VPS4A

Chr 16

vacuolar protein sorting 4 homolog A

Also known as: CIMDAG, SKD1, SKD1A, SKD2, VPS4, VPS4-1

NCBI Gene: 27183 ENSG00000132612 UniProt: Q9UN37

The VPS4A protein is an ATPase that disassembles ESCRT-III complexes during endosomal protein trafficking and is essential for cellular processes including cytokinesis, chromosome segregation, and primary cilium organization. Mutations cause CIMDAG syndrome, which is inherited in an autosomal dominant pattern. This gene is highly constrained against loss-of-function variants, indicating that functional copies are critical for normal cellular function.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the AAA protein family (ATPases associated with diverse cellular activities), and is the homolog of the yeast Vps4 protein. In humans, two paralogs of the yeast protein have been identified. The former share a high degree of aa sequence similarity with each other, and also with yeast Vps4 and mouse Skd1 proteins. The mouse Skd1 (suppressor of K+ transport defect 1) has been shown to be really an yeast Vps4 ortholog. Functional studies indicate that both human paralogs associate with the endosomal compartments, and are involved in intracellular protein trafficking, similar to Vps4 protein in yeast. The gene encoding this paralog has been mapped to chromosome 16; the gene for the other resides on chromosome 18. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCIMDAG syndrome

Clinical highlights

Interpreting a novel variant

A dominant-negative effect is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.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

0.35

LOEUF· LoF intol.

DN*

Mechanism· G2P

Some data sources returned errors (1)

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