CHRNE

Chr 17ADAR

cholinergic receptor nicotinic epsilon subunit

Also known as: ACHRE, CMS1A1, CMS1D, CMS1E, CMS2A, CMS4A, CMS4B, CMS4C

The epsilon subunit is a component of the pentameric acetylcholine receptor at the neuromuscular junction that replaces the embryonic gamma subunit after birth. Mutations cause congenital myasthenic syndrome through gain-of-function (slow-channel), loss-of-function (fast-channel), or receptor deficiency mechanisms. Inheritance is autosomal dominant for slow-channel forms and autosomal recessive for fast-channel and deficiency forms.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismAD/ARLOEUF 0.993 OMIM phenotypes
Clinical SummaryCHRNE
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — CHRNE
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.99LOEUF
pLI 0.000
Z-score 1.60
OE 0.66 (0.450.99)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.85Z-score
OE missense 1.13 (1.041.24)
359 obs / 316.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.66 (0.450.99)
00.351.4
Missense OE1.13 (1.041.24)
00.61.4
Synonymous OE1.31
01.21.6
LoF obs/exp: 17 / 25.8Missense obs/exp: 359 / 316.4Syn Z: -2.92
DN
0.76top 25%
GOF
0.86top 5%
LOF
0.2093th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). 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.

GOFprediction above median
DNprediction 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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CHRNE · 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.

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Clinical Literature
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