HOXA4

Chr 7

homeobox A4

Also known as: HOX1, HOX1D

NCBI Gene: 3201ENSG00000197576UniProt: Q00056

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. [provided by RefSeq, Jul 2008]

134
ClinVar variants
30
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— HOXA4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
30 Pathogenic / Likely Pathogenic· 84 VUS of 134 total submissions

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.
1.63LOEUF
pLI 0.000
Z-score 0.19
OE 0.93 (0.54–1.63)
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.
-0.33Z-score
OE missense 1.08 (0.94–1.24)
142 obs / 131.3 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.0.93 (0.54–1.63)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.08 (0.94–1.24)
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.1.05
0≤1.21.6
LoF obs/exp: 8 / 8.6Missense obs/exp: 142 / 131.3Syn Z: -0.27

ClinVar Variant Classifications

134 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic3
VUS84
Likely Benign8
Benign12
27
Pathogenic
3
Likely Pathogenic
84
VUS
8
Likely Benign
12
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
27
0
27
Likely Pathogenic
0
0
3
0
3
VUS
0
79
4
1
84
Likely Benign
0
2
0
6
8
Benign
0
3
8
1
12
Total084428134

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

View in ClinVar →

Protein Context — Lollipop Plot

HOXA4 · 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 A4; HOXA4
MIM #142953 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Expression Landscape and Functional Roles of HOXA4 and HOXA5 in Lung Adenocarcinoma.
Gao L et al.·Int J Med Sci
2022Functional
High expression of HOXA4 in patients with glioma indicates unfavorable clinical outcomes.
Yu Z et al.·Cell Cycle
2022Cohort
Overexpression of HOXA4 and HOXA9 genes promotes self-renewal and contributes to colon cancer stem cell overpopulation.
Bhatlekar S et al.·J Cell Physiol
2018
ZNF718, HOXA4, and ZFP57 are differentially methylated in periodontitis in comparison with periodontal health: Epigenome-wide DNA methylation pilot study.
Hernández HG et al.·J Periodontal Res
2021
HOXA4 induces expansion of hematopoietic stem cells in vitro and confers enhancement of pro-B-cells in vivo.
Fournier M et al.·Stem Cells Dev
2012
German longevity study reveals novel rare pro-longevity alleles clustering in mTOR signaling pathway.
Kolbe D et al.·Geroscience
2025
Microarray-based analysis of whole-genome DNA methylation profiling in early detection of breast cancer.
Li SY et al.·J Cell Biochem
2019
In silico interaction of HOX cluster-embedded microRNAs and long non-coding RNAs in oral cancer.
Padam KSR et al.·J Oral Pathol Med
2022Review
Epigenome-wide analysis reveals functional modulators of drug sensitivity and post-treatment survival in chronic lymphocytic leukaemia.
Barrow TM et al.·Br J Cancer
2021Functional
Association of peripheral blood DNA methylation level with Alzheimer's disease progression.
Li QS et al.·Clin Epigenetics
2021
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