VPS37A
Chr 8ARVPS37A subunit of ESCRT-I
Also known as: HCRP1, PQBP2, SPG53
VPS37A encodes a component of the ESCRT-I complex that sorts ubiquitinated transmembrane proteins into multivesicular bodies for degradation. Mutations cause autosomal recessive spastic paraplegia-53, a hereditary spastic paraplegia primarily affecting the pyramidal motor system. The gene shows low constraint to loss-of-function variation (pLI 0.0007, LOEUF 0.722), consistent with its recessive inheritance pattern.
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
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
VPS37A · 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