Hereditary site-specific ovarian cancer syndrome

Summary

Hereditary site-specific ovarian cancer syndrome (MONDO:0016249) is a cancer with 2 cohort genes (2 CIViC-evidence somatic drivers; 4 ClinVar predisposition records).

At a glance

• Classification: Cancer
• Cohort genes: 2
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hereditary site-specific ovarian cancer syndrome
Mondo ID	MONDO:0016249
Orphanet	213524
ICD-11	123305976
GARD	0020468
Is cancer (heuristic)	yes

Data availability: 4 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › familial ovarian cancer › hereditary site-specific ovarian cancer syndrome

Related subtypes (1): familial ovarian carcinoma

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

4 retrieved; paginated sample, class counts are floors:

3 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
128201	NM_058216.3(RAD51C):c.1026+5_1026+7del	RAD51C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
142762	NM_058216.3(RAD51C):c.904+5G>T	RAD51C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
472631	NM_002878.4(RAD51D):c.904-2A>T	RAD51L3-RFFL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
141519	NM_002878.4(RAD51D):c.796C>T (p.Arg266Cys)	RAD51D	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
RAD51C			CIViC #4762
RAD51D			CIViC #4765

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
RAD51D	Orphanet:1331	Familial prostate cancer
RAD51D	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RAD51C	HGNC:9820	ENSG00000108384	O43502	DNA repair protein RAD51 homolog 3	clinvar
RAD51D	HGNC:9823	ENSG00000185379	O75771	DNA repair protein RAD51 homolog 4	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.
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.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
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

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
right testis	1
male germ cell	1
oocyte	1
sperm	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
RAD51D	187	ubiquitous	yes	sperm, male germ cell, oocyte

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RAD51C	3,396
RAD51D	3,089

Intra-cohort edges

A	B	Sources
RAD51C	RAD51D	biogrid_interaction, intact, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RAD51C	O43502	17
RAD51D	O75771	17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. Enrichment computed across 2 evidence-associated genes (2 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 2 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	456.8×	1e-05	RAD51C, RAD51D
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	2	423.0×	1e-05	RAD51C, RAD51D
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	2	423.0×	1e-05	RAD51C, RAD51D
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	2	423.0×	1e-05	RAD51C, RAD51D
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	2	393.8×	1e-05	RAD51C, RAD51D
Homologous DNA Pairing and Strand Exchange	2	380.7×	1e-05	RAD51C, RAD51D
Resolution of D-loop Structures through Holliday Junction Intermediates	2	300.5×	2e-05	RAD51C, RAD51D
Presynaptic phase of homologous DNA pairing and strand exchange	2	271.9×	2e-05	RAD51C, RAD51D
HDR through Homologous Recombination (HRR)	2	190.3×	4e-05	RAD51C, RAD51D
TP53 Regulates Transcription of DNA Repair Genes	1	90.6×	0.013	RAD51D
Meiotic recombination	1	64.9×	0.017	RAD51C
Factors involved in megakaryocyte development and platelet production	1	33.2×	0.030	RAD51C

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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	1532.0×	6e-06	RAD51C, RAD51D
reciprocal meiotic recombination	2	561.7×	2e-05	RAD51C, RAD51D
double-strand break repair via homologous recombination	2	156.0×	2e-04	RAD51C, RAD51D
meiotic DNA recombinase assembly	1	8426.0×	4e-04	RAD51C
female meiosis sister chromatid cohesion	1	8426.0×	4e-04	RAD51C
DNA repair	2	63.8×	6e-04	RAD51C, RAD51D
DNA strand invasion	1	2106.5×	0.001	RAD51D
sister chromatid cohesion	1	383.0×	0.005	RAD51C
positive regulation of G2/M transition of mitotic cell cycle	1	300.9×	0.005	RAD51C
male meiosis I	1	290.6×	0.005	RAD51C
interstrand cross-link repair	1	216.1×	0.006	RAD51D
DNA recombination	1	168.5×	0.007	RAD51C
telomere maintenance	1	133.8×	0.009	RAD51D
regulation of cell cycle	1	37.3×	0.029	RAD51D
spermatogenesis	1	17.6×	0.056	RAD51C

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RAD51C	0	0
RAD51D	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	RAD51C, RAD51D

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	—
RAD51D	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.