VPS50
Chr 7ARVPS50 subunit of EARP/GARPII complex
Also known as: CCDC132, NEDMSC, VPS54L
The VPS50 protein is a component of the EARP complex that mediates endocytic recycling by tethering the complex to recycling endosomes and promoting recycling of internalized receptors like transferrin receptor to the plasma membrane. Biallelic mutations cause a neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis, reflecting involvement of the nervous system, brain development, and hepatic function. This condition follows autosomal recessive inheritance.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
VPS50 · 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