VPS35

Chr 16AD

VPS35 retromer complex component

Also known as: MEM3, PARK17

NCBI Gene: 55737 ENSG00000069329 UniProt: Q96QK1 OMIM: 601501

The protein acts as a core component of the retromer complex, which mediates retrograde transport of proteins from endosomes to the trans-Golgi network and prevents their missorting into lysosomal degradation pathways. Mutations cause Parkinson disease 17, inherited in an autosomal dominant pattern. This gene is highly constrained against loss-of-function variants, indicating that proper protein dosage is critical for normal cellular function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene belongs to a group of vacuolar protein sorting (VPS) genes. The encoded protein is a component of a large multimeric complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network. The close structural similarity between the yeast and human proteins that make up this complex suggests a similarity in function. Expression studies in yeast and mammalian cells indicate that this protein interacts directly with VPS35, which serves as the core of the retromer complex. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Parkinson disease 17}MIM #614203

Clinical highlights

Gene-disease validity (ClinGen)

Parkinson disease · ADDefinitivesufficient evidence for diagnostic panels

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

0.31

LOEUF· LoF intol.

Multiple*

Mechanism· predicted