CHRND
Chr 2ADARcholinergic receptor nicotinic delta subunit
Also known as: ACHRD, CMS2A, CMS3A, CMS3B, CMS3C, FCCMS, SCCMS
The delta subunit of the muscle acetylcholine receptor forms part of the pentameric receptor complex that opens an ion-conducting channel across the postsynaptic membrane following acetylcholine binding. Mutations cause congenital myasthenic syndromes (slow-channel, fast-channel, and acetylcholine receptor deficiency types) and multiple pterygium syndrome lethal type through both autosomal dominant and autosomal recessive inheritance patterns. The pathogenic mechanism involves gain-of-function effects that disrupt normal neuromuscular transmission.
Primary Disease Associations & Inheritance
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 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.
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
400 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 8 | 0 | 17 | 0 | 25 |
Likely Pathogenic | 12 | 5 | 0 | 0 | 17 |
VUS | 1 | 174 | 33 | 1 | 209 |
Likely Benign | 0 | 8 | 63 | 51 | 122 |
Benign | 0 | 1 | 6 | 0 | 7 |
Conflicting | — | 16 | |||
| Total | 21 | 188 | 119 | 52 | 396 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CHRND · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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