CHRNA5 Gene: Nicotinic Acetylcholine Receptor Alpha 5 Subunit
Genetic insights into CHRNA5: role in nicotine dependence, lung cancer risk, and neurological disorders
Gene Information Card
| Symbol | CHRNA5 |
|---|---|
| Full Name | Cholinergic Receptor Nicotinic Alpha 5 Subunit |
| Gene Type | protein coding |
| Chromosomal Location | 15q25.1 |
| NCBI Gene ID | 1138 ncbi.nlm.nih.gov/gene/1138 |
| Ensembl ID | ENSG00000169684 |
| UniProt ID | P30532 |
| OMIM ID | 118505 |
| HGNC ID | 1958 |
| Aliases | LNCR2; NACHRA5; cholinergic receptor, nicotinic, alpha polypeptide 5 |
Description
The CHRNA5 gene encodes the alpha-5 subunit of the neuronal nicotinic acetylcholine receptor (nAChR). These receptors are pentameric ligand-gated ion channels that mediate fast synaptic transmission and are involved in various neurological processes. The alpha-5 subunit is a structural component that can incorporate into multiple nAChR subtypes, particularly in the brain and peripheral tissues. CHRNA5 is strongly associated with nicotine dependence, lung cancer risk, and chronic obstructive pulmonary disease (COPD).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Nicotine dependence | Altered receptor function due to variants (e.g., rs16969968) affects nicotine response and reward pathways. | ClinVar, PMID: 20418890 |
| Lung cancer | CHRNA5 variants increase susceptibility, possibly through altered receptor signaling and nicotine-derived nitrosamine metabolism. | COSMIC, PMID: 20418890 |
| Chronic obstructive pulmonary disease (COPD) | CHRNA5 variants are associated with reduced lung function and increased COPD risk. | ClinVar, PMID: 20418890 |
| Alcohol dependence | CHRNA5 variants may influence alcohol consumption and dependence risk. | ClinVar, PMID: 20418890 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 1.2 | Low |
| Brain (frontal cortex) | 2.5 | Low |
| Lung | 0.8 | Low |
| Adrenal gland | 3.1 | Low |
| Pituitary | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 2.0 | Endogenous expression |
| A549 (lung carcinoma) | 0.5 | Low expression |
| HEK293 (embryonic kidney) | 0.1 | Not typically expressed; used for recombinant studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs16969968 (D398N) | SNV (missense) | ~35% in European populations | Reduced receptor function; associated with nicotine dependence and lung cancer risk. |
| rs588765 | SNV (intronic) | ~40% in European populations | Alters CHRNA5 mRNA splicing; associated with nicotine dependence. |
| rs514743 | SNV (intronic) | ~30% in European populations | Associated with lung cancer risk. |
Mutation functional classification
Loss of Function (LOF)
The D398N variant (rs16969968) reduces receptor function, leading to altered nicotine response and increased addiction risk.
Gain of Function (GOF)
No common gain-of-function mutations have been reported in CHRNA5.
Dominant Negative (DN)
Some rare variants may exert dominant-negative effects on receptor assembly, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • acetylcholine receptor activity | • ligand-gated ion channel activity |
| • ion channel activity | • plasma membrane |
| • integral component of plasma membrane | • response to nicotine |
| • chemical synaptic transmission |
Pathways
• Nicotine addiction
• Acetylcholine signaling
• Neuroactive ligand-receptor interaction
Protein Summary
The CHRNA5 protein is a 468-amino acid subunit that forms part of pentameric nicotinic acetylcholine receptors. It is not a ligand-binding subunit but contributes to receptor assembly and modulates channel properties. The protein has four transmembrane domains and a large extracellular N-terminal domain. Variants like D398N alter receptor function and are linked to nicotine dependence and lung cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CHRNA5 Knockout HEK293 Cell Line | EDJ-KQ2294 | Human | 1138 | Details Get a Quote |
| CHRNA5 Knockout A-549 Cell Line | EDC90554 | Human | 1138 | Details Get a Quote |
| CHRNA5 Knockout HCT 116 Cell Line | EDJ-KQ22657 | Human | 1138 | Details Get a Quote |
| CHRNA5 Knockout HeLa Cell Line | EDJ-KQ22658 | Human | 1138 | Details Get a Quote |
| CHRNA5 Knockdown 5637 stable cell line | EDJ-KD005 | Human | 1138 | Details Get a Quote |
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