HOXA2

Chr 7ADAR

homeobox A2

ENSG00000105996UniProt: O43364

Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis

Primary Disease Associations & Inheritance

?Microtia, hearing impairment, and cleft palate (AR)MIM #612290
ADAR
Microtia with or without hearing impairment (AD)MIM #612290
ADAR
0
ClinVar variants
0
Pathogenic / LP
0.20
pLI score
0
Active trials
Clinical Summary— HOXA2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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.
0.70LOEUF
pLI 0.199
Z-score 2.25
OE 0.27 (0.12–0.70)
Tolerant

Typical tolerance to LoF variation

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.
0.41Z-score
OE missense 0.92 (0.81–1.04)
175 obs / 191.1 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.0.27 (0.12–0.70)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.81–1.04)
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.1.00
0≤1.21.6
LoF obs/exp: 3 / 11.1Missense obs/exp: 175 / 191.1Syn Z: 0.02

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

HOXA2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
HOMEOBOX A2; HOXA2
MIM #604685 · *

?Microtia, hearing impairment, and cleft palate (AR)

MIM #612290

Molecular basis of disorder known

Autosomal dominantAutosomal recessive

Microtia with or without hearing impairment (AD)

MIM #612290

Molecular basis of disorder known

Autosomal dominantAutosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
HOXA2 exerts anti-renal fibrosis effects through reducing endoplasmic reticulum stress via the upregulation of SIRT1.
Li X et al.·Commun Biol
2025
Epigenetic regulation of HOXA2 expression affects tumor progression and predicts breast cancer patient survival.
De Palma FDE et al.·Cell Death Differ
2025🔓 Open Access
NSD2-mediated H3K36me2 exacerbates osteoporosis via activation of hoxa2 in bone marrow mesenchymal stem cells.
He G et al.·Cell Signal
2024
Comprehensive Landscape of HOXA2, HOXA9, and HOXA10 as Potential Biomarkers for Predicting Progression and Prognosis in Prostate Cancer.
Song YP et al.·J Immunol Res
2022🔓 Open Access
Different Ectopic Hoxa2 Expression Levels in Mouse Cranial Neural Crest Cells Result in Distinct Craniofacial Anomalies and Homeotic Phenotypes.
Kitazawa T et al.·J Dev Biol
2022🔓 Open AccessFunctional
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