CST5
Chr 20cystatin D
CST5 encodes cystatin D, a cysteine protease inhibitor found in saliva and tears that protects against proteinases in the oral cavity, with preferential inhibition of cathepsin S. Mutations cause autosomal recessive cerebellar ataxia, mental retardation, and dysequilibrium syndrome (CAMRQ), a neurodevelopmental disorder affecting cerebellar function and cognitive development. The gene shows very low constraint against loss-of-function variants (pLI near 0), consistent with the recessive inheritance pattern.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
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
CST5 · 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