VPS53
Chr 17ARVPS53 subunit of GARP complex
Also known as: HCCS1, PCH2E, hVps53L, pp13624
The VPS53 protein functions as a component of the GARP and EARP complexes that mediate retrograde transport from endosomes to the trans-Golgi network and endocytic recycling to the plasma membrane, maintaining proper lysosomal sorting and cellular trafficking. Biallelic mutations cause pontocerebellar hypoplasia type 2E, an autosomal recessive neurodevelopmental disorder characterized by cerebellar and brainstem underdevelopment. The gene shows significant constraint against loss-of-function variants (LOEUF 0.611), reflecting its essential cellular role.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
VPS53 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools