CST3
Chr 20ADcystatin C
Also known as: ADLDWA, ARMD11, HEL-S-2
Cystatin C functions as an extracellular inhibitor of cysteine proteases and is found in high concentrations throughout biological fluids and virtually all organs. Mutations cause autosomal dominant cerebral amyloid angiopathy and adult-onset leukodystrophy, with some variants also associated with age-related macular degeneration. The gene shows low constraint to loss-of-function variants (pLI 0.004, LOEUF 1.6), consistent with dominant conditions that may not require complete protein loss.
Limited evidence — not for standalone diagnostic reporting
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
CST3 · 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
Safety and Efficacy of Injectable Klotho Plasmid Gene Therapy in Humans
RECRUITINGPathogenesis of Chronic Kidney Disease Associated With Metabolic Dysfunction- Associated Fatty Liver Disease (MAFLD) and Treatment Response of Oral Semaglutide.
NOT YET RECRUITINGEvaluate the Safety and Therapeutic Effects of a Single Intravenous Infusion (IV) of Autologous CD34+ Cells Enriched With Allogenic Placenta-derived Mitochondria in Patients With a Diagnosis of Pearson Syndrome (PS)
RECRUITINGSafety and Efficacy of Klotho and Follistatin Gene Therapy
RECRUITINGA Study to Find Out if BI 764198 Helps Adults and Adolescents With a Kidney Condition Called Focal Segmental Glomerulosclerosis (FSGS)
RECRUITINGCALM-AF-AI: Counteracting Age-related Loss of Muscle With AAV-Follistatin Combined With Angiogenesis-Inducing VEGF Plasmid Gene Therapy
RECRUITINGNatural History of Sphingosine Phosphate Lyase Insufficiency Syndrome (SPLIS)
RECRUITINGDietary Strategy to Tackle Cognitive and Locomotor Abilities in Early Elderly Subjects
RECRUITINGAcute Reno-Cardiac Action of Dapagliflozin In Advanced Heart Failure Patients on Heart Transplant Waiting List
RECRUITINGEffect of Inulin on Gut Microbiota and Gut Barrier in Chronic Kidney Disease
RECRUITINGPhysical Exercise and Biomolecular Analysis to Reduce Uremic Toxins in Chronic Kidney Disease: An Exploratory Study
ENROLLING BY INVITATIONExploring Biomarkers in Hereditary Transthyretin Amyloidosis
RECRUITINGExternal Resources
Links to major genomics databases and tools