CHMP1A

Chr 16AR

charged multivesicular body protein 1A

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

NCBI Gene: 5119 ENSG00000131165 UniProt: Q9HD42 OMIM: 164010

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the CHMP/Chmp family of proteins which are involved in multivesicular body sorting of proteins to the interiors of lysosomes. The initial prediction of the protein sequence encoded by this gene suggested that the encoded protein was a metallopeptidase. The nomenclature has been updated recently to reflect the correct biological function of this encoded protein. Several transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Pontocerebellar hypoplasia, type 8MIM #614961

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

1.18

LOEUF

LOF

Mechanism· G2P