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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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HOXA6
homeobox A6
Chromosome 7 · 7p15.2
NCBI Gene: 3203Ensembl: ENSG00000106006.6HGNC: HGNC:5107UniProt: P31267
23PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleoplasmsequence-specific double-stranded DNA bindingnuclear speckRNA polymerase II cis-regulatory region sequence-specific DNA bindingneurodegenerative diseasehypertensiongastric cancermetabolic syndrome
✦AI Summary

HOXA6 is a sequence-specific transcription factor that regulates anterior-posterior pattern specification during development 1. As part of the homeobox A cluster, HOXA6 is preferentially expressed in primitive hematopoietic stem and progenitor cells where it promotes cell proliferation and self-renewal 2. HOXA6 functions as both a developmental regulator and an oncogenic factor across multiple cancer types. In myelodysplastic syndrome, HOXA6 forms part of aberrant gene regulatory networks specifically active in disease cells, suggesting direct involvement in malignant transformation 1. In gastric cancer, HOXA6 overexpression promotes cell proliferation, migration, and invasion through interaction with PBX2, and correlates with poor survival outcomes 3. Similarly, HOXA6 is highly expressed and functionally involved in low-grade glioma progression 4. In bladder cancer, HOXA6 mediates DDR1-driven progression by inhibiting ferroptosis 5. Conversely, HOXA6 expression is typically silenced in colorectal and meningiomas through promoter hypermethylation, with methylation status serving as a diagnostic biomarker [PMID:31165042; 62]. In oxaliplatin-induced neuropathic pain, HOXA6 upregulation through TET1-mediated demethylation of SOX10 contributes to pain pathogenesis 7. These findings establish HOXA6 as a context-dependent regulator with significant roles in hematopoiesis, developmental patterning, and cancer biology.

Sources cited
1
HOXA6 forms part of gene regulatory networks specifically active in myelodysplastic syndrome and is implicated in altered hematopoietic differentiation
PMID: 36629404
2
HOXA6 is preferentially expressed in primitive hematopoietic cells and enforced overexpression increases proliferation and factor-independent growth
PMID: 19157684
3
HOXA6 overexpression in gastric cancer promotes cell proliferation, migration, invasion, and interacts with PBX2 to enhance metastasis
PMID: 33535170
4
HOXA6 is upregulated and functionally involved in low-grade glioma progression, affecting proliferation and migration
PMID: 35349479
5
DDR1 targets HOXA6 to inhibit ferroptosis and promote bladder cancer progression
PMID: 40105492
6
HOXA6 is hypermethylated in colorectal cancer tissues with methylation levels declining as tumors progress and associated with age and KRAS mutation
PMID: 31165042
7
HOXA6 hypermethylation occurs in meningiomas with increasing frequency according to tumor grade
PMID: 28527972
8
HOXA6 upregulation through TET1-mediated demethylation of SOX10 promoter contributes to oxaliplatin-induced neuropathic pain
PMID: 32428246
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.50Moderate
hypertensionOpen Targets
0.08Suggestive
gastric cancerOpen Targets
0.07Suggestive
metabolic syndromeOpen Targets
0.07Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.05Suggestive
spondylocostal dysostosis 2, autosomal recessiveOpen Targets
0.05Suggestive
colorectal carcinomaOpen Targets
0.05Suggestive
spondylocostal dysostosis 5Open Targets
0.05Suggestive
central nervous system cancerOpen Targets
0.05Suggestive
autosomal recessive spondylocostal dysostosisOpen Targets
0.05Suggestive
Becker nevus syndromeOpen Targets
0.04Suggestive
thoracic dysostosis, isolatedOpen Targets
0.04Suggestive
thoracomelic dysplasiaOpen Targets
0.04Suggestive
Klippel-Feil syndrome 3, autosomal dominantOpen Targets
0.04Suggestive
colorectal cancerOpen Targets
0.04Suggestive
neoplasmOpen Targets
0.04Suggestive
thoracolaryngopelvic dysplasiaOpen Targets
0.04Suggestive
spondylocostal dysostosis 1, autosomal recessiveOpen Targets
0.04Suggestive
short-rib thoracic dysplasia 17 with or without polydactylyOpen Targets
0.04Suggestive
diaphanospondylodysostosisOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
HES4Shared pathway100%HOXA3Protein interaction97%HOXA5Protein interaction97%HOXB6Protein interaction94%HOXD4Protein interaction94%HOXC6Protein interaction92%
Tissue Expression6 tissues
Brain
100%
Lung
35%
Bone Marrow
6%
Ovary
4%
Liver
0%
Heart
0%
Gene Interaction Network
Click a node to explore
HOXA6HES4HOXA3HOXA5HOXB6HOXD4HOXC6
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt P31267
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.12LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.76 [0.53–1.12]
RankingsWhere HOXA6 stands among ~20K protein-coding genes
  • #13,434of 20,598
    Most Researched23
  • #11,563of 17,882
    Most Constrained (LOEUF)1.12
Genes detectedHOXA6
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Uncovering perturbations in human hematopoiesis associated with healthy aging and myeloid malignancies at single-cell resolution.
PMID: 36629404
Elife · 2023
1.00
2
DDR1 Targeting HOXA6 Facilitates Bladder Cancer Progression via Inhibiting Ferroptosis.
PMID: 40105492
J Cell Mol Med · 2025
0.90
3
Coexpression of HOXA6 and PBX2 promotes metastasis in gastric cancer.
PMID: 33535170
Aging (Albany NY) · 2021
0.80
4
Oxaliplatin-induced neuropathic pain involves HOXA6 via a TET1-dependent demethylation of the SOX10 promoter.
PMID: 32428246
Int J Cancer · 2020
0.70
5
Study of Promoter Methylation Patterns of HOXA2, HOXA5, and HOXA6 and Its Clinicopathological Characteristics in Colorectal Cancer.
PMID: 31165042
Front Oncol · 2019
0.60