CHMP1A

Chr 16AR

charged multivesicular body protein 1A

Also known as: CHMP1, PCH8, PCOLN3, PRSM1, VPS46-1, VPS46A

The CHMP1A protein is a component of the ESCRT-III complex that mediates endosomal cargo sorting into multivesicular bodies for lysosomal degradation and functions in cytokinesis and chromosome condensation. Mutations cause pontocerebellar hypoplasia type 8, a severe neurodevelopmental disorder affecting the brainstem and cerebellum, inherited in an autosomal recessive pattern. The gene shows low constraint against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.181 OMIM phenotype
Clinical SummaryCHMP1A
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.18LOEUF
pLI 0.000
Z-score 1.16
OE 0.63 (0.361.18)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.76Z-score
OE missense 0.81 (0.690.95)
102 obs / 126.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.63 (0.361.18)
00.351.4
Missense OE0.81 (0.690.95)
00.61.4
Synonymous OE1.22
01.21.6
LoF obs/exp: 7 / 11.2Missense obs/exp: 102 / 126.0Syn Z: -1.31
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCHMP1A-related pontocerebellar hypoplasia and microcephalyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.86top 5%
GOF
0.74top 25%
LOF
0.2092th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CHMP1A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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