HOXD9: A Homeobox Transcription Factor in Limb and Neural Development
Comprehensive genomic and functional analysis of HOXD9, a member of the HOXD cluster involved in morphogenesis and cancer.
Gene Information Card
| Symbol | HOXD9 |
|---|---|
| Full Name | Homeobox D9 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q31.1 |
| NCBI Gene ID | 3237 ncbi.nlm.nih.gov/gene/3237 |
| Ensembl ID | ENSG00000128709 |
| UniProt ID | P28356 |
| OMIM ID | 142982 |
| HGNC ID | 5133 |
| Aliases | HOX4C, HOX4D, HOXD10 |
Description
HOXD9 is a member of the HOXD cluster of homeobox transcription factors, located on chromosome 2q31.1. It plays a critical role in embryonic development, particularly in limb patterning and neural tube closure. HOXD9 regulates gene expression by binding to DNA via its homeodomain and is involved in cell differentiation, proliferation, and migration. Dysregulation of HOXD9 is associated with congenital limb malformations and various cancers, including breast, lung, and colorectal cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Limb malformations (e.g., synpolydactyly) | Altered HOXD9 expression disrupts limb bud patterning | OMIM #186000; case reports |
| Breast cancer | HOXD9 overexpression promotes cell proliferation and invasion | COSMIC; PMID: 25636800 |
| Colorectal cancer | HOXD9 upregulation correlates with poor prognosis and metastasis | COSMIC; PMID: 28925394 |
| Lung cancer | HOXD9 silencing reduces tumor growth in vitro | COSMIC; PMID: 27323851 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 nTPM | Medium |
| Kidney | 8.3 nTPM | Low |
| Breast | 6.7 nTPM | Low |
| Colon | 5.9 nTPM | Low |
| Brain | 2.1 nTPM | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung cancer) | 15.2 nTPM | High expression |
| MCF7 (breast cancer) | 9.8 nTPM | Moderate expression |
| HCT116 (colorectal cancer) | 11.4 nTPM | High expression |
| HEK293 (embryonic kidney) | 4.3 nTPM | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.701G>A (p.Arg234Gln) | Missense | <0.01% | Altered DNA-binding affinity; ClinVar |
| c.1123C>T (p.Arg375Ter) | Nonsense | <0.01% | Loss of function; COSMIC |
| c.456_457insA (p.Glu153Argfs*12) | Frameshift | <0.01% | Truncated protein; COSMIC |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg375Ter, p.Glu153Argfs*12) lead to truncated, non-functional HOXD9 protein, impairing transcriptional regulation.
Gain of Function (GOF)
Missense mutations (e.g., p.Arg234Gln) may alter DNA-binding specificity, potentially enhancing oncogenic activity in cancer contexts.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported; however, some missense variants may interfere with wild-type HOXD9 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• HOX signaling pathway
• Developmental biology (Reactome: R-HSA-1266738)
• Transcriptional regulation by HOX proteins
Protein Summary
HOXD9 is a 375-amino acid homeobox transcription factor containing a conserved homeodomain that mediates sequence-specific DNA binding. It localizes to the nucleus and regulates target genes involved in cell differentiation, proliferation, and embryonic patterning. Post-translational modifications such as phosphorylation may modulate its activity. The protein is expressed in developing limbs and neural tube, and aberrant expression is linked to cancer progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HOXD9 Knockout HEK293 Cell Line | EDJ-KQ3501 | Human | 3235 | Details Get a Quote |
| HOXD9 Knockout HeLa Cell Line | EDJ-KQ23928 | Human | 3235 | Details Get a Quote |
| HOXD9 Knockout A-549 Cell Line | EDJ-KQ62028 | Human | 3235 | Details Get a Quote |
| HOXD9 Knockout HCT 116 Cell Line | EDJ-KQ70506 | Human | 3235 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
