Prostate cancer/brain cancer susceptibility

Summary

Prostate cancer/brain cancer susceptibility (MONDO:0011361) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver; 5 ClinVar predisposition records).

At a glance

• Classification: Cancer
• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	prostate cancer/brain cancer susceptibility
Mondo ID	MONDO:0011361
OMIM	603688
UMLS	C1863600
MedGen	400334
GARD	0027800
Is cancer (heuristic)	yes

Also known as: prostate cancer/brain cancer susceptibility · prostate cancer/brain cancer susceptibility, somatic

Data availability: 5 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › prostate cancer/brain cancer susceptibility

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, Brooke-Spiegler syndrome, pancreatic cancer, susceptibility to, 1, Carney-Stratakis syndrome, nasopharyngeal carcinoma, susceptibility to, 1, ovarian cancer, 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

5 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 pathogenic, 1 benign, 1 likely benign, 1 risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
8532	NM_017449.5(EPHB2):c.2164C>T (p.Gln722Ter)	EPHB2	Pathogenic	no assertion criteria provided
8535	NM_017449.5(EPHB2):c.*187A>T	EPHB2	risk factor	no assertion criteria provided
3893102	NM_017449.5(EPHB2):c.*214_*215del	EPHB2	Uncertain significance	criteria provided, single submitter
8533	NM_017449.5(EPHB2):c.835G>T (p.Ala279Ser)	EPHB2	Benign	criteria provided, multiple submitters, no conflicts
8534	NM_017449.5(EPHB2):c.2032G>A (p.Asp678Asn)	EPHB2	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
EPHB2			CIViC #1719

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EPHB2	Orphanet:1331	Familial prostate cancer

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EPHB2	HGNC:3393	ENSG00000133216	P29323	Ephrin type-B receptor 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EPHB2	Ephrin type-B receptor 2	Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.

Protein-family classification

Druggable: 1 · 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	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EPHB2	Kinase	yes	2.7.10.1	Prot_kinase_dom, EPH_LBD, Ser-Thr/Tyr_kinase_cat_dom

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EPHB2	214	ubiquitous	marker	ganglionic eminence, ventricular zone, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EPHB2	3,042

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EPHB2	P29323	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Ephrin signaling	1	571.0×	0.008	EPHB2
EPHB-mediated forward signaling	1	265.6×	0.008	EPHB2
EPH-ephrin mediated repulsion of cells	1	219.6×	0.008	EPHB2
EPH-Ephrin signaling	1	165.5×	0.008	EPHB2
L1CAM interactions	1	120.2×	0.008	EPHB2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of T-helper 17 type immune response	1	16852.0×	0.002	EPHB2
neuron projection retraction	1	8426.0×	0.002	EPHB2
negative regulation of glutamate receptor signaling pathway	1	8426.0×	0.002	EPHB2
hindbrain tangential cell migration	1	5617.3×	0.002	EPHB2
vesicle-mediated intercellular transport	1	5617.3×	0.002	EPHB2
regulation of body fluid levels	1	4213.0×	0.002	EPHB2
regulation of behavioral fear response	1	4213.0×	0.002	EPHB2
optic nerve morphogenesis	1	3370.4×	0.002	EPHB2
postsynaptic membrane assembly	1	2407.4×	0.002	EPHB2
tight junction assembly	1	2407.4×	0.002	EPHB2
central nervous system projection neuron axonogenesis	1	1872.4×	0.002	EPHB2
regulation of blood coagulation	1	1872.4×	0.002	EPHB2
positive regulation of long-term neuronal synaptic plasticity	1	1872.4×	0.002	EPHB2
positive regulation of synaptic plasticity	1	1532.0×	0.002	EPHB2
positive regulation of glutamate receptor signaling pathway	1	1532.0×	0.002	EPHB2
regulation of receptor signaling pathway via JAK-STAT	1	1404.3×	0.002	EPHB2
phosphorylation	1	1296.3×	0.002	EPHB2
negative regulation of axonogenesis	1	1296.3×	0.002	EPHB2
dendritic spine development	1	1203.7×	0.002	EPHB2
neuron projection maintenance	1	1123.5×	0.002	EPHB2
regulation of filopodium assembly	1	1053.2×	0.002	EPHB2
urogenital system development	1	991.3×	0.002	EPHB2
commissural neuron axon guidance	1	991.3×	0.002	EPHB2
axonal fasciculation	1	936.2×	0.002	EPHB2
dendritic spine morphogenesis	1	887.0×	0.002	EPHB2
positive regulation of dendritic spine morphogenesis	1	887.0×	0.002	EPHB2
corpus callosum development	1	842.6×	0.002	EPHB2
retinal ganglion cell axon guidance	1	766.0×	0.002	EPHB2
camera-type eye morphogenesis	1	766.0×	0.002	EPHB2
positive regulation of protein localization to cell surface	1	766.0×	0.002	EPHB2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
EPHB2	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EPHB2	30	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	EPHB2
FEDRATINIB	4	EPHB2
TIVOZANIB	4	EPHB2
SORAFENIB	4	EPHB2
DASATINIB ANHYDROUS	4	EPHB2
VANDETANIB	4	EPHB2
NILOTINIB	4	EPHB2
BOSUTINIB	4	EPHB2
DASATINIB	4	EPHB2
SARACATINIB	3	EPHB2
LINIFANIB	3	EPHB2
CANERTINIB	3	EPHB2
TESEVATINIB	3	EPHB2
POZIOTINIB	3	EPHB2
LESTAURTINIB	3	EPHB2
DORAMAPIMOD	2	EPHB2
FORETINIB	2	EPHB2
REBASTINIB	2	EPHB2
BAFETINIB	2	EPHB2
SAPITINIB	2	EPHB2
GOLVATINIB	2	EPHB2
DANUSERTIB	2	EPHB2
TG100-801	2	EPHB2
R-406	2	EPHB2
MILCICLIB	2	EPHB2
TOZASERTIB	2	EPHB2
TAK-901	1	EPHB2
XL-228	1	EPHB2
CYC-116	1	EPHB2
AST-487	1	EPHB2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
EPHB2	312	Binding:311, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EPHB2	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
EPHB2	312

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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)
PONATINIB	4	EPHB2
FEDRATINIB	4	EPHB2
TIVOZANIB	4	EPHB2
SORAFENIB	4	EPHB2
DASATINIB ANHYDROUS	4	EPHB2
VANDETANIB	4	EPHB2
NILOTINIB	4	EPHB2
BOSUTINIB	4	EPHB2
DASATINIB	4	EPHB2
SARACATINIB	3	EPHB2
LINIFANIB	3	EPHB2
CANERTINIB	3	EPHB2
TESEVATINIB	3	EPHB2
POZIOTINIB	3	EPHB2
LESTAURTINIB	3	EPHB2
DORAMAPIMOD	2	EPHB2
FORETINIB	2	EPHB2
REBASTINIB	2	EPHB2
BAFETINIB	2	EPHB2
SAPITINIB	2	EPHB2
GOLVATINIB	2	EPHB2
DANUSERTIB	2	EPHB2
TG100-801	2	EPHB2
R-406	2	EPHB2
MILCICLIB	2	EPHB2
TOZASERTIB	2	EPHB2
TAK-901	1	EPHB2
XL-228	1	EPHB2
CYC-116	1	EPHB2
AST-487	1	EPHB2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	EPHB2
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.