CHRNA4

Chr 20AD

cholinergic receptor nicotinic alpha 4 subunit

Also known as: BFNC, EBN, EBN1, NACHR, NACHRA4, NACRA4

NCBI Gene: 1137 ENSG00000101204 UniProt: P43681 OMIM: 118504

This gene encodes the α4 subunit of neuronal nicotinic acetylcholine receptors, which are pentameric ligand-gated cation channels that mediate excitatory synaptic transmission in the central nervous system. Mutations cause autosomal dominant nocturnal frontal lobe epilepsy type 1, a seizure disorder typically beginning in childhood or adolescence with brief nocturnal seizures arising from the frontal lobe. The gene shows low constraint to loss-of-function variation (pLI = 0.00009, LOEUF = 0.822), consistent with autosomal dominant inheritance where heterozygous mutations are pathogenic.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a nicotinic acetylcholine receptor, which belongs to a superfamily of ligand-gated ion channels that play a role in fast signal transmission at synapses. These pentameric receptors can bind acetylcholine, which causes an extensive change in conformation that leads to the opening of an ion-conducting channel across the plasma membrane. This protein is an integral membrane receptor subunit that can interact with either nAChR beta-2 or nAChR beta-4 to form a functional receptor. Mutations in this gene cause nocturnal frontal lobe epilepsy type 1. Polymorphisms in this gene that provide protection against nicotine addiction have been described. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Nicotine addiction, susceptibility to}MIM #188890

Epilepsy, nocturnal frontal lobe, 1MIM #600513

Clinical highlights

Gene-disease validity (ClinGen)

familial sleep-related hypermotor epilepsy · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.82

LOEUF

GOF*

Mechanism· G2P

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GeneReview available — CHRNA4