Breast-ovarian cancer, familial, susceptibility to, 3

Summary

Breast-ovarian cancer, familial, susceptibility to, 3 (MONDO:0013253) is a cancer caused by RAD51C (GenCC Strong), with 4 cohort genes (3 CIViC-evidence somatic drivers; 897 ClinVar predisposition records).

At a glance

• Classification: Cancer
• Causal gene: RAD51C (GenCC Strong)
• Cohort genes: 4
• ClinVar variants: 897

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	breast-ovarian cancer, familial, susceptibility to, 3
Mondo ID	MONDO:0013253
OMIM	613399
UMLS	C3150659
MedGen	462009
Is cancer (heuristic)	yes

Also known as: breast-ovarian cancer, familial, susceptibility to, 3 · breast-ovarian cancer, familial, susceptibility to, type 3 · BROVCA3 · hereditary breast ovarian cancer syndrome caused by mutation in RAD51C · hereditary breast ovarian cancer syndrome caused by mutation in Rad51C · RAD51C hereditary breast ovarian cancer syndrome · Rad51C hereditary breast ovarian cancer syndrome

Data availability: 897 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › breast-ovarian cancer, familial, susceptibility to › breast-ovarian cancer, familial, susceptibility to, 3

Related subtypes (4): breast-ovarian cancer, familial, susceptibility to, 1, breast-ovarian cancer, familial, susceptibility to, 2, breast-ovarian cancer, familial, susceptibility to, 4, breast-ovarian cancer, familial, susceptibility to, 5

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:

132 conflicting classifications of pathogenicity, 130 benign/likely benign, 77 likely benign, 71 pathogenic, 64 uncertain significance, 50 benign, 41 pathogenic/likely pathogenic, 34 likely pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1072935	NM_058216.3(RAD51C):c.612del (p.Leu205fs)	LOC129390903	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1098903	NM_058216.3(RAD51C):c.656T>A (p.Leu219Ter)	LOC129390903	Pathogenic	criteria provided, multiple submitters, no conflicts
1098905	NM_058216.3(RAD51C):c.704dup (p.Val236fs)	LOC129390903	Pathogenic	criteria provided, multiple submitters, no conflicts
1098906	NM_058216.3(RAD51C):c.705+1G>T	LOC129390903	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
142919	NM_058216.3(RAD51C):c.701C>G (p.Ser234Ter)	LOC129390903	Pathogenic	criteria provided, multiple submitters, no conflicts
185074	NM_058216.3(RAD51C):c.630T>G (p.Tyr210Ter)	LOC129390903	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
186604	NM_058216.3(RAD51C):c.653_654del (p.Glu218fs)	LOC129390903	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2021697	NM_058216.3(RAD51C):c.615_618del (p.Ser206fs)	LOC129390903	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
230577	NM_058216.3(RAD51C):c.705+1G>A	LOC129390903	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
232018	NM_058216.3(RAD51C):c.622_623del (p.Ile208fs)	LOC129390903	Pathogenic	criteria provided, multiple submitters, no conflicts
2705286	NM_058216.3(RAD51C):c.627T>G (p.Tyr209Ter)	LOC129390903	Pathogenic	criteria provided, multiple submitters, no conflicts
3148354	NM_058216.3(RAD51C):c.616dup (p.Ser206fs)	LOC129390903	Pathogenic	criteria provided, single submitter
3148608	NM_058216.3(RAD51C):c.699_702del (p.His233fs)	LOC129390903	Pathogenic	criteria provided, single submitter
372087	NM_058216.3(RAD51C):c.145+2T>G	LOC130061310	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069820	NM_058216.3(RAD51C):c.472dup (p.Ile158fs)	RAD51C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069913	NM_058216.3(RAD51C):c.961C>T (p.Gln321Ter)	RAD51C	Pathogenic	criteria provided, multiple submitters, no conflicts
1072950	NM_058216.3(RAD51C):c.401T>G (p.Leu134Ter)	RAD51C	Pathogenic	criteria provided, multiple submitters, no conflicts
1073709	NM_058216.3(RAD51C):c.795del (p.Ala266fs)	RAD51C	Pathogenic	criteria provided, multiple submitters, no conflicts
1075016	NM_058216.3(RAD51C):c.905-1G>A	RAD51C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1098890	NM_058216.3(RAD51C):c.-13_14del (p.Met1_Thr5del)	RAD51C	Pathogenic	criteria provided, single submitter
1098898	NM_058216.3(RAD51C):c.522_523insC (p.Ala175fs)	RAD51C	Pathogenic	criteria provided, single submitter
1098899	NM_058216.3(RAD51C):c.572-1G>T	RAD51C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1098902	NM_058216.3(RAD51C):c.635del (p.Arg212fs)	RAD51C	Pathogenic	criteria provided, single submitter
1098904	NM_058216.3(RAD51C):c.672dup (p.Leu225fs)	RAD51C	Pathogenic	no assertion criteria provided
1098907	NM_058216.3(RAD51C):c.706-1G>A	RAD51C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1098911	NM_058216.3(RAD51C):c.862del (p.Thr288fs)	RAD51C	Pathogenic	criteria provided, single submitter
1098925	NM_058216.3(RAD51C):c.706_837+2del	RAD51C	Pathogenic	criteria provided, single submitter
1177647	GRCh37/hg19 17q22(chr17:56809845-56811583)	RAD51C	Pathogenic	criteria provided, single submitter
1177648	NM_058216.3:c.1_705del	RAD51C	Pathogenic	criteria provided, single submitter
1177649	NM_058216.3(RAD51C):c.405_571del	RAD51C	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 25 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
RAD51C			CIViC #4762
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
RAD50	Act	GBM	CIViC #8032

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
RAD51C	Strong	Autosomal dominant	breast-ovarian cancer, familial, susceptibility to, 3	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RAD51C	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
RAD51C	Orphanet:84	Fanconi anemia
TEX14	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
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
RAD50	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
RAD50	Orphanet:240760	Nijmegen breakage syndrome-like disorder

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RAD51C	HGNC:9820	ENSG00000108384	O43502	DNA repair protein RAD51 homolog 3	gencc,clinvar
TEX14	HGNC:11737	ENSG00000121101	Q8IWB6	Inactive serine/threonine-protein kinase TEX14	clinvar
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar
RAD50	HGNC:9816	ENSG00000113522	Q92878	DNA repair protein RAD50	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RAD51C	DNA repair protein RAD51 homolog 3	Essential for the homologous recombination (HR) pathway of DNA repair.
TEX14	Inactive serine/threonine-protein kinase TEX14	Required both for the formation of intercellular bridges during meiosis and for kinetochore-microtubule attachment during mitosis.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
RAD50	DNA repair protein RAD50	Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.25

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	1	6.9×	0.410
Transcription factor	1	2.1×	0.605
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RAD51C	Other/Unknown	no		Rad51_C, DNA_recomb/repair_RecA-like, RecA_ATP-bd
TEX14	Kinase	yes		Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ankyrin_rpt
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
RAD50	Other/Unknown	no		Rad50_eukaryotes, Zn_hook_RAD50, P-loop_NTPase

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right testis	2
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
left testis	1
testis	1
ganglionic eminence	1
tendon of biceps brachii	1
ventricular zone	1
calcaneal tendon	1
colonic epithelium	1
corpus callosum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RAD51C	281	ubiquitous	marker	primordial germ cell in gonad, right testis, male germ line stem cell (sensu Vertebrata) in testis
TEX14	162	broad	marker	right testis, left testis, testis
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
RAD50	134	ubiquitous	marker	corpus callosum, calcaneal tendon, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
RAD51C	3,396
RAD50	2,552
TEX14	943

Structural data

PDB: 4 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TP53	P04637	313
RAD51C	O43502	17
RAD50	Q92878	6
TEX14	Q8IWB6	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 63. Enrichment computed across 4 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Impaired BRCA2 binding to PALB2	2	304.5×	2e-04	RAD51C, RAD50
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	2	282.0×	2e-04	RAD51C, RAD50
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	2	282.0×	2e-04	RAD51C, RAD50
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	2	282.0×	2e-04	RAD51C, RAD50
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	2	262.5×	2e-04	RAD51C, RAD50
Homologous DNA Pairing and Strand Exchange	2	253.8×	2e-04	RAD51C, RAD50
Resolution of D-loop Structures through Holliday Junction Intermediates	2	200.3×	3e-04	RAD51C, RAD50
Presynaptic phase of homologous DNA pairing and strand exchange	2	181.3×	3e-04	RAD51C, RAD50
HDR through Homologous Recombination (HRR)	2	126.9×	6e-04	RAD51C, RAD50
DNA Damage/Telomere Stress Induced Senescence	2	108.8×	7e-04	TP53, RAD50
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	2	97.6×	8e-04	TP53, RAD50
Meiotic recombination	2	86.5×	9e-04	RAD51C, RAD50
G2/M DNA damage checkpoint	2	80.1×	1e-03	TP53, RAD50
Regulation of TP53 Activity through Phosphorylation	2	78.5×	1e-03	TP53, RAD50
Loss of function of TP53 in cancer due to loss of tetramerization ability	1	3806.7×	0.001	TP53
Regulation of TP53 Expression	1	1903.3×	0.002	TP53
Factors involved in megakaryocyte development and platelet production	2	44.3×	0.002	RAD51C, TP53
Transcriptional activation of cell cycle inhibitor p21	1	951.7×	0.004	TP53
Activation of NOXA and translocation to mitochondria	1	634.4×	0.005	TP53
Sensing of DNA Double Strand Breaks	1	634.4×	0.005	RAD50
RUNX3 regulates CDKN1A transcription	1	543.8×	0.006	TP53
PI5P Regulates TP53 Acetylation	1	423.0×	0.007	TP53
Activation of PUMA and translocation to mitochondria	1	380.7×	0.007	TP53
TP53 Regulates Transcription of Caspase Activators and Caspases	1	317.2×	0.008	TP53
TP53 Regulates Transcription of Death Receptors and Ligands	1	317.2×	0.008	TP53
HDR through MMEJ (alt-NHEJ)	1	292.8×	0.008	RAD50
Urea cycle	1	292.8×	0.008	TP53
Regulation of TP53 Activity through Association with Co-factors	1	271.9×	0.008	TP53
TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain	1	253.8×	0.008	TP53
Stabilization of p53	1	253.8×	0.008	TP53

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
telomere maintenance via recombination	2	766.0×	4e-04	RAD51C, RAD50
reciprocal meiotic recombination	2	280.9×	0.001	RAD51C, RAD50
DNA recombination	2	168.5×	0.003	RAD51C, RAD50
meiotic DNA recombinase assembly	1	4213.0×	0.003	RAD51C
female meiosis sister chromatid cohesion	1	4213.0×	0.003	RAD51C
intercellular bridge organization	1	4213.0×	0.003	TEX14
negative regulation of helicase activity	1	4213.0×	0.003	TP53
cellular response to actinomycin D	1	4213.0×	0.003	TP53
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	4213.0×	0.003	TP53
negative regulation of G1 to G0 transition	1	4213.0×	0.003	TP53
double-strand break repair	2	101.5×	0.003	TP53, RAD50
double-strand break repair via homologous recombination	2	78.0×	0.003	RAD51C, RAD50
regulation of mitotic recombination	1	2106.5×	0.004	RAD50
positive regulation of mitochondrial membrane permeability	1	2106.5×	0.004	TP53
oligodendrocyte apoptotic process	1	2106.5×	0.004	TP53
negative regulation of glucose catabolic process to lactate via pyruvate	1	2106.5×	0.004	TP53
negative regulation of pentose-phosphate shunt	1	2106.5×	0.004	TP53
obsolete homolactic fermentation	1	1404.3×	0.005	TP53
signal transduction by p53 class mediator	1	1404.3×	0.005	TP53
negative regulation of miRNA processing	1	1404.3×	0.005	TP53
intrinsic apoptotic signaling pathway in response to hypoxia	1	1404.3×	0.005	TP53
regulation of fibroblast apoptotic process	1	1404.3×	0.005	TP53
T cell proliferation involved in immune response	1	1053.2×	0.005	TP53
telomeric 3’ overhang formation	1	1053.2×	0.005	RAD50
positive regulation of programmed necrotic cell death	1	1053.2×	0.005	TP53
oxidative stress-induced premature senescence	1	1053.2×	0.005	TP53
B cell lineage commitment	1	842.6×	0.005	TP53
T cell lineage commitment	1	842.6×	0.005	TP53
mRNA transcription	1	842.6×	0.005	TP53
positive regulation of RNA polymerase II transcription preinitiation complex assembly	1	842.6×	0.005	TP53

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 2

Druggability breadth: 2 of 4 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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
RAD50	1	2
RAD51C	0	0
TEX14	0	0

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	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
RAD50	7	Binding:7

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TP53	869

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TP53
B	Phased (≥1) drug, not yet approved	1	RAD50
C	Druggable family + PDB, no drug	1	TEX14
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	RAD51C

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RAD51C	0	—
TEX14	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.