HOXA3

Chr 7

homeobox A3

Also known as: HOX1, HOX1E

NCBI Gene: 3200ENSG00000105997UniProt: O43365

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. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

268
ClinVar variants
31
Pathogenic / LP
0.94
pLI score· haploinsufficient
0
Active trials
Clinical Summary— HOXA3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 211 VUS of 268 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
0.35LOEUF
pLI 0.945
Z-score 3.16
OE 0.07 (0.03–0.35)
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.
0.28Z-score
OE missense 0.95 (0.86–1.05)
264 obs / 277.2 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.0.07 (0.03–0.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.86–1.05)
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.0.99
0≤1.21.6
LoF obs/exp: 1 / 13.5Missense obs/exp: 264 / 277.2Syn Z: 0.05

ClinVar Variant Classifications

268 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic4
VUS211
Likely Benign12
Benign14
27
Pathogenic
4
Likely Pathogenic
211
VUS
12
Likely Benign
14
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
27
0
27
Likely Pathogenic
0
0
4
0
4
VUS
0
206
4
1
211
Likely Benign
0
5
0
7
12
Benign
0
3
9
2
14
Total02144410268

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

View in ClinVar →

Protein Context — Lollipop Plot

HOXA3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Epigenetic regulation of HOXA3 and its impact on oral squamous cell carcinoma progression.
Padam KSR et al.·Oral Surg Oral Med Oral Pathol Oral Radiol
2025
HOXA3 promotes tumor growth of human colon cancer through activating EGFR/Ras/Raf/MEK/ERK signaling pathway.
Zhang X et al.·J Cell Biochem
2018
High expression and regulatory mechanisms of ANGPT1 and HOXA3 in acute myeloid leukemia.
Xuan F et al.·Bull Cancer
2025Functional
ENPP4 and HOXA3 as potential leukaemia stem cell markers in acute myeloid leukaemia.
Mohd Amin A et al.·Malays J Pathol
2023
Tumour-regulatory role of long non-coding RNA HOXA-AS3.
Chong ZX et al.·Prog Biophys Mol Biol
2024Review
Downregulation of HOXA3 in lung adenocarcinoma and its relevant molecular mechanism analysed by RT-qPCR, TCGA and in silico analysis.
Gan BL et al.·Int J Oncol
2018Functional
Macrophage Phenotypes in Normal and Diabetic Wound Healing and Therapeutic Interventions.
Al Sadoun H·Cells
2022Review
Identification of the clinical and genetic characteristics of gliomas with gene fusions by integrated genomic and transcriptomic analysis.
Yi GZ et al.·Eur J Med Res
2025
miR‑338‑3p suppresses the malignancy of T‑cell lymphoblastic lymphoma by downregulating HOXA3.
Wang L et al.·Mol Med Rep
2019
Dysregulation of macrophage development and phenotype in diabetic human macrophages can be rescued by Hoxa3 protein transduction.
Alrdahe S et al.·PLoS One
2019
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