HOXA5: A Key Homeobox Transcription Factor in Development and Disease
Comprehensive genomic and functional analysis of HOXA5, a member of the HOX gene cluster involved in embryogenesis, cancer, and congenital disorders.
Gene Information Card
| Symbol | HOXA5 |
|---|---|
| Full Name | Homeobox A5 |
| Gene Type | Protein-coding |
| Chromosomal Location | 7p15.2 |
| NCBI Gene ID | 3202 ncbi.nlm.nih.gov/gene/3202 |
| Ensembl ID | ENSG00000106004 |
| UniProt ID | P20719 |
| OMIM ID | 142952 |
| HGNC ID | 5106 |
| Aliases | HOX1C, HOX1.3 |
Description
HOXA5 (Homeobox A5) is a protein-coding gene located on chromosome 7p15.2, part of the HOXA cluster of homeobox transcription factors. It encodes a DNA-binding protein that regulates gene expression during embryonic development, particularly in the patterning of the anterior-posterior axis, limb formation, and organogenesis. HOXA5 is also implicated in cell differentiation, apoptosis, and tumor suppression. Dysregulation of HOXA5 is associated with various cancers (e.g., breast, lung, colorectal) and congenital anomalies such as hand-foot-genital syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hand-foot-genital syndrome | Loss-of-function mutations in HOXA5 disrupt limb and urogenital development, leading to characteristic malformations. | ClinVar, OMIM |
| Breast cancer | HOXA5 acts as a tumor suppressor; promoter hypermethylation and reduced expression are linked to poor prognosis. | NCBI Gene, COSMIC |
| Colorectal cancer | HOXA5 downregulation via methylation contributes to tumor progression and metastasis. | COSMIC, PubMed |
| Acute myeloid leukemia | HOXA5 overexpression or fusion events (e.g., NUP98-HOXA5) drive leukemogenesis. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.3 | Medium |
| Breast | 8.7 | Medium |
| Colon | 6.5 | Low |
| Kidney | 4.2 | Low |
| Uterus | 15.1 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 9.8 | Reduced expression due to methylation |
| A549 (lung cancer) | 11.2 | Moderate expression |
| HCT116 (colorectal cancer) | 5.4 | Low expression |
| K562 (leukemia) | 18.5 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.83G>A (p.Arg28Gln) | Missense | Rare | Altered DNA-binding affinity; associated with hand-foot-genital syndrome |
| c.184C>T (p.Arg62*) | Nonsense | Rare | Premature truncation; loss of function |
| c.236_237insA | Frameshift | Rare | Loss of function; developmental defects |
| NUP98-HOXA5 fusion | Chromosomal rearrangement | Rare | Oncogenic; drives AML |
Mutation functional classification
Loss of Function (LOF)
Missense, nonsense, and frameshift mutations in HOXA5 reduce or abolish DNA-binding and transcriptional activity, leading to developmental disorders (e.g., hand-foot-genital syndrome) and tumor suppression loss.
Gain of Function (GOF)
Fusion events such as NUP98-HOXA5 create chimeric proteins with aberrant transcriptional activity, promoting leukemogenesis.
Dominant Negative (DN)
Not well-documented; some missense variants may interfere with wild-type HOXA5 function, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• HOX gene regulation in development (Reactome: R-HSA-5619507)
• Transcriptional regulation by HOX proteins (KEGG: hsa04340)
• Apoptosis modulation (WikiPathways: WP254)
Protein Summary
The HOXA5 protein (UniProt P20719) is a 270-amino-acid homeobox transcription factor containing a conserved 60-residue homeodomain that mediates sequence-specific DNA binding. It regulates target genes involved in cell differentiation, apoptosis, and morphogenesis. Post-translational modifications include phosphorylation, which modulates its stability and activity. HOXA5 is predominantly nuclear and interacts with co-factors such as PBX and MEIS to fine-tune transcriptional outcomes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HOXA5 Knockout HEK293 Cell Line | EDJ-KQ4901 | Human | 3202 | Details Get a Quote |
| HOXA5 Knockout A-549 Cell Line | EDJ-KQ27721 | Human | 3202 | Details Get a Quote |
| HOXA5 Knockout HCT 116 Cell Line | EDJ-KQ27722 | Human | 3202 | Details Get a Quote |
| HOXA5 Knockout HeLa Cell Line | EDJ-KQ27723 | Human | 3202 | Details Get a Quote |
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