CHRNA4
Chr 20ADcholinergic receptor nicotinic alpha 4 subunit
Also known as: BFNC, EBN, EBN1, NACHR, NACHRA4, NACRA4
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.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CHRNA4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools