CHMP2B

Chr 3AD

charged multivesicular body protein 2B

Also known as: ALS17, CHMP2.5, DMT1, FTDALS7, VPS2-2, VPS2B

NCBI Gene: 25978ENSG00000083937UniProt: Q9UQN3

This gene encodes a component of the heteromeric ESCRT-III complex (Endosomal Sorting Complex Required for Transport III) that functions in the recycling or degradation of cell surface receptors. ESCRT-III functions in the concentration and invagination of ubiquitinated endosomal cargos into intralumenal vesicles. The protein encoded by this gene is found as a monomer in the cytosol or as an oligomer in ESCRT-III complexes on endosomal membranes. It is expressed in neurons of all major regions of the brain. Mutations in this gene result in one form of familial frontotemporal lobar degeneration. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Frontotemporal dementia and/or amyotrophic lateral sclerosis 7MIM #600795
AD
207
ClinVar variants
14
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CHMP2B
🧬
Gene-Disease Validity (ClinGen)
frontotemporal dementia and/or amyotrophic lateral sclerosis 7 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 122 VUS of 207 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.22LOEUF
pLI 0.000
Z-score 0.98
OE 0.72 (0.44–1.22)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.34Z-score
OE missense 0.91 (0.78–1.07)
103 obs / 113.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.72 (0.44–1.22)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.78–1.07)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 10 / 14.0Missense obs/exp: 103 / 113.2Syn Z: 0.14

ClinVar Variant Classifications

207 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic4
VUS122
Likely Benign48
Benign18
Conflicting5
10
Pathogenic
4
Likely Pathogenic
122
VUS
48
Likely Benign
18
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
7
0
10
Likely Pathogenic
0
2
2
0
4
VUS
5
69
47
1
122
Likely Benign
0
3
25
20
48
Benign
0
0
14
4
18
Conflicting
—5
Total6769525207

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Frontotemporal dementia and/or amyotrophic lateral sclerosis 7

MIM #600795

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — CHMP2B
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autophagy and ALS: mechanistic insights and therapeutic implications.
Chua JP et al.·Autophagy
2022Review
Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced motor neurons.
Shi Y et al.·Nat Med
2018
The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy.
Deneubourg C et al.·Autophagy
2022
Axonal transport of CHMP2b is regulated by kinesin-binding protein and disrupted by CHMP2b(intron5).
Kirwan KR et al.·Life Sci Alliance
2025
Lessons learned from CHMP2B, implications for frontotemporal dementia and amyotrophic lateral sclerosis.
Ugbode C et al.·Neurobiol Dis
2021Review
Genetic and clinical landscape of Chinese frontotemporal dementia: dominance of TBK1 and OPTN mutations.
Nan H et al.·Alzheimers Res Ther
2024
A novel splice-site mutation in CHMP2B associated with frontotemporal dementia: The first report from China and literature review.
Li C et al.·Mol Genet Genomic Med
2023Review
Six generations of CHMP2B-mediated Frontotemporal Dementia: Clinical features, predictive testing, progression, and survival.
Roos P et al.·Acta Neurol Scand
2022
The role of CHMP2B in frontotemporal dementia.
Urwin H et al.·Biochem Soc Trans
2009Review
Genetics of Frontotemporal Dementia.
Olszewska DA et al.·Curr Neurol Neurosci Rep
2016Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools