-circle formation	4	38.5×	1e-04	BLM, SLX4, EXO1, NBN

Therapeutics

Drugs indicated for this disease

0 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Letrozole	Phase 3 (in late-stage trials)
Niraparib	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Carboplatin, Cholecalciferol, Dostarlimab, Doxorubicin, Epacadostat, Eribulin, Estradiol, Paclitaxel, Pembrolizumab, Rucaparib, Talazoparib, Temozolomide, Testosterone, Trabectedin, Veliparib.

Drug target analysis

Approved (phase 4): 12 · Phase ≥3: 13 · Phased (≥1): 14 · Undrugged: 61

Druggability breadth: 86 of 151 evidence-associated genes (57%) 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
RIPK1	PONATINIB
BLM	AMIFOSTINE
SLC34A2	LORLATINIB
STK11	FEDRATINIB
TERT	BERBERINE
TP53	NITROFURANTOIN
TSHR	LEVOSALBUTAMOL
TYRO3	CABOZANTINIB
PAK4	FEDRATINIB
CHEK2	NERATINIB
MELK	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TSHR	354	4
BLM	284	4
TP53	196	4
MELK	44	4
PAK4	35	4
TYRO3	30	4
CHEK2	30	4
RIPK1	24	4
STK11	17	4
CDK12	17	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BLM, BRCA1, TSHR
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BLM, BRCA1, TP53
DOXORUBICIN HYDROCHLORIDE	4	BLM, BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	BLM, BRCA1, TSHR
PONATINIB	4	MELK, RIPK1
FEDRATINIB	4	MELK, PAK4, RIPK1, STK11
AXITINIB	4	PAK4, RIPK1
SORAFENIB	4	RIPK1
DABRAFENIB	4	MELK, RIPK1
PAZOPANIB	4	RIPK1
NINTEDANIB	4	MELK, PAK4, RIPK1, STK11, TYRO3
SUNITINIB	4	CHEK2, MELK, PAK4, RIPK1, STK11, TYRO3
QUIZARTINIB	4	RIPK1
CRIZOTINIB	4	RIPK1, SLC34A2, TYRO3
AMIFOSTINE	4	BLM
BEXAROTENE	4	BLM
DICLOFENAC SODIUM	4	BLM, TSHR
CLOTRIMAZOLE	4	BLM, TP53, TSHR
FLUORESCEIN	4	BLM
OXCARBAZEPINE	4	BLM
BUMETANIDE	4	BLM, TSHR
GLIPIZIDE	4	BLM, TSHR
SALMETEROL XINAFOATE	4	BLM, TP53
AMIODARONE HYDROCHLORIDE	4	BLM, TP53
INDIGOTINDISULFONATE	4	BLM
TRIHEXYPHENIDYL HYDROCHLORIDE	4	BLM
RALOXIFENE HYDROCHLORIDE	4	BLM, TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 15.

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

Symbol	Assays	Type breakdown
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
CHEK2	690	Binding:687, Functional:2, ADMET:1
PAK4	536	Binding:534, Functional:1, ADMET:1
RIPK1	400	Binding:391, ADMET:7, Functional:2
MELK	392	Binding:390, Functional:2
TERT	391	Binding:389, Functional:2
TYRO3	380	Binding:376, Functional:3, Toxicity:1
CDK12	347	Binding:341, Functional:6
STK11	244	Binding:244
BLM	82	Binding:78, Functional:4
VRK1	74	Binding:74
CDK20	40	Binding:40
TSHR	33	Functional:24, Binding:9
SLC34A2	31	Binding:30, ADMET:1
CDH1	18	Binding:18
PHIP	17	Binding:17
BRCA1	13	Binding:9, Functional:4
TDG	9	Binding:8, Functional:1
RPN1	8	Binding:8
UNG	7	Binding:6, Functional:1
TOX4	6	Binding:6
TPM4	4	Binding:4
CHD1L	4	Binding:4
TACC3	3	Binding:3
CPS1	3	Binding:3
SP100	2	Binding:2
TES	2	Binding:2
COL2A1	2	Binding:2
CTNNA1	2	Binding:2
EPCAM	1	Binding:1
HNF1A	1	Binding:1
TFRC	1	Binding:1
AOPEP	1	ADMET:1
PUM1	1	Binding:1
SAV1	1	Binding:1
UFL1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
RIPK1	2.7.10.2	non-specific protein-tyrosine kinase
RPN1	2.4.99.18	dolichyl-diphosphooligosaccharide-protein glycotransferase
BLM	3.6.4.12	DNA helicase
STK11	2.7.11.1	non-specific serine/threonine protein kinase
EPCAM	2.4.1.37, 2.4.1.40	fucosylgalactoside 3-alpha-galactosyltransferase, glycoprotein-fucosylgalactoside alpha-N-acetylgalactosaminyltransferase
TDG	3.2.2.29	thymine-DNA glycosylase
TYRO3	2.7.10.1	receptor protein-tyrosine kinase
UNG	3.2.2.27	uracil-DNA glycosylase
PAK4	2.7.11.1	non-specific serine/threonine protein kinase
CHEK2	2.7.11.1	non-specific serine/threonine protein kinase
DROSHA	3.1.26.3	ribonuclease III
BRIP1	3.6.4.12	DNA helicase
CPS1	6.3.4.16	carbamoyl-phosphate synthase (ammonia)
CDK12	2.7.11.22, 2.7.11.23	cyclin-dependent kinase, [RNA-polymerase]-subunit kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
RIPK1	400
STK11	244
TERT	391
TP53	869
TYRO3	380
PAK4	536
CHEK2	690
MELK	392
CDK12	347

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

30 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BLM, BRCA1, TSHR
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BLM, BRCA1, TP53
DOXORUBICIN HYDROCHLORIDE	4	BLM, BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	BLM, BRCA1, TSHR
PONATINIB	4	MELK, RIPK1
FEDRATINIB	4	MELK, PAK4, RIPK1, STK11
AXITINIB	4	PAK4, RIPK1
SORAFENIB	4	RIPK1
DABRAFENIB	4	MELK, RIPK1
PAZOPANIB	4	RIPK1
NINTEDANIB	4	MELK, PAK4, RIPK1, STK11, TYRO3
SUNITINIB	4	CHEK2, MELK, PAK4, RIPK1, STK11, TYRO3
QUIZARTINIB	4	RIPK1
CRIZOTINIB	4	RIPK1, SLC34A2, TYRO3
AMIFOSTINE	4	BLM
BEXAROTENE	4	BLM
DICLOFENAC SODIUM	4	BLM, TSHR
CLOTRIMAZOLE	4	BLM, TP53, TSHR
FLUORESCEIN	4	BLM
OXCARBAZEPINE	4	BLM
BUMETANIDE	4	BLM, TSHR
GLIPIZIDE	4	BLM, TSHR
SALMETEROL XINAFOATE	4	BLM, TP53
AMIODARONE HYDROCHLORIDE	4	BLM, TP53
INDIGOTINDISULFONATE	4	BLM
TRIHEXYPHENIDYL HYDROCHLORIDE	4	BLM
RALOXIFENE HYDROCHLORIDE	4	BLM, TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	12	BRCA1, RIPK1, BLM, SLC34A2, STK11, TERT, TP53, TSHR, TYRO3, PAK4 (+2 more)
B	Phased (≥1) drug, not yet approved	2	CDK20, CDK12
C	Druggable family + PDB, no drug	9	RPN1, EPCAM, TDG, TFRC, UNG, VRK1, DROSHA, BRIP1, CPS1
D	Druggable family + AlphaFold only, no drug	4	AOPEP, CSMD3, MTMR10, PM20D1
E	Difficult family or no structure, no drug	48	BRCA2, RAD51C, RAD51D, NEMF, SLC25A15, SP100, TACC3, HNF1A, TG, TPM4 (+38 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BRCA2	0	BRCA1
RAD51D	0	BRCA1
TG	0	TSHR
CCNG1	0	TP53
DROSHA	0	TP53
BRIP1	0	BRCA1
ABRAXAS1	0	BRCA1
PALB2	0	BRCA1
RAD51C	0	—
RPN1	8	—
NEMF	0	—
SLC25A15	0	—
SP100	2	—
TACC3	3	—
EPCAM	1	—
HNF1A	1	—
TDG	9	—
TFRC	1	—
TPM4	4	—
UNG	7	—
VRK1	74	—
WWOX	0	—
XRCC2	0	—
BIRC6	0	—
TLX3	0	—
AOPEP	1	—
HERPUD1	0	—
WDR11	0	—
TES	2	—
PUM1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 51.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	39
PHASE2	5
PHASE3	3
PHASE1	2
PHASE4	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT05130606	Not specified	RECRUITING	CONTIGO - A Narrative Intervention to Enhance Genetic Counseling and Testing
NCT05677048	Not specified	ACTIVE_NOT_RECRUITING	Feasibility Study: IGNITE-TX (Identifying Individuals for Genetic Testing & Treatment) Intervention
NCT06892275	Not specified	RECRUITING	The FYI on MRI: A Multilevel Decision Support Intervention for Screening Breast MRI
NCT06914726	Not specified	ENROLLING_BY_INVITATION	Patient Centered Clinical Decision Support for Hereditary Cancer Syndromes
NCT07039552	Not specified	RECRUITING	Development and Validation of an Ovarian Cancer Risk Prediction Model for Family Members of Ovarian Cancer Probands
NCT07236359	Not specified	NOT_YET_RECRUITING	Evaluation of Well Being and Patient Reported Outcomes After Robotic Single-port Nipple Sparing Mastectomy and Implant Reconstruction
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LETROZOLE	4	1
VELIPARIB	3	4
ARZOXIFENE HYDROCHLORIDE	2	1