VPS35

Chr 16q11.2

VPS35 retromer complex component

Aliases:: FLJ10752, MEM3, PARK17
MANE:: ENST00000299138.12

OMIM: 601501 ↗NCBI: 55737 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

VPS35 · Q96QK1

v62025-08-01

Predicted Aligned Error matrix for VPS35 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

91.3/ 100

Very high

796 residues

Confidence breakdown

Very high(≥ 90)74%
Confident(70–90)23%
Low(50–70)2%
Very low(< 50)1%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Adult onset dystonia, chorea or related movement disorder
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset neurodegenerative disorder
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Parkinson Disease and Complex Parkinsonism
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Disease associations (Open Targets)

Hereditary late-onset Parkinson disease
0.73
neurodegenerative disease
0.55
Young adult-onset Parkinsonism
0.50
Parkinson disease
0.48
late-onset Parkinson disease
0.40
Parkinson disease, dominant
0.37
hereditary disease
0.34
lysosomal storage disease
0.30
neoplasm
0.11
hepatocellular carcinoma
0.10

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Vacuolar protein sorting-associated protein 35

Acts as a component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The CSC seems to associate with the cytoplasmic domain of cargo proteins predominantly via VPS35; however, these interactions seem to be of low affinity and retromer SNX proteins may also contribute to cargo selectivity thus questioning the classical function of the CSC. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway (PubMed:30213940). The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5 (Probable). Required for retrograde transport of lysosomal enzyme receptor IGF2R and SLC11A2. Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA) (PubMed:15078903, PubMed:15247922, PubMed:20164305). Required for endosomal localization of WASHC2C (PubMed:22070227, PubMed:28892079). Mediates the association of the CSC with the WASH complex via WASHC2 (PubMed:22070227, PubMed:24819384, PubMed:24980502). Required for the endosomal localization of TBC1D5 (PubMed:20923837)