Prostate cancer, hereditary, 9

Summary

Prostate cancer, hereditary, 9 (MONDO:0012597) is a cancer caused by HOXB13 (GenCC Strong), with 1 cohort gene (1 CIViC-evidence somatic driver; 294 ClinVar predisposition records).

At a glance

• Classification: Cancer
• Causal gene: HOXB13 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 294

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	prostate cancer, hereditary, 9
Mondo ID	MONDO:0012597
MeSH	C567031
OMIM	610997
UMLS	C1970250
MedGen	369689
GARD	0015505
Is cancer (heuristic)	yes

Also known as: HPC9 · prostate cancer, hereditary, 9 · prostate cancer, hereditary, type 9

Data availability: 294 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › prostate cancer, hereditary › prostate cancer, hereditary, 9

Related subtypes (17): prostate cancer, hereditary, X-linked 1, prostate cancer, hereditary, X-linked 2, prostate cancer, hereditary, 1, prostate cancer, hereditary, 8, prostate cancer, hereditary, 3, prostate cancer, hereditary, 4, prostate cancer, hereditary, 5, prostate cancer, hereditary, 6, prostate cancer, hereditary, 7, prostate cancer, hereditary, 10, prostate cancer, hereditary, 12, prostate cancer, hereditary, 13, prostate cancer, hereditary, 11, prostate cancer, hereditary, 14, prostate cancer, hereditary, 15, prostate cancer, hereditary, 2, familial prostate 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

294 retrieved; paginated sample, class counts are floors:

185 benign/likely benign, 38 uncertain significance, 36 benign, 19 conflicting classifications of pathogenicity, 14 likely benign, 1 pathogenic/likely pathogenic; association, 1 conflicting classifications of pathogenicity; association

ClinVar	Variant (HGVS)	Gene	Classification	Review
128031	NM_006361.6(HOXB13):c.251G>A (p.Gly84Glu)	HOXB13	Pathogenic/Likely pathogenic; association	criteria provided, multiple submitters, no conflicts
1104416	NM_006361.6(HOXB13):c.601+7C>G	HOXB13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1149575	NM_006361.6(HOXB13):c.828C>T (p.Ala276=)	HOXB13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
128036	NM_006361.6(HOXB13):c.634G>A (p.Ala212Thr)	HOXB13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
128038	NM_006361.6(HOXB13):c.832G>T (p.Val278Leu)	HOXB13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1799130	NM_006361.6(HOXB13):c.303C>T (p.Ala101=)	HOXB13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
182506	NM_006361.6(HOXB13):c.853del (p.Ter285LysextTer?)	HOXB13	Conflicting classifications of pathogenicity; association	criteria provided, conflicting classifications
3225542	NM_006361.6(HOXB13):c.498G>A (p.Val166=)	HOXB13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3572264	NM_006361.6(HOXB13):c.*8_*10del	HOXB13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
483475	NM_006361.6(HOXB13):c.122C>T (p.Thr41Met)	HOXB13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
483482	NM_006361.6(HOXB13):c.302C>T (p.Ala101Val)	HOXB13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
483484	NM_006361.6(HOXB13):c.177G>A (p.Pro59=)	HOXB13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
483485	NM_006361.6(HOXB13):c.6G>A (p.Glu2=)	HOXB13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
483487	NM_006361.6(HOXB13):c.140A>G (p.Asn47Ser)	HOXB13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
483502	NM_006361.6(HOXB13):c.216G>T (p.Gly72=)	HOXB13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
795912	NM_006361.6(HOXB13):c.64G>A (p.Gly22Arg)	HOXB13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
819608	NM_006361.6(HOXB13):c.159G>T (p.Leu53=)	HOXB13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
821371	NM_006361.6(HOXB13):c.24C>T (p.Thr8=)	HOXB13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
826143	NM_006361.6(HOXB13):c.602-5C>T	HOXB13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
827281	NM_006361.6(HOXB13):c.783C>A (p.Thr261=)	HOXB13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
827418	NM_006361.6(HOXB13):c.804G>T (p.Arg268=)	HOXB13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1000173	NM_006361.6(HOXB13):c.308C>T (p.Ala103Val)	HOXB13	Uncertain significance	criteria provided, multiple submitters, no conflicts
1001052	NM_006361.6(HOXB13):c.457G>T (p.Gly153Cys)	HOXB13	Uncertain significance	criteria provided, multiple submitters, no conflicts
1035500	NM_006361.6(HOXB13):c.254G>A (p.Gly85Asp)	HOXB13	Uncertain significance	criteria provided, multiple submitters, no conflicts
1047153	NM_006361.6(HOXB13):c.646G>T (p.Gly216Cys)	HOXB13	Uncertain significance	criteria provided, multiple submitters, no conflicts
128032	NM_006361.6(HOXB13):c.366C>A (p.Ser122Arg)	HOXB13	Uncertain significance	criteria provided, multiple submitters, no conflicts
128035	NM_006361.6(HOXB13):c.499G>A (p.Asp167Asn)	HOXB13	Uncertain significance	criteria provided, multiple submitters, no conflicts
1492546	NM_006361.6(HOXB13):c.327C>A (p.Tyr109Ter)	HOXB13	Uncertain significance	criteria provided, multiple submitters, no conflicts
2891600	NM_006361.6(HOXB13):c.647_650dup (p.Lys218fs)	HOXB13	Uncertain significance	criteria provided, multiple submitters, no conflicts
3526302	NM_006361.6(HOXB13):c.574G>T (p.Gly192Cys)	HOXB13	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
HOXB13			CIViC #8351

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
HOXB13	Definitive	Autosomal dominant	prostate cancer	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HOXB13	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
HOXB13	HGNC:5112	ENSG00000159184	Q92826	Homeobox protein Hox-B13	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HOXB13	Homeobox protein Hox-B13	Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HOXB13	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS

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
mucosa of sigmoid colon	1
prostate gland	1
rectum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HOXB13	38	broad	marker	rectum, mucosa of sigmoid colon, prostate gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HOXB13	1,393

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HOXB13	Q92826	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
epithelial cell maturation involved in prostate gland development	1	5617.3×	0.002	HOXB13
prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis	1	2407.4×	0.002	HOXB13
regulation of growth	1	936.2×	0.003	HOXB13
response to testosterone	1	468.1×	0.005	HOXB13
response to wounding	1	221.7×	0.007	HOXB13
epidermis development	1	210.7×	0.007	HOXB13
angiogenesis	1	62.4×	0.021	HOXB13
negative regulation of transcription by RNA polymerase II	1	17.7×	0.063	HOXB13
regulation of transcription by RNA polymerase II	1	11.7×	0.086	HOXB13

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
HOXB13	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	1	HOXB13

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)
HOXB13	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.