HOXA13

Chr 7AD

homeobox A13

Also known as: HOX1, HOX1J

NCBI Gene: 3209ENSG00000106031UniProt: P31271

In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. Expansion of a polyalanine tract in the encoded protein can cause hand-foot-uterus syndrome, also known as hand-foot-genital syndrome. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Guttmacher syndromeMIM #176305
AD
Hand-foot-genital syndromeMIM #140000
AD
185
ClinVar variants
41
Pathogenic / LP
0.96
pLI score· haploinsufficient
0
Active trials
Clinical Summary— HOXA13
🧬
Gene-Disease Validity (ClinGen)
hand-foot-genital syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
41 Pathogenic / Likely Pathogenic· 92 VUS of 185 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.31LOEUF
pLI 0.955
Z-score 2.89
OE 0.00 (0.00–0.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
0.56Z-score
OE missense 0.88 (0.77–1.01)
143 obs / 163.1 exp
Tolerant

Mild missense constraint

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.0.00 (0.00–0.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.77–1.01)
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.1.17
0≤1.21.6
LoF obs/exp: 0 / 9.7Missense obs/exp: 143 / 163.1Syn Z: -1.09

ClinVar Variant Classifications

185 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic8
VUS92
Likely Benign39
Benign9
Conflicting4
33
Pathogenic
8
Likely Pathogenic
92
VUS
39
Likely Benign
9
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
30
0
33
Likely Pathogenic
2
1
5
0
8
VUS
2
70
14
6
92
Likely Benign
0
4
6
29
39
Benign
0
1
4
4
9
Conflicting
—4
Total5785939185

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

View in ClinVar →

Protein Context — Lollipop Plot

HOXA13 · protein map & ClinVar variants

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

Gene2Phenotype Curations

HOXA13-related hand-foot-genital syndrome

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
HOMEOBOX A13; HOXA13
MIM #142959 · *

?Guttmacher syndrome

MIM #176305

Molecular basis of disorder known

Autosomal dominant

Hand-foot-genital syndrome

MIM #140000

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — HOXA13
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
HOXA9 and HOXA13 along with their shared gene targets act as common immune biomarkers in recurrent implantation failure and pre-eclampsia.
Hazra S et al.·Hum Immunol
2025
HOXA13 promotes colon cancer progression through β-catenin-dependent WNT pathway.
Gu Y et al.·Exp Cell Res
2020
HOXA13 in etiology and oncogenic potential of Barrett's esophagus.
Janmaat VT et al.·Nat Commun
2021
Acute lymphoblastic leukaemia with T- and B-lineage defining markers.
E S et al.·Pathology
2025
A novel stable polyalanine [poly(A)] expansion in the HOXA13 gene associated with hand-foot-genital syndrome: proper function of poly(A)-harbouring transcription factors depends on a critical repeat length?
Utsch B et al.·Hum Genet
2002Review
HoxA13 Regulates Phenotype Regionalization of Human Pregnant Myometrium.
Liu L et al.·J Clin Endocrinol Metab
2015
The pathophysiology of HOX genes and their role in cancer.
Grier DG et al.·J Pathol
2005Review
HOXA13 is associated with unfavorable survival and acts as a novel oncogene in prostate carcinoma.
Dong Y et al.·Future Oncol
2017
Integrative analysis of bulk RNA and single-cell sequencing data reveals a liquid-liquid phase separation signature for clear cell renal cell carcinoma.
Wang H et al.·Gene
2025
[HOX genes and the limb development in the clinical praxis and in the experiment].
Snajdr P et al.·Cas Lek Cesk
2010Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools