HOXA1

Chr 7

homeobox A1

Also known as: BSAS, HOX1, HOX1F

NCBI Gene: 3198ENSG00000105991UniProt: P49639

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. The encoded protein may be involved in the placement of hindbrain segments in the proper location along the anterior-posterior axis during development. Two transcript variants encoding two different isoforms have been found for this gene, with only one of the isoforms containing the homeodomain region. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

UniProtAthabaskan brainstem dysgenesis syndrome
UniProtBosley-Salih-Alorainy syndrome
149
ClinVar variants
35
Pathogenic / LP
0.29
pLI score
0
Active trials
Clinical Summary— HOXA1
🧬
Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
35 Pathogenic / Likely Pathogenic· 81 VUS of 149 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
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.
0.63LOEUF
pLI 0.285
Z-score 2.46
OE 0.24 (0.11–0.63)
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.
-0.10Z-score
OE missense 1.02 (0.91–1.15)
196 obs / 192.0 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.0.24 (0.11–0.63)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.02 (0.91–1.15)
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.1.10
0≤1.21.6
LoF obs/exp: 3 / 12.3Missense obs/exp: 196 / 192.0Syn Z: -0.73

ClinVar Variant Classifications

149 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic4
VUS81
Likely Benign24
Benign8
Conflicting1
31
Pathogenic
4
Likely Pathogenic
81
VUS
24
Likely Benign
8
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
29
0
31
Likely Pathogenic
0
0
4
0
4
VUS
0
61
17
3
81
Likely Benign
0
3
8
13
24
Benign
0
1
5
2
8
Conflicting
—1
Total2656318149

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

View in ClinVar →

Protein Context — Lollipop Plot

HOXA1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

HOXA1-related Bosley-Salih-Alorainy syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — HOXA1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Transcriptome sequencing and Mendelian randomization analysis identified biomarkers related to neutrophil extracellular traps in diabetic retinopathy.
Hao L et al.·Front Immunol
2024
An integrated meta-analysis of two variants in HOXA1/HOXB1 and their effect on the risk of autism spectrum disorders.
Song RR et al.·PLoS One
2011Meta-analysis
Nortriptyline Inhibits Lysosomal Exocytosis-Mediated SASP During Gastric Cancer Progression via Targeting HOXA1-PITX2 Phase Separation.
Zhou Y et al.·Adv Sci (Weinh)
2025
The genetic basis of complex strabismus.
Engle EC·Pediatr Res
2006Review
HOXA1 Promotes Migration, Invasion and Cell Cycle, and Suppresses Cisplatin Sensitivity of Laryngeal Cancer Cells By Mediating AKT/mTOR Pathway.
Luo S et al.·Tohoku J Exp Med
2025
Clinical characterization of the HOXA1 syndrome BSAS variant.
Bosley TM et al.·Neurology
2007
HOXA1 drives melanoma tumor growth and metastasis and elicits an invasion gene expression signature that prognosticates clinical outcome.
Wardwell-Ozgo J et al.·Oncogene
2014
Elevated HOXA1 expression correlates with accelerated tumor cell proliferation and poor prognosis in gastric cancer partly via cyclin D1.
Yuan C et al.·J Exp Clin Cancer Res
2016
Axons get ahead: Insights into axon guidance and congenital cranial dysinnervation disorders.
Chilton JK et al.·Dev Neurobiol
2017Review
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
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