CHRNA9: Cholinergic Receptor Nicotinic Alpha 9 Subunit
Key player in auditory function, immune modulation, and cancer biology
Gene Information Card
| Symbol | CHRNA9 |
|---|---|
| Full Name | Cholinergic Receptor Nicotinic Alpha 9 Subunit |
| Gene Type | protein-coding |
| Chromosomal Location | 4p14 |
| NCBI Gene ID | 55584 ncbi.nlm.nih.gov/gene/55584 |
| Ensembl ID | ENSG00000174348 |
| UniProt ID | Q9UGM1 |
| OMIM ID | 605116 |
| HGNC ID | 1966 |
| Aliases | NACHRA9, CHRNA9alpha |
Description
CHRNA9 encodes the alpha 9 subunit of the nicotinic acetylcholine receptor (nAChR), a ligand-gated ion channel. This subunit is essential for cholinergic signaling in cochlear hair cells, mediating synaptic transmission between efferent olivocochlear fibers and hair cells. It also plays roles in immune cells and epithelial tissues, and its dysregulation is implicated in hearing loss, autoimmune disorders, and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hearing loss (autosomal dominant, nonsyndromic) | Altered ion channel function due to missense mutations disrupts efferent cholinergic signaling in cochlear hair cells | ClinVar, OMIM |
| Nicotine dependence | Variants in CHRNA9 may modulate receptor sensitivity to nicotine, influencing addiction risk | NCBI, ClinVar |
| Breast cancer | Overexpression of CHRNA9 promotes cell proliferation and migration via cholinergic signaling; potential oncogenic role | COSMIC, PubMed |
| Autoimmune disorders (e.g., Sjögren's syndrome) | Autoantibodies against alpha 9 nAChR may contribute to cholinergic dysfunction in salivary glands | PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cochlea | Not available | High (specific to hair cells) |
| Brain (cerebellum, hippocampus) | 0.5 | Low |
| Lung | 1.2 | Low |
| Breast | 3.8 | Medium |
| Salivary gland | 2.1 | Low |
| Skin | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | Not available | Used for heterologous expression studies |
| MCF-7 (breast cancer) | 5.2 | Overexpressed relative to normal breast epithelium |
| SH-SY5Y (neuroblastoma) | 1.0 | Low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.107C>T (p.Thr36Ile) | Missense | Rare | Alters channel gating; associated with hearing loss |
| c.413G>A (p.Arg138His) | Missense | Rare | Reduced receptor function; linked to auditory dysfunction |
| c.1-? (promoter variants) | Regulatory | Unknown | May affect expression levels in cancer |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Thr36Ile, p.Arg138His) reduce or abolish ion channel activity, leading to impaired cholinergic signaling in hair cells.
Gain of Function (GOF)
Not well documented; overexpression in cancer may reflect transcriptional upregulation rather than activating mutations.
Dominant Negative (DN)
Not reported for CHRNA9.
View complete mutation data：
Gene Ontology (GO)
| • acetylcholine-gated cation-selective channel activity (GO:0004889) | • extracellular ligand-gated ion channel activity (GO:0005230) |
| • synaptic transmission (GO:0007270) | • plasma membrane (GO:0005886) |
| • postsynaptic membrane (GO:0045211) | • ion transport (GO:0006811) |
Pathways
• Nicotinic acetylcholine receptor signaling pathway
• Cholinergic synapse (KEGG: hsa04725)
• Neuroactive ligand-receptor interaction (KEGG: hsa04080)
Protein Summary
The alpha 9 nicotinic acetylcholine receptor subunit (UniProt Q9UGM1) is a 479-amino acid protein with four transmembrane domains. It forms functional homomeric or heteromeric (with alpha 10) channels that are permeable to calcium. The protein is highly expressed in cochlear hair cells, where it mediates fast cholinergic transmission from efferent olivocochlear neurons. It also appears in immune cells and epithelial tissues, where it modulates cell proliferation and inflammation. Structural features include a large extracellular N-terminal domain containing the acetylcholine-binding site and a conserved cysteine loop.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CHRNA9 Knockout HEK293 Cell Line | EDJ-KQ12916 | Human | 55584 | Details Get a Quote |
| CHRNA9 Knockout A-549 Cell Line | EDJ-KQ42118 | Human | 55584 | Details Get a Quote |
| CHRNA9 Knockout HeLa Cell Line | EDJ-KQ56604 | Human | 55584 | Details Get a Quote |
| CHRNA9 Knockout HCT 116 Cell Line | EDJ-KQ73549 | Human | 55584 | Details Get a Quote |
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