CHRNA1: Cholinergic Receptor Nicotinic Alpha 1 Subunit
Key subunit of the nicotinic acetylcholine receptor at the neuromuscular junction; mutations cause congenital myasthenic syndromes.
Gene Information Card
| Symbol | CHRNA1 |
|---|---|
| Full Name | Cholinergic Receptor Nicotinic Alpha 1 Subunit |
| Gene Type | protein-coding |
| Chromosomal Location | 2q31.1 |
| NCBI Gene ID | 1134 ncbi.nlm.nih.gov/gene/1134 |
| Ensembl ID | ENSG00000138435 |
| UniProt ID | P02708 |
| OMIM ID | 100690 |
| HGNC ID | 1955 |
| Aliases | ACHR, ACHRA, CHNRA, CMS2A, FCCMS, SCCMS |
Description
CHRNA1 encodes the alpha-1 subunit of the nicotinic acetylcholine receptor (nAChR), a pentameric ligand-gated ion channel expressed at the postsynaptic membrane of the neuromuscular junction. This subunit is essential for acetylcholine binding and channel gating. Mutations in CHRNA1 are associated with congenital myasthenic syndromes (CMS), including fast-channel and slow-channel syndromes, due to altered receptor kinetics.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital Myasthenic Syndrome 2A (CMS2A) | Loss-of-function mutations reduce acetylcholine response, causing fast-channel CMS | ClinVar, OMIM |
| Congenital Myasthenic Syndrome 2C (CMS2C) | Gain-of-function mutations prolong channel open time, causing slow-channel CMS | ClinVar, OMIM |
| Myasthenia Gravis (autoimmune) | Autoantibodies target the alpha-1 subunit, impairing neuromuscular transmission | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal Muscle | 28.5 | High |
| Cerebellum | 1.2 | Low |
| Heart | 0.8 | Low |
| Liver | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| RH-30 (rhabdomyosarcoma) | 15.3 | High expression |
| SK-N-SH (neuroblastoma) | 2.1 | Moderate |
| HEK 293 | 0.0 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.121C>T (p.Arg41Trp) | Missense | Rare | Reduced acetylcholine binding; fast-channel CMS |
| c.866G>A (p.Gly289Asp) | Missense | Rare | Prolonged channel opening; slow-channel CMS |
| c.1327delC (p.Leu443Trpfs*28) | Frameshift | Rare | Loss of function; severe CMS |
Mutation functional classification
Loss of Function (LOF)
Missense or truncating mutations that reduce acetylcholine binding or channel conductance (e.g., p.Arg41Trp) cause fast-channel CMS.
Gain of Function (GOF)
Missense mutations that prolong channel open time (e.g., p.Gly289Asp) cause slow-channel CMS.
Dominant Negative (DN)
Some slow-channel mutations act in a dominant-negative manner by incorporating mutant subunits into the pentamer, altering receptor kinetics.
View complete mutation data：
Gene Ontology (GO)
| • transmembrane signaling receptor activity (GO:0004888) | • extracellular ligand-gated ion channel activity (GO:0005230) |
| • nicotinic acetylcholine-gated receptor complex (GO:0005892) | • synaptic transmission (GO:0007271) |
| • membrane (GO:0016020) |
Pathways
• Acetylcholine binding and channel opening (Reactome: R-HSA-629587)
• Neurotransmitter receptor binding and downstream transmission (KEGG: hsa04725)
Protein Summary
The CHRNA1 protein (alpha-1 subunit) is a 437-amino acid transmembrane protein that forms part of the pentameric nicotinic acetylcholine receptor (nAChR). It contains an extracellular N-terminal domain with a conserved acetylcholine-binding site, four transmembrane domains (M1-M4), and a cytoplasmic loop. The alpha-1 subunit is critical for ligand binding and ion channel function. Mutations disrupt neuromuscular transmission, leading to congenital myasthenic syndromes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CHRNA1 Knockout HEK293 Cell Line | EDJ-KQ4276 | Human | 1134 | Details Get a Quote |
| CHRNA10 Knockout HEK293 Cell Line | EDJ-KQ12917 | Human | 57053 | Details Get a Quote |
| CHRNA10 Knockout HCT 116 Cell Line | EDJ-KQ42119 | Human | 57053 | Details Get a Quote |
| CHRNA10 Knockout HeLa Cell Line | EDJ-KQ42120 | Human | 57053 | Details Get a Quote |
| CHRNA1 Knockout HeLa Cell Line | EDJ-KQ52900 | Human | 1134 | Details Get a Quote |
| CHRNA1 Knockout A-549 Cell Line | EDJ-KQ61369 | Human | 1134 | Details Get a Quote |
| CHRNA10 Knockout A-549 Cell Line | EDJ-KQ65298 | Human | 57053 | Details Get a Quote |
| CHRNA1 Knockout HCT 116 Cell Line | EDJ-KQ69865 | Human | 1134 | Details Get a Quote |
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