Ovarian cancer, susceptibility to, 1

Summary

Ovarian cancer, susceptibility to, 1 (MONDO:0011931) is a cancer with 2 cohort genes (2 CIViC-evidence somatic drivers; 2 ClinVar predisposition records).

At a glance

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

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ovarian cancer, susceptibility to, 1
Mondo ID	MONDO:0011931
OMIM	607893
UMLS	C2675601
MedGen	390836
GARD	0027808
Is cancer (heuristic)	yes

Also known as: ovarian cancer, susceptibility to · ovarian cancer, susceptibility to, 1 · OVCAS1

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › ovarian cancer, susceptibility to, 1

Related subtypes (116): mosaic variegated aneuploidy syndrome, tuberous sclerosis, hereditary breast ovarian cancer syndrome, hereditary multiple osteochondromas, nevoid basal cell carcinoma syndrome, leukemia, chronic lymphocytic, susceptibility to, 2, blue rubber bleb nevus, cherubism, Beckwith-Wiedemann syndrome, multiple self-healing squamous epithelioma, erythroleukemia, familial, susceptibility to, goiter, multinodular 1, with or without Sertoli-Leydig cell tumors, hyperparathyroidism 2 with jaw tumors, Kaposi sarcoma, susceptibility to, hereditary leiomyomatosis and renal cell cancer, susceptibility to uveal melanoma, melanoma and neural system tumor syndrome, nasopharyngeal carcinoma, susceptibility to, 2, WAGR syndrome, neuroblastoma, susceptibility to, 1, Rothmund-Thomson syndrome, mismatch repair cancer syndrome 1, Wiskott-Aldrich syndrome, N syndrome, hereditary thrombocytopenia and hematologic cancer predisposition syndrome, prostate cancer/brain cancer susceptibility, Brooke-Spiegler syndrome, pancreatic cancer, susceptibility to, 1, Carney-Stratakis syndrome, nasopharyngeal carcinoma, susceptibility to, 1, colorectal cancer, susceptibility to, 1, lung cancer susceptibility 1, leukemia, chronic lymphocytic, susceptibility to, 1, Kostmann syndrome, colorectal cancer, susceptibility to, 2, colorectal cancer, susceptibility to, 3, colorectal cancer, susceptibility to, 5, colorectal cancer, susceptibility to, 6, colorectal cancer, susceptibility to, 7, leukemia, chronic lymphocytic, susceptibility to, 3, leukemia, chronic lymphocytic, susceptibility to, 4, leukemia, chronic lymphocytic, susceptibility to, 5, lung cancer susceptibility 3, colorectal cancer, susceptibility to, 8, colorectal cancer, susceptibility to, 9, colorectal cancer, susceptibility to, 10, colorectal cancer, susceptibility to, 11, lung cancer susceptibility 4, neuroblastoma, susceptibility to, 3, neuroblastoma, susceptibility to, 4, neuroblastoma, susceptibility to, 5, neuroblastoma, susceptibility to, 6, leukemia, acute lymphocytic, susceptibility to, 1, leukemia, acute lymphocytic, susceptibility to, 2, lung cancer susceptibility 5, BAP1-related tumor predisposition syndrome, familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome, Maffucci syndrome, basal cell carcinoma, susceptibility to, 7, colorectal cancer, susceptibility to, 12, leukemia, acute lymphoblastic, susceptibility to, 3, cholangiocarcinoma, susceptibility to, progeroid features-hepatocellular carcinoma predisposition syndrome, neuroblastoma, susceptibility to, 7, DDX41-related hematologic malignancy predisposition syndrome, nasopharyngeal carcinoma, susceptibility to, 3, familial isolated hyperparathyroidism, intestinal polyposis syndrome, dyskeratosis congenita, familial rhabdoid tumor, multiple endocrine neoplasia, hereditary pheochromocytoma-paraganglioma, PTEN hamartoma tumor syndrome, familial multiple fibrofolliculoma, hereditary retinoblastoma, familial atypical multiple mole melanoma syndrome, hereditary nonpolyposis colon cancer, Li-Fraumeni syndrome, Cobb syndrome, neurofibromatosis, susceptibility to familial cutaneous melanoma, pancreatic cancer, susceptibility to, 5, leukemia, acute myeloid, susceptibility to, diffuse gastric and lobular breast cancer syndrome with or without cleft lip and/or palate, glioma susceptibility, hemangioma, capillary infantile, susceptibility to, CDH1-related diffuse gastric and lobular breast cancer syndrome, NTHL1-deficiency tumor predisposition syndrome, SAMD9-related spectrum and myeloid neoplasm risk, neuroblastoma, susceptibility to, 2, BARD1-related cancer predisposition, BRCA1-related cancer predisposition, BRCA2-related cancer predisposition, ATM-related cancer predisposition, CHEK2-related cancer predisposition, PALB2-related cancer predisposition, RAD51C-related cancer predisposition, RAD51D-related cancer predisposition, Li-fraumeni-like syndrome, breast cancer, familial, susceptibility to, 1, breast cancer, familial, susceptibility to, 2, breast cancer, familial, susceptibility to, 3, colorectal cancer, susceptibility to, 4, colorectal cancer, susceptibility to, on chromosome 15, ovarian cancer, familial, susceptibility to, 1, ovarian cancer, familial, susceptibility to, 2, ovarian cancer, familial, susceptibility to, 3, inherited hematologic cancer-predisposing syndrome, mosaic neurofibromatosis/schwannomatosis, tumor predisposition syndrome 2, prostate cancer, hereditary, X-linked 3, follicular lymphoma, susceptibility to, GPR161-related medulloblastoma predisposition, SAMD9L-related spectrum and myeloid neoplasm risk, HAVCR2-related cancer predisposition, EGLN1-related erythrocytosis and pheochromocytoma/paraganglioma predisposition

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

2 retrieved; paginated sample, class counts are floors:

2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
449345	NM_000051.4(ATM):c.5497-2A>C	ATM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
141319	NM_032043.3(BRIP1):c.918+1G>A	BRIP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
BRIP1			CIViC #15955
ATM	LoF	BLCA,BRCA,CCRCC,CHOL,CLLSLL,COAD,COADREAD,ESCA,HCC,LUAD,LUSC,MEL,NSCLC,PAAD,PANCREAS,PANET,PCM,PLMESO,PRAD,PROSTATE,STAD,UCEC,UTUC,WDTC	CIViC #69

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BRIP1	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRIP1	Orphanet:84	Fanconi anemia
ATM	Orphanet:100	Ataxia-telangiectasia
ATM	Orphanet:1331	Familial prostate cancer
ATM	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
ATM	Orphanet:227535	Hereditary breast cancer
ATM	Orphanet:370109	Ataxia-telangiectasia variant
ATM	Orphanet:440437	Familial colorectal cancer Type X
ATM	Orphanet:52416	Mantle cell lymphoma
ATM	Orphanet:67038	B-cell chronic lymphocytic leukemia

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
BRIP1	HGNC:20473	ENSG00000136492	Q9BX63	Fanconi anemia group J protein	clinvar
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRIP1	Fanconi anemia group J protein	DNA-dependent ATPase and 5’-3’ DNA helicase required for the maintenance of chromosomal stability.
ATM	Serine-protein kinase ATM	Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	13.9×	0.142
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BRIP1	Enzyme (other)	yes	3.6.4.12	Helicase-like_DEXD_c2, ATP-dep_Helicase_C, RAD3-like_helicase_DEAD
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom

Expression context

Cohort genes with no expression data: 0.

2 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)	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
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
BRIP1	181	ubiquitous	marker	ventricular zone, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
ATM	286	ubiquitous	marker	calcaneal tendon, colonic epithelium, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATM	7,383
BRIP1	2,272

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATM	Q13315	14
BRIP1	Q9BX63	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 62. 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×	7e-05	BRIP1, ATM
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	2	423.0×	7e-05	BRIP1, ATM
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	2	423.0×	7e-05	BRIP1, ATM
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	2	423.0×	7e-05	BRIP1, ATM
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	2	393.8×	7e-05	BRIP1, ATM
Homologous DNA Pairing and Strand Exchange	2	380.7×	7e-05	BRIP1, ATM
Impaired BRCA2 binding to RAD51	2	308.6×	8e-05	BRIP1, ATM
Resolution of D-loop Structures through Holliday Junction Intermediates	2	300.5×	8e-05	BRIP1, ATM
HDR through Single Strand Annealing (SSA)	2	292.8×	8e-05	BRIP1, ATM
Presynaptic phase of homologous DNA pairing and strand exchange	2	271.9×	8e-05	BRIP1, ATM
HDR through Homologous Recombination (HRR)	2	190.3×	2e-04	BRIP1, ATM
G2/M DNA damage checkpoint	2	120.2×	3e-04	BRIP1, ATM
Regulation of TP53 Activity through Phosphorylation	2	117.7×	3e-04	BRIP1, ATM
Processing of DNA double-strand break ends	2	114.2×	3e-04	BRIP1, ATM
Sensing of DNA Double Strand Breaks	1	951.7×	0.004	ATM
TP53 Regulates Transcription of Caspase Activators and Caspases	1	475.8×	0.007	ATM
Pexophagy	1	475.8×	0.007	ATM
Defective homologous recombination repair (HRR) due to PALB2 loss of function	1	475.8×	0.007	ATM
Diseases of DNA Double-Strand Break Repair	1	407.9×	0.007	ATM
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1	407.9×	0.007	ATM
Cytosolic iron-sulfur cluster assembly	1	380.7×	0.007	BRIP1
Stabilization of p53	1	380.7×	0.007	ATM
p53-Dependent G1 DNA Damage Response	1	356.9×	0.007	ATM
p53-Dependent G1/S DNA damage checkpoint	1	356.9×	0.007	ATM
G1/S DNA Damage Checkpoints	1	335.9×	0.007	ATM
Resolution of D-Loop Structures	1	317.2×	0.008	ATM
Diseases of DNA repair	1	285.5×	0.008	ATM
TP53 Regulates Transcription of Cell Death Genes	1	271.9×	0.008	ATM
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	1	271.9×	0.008	ATM
Regulation of TP53 Activity through Methylation	1	271.9×	0.008	ATM

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
DNA damage checkpoint signaling	2	391.9×	5e-04	BRIP1, ATM
double-strand break repair	2	203.0×	9e-04	BRIP1, ATM
establishment of RNA localization to telomere	1	4213.0×	0.004	ATM
establishment of protein-containing complex localization to telomere	1	4213.0×	0.004	ATM
positive regulation of telomerase catalytic core complex assembly	1	4213.0×	0.004	ATM
pre-B cell allelic exclusion	1	2808.7×	0.004	ATM
meiotic DNA double-strand break processing involved in reciprocal meiotic recombination	1	2808.7×	0.004	BRIP1
cellular response to nitrosative stress	1	2808.7×	0.004	ATM
spermatogonial cell division	1	1685.2×	0.004	BRIP1
peptidyl-serine autophosphorylation	1	1685.2×	0.004	ATM
negative regulation of telomere capping	1	1685.2×	0.004	ATM
regulation of telomere maintenance via telomerase	1	1404.3×	0.004	ATM
positive regulation of telomere maintenance via telomere lengthening	1	1404.3×	0.004	ATM
lipoprotein catabolic process	1	1203.7×	0.004	ATM
V(D)J recombination	1	1053.2×	0.004	ATM
meiotic telomere clustering	1	936.2×	0.004	ATM
chiasma assembly	1	936.2×	0.004	BRIP1
female meiotic nuclear division	1	842.6×	0.004	ATM
histone mRNA catabolic process	1	842.6×	0.004	ATM
cellular response to X-ray	1	842.6×	0.004	ATM
protein-DNA covalent cross-linking repair	1	842.6×	0.004	BRIP1
DNA double-strand break processing	1	766.0×	0.005	ATM
homologous recombination	1	702.2×	0.005	BRIP1
double-strand break repair involved in meiotic recombination	1	648.1×	0.005	BRIP1
regulation of autophagosome assembly	1	561.7×	0.005	ATM
pexophagy	1	526.6×	0.005	ATM
regulation of cellular response to heat	1	526.6×	0.005	ATM
positive regulation of DNA damage response, signal transduction by p53 class mediator	1	495.6×	0.005	ATM
replicative senescence	1	495.6×	0.005	ATM
negative regulation of B cell proliferation	1	468.1×	0.005	ATM

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 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
ATM	AMIODARONE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATM	35	4
BRIP1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AMIODARONE HYDROCHLORIDE	4	ATM
FURAZOLIDONE	4	ATM
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM
FENOFIBRATE	4	ATM
DIPYRIDAMOLE	4	ATM
DACTOLISIB	3	ATM
STREPTONIGRIN	2	ATM
CALCIMYCIN	2	ATM
ENPIROLINE	2	ATM
OXACEPROL	2	ATM
TOLONIUM CHLORIDE	2	ATM
ESTRADIOL BENZOATE	2	ATM
BERZOSERTIB	2	ATM
LARTESERTIB	2	ATM
ALTHIAZIDE	2	ATM

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
ATM	240	Binding:233, Functional:5, ADMET:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRIP1	3.6.4.12	DNA helicase
ATM	2.7.11.1	non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ATM	240

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

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)
AMIODARONE HYDROCHLORIDE	4	ATM
FURAZOLIDONE	4	ATM
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM
FENOFIBRATE	4	ATM
DIPYRIDAMOLE	4	ATM
DACTOLISIB	3	ATM
STREPTONIGRIN	2	ATM
CALCIMYCIN	2	ATM
ENPIROLINE	2	ATM
OXACEPROL	2	ATM
TOLONIUM CHLORIDE	2	ATM
ESTRADIOL BENZOATE	2	ATM
BERZOSERTIB	2	ATM
LARTESERTIB	2	ATM
ALTHIAZIDE	2	ATM

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ATM
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	BRIP1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BRIP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.