CST4
Chr 20cystatin S
CST4 encodes a type 2 cystatin that functions as a cysteine protease inhibitor with strong activity against papain and ficin, and is highly expressed in saliva, tears, and other body fluids where it provides antibacterial and antiviral protection. Mutations in CST4 cause autosomal recessive amelogenesis imperfecta, a disorder affecting tooth enamel formation. The gene shows minimal constraint against loss-of-function variants, consistent with its 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
62 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 17 | 0 | 17 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 27 | 2 | 0 | 29 |
Likely Benign | 0 | 3 | 0 | 3 | 6 |
Benign | 0 | 3 | 1 | 2 | 6 |
| Total | 0 | 33 | 23 | 5 | 61 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CST4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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