HOXA2: Homeobox A2 - A Key Regulator in Craniofacial Development and Hearing
Comprehensive genomic and clinical overview of HOXA2, a transcription factor critical for ear and jaw development, associated with autosomal dominant hearing loss and microtia.
Gene Information Card
| Symbol | HOXA2 |
|---|---|
| Full Name | Homeobox A2 |
| Gene Type | Protein-coding |
| Chromosomal Location | 7p15.2 |
| NCBI Gene ID | 3199 ncbi.nlm.nih.gov/gene/3199 |
| Ensembl ID | ENSG00000105991 |
| UniProt ID | O43364 |
| OMIM ID | 600997 |
| HGNC ID | 5105 |
| Aliases | HOX1K, MGC133252 |
Description
HOXA2 (Homeobox A2) is a protein-coding gene belonging to the homeobox family of transcription factors, which are critical regulators of embryonic development. HOXA2 is specifically involved in patterning of the hindbrain, craniofacial structures, and inner ear. Mutations in HOXA2 cause autosomal dominant nonsyndromic hearing loss (DFNA) and microtia, a congenital malformation of the external ear. The gene encodes a DNA-binding homeodomain protein that regulates downstream target genes essential for neural crest cell migration and differentiation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal dominant nonsyndromic hearing loss (DFNA) | Loss-of-function mutations in HOXA2 disrupt transcription factor activity, impairing inner ear development and auditory function. | ClinVar, OMIM #600997 |
| Microtia (congenital ear malformation) | Heterozygous missense or nonsense mutations reduce HOXA2 protein function, leading to defective external ear morphogenesis. | ClinVar, OMIM #600997 |
| Craniofacial abnormalities (including jaw hypoplasia) | HOXA2 haploinsufficiency alters hindbrain segmentation and neural crest cell patterning, affecting mandibular and maxillary development. | OMIM, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 5.2 | Low |
| Brain (hindbrain) | 8.1 | Medium |
| Ear (inner ear tissue) | 12.4 | High |
| Kidney | 1.3 | Not detected |
| Liver | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 3.5 | Low expression |
| HEK293 (embryonic kidney) | 0.2 | Not detected |
| HepG2 (hepatocellular carcinoma) | 0.1 | Not detected |
| K562 (leukemia) | 0.3 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.700C>T (p.Arg234*) | Nonsense | Rare | Loss of function; truncation of homeodomain, associated with hearing loss and microtia |
| c.649G>A (p.Gly217Ser) | Missense | Rare | Reduced DNA-binding affinity; dominant negative effect, associated with microtia |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of translation initiation; complete loss of function, associated with hearing loss |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg234*) lead to premature termination and nonsense-mediated decay, resulting in haploinsufficiency. This is the primary mechanism for autosomal dominant hearing loss.
Gain of Function (GOF)
No gain-of-function mutations have been reported for HOXA2 in human disease.
Dominant Negative (DN)
Missense mutations in the homeodomain (e.g., p.Gly217Ser) can produce a protein that interferes with wild-type HOXA2 function, causing a dominant negative effect, particularly in microtia.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hox gene regulation in development (Reactome: R-HSA-5617472)
• Retinoic acid signaling pathway (KEGG: hsa04330)
• Transcriptional regulation by HOX proteins (Reactome: R-HSA-5619507)
Protein Summary
The HOXA2 protein (UniProt O43364) is a 372-amino acid transcription factor containing a highly conserved homeodomain that binds to specific DNA sequences (TAAT motifs). It functions as a master regulator of hindbrain segmentation and craniofacial development, particularly the second pharyngeal arch. HOXA2 interacts with other HOX proteins and cofactors (e.g., PBX, MEIS) to modulate target gene expression. Loss of HOXA2 function leads to defects in ear and jaw formation, while missense mutations can impair DNA binding and cause dominant negative effects.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HOXA2 Knockout HEK293 Cell Line | EDJ-KQ4897 | Human | 3199 | Details Get a Quote |
| HOXA2 Knockout A-549 Cell Line | EDJ-KQ27715 | Human | 3199 | Details Get a Quote |
| HOXA2 Knockout HeLa Cell Line | EDJ-KQ53546 | Human | 3199 | Details Get a Quote |
| HOXA2 Knockout HCT 116 Cell Line | EDJ-KQ70493 | Human | 3199 | Details Get a Quote |
