SLC18A3
Chr 10ARsolute carrier family 18 member A3
Also known as: CMS21, VACHT
The encoded protein is a vesicular acetylcholine transporter that uses a proton gradient to transport acetylcholine into synaptic vesicles for neurotransmitter release at cholinergic synapses. Biallelic mutations cause congenital myasthenic syndrome type 21, a presynaptic neuromuscular transmission disorder inherited in an autosomal recessive pattern. This gene has moderate constraint against loss-of-function variants (LOEUF 0.636), suggesting some tolerance to complete protein loss.
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 | 0 | 0 | 38 | 0 | 38 |
Likely Pathogenic | 1 | 1 | 22 | 0 | 24 |
VUS | 2 | 178 | 34 | 6 | 220 |
Likely Benign | 0 | 5 | 0 | 95 | 100 |
Benign | 0 | 3 | 1 | 7 | 11 |
Conflicting | — | 6 | |||
| Total | 3 | 187 | 95 | 108 | 399 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SLC18A3 · 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