CHMP2B
Chr 3ADcharged multivesicular body protein 2B
Also known as: ALS17, CHMP2.5, DMT1, FTDALS7, VPS2-2, VPS2B
The protein is a core component of the ESCRT-III complex that sorts endosomal cargo proteins into multivesicular bodies for lysosomal degradation and functions in membrane fission events including cytokinesis. Mutations cause frontotemporal dementia and/or amyotrophic lateral sclerosis 7, typically presenting in adulthood with progressive cognitive decline and/or motor neuron degeneration. Inheritance is autosomal dominant.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative 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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CHMP2B · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
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