CHRNA1

The CHRNA1 gene encodes the alpha-1 subunit of the nicotinic acetylcholine receptor (nAChR), a ligand-gated ion channel critical for neuromuscular signal transmission. This protein, formally named Neuronal Acetylcholine Receptor Subunit Alpha-1, is also designated as the muscle-type nAChR α1 subunit. It assembles with β1, δ, and γ/ε subunits to form pentameric receptors at the neuromuscular junction. Activation by acetylcholine triggers rapid sodium influx, initiating muscle contraction through depolarization of postsynaptic membranes. Functionally indispensable, it mediates synaptic transmission between motor neurons and skeletal muscles via the cholinergic signaling pathway.
Mutations in CHRNA1 are strongly associated with congenital myasthenic syndromes (CMS) and multiple pterygium syndrome, characterized by impaired neuromuscular transmission. The receptor's critical role has made it a therapeutic target for neuromuscular disorders. Anticholinesterase agents like pyridostigmine remain first-line treatments for CMS, while emerging therapies explore subunit-specific modulators. Recent drug development focuses on pharmacochaperones to rescue trafficking-deficient mutants and antisense oligonucleotides to regulate subunit expression. Paradoxically, autoantibodies against this receptor drive myasthenia gravis pathology, spurring immunotherapy advancements including complement inhibitors and FcRn antagonists.