CHRNB1

The CHRNB1 gene encodes the neuronal acetylcholine receptor subunit beta-1 (nAChR β1), a critical component of ligand-gated ion channels mediating synaptic transmission. Also termed ACHRB1, this protein forms heteropentameric receptors with α-subunits (e.g., α1 in muscle-type receptors) to bind acetylcholine, triggering cation influx (Na⁺, Ca²⁺) and depolarization. It is predominantly expressed in the neuromuscular junction and central nervous system, functioning in neuromuscular signal transduction and modulating neurotransmitter release. Key pathways include cholinergic synapse signaling and neuromuscular junction development. Mutations in CHRNB1 are linked to congenital myasthenic syndromes (CMS), characterized by muscle weakness and fatigability due to impaired neuromuscular transmission. Rare variants may also associate with epilepsy and neurodegenerative disorders.
Drug targeting nAChRs typically focuses on broader subtypes, though β1-specific therapies remain limited. Recent preclinical studies explore allosteric modulators or subunit-selective agonists/antagonists to address CMS or cognitive deficits. For example, cholinesterase inhibitors (e.g., pyridostigmine) are empirically used in CMS, while novel compounds like benzodiazepine derivatives show potential in enhancing channel gating efficiency. However, challenges persist in achieving subunit specificity without off-target effects on other nAChR isoforms. Ongoing research leverages cryo-EM structures of β1-containing receptors to design precision therapeutics.