HOXB13

Chr 17

homeobox B13

Also known as: HPC9, PSGD

NCBI Gene: 10481ENSG00000159184UniProt: Q92826

This gene encodes a transcription factor that belongs to the homeobox gene family. Genes of this family are highly conserved among vertebrates and essential for vertebrate embryonic development. This gene has been implicated to play a role in fetal skin development and cutaneous regeneration. In mice, a similar gene was shown to exhibit temporal and spatial colinearity in the main body axis of the embryo, but was not expressed in the secondary axes, which suggests functions in body patterning along the axis. This gene and other HOXB genes form a gene cluster at chromosome the 17q21-22 region. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

{Prostate cancer, hereditary, 9}MIM #610997
7
Active trials
1
Pathogenic / LP
300
ClinVar variants
7
Pubs (1 yr)
-0.0
Missense Z
1.71
LOEUF
Clinical Summary— HOXB13
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
1 Pathogenic / Likely Pathogenic· 199 VUS of 300 total submissions
💊
Clinical Trials
7 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.71LOEUF
pLI 0.000
Z-score -0.21
OE 1.07 (0.67–1.71)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.00Z-score
OE missense 1.00 (0.88–1.14)
166 obs / 165.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.07 (0.67–1.71)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.88–1.14)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.09
0≤1.21.6
LoF obs/exp: 11 / 10.3Missense obs/exp: 166 / 165.8Syn Z: -0.59
DN
0.6551th %ile
GOF
0.4283th %ile
LOF
0.63top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
VUS199
Likely Benign65
Benign33
Conflicting2
1
Pathogenic
199
VUS
65
Likely Benign
33
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
0
0
0
0
0
VUS
22
157
17
3
199
Likely Benign
0
2
17
46
65
Benign
0
0
7
26
33
Conflicting
—2
Total221594275300

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HOXB13 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Prostate Cancer

Analysing Outcomes After Prostate Cancer Diagnosis and Treatment in Carriers of Rare Germline Mutations

RECRUITING
NCT02705846Institute of Cancer Research, United KingdomStarted 2014-09
Observation of treatment outcomes via Questionnaire
Prostate CancerBRCA MutationMismatch Repair Gene Mutation

The GENPET Study - An Imaging Study of FCH-PET-CT in Men With Prostate Cancer and a DNA Repair Gene Mutation.

RECRUITING
NCT05097274Institute of Cancer Research, United KingdomStarted 2015-10-15
MRI pelvis or CT imaging under clinical management for Pr CaWhole body bone scan imagingPET-CT imaging
Prostate CancerGenetic Predisposition

Prostate Tissue BioBank

RECRUITING
NCT06659614Abramson Cancer Center at Penn MedicineStarted 2024-01-01
Prostate Cancer

PROMISE Registry: A Prostate Cancer Registry of Outcomes and Germline Mutations for Improved Survival and Treatment Effectiveness

RECRUITING
NCT04995198Prostate Cancer Clinical Trials ConsortiumStarted 2021-05-03
Prostate CancerFamilial Prostate Cancer

Prostate Cancer Prevention Clinic for Men With Risk of Familial Prostate Cancer

NOT YET RECRUITING
NCT05681416Phase NAHeinrich-Heine University, DuesseldorfStarted 2023-02-01
Panel sequencing, whole exome sequencing, whole genome sequencing
Prostatic NeoplasmProstate CancerBRCA2 Mutation

Prostate Cancer Genetic Risk Evaluation and Screening Study

RECRUITING
NCT05129605Massachusetts General HospitalStarted 2020-02-12
Prostate cancer screening
Prostate Cancer

Prevalence of the c.853delT Mutation of the HOXB13 Gene in Prostate Cancer in Martinique

RECRUITING
NCT05231915Phase NAUniversity Hospital Center of MartiniqueStarted 2021-04-09
HOXB13 c.853delT mutation
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients