GENE REFERENCE / HGNC:1958

CHRNA4

cholinergic receptor nicotinic alpha 4 subunit

protein-coding gene20q13.33Gene information

What does this gene do?

The CHRNA4 gene provides instructions for making one part (subunit) of a larger protein complex called a nicotinic acetylcholine receptor (nAChR). Each nAChR complex is made up of a combination of five subunits, usually two alpha (α) and three beta (β) subunits. Many different combinations are possible; the characteristics of each nAChR complex depend on its specific subunits. In the brain, the complex most commonly consists of two α4 subunits and three β2 subunits. The CHRNA4 gene is responsible for producing the α4 subunit.

In the brain, the nAChR complex plays an important role in chemical signaling between nerve cells (neurons). The nAChR acts as a channel, allowing charged atoms (ions), including calcium, sodium, and potassium, to cross the cell membrane. These channels open when they attach to a chemical messenger (neurotransmitter) called acetylcholine. The channels also open in response to nicotine, the addictive substance in tobacco. As these channels open, the increased flow of ions across the cell membrane alters the release of neurotransmitters.

Communication between neurons depends on neurotransmitters. The release and uptake of these chemicals are tightly regulated to ensure that signals are passed efficiently and accurately between neurons. Researchers believe that nAChR channels play an important role in controlling the normal release and uptake of neurotransmitters.

A wide range of brain functions depend on nAChR channels, including sleep and arousal, fatigue, anxiety, attention, pain perception, and memory. The channels are also active before birth, which suggests that they are involved in early brain development.

Source: MedlinePlus, National Library of Medicine. Source publication: 2025-08-14. Source review: 2025-08.

ClinGen reviews

ClinGen reviews the evidence linking a particular gene to a condition. Each rating below describes the strength of that link. It does not classify a variant in your DNA file.

Condition	Inheritance	Evidence
familial sleep-related hypermotor epilepsyMONDO:0000030 · Evaluated 2020-02-18	Autosomal dominant	DefinitiveEpilepsy Gene Curation Expert Panel

ClinVar records

These numbers show what has been submitted to ClinVar. They cannot tell you how likely you are to have a condition.

Submitted alleles: 1,287
Submissions for variants in or overlapping this gene: 2,303
Submissions explicitly reporting this gene: 2,186
Alleles reported pathogenic / likely pathogenic: 26
VariationIDs with uncertain significance: 513
VariationIDs with conflicting classifications: 133

The rows count different things: alleles, submissions or VariationIDs. Their categories can overlap, so do not add them together. Pathogenic/likely pathogenic counts exclude structural variants that merely overlap a gene. A dash in the source means “not reported,” not zero.

NCBI produces the gene-summary file each week using counts recorded at the start of the month. The numbers may differ from those on the live ClinVar website. Read the field definitions ↗

View this gene in ClinVar ↗

YOUR DNA FILE

Can your DNA file tell you about CHRNA4?

From a DNA test kit (such as 23andMe, AncestryDNA or MyHeritage). These kits check a fixed list of about 600,000 to 700,000 positions across your whole genome. ClinVar lists 26 alleles in CHRNA4 reported as pathogenic or likely pathogenic. A kit checks only some of these positions, and often none of them.

From whole genome sequencing (a VCF file). Sequencing reads most of your genome. Your file lists the places where your DNA differs from the reference genome. Some regions are hard to sequence, including parts of some genes that have near-identical copies elsewhere, and a VCF file does not record which positions were read well.

If a variant is not in your file, that does not mean you don’t have it.

What BioDecode checks

BioDecode compares every variant in your file with ClinVar, on your own computer. For each match, it shows the ClinVar classification, the review status and the condition it was reported for. Your file is not uploaded.

A ClinVar classification applies to one particular variant and the condition it was reported for. It does not tell you about other variants in CHRNA4.

BioDecode cannot fill gaps in your test, diagnose a condition or replace clinical testing.

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