CHRNE

Chr 17ADAR

cholinergic receptor nicotinic epsilon subunit

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

NCBI Gene: 1145ENSG00000108556UniProt: Q04844

Acetylcholine receptors at mature mammalian neuromuscular junctions are pentameric protein complexes composed of four subunits in the ratio of two alpha subunits to one beta, one epsilon, and one delta subunit. The acetylcholine receptor changes subunit composition shortly after birth when the epsilon subunit replaces the gamma subunit seen in embryonic receptors. Mutations in the epsilon subunit are associated with congenital myasthenic syndrome. [provided by RefSeq, Sep 2009]

Primary Disease Associations & Inheritance

Myasthenic syndrome, congenital, 4A, slow-channelMIM #605809
ADAR
Myasthenic syndrome, congenital, 4B, fast-channelMIM #616324
AR
Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiencyMIM #608931
AR
0
Active trials
133
Pathogenic / LP
689
ClinVar variants
17
Pubs (1 yr)
-0.9
Missense Z
0.99
LOEUF
Clinical Summary— CHRNE
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
133 Pathogenic / Likely Pathogenic· 199 VUS of 689 total submissions
📖
GeneReview available — CHRNE
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.99LOEUF
pLI 0.000
Z-score 1.60
OE 0.66 (0.45–0.99)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.85Z-score
OE missense 1.13 (1.04–1.24)
359 obs / 316.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.66 (0.45–0.99)
0≤0.351.4
Missense OE1.13 (1.04–1.24)
0≤0.61.4
Synonymous OE1.31
0≤1.21.6
LoF obs/exp: 17 / 25.8Missense obs/exp: 359 / 316.4Syn Z: -2.92
GOFDN
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

689 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic55
Likely Pathogenic78
VUS199
Likely Benign347
Benign4
Conflicting6
55
Pathogenic
78
Likely Pathogenic
199
VUS
347
Likely Benign
4
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
37
1
17
0
55
Likely Pathogenic
50
12
16
0
78
VUS
0
161
27
11
199
Likely Benign
0
1
168
178
347
Benign
0
0
4
0
4
Conflicting
—6
Total87175232189689

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

View in ClinVar →

CHRNE · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Blood biomarker fingerprints in a cohort of patients with CHRNE-related congenital myasthenic syndrome.
Della Marina A et al.·Acta Neuropathol Commun
2025Open AccessCohort
CHRNE-related congenital myasthenic syndrome in Iran: Clinical and molecular insights.
Karimi N et al.·Neuromuscul Disord
2025
Calcitriol ameliorates motor deficits and prolongs survival of Chrne-deficient mouse, a model for congenital myasthenic syndrome, by inducing Rspo2.
Ohkawara B et al.·Neurotherapeutics
2024Open AccessFunctional
Characterization of Clinical Phenotypes in Congenital Myasthenic Syndrome Associated with the c.1327delG Frameshift Mutation in CHRNE Encoding the Acetylcholine Receptor Epsilon Subunit.
Kastreva K et al.·J Neuromuscul Dis
2024Open Access
Homozygous Duplication in the CHRNE in a Family with Congenital Myasthenic Syndrome 4C: 18-Year Follow Up.
Almatrafi AM et al.·Biomedicines
2023Natural history
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients