CHRNA7

Chr 15

cholinergic receptor nicotinic alpha 7 subunit

Also known as: CHRNA7-2, NACHRA7, a7nAChR, nAChR7

The protein forms homopentameric nicotinic acetylcholine receptors that function as ligand-gated calcium-permeable ion channels mediating synaptic transmission in the central nervous system, and also plays roles in cholinergic anti-inflammatory signaling in immune cells. Mutations cause autosomal dominant nocturnal frontal lobe epilepsy and are associated with benign familial neonatal-infantile seizures, typically presenting in infancy or childhood. This gene is not highly constrained against loss-of-function variants and has a GeneReviews entry available for detailed clinical guidance.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.77
Clinical SummaryCHRNA7
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Gene-Disease Validity (ClinGen)
epilepsy · UDRefuted

Refuted — evidence has disproved this relationship

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
65 unique Pathogenic / Likely Pathogenic· 15 VUS of 98 total submissions
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GeneReview available — CHRNA7
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.77LOEUF
pLI 0.000
Z-score 2.34
OE 0.44 (0.260.77)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.25Z-score
OE missense 0.78 (0.690.88)
190 obs / 245.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.44 (0.260.77)
00.351.4
Missense OE0.78 (0.690.88)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 9 / 20.4Missense obs/exp: 190 / 245.0Syn Z: 0.71
DN
0.88top 5%
GOF
0.86top 5%
LOF
0.1697th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

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.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

98 submitted variants in ClinVar

Classification Summary

Pathogenic58
Likely Pathogenic7
VUS15
Likely Benign14
Benign4
58
Pathogenic
7
Likely Pathogenic
15
VUS
14
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
58
0
58
Likely Pathogenic
0
0
7
0
7
VUS
1
0
14
0
15
Likely Benign
0
1
4
9
14
Benign
0
1
2
1
4
Total12851098

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CHRNA7 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →