VPS4B

Chr 18

vacuolar protein sorting 4 homolog B

Also known as: DTDP1B, MIG1, SKD1, SKD1B, VPS4-2

NCBI Gene: 9525 ENSG00000119541 UniProt: O75351

VPS4B encodes an ATPase that catalyzes the disassembly of ESCRT-III protein complexes during the late steps of endosomal multivesicular body formation, enabling proper intracellular protein trafficking and degradation of membrane proteins. Mutations cause dentin dysplasia type IB, a dental developmental disorder affecting tooth structure. This condition follows autosomal dominant inheritance.

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. Mouse Skd1 (suppressor of K+ transport defect 1) has been shown to be a 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 18; the gene for the other resides on chromosome 16. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDentin dysplasia 1B

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.48

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

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