CHMP6
Chr 17charged multivesicular body protein 6
Also known as: VPS20
The protein is a core component of the ESCRT-III complex that sorts endosomal cargo proteins into multivesicular bodies and mediates membrane fission events including cytokinesis. Mutations in CHMP6 cause autosomal recessive developmental delay with language impairment and behavioral abnormalities through disruption of endosomal trafficking and cellular membrane dynamics. The pathogenic mechanism involves impaired formation of intraluminal vesicles and defective protein degradation pathways essential for normal neuronal function.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). 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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
69 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 | 15 | 0 | 15 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 30 | 5 | 0 | 35 |
Likely Benign | 0 | 1 | 0 | 1 | 2 |
Benign | 0 | 1 | 1 | 1 | 3 |
| Total | 0 | 32 | 22 | 2 | 56 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CHMP6 · 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