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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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HOXC9
homeobox C9
Chromosome 12 · 12q13.13
NCBI Gene: 3225Ensembl: ENSG00000180806.5HGNC: HGNC:5130UniProt: P31274
51PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleoplasmprotein bindingsequence-specific double-stranded DNA bindingRNA polymerase II cis-regulatory region sequence-specific DNA bindingAbnormality of the skeletal systemgastroesophageal reflux diseaseneuroblastomaosteoporosis
✦AI Summary

HOXC9 is a homeobox transcription factor that functions as a sequence-specific DNA-binding regulator with diverse roles across developmental and pathological contexts. In vascular biology, HOXC9 maintains endothelial cell quiescence by directly repressing interleukin-8 transcription, thereby inhibiting angiogenesis and vascular morphogenesis 12. HOXC9 also regulates adipose tissue development in a depot-specific manner, with higher expression in subcutaneous versus omental adipose tissue, correlating with body fat mass and metabolic parameters 3. In neuroblastoma, HOXC9 links cell-cycle exit to neuronal differentiation by targeting both proliferation and differentiation genes, with high expression associated with improved prognosis and retinoic acid responsiveness 4. Conversely, HOXC9 functions as an oncogene in multiple cancers: it is upregulated in lung adenocarcinoma and glioblastoma stem cells, promoting proliferation, migration, and invasion 56. In gastric cancer, HOXC9 promotes metastasis and stem cell-like phenotype through dysregulation of the miR-26a/HOXC9 axis 7. These findings establish HOXC9 as a context-dependent regulator with therapeutic potential in both cancer immunotherapy and differentiation-based treatments.

Sources cited
1
HOXC9 maintains endothelial cell quiescence and inhibits vascular development via interleukin-8 repression
PMID: 22841837
2
HOXC9 directly binds interleukin-8 promoter to suppress angiogenesis and endothelial cell activation
PMID: 21493894
3
HOXC9 expression is fat depot-specific and correlates with body fat mass and metabolic parameters
PMID: 26647900
4
HOXC9 induces growth arrest and neuronal differentiation in neuroblastoma, associated with better prognosis
PMID: 21507931
5
HOXC9 is upregulated in lung adenocarcinoma and promotes cell proliferation, migration, and invasion
PMID: 36272177
6
HOXC9 is aberrantly expressed in glioblastoma CD133+ cancer stem cells and associates with malignancy
PMID: 17588684
7
HOXC9 promotes gastric cancer metastasis and stem cell phenotype, regulated by miR-26a
PMID: 30205370
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.25Weak
gastroesophageal reflux diseaseOpen Targets
0.14Weak
neuroblastomaOpen Targets
0.09Suggestive
osteoporosisOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.08Suggestive
lung adenocarcinomaOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
papillary thyroid carcinomaOpen Targets
0.07Suggestive
hepatocellular carcinomaOpen Targets
0.07Suggestive
gastric cancerOpen Targets
0.07Suggestive
autosomal dominant brachyolmiaOpen Targets
0.06Suggestive
spondylometaphyseal dysplasia, A4 typeOpen Targets
0.06Suggestive
carpal tunnel syndromeOpen Targets
0.06Suggestive
thoracolaryngopelvic dysplasiaOpen Targets
0.06Suggestive
central nervous system cancerOpen Targets
0.06Suggestive
autosomal recessive spondylocostal dysostosisOpen Targets
0.05Suggestive
oral squamous cell carcinomaOpen Targets
0.05Suggestive
spondylometaphyseal dysplasia, Schmidt typeOpen Targets
0.05Suggestive
endometriosisOpen Targets
0.05Suggestive
Acromesomelic dysplasia, Maroteaux typeOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
HOXC6Protein interaction88%HOXC8Protein interaction88%HOXD9Shared pathway80%PBX2Protein interaction79%HOXC4Protein interaction77%PBX3Protein interaction77%
Tissue Expression6 tissues
Ovary
100%
Lung
5%
Brain
1%
Bone Marrow
0%
Heart
0%
Liver
0%
Gene Interaction Network
Click a node to explore
HOXC9HOXC6HOXC8HOXD9PBX2HOXC4PBX3
PROTEIN STRUCTURE
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PDB2LP0 · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.93LoF Tolerant
pLIⓘ
0.02Tolerant
Observed/Expected LoF0.55 [0.34–0.93]
RankingsWhere HOXC9 stands among ~20K protein-coding genes
  • #8,688of 20,598
    Most Researched51
  • #8,651of 17,882
    Most Constrained (LOEUF)0.93
Genes detectedHOXC9
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Single-cell RNA-seq unravels alterations of the human spermatogonial stem cell compartment in patients with impaired spermatogenesis.
PMID: 34622232
Cell Rep Med · 2021
1.00
2
HOXC9: a key regulator of endothelial cell quiescence and vascular morphogenesis.
PMID: 22841837
Trends Cardiovasc Med · 2012
0.90
3
Fat depot-specific expression of HOXC9 and HOXC10 may contribute to adverse fat distribution and related metabolic traits.
PMID: 26647900
Obesity (Silver Spring) · 2016
0.80
4
circRNA-mediated upregulation of HOXC9 is correlated with poor outcome and immune microenvironment infiltrates in LUAD.
PMID: 36272177
Biochem Biophys Res Commun · 2022
0.70
5
Expression of HOXC9 and E2F2 are up-regulated in CD133(+) cells isolated from human astrocytomas and associate with transformation of human astrocytes.
PMID: 17588684
Biochim Biophys Acta · 2007
0.60