Breast-ovarian cancer, familial, susceptibility to, 5

Summary

Breast-ovarian cancer, familial, susceptibility to, 5 (MONDO:0957530) is a cancer with 5 cohort genes (3 CIViC-evidence somatic drivers; 321 ClinVar predisposition records).

At a glance

• Classification: Cancer
• Cohort genes: 5
• ClinVar variants: 321

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	breast-ovarian cancer, familial, susceptibility to, 5
Mondo ID	MONDO:0957530
OMIM	620442
UMLS	C5830615
MedGen	1841251
Is cancer (heuristic)	yes

Data availability: 321 ClinVar variants.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › breast-ovarian cancer, familial, susceptibility to › breast-ovarian cancer, familial, susceptibility to, 5

Related subtypes (4): breast-ovarian cancer, familial, susceptibility to, 1, breast-ovarian cancer, familial, susceptibility to, 2, breast-ovarian cancer, familial, susceptibility to, 3, breast-ovarian cancer, familial, susceptibility to, 4

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

321 retrieved; paginated sample, class counts are floors:

99 conflicting classifications of pathogenicity, 65 uncertain significance, 47 pathogenic, 44 pathogenic/likely pathogenic, 42 benign/likely benign, 14 likely pathogenic, 6 likely benign, 4 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
188814	NM_000053.4(ATP7B):c.2383C>T (p.Leu795Phe)	ATP7B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126623	NM_024675.4(PALB2):c.172_175del (p.Gln60fs)	DCTN5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1050102	NM_024675.4(PALB2):c.892_893del (p.Val298fs)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072355	NM_024675.4(PALB2):c.3351-1G>A	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1243	NM_024675.4(PALB2):c.1653T>A (p.Tyr551Ter)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1245	NM_024675.4(PALB2):c.3549C>G (p.Tyr1183Ter)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1246	NM_024675.4(PALB2):c.2962C>T (p.Gln988Ter)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
126583	NM_024675.4(PALB2):c.1027C>T (p.Gln343Ter)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
126609	NM_024675.4(PALB2):c.1592del (p.Leu531fs)	PALB2	Pathogenic	reviewed by expert panel
126611	NM_024675.4(PALB2):c.1633G>T (p.Glu545Ter)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
126629	NM_024675.4(PALB2):c.196C>T (p.Gln66Ter)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126646	NM_024675.4(PALB2):c.2323C>T (p.Gln775Ter)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
126675	NM_024675.4(PALB2):c.2718G>A (p.Trp906Ter)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126688	NM_024675.4(PALB2):c.2835-1G>C	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126697	NM_024675.4(PALB2):c.2982dup (p.Ala995fs)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126711	NM_024675.4(PALB2):c.3113G>A (p.Trp1038Ter)	PALB2	Pathogenic	reviewed by expert panel
126715	NM_024675.4(PALB2):c.3116del (p.Asn1039fs)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126729	NM_024675.4(PALB2):c.3256C>T (p.Arg1086Ter)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126748	NM_024675.4(PALB2):c.395del (p.Val132fs)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
126757	NM_024675.4(PALB2):c.509_510del (p.Arg170fs)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
126764	NM_024675.4(PALB2):c.697del (p.Val233fs)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
126766	NM_024675.4(PALB2):c.72del (p.Arg26fs)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126767	NM_024675.4(PALB2):c.751C>T (p.Gln251Ter)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
126768	NM_024675.4(PALB2):c.757_758del (p.Leu253fs)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
126769	NM_024675.4(PALB2):c.758dup (p.Ser254fs)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
128117	NM_024675.4(PALB2):c.1240C>T (p.Arg414Ter)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
128142	NM_024675.4(PALB2):c.3456dup (p.Pro1153fs)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
128144	NM_024675.4(PALB2):c.3549C>A (p.Tyr1183Ter)	PALB2	Pathogenic	reviewed by expert panel
1319617	NM_024675.4(PALB2):c.2275C>T (p.Gln759Ter)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
136132	NM_024675.4(PALB2):c.2167_2168del (p.Met723fs)	PALB2	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
PALB2	LoF	OVT	CIViC #15013
ATP7B			CIViC #519
PRKD1	Act	CHOL,COADREAD,PRAD

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PALB2	Orphanet:1333	Familial pancreatic carcinoma
PALB2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
PALB2	Orphanet:178	Chordoma
PALB2	Orphanet:227535	Hereditary breast cancer
PALB2	Orphanet:84	Fanconi anemia
ATP7B	Orphanet:905	Wilson disease
PKD1	Orphanet:730	Autosomal dominant polycystic kidney disease
PKD1	Orphanet:88924	Autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis
PRKD1	Orphanet:276145	Malignant epithelial tumor of salivary glands
PRKD1	Orphanet:708019	Congenital heart defect-ectodermal dysplasia- brachydactyly-telangiectasia syndrome

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DCTN5	HGNC:24594	ENSG00000166847	Q9BTE1	Dynactin subunit 5	clinvar
PALB2	HGNC:26144	ENSG00000083093	Q86YC2	Partner and localizer of BRCA2	clinvar
ATP7B	HGNC:870	ENSG00000123191	P35670	Copper-transporting ATPase 2	clinvar
PKD1	HGNC:9008	ENSG00000008710	P98161	Polycystin-1	clinvar
PRKD1	HGNC:9407	ENSG00000184304	Q15139	Serine/threonine-protein kinase D1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DCTN5	Dynactin subunit 5	Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules.
PALB2	Partner and localizer of BRCA2	Plays a critical role in homologous recombination repair (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks.
ATP7B	Copper-transporting ATPase 2	Copper ion transmembrane transporter involved in the export of copper out of the cells.
PKD1	Polycystin-1	Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B.
PRKD1	Serine/threonine-protein kinase D1	Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and tr…

Protein-family classification

Druggable: 2 · Difficult: 2 · Unknown: 1 · Druggable fraction: 0.4

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
Antibody/Immunoglobulin	1	5.8×	0.420
Kinase	1	5.5×	0.420
Scaffold/PPI	1	3.5×	0.429
Transcription factor	1	1.6×	0.595
Other/Unknown	1	0.4×	0.983

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DCTN5	Other/Unknown	no		Trimer_LpxA-like_sf, DCTN5
PALB2	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, PALB2_WD40, WD40_repeat_dom_sf
ATP7B	Transcription factor	no	7.2.2.8	P_typ_ATPase, HMA_dom, HMA_Cu_ion-bd
PKD1	Antibody/Immunoglobulin	yes		GPS, LRRNT, PC1
PRKD1	Kinase	yes	2.7.11.13	Prot_kinase_dom, PH_domain, PKC_DAG/PE

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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
islet of Langerhans	1
rectum	1
stromal cell of endometrium	1
buccal mucosa cell	1
oocyte	1
secondary oocyte	1
nasal cavity epithelium	1
nasal cavity mucosa	1
right testis	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
seminal vesicle	1
thoracic aorta	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DCTN5	288	ubiquitous	marker	islet of Langerhans, rectum, stromal cell of endometrium
PALB2	232	ubiquitous	yes	secondary oocyte, buccal mucosa cell, oocyte
ATP7B	205	ubiquitous	marker	nasal cavity epithelium, right testis, nasal cavity mucosa
PKD1	290		marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
PRKD1	239	ubiquitous	marker	ventricular zone, seminal vesicle, thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PALB2	5,641
ATP7B	2,536
PRKD1	2,131
DCTN5	1,910
PKD1	1,370

Intra-cohort edges

A	B	Sources
PKD1	PRKD1	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATP7B	P35670	13
PKD1	P98161	13
PALB2	Q86YC2	4
DCTN5	Q9BTE1	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PRKD1	Q15139	68.99

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. Enrichment computed across 5 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
VxPx cargo-targeting to cilium	1	103.8×	0.041	PKD1
Impaired BRCA2 binding to PALB2	1	91.4×	0.041	PALB2
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	84.6×	0.041	PALB2
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	84.6×	0.041	PALB2
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	84.6×	0.041	PALB2
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	78.8×	0.041	PALB2
Homologous DNA Pairing and Strand Exchange	1	76.1×	0.041	PALB2
Resolution of D-loop Structures through Holliday Junction Intermediates	1	60.1×	0.043	PALB2
Sphingolipid de novo biosynthesis	1	57.1×	0.043	PRKD1
COPI-independent Golgi-to-ER retrograde traffic	1	41.5×	0.044	DCTN5
Ion transport by P-type ATPases	1	41.5×	0.044	ATP7B
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	1	38.7×	0.044	DCTN5
HDR through Homologous Recombination (HRR)	1	38.1×	0.044	PALB2
Sphingolipid metabolism	1	33.6×	0.046	PRKD1
KEAP1-NFE2L2 pathway	1	24.0×	0.060	PALB2
COPI-mediated anterograde transport	1	22.0×	0.061	DCTN5
Ion channel transport	1	19.2×	0.066	ATP7B
MHC class II antigen presentation	1	17.8×	0.067	DCTN5
Neddylation	1	9.5×	0.117	PALB2
Metabolism of lipids	1	6.3×	0.164	PRKD1
Transport of small molecules	1	5.0×	0.192	ATP7B
Metabolism	1	2.3×	0.362	PRKD1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
metanephric distal tubule morphogenesis	1	3370.4×	0.014	PKD1
regulation of skeletal muscle contraction by modulation of calcium ion sensitivity of myofibril	1	1685.2×	0.014	PRKD1
nitrogen cycle metabolic process	1	1685.2×	0.014	PKD1
mesonephric tubule development	1	1685.2×	0.014	PKD1
lymph vessel morphogenesis	1	1123.5×	0.014	PKD1
copper ion export	1	1123.5×	0.014	ATP7B
metanephric proximal tubule development	1	1123.5×	0.014	PKD1
calcium-independent cell-matrix adhesion	1	842.6×	0.014	PKD1
cellular response to norepinephrine stimulus	1	842.6×	0.014	PRKD1
metanephric ascending thin limb development	1	842.6×	0.014	PKD1
obsolete sequestering of calcium ion	1	674.1×	0.014	ATP7B
mesonephric duct development	1	674.1×	0.014	PKD1
positive regulation of sarcomere organization	1	561.7×	0.014	PRKD1
viral translational frameshifting	1	561.7×	0.014	ATP7B
mitocytosis	1	561.7×	0.014	PKD1
copper ion import	1	481.5×	0.014	ATP7B
lung epithelium development	1	421.3×	0.014	PKD1
cellular response to hydroperoxide	1	421.3×	0.014	PRKD1
regulation of integrin-mediated signaling pathway	1	421.3×	0.014	PRKD1
response to fluid shear stress	1	374.5×	0.014	PKD1
copper ion transport	1	337.0×	0.014	ATP7B
genitalia development	1	337.0×	0.014	PKD1
metanephric collecting duct development	1	337.0×	0.014	PKD1
regulation of keratinocyte proliferation	1	306.4×	0.014	PRKD1
response to copper ion	1	306.4×	0.014	ATP7B
Golgi vesicle transport	1	306.4×	0.014	PRKD1
positive regulation of peptide hormone secretion	1	306.4×	0.014	PRKD1
placenta blood vessel development	1	280.9×	0.014	PKD1
cellular response to endothelin	1	280.9×	0.014	PRKD1
positive regulation of cell size	1	259.3×	0.015	PRKD1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 5 evidence-associated genes (40%) 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
PRKD1	INGENOL MEBUTATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PRKD1	26	4
DCTN5	0	0
PALB2	0	0
ATP7B	0	0
PKD1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
INGENOL MEBUTATE	4	PRKD1
MIDOSTAURIN	4	PRKD1
TAMOXIFEN	4	PRKD1
NERATINIB	4	PRKD1
BRIGATINIB	4	PRKD1
NINTEDANIB	4	PRKD1
SUNITINIB	4	PRKD1
CRIZOTINIB	4	PRKD1
GEFITINIB	4	PRKD1
SURAMIN	3	PRKD1
FASUDIL	3	PRKD1
ALVOCIDIB	3	PRKD1
LESTAURTINIB	3	PRKD1
PHORBOL MYRISTATE ACETATE	2	PRKD1
EDELFOSINE	2	PRKD1
UPROSERTIB	2	PRKD1
UCN-01	2	PRKD1
SU-014813	2	PRKD1
AT-9283	2	PRKD1
BI-2536	2	PRKD1
KW-2449	1	PRKD1
BMS-387032	1	PRKD1
PF-03758309	1	PRKD1
SRA-737	1	PRKD1
GSK-690693	1	PRKD1
AST-487	1	PRKD1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
PRKD1	660	Binding:650, Functional:10
PKD1	27	Binding:27

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ATP7B	7.2.2.8, 7.2.2.9	P-type Cu+ transporter, P-type Cu2+ transporter
PRKD1	2.7.11.13	protein kinase C

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PRKD1	660

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

26 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)
INGENOL MEBUTATE	4	PRKD1
MIDOSTAURIN	4	PRKD1
TAMOXIFEN	4	PRKD1
NERATINIB	4	PRKD1
BRIGATINIB	4	PRKD1
NINTEDANIB	4	PRKD1
SUNITINIB	4	PRKD1
CRIZOTINIB	4	PRKD1
GEFITINIB	4	PRKD1
SURAMIN	3	PRKD1
FASUDIL	3	PRKD1
ALVOCIDIB	3	PRKD1
LESTAURTINIB	3	PRKD1
PHORBOL MYRISTATE ACETATE	2	PRKD1
EDELFOSINE	2	PRKD1
UPROSERTIB	2	PRKD1
UCN-01	2	PRKD1
SU-014813	2	PRKD1
AT-9283	2	PRKD1
BI-2536	2	PRKD1
KW-2449	1	PRKD1
BMS-387032	1	PRKD1
PF-03758309	1	PRKD1
SRA-737	1	PRKD1
GSK-690693	1	PRKD1
AST-487	1	PRKD1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PRKD1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	PKD1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	DCTN5, PALB2, ATP7B

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PKD1	27	PRKD1
DCTN5	0	—
PALB2	0	—
ATP7B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.