CST3

Chr 20AD

cystatin C

ENSG00000101439UniProt: P01034

As an inhibitor of cysteine proteinases, this protein is thought to serve an important physiological role as a local regulator of this enzyme activity

Primary Disease Associations & Inheritance

{Macular degeneration, age-related, 11}MIM #611953
Cerebral amyloid angiopathyMIM #105150
AD
Leukodystrophy, adult-onset, autosomal dominant, without amyloid angiopathyMIM #621214
AD
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
12
Active trials
Clinical Summary— CST3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.60LOEUF
pLI 0.004
Z-score 0.58
OE 0.73 (0.36–1.60)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.50Z-score
OE missense 1.17 (0.97–1.41)
81 obs / 69.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.73 (0.36–1.60)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.17 (0.97–1.41)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.12
0≤1.21.6
LoF obs/exp: 4 / 5.5Missense obs/exp: 81 / 69.4Syn Z: -0.52

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
CYSTATIN 3; CST3
MIM #604312 · *

{Macular degeneration, age-related, 11}

MIM #611953

Molecular basis of disorder known

Cerebral amyloid angiopathy

MIM #105150

Molecular basis of disorder known

Autosomal dominant

Leukodystrophy, adult-onset, autosomal dominant, without amyloid angiopathy

MIM #621214

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Cognitive DisordersMuscular Disorders, Atrophic

Dietary Strategy to Tackle Cognitive and Locomotor Abilities in Early Elderly Subjects

RECRUITING
NCT06871384Phase NAUniversity Rovira i VirgiliStarted 2025-03-26
Nonalcoholic red wine group (Intervention group)Drinking water group (Control group)
Chronic Kidney Disease 5D

Effect of Inulin on Gut Microbiota and Gut Barrier in Chronic Kidney Disease

RECRUITING
NCT05071131Phase NACharite University, Berlin, GermanyStarted 2022-02-01
InulinPlacebo
Healthy Adults

Safety and Efficacy of Klotho and Follistatin Gene Therapy

RECRUITING
NCT07285629Phase EARLY_PHASE1MinicircleStarted 2025-12-16
Follistatin and klotho gene therapy
Healthy Adults

Safety and Efficacy of Injectable Klotho Plasmid Gene Therapy in Humans

RECRUITING
NCT07216781Phase PHASE1MinicircleStarted 2025-10-06
Injectable Plasmid Klotho Gene Therapy
Age-related Muscle Decline

CALM-AF-AI: Counteracting Age-related Loss of Muscle With AAV-Follistatin Combined With Angiogenesis-Inducing VEGF Plasmid Gene Therapy

RECRUITING
NCT07443826Phase PHASE1, PHASE2Unlimited Biotechnology LLCStarted 2026-03-31
AAV9-Follistatin gene therapyVEGF Plasmid
Kidney Disease, ChronicKidney Failure Chronic

Physical Exercise and Biomolecular Analysis to Reduce Uremic Toxins in Chronic Kidney Disease: An Exploratory Study

NOT YET RECRUITING
NCT06910475Phase NACatholic University of BrasíliaStarted 2025-04-01
Resistance trainingEndurance trainingConcurrent training
Mitochondrial DiseasesPearson Syndrome

Evaluate 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)

RECRUITING
NCT06017869Phase PHASE2Minovia Therapeutics Ltd.Started 2023-07-31
MNV-201
Hereditary Transthyretin Amyloidosis

Exploring Biomarkers in Hereditary Transthyretin Amyloidosis

RECRUITING
NCT05929209Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2023-05-01
Assessment of disease biomarkers
Heart Failure

Acute Reno-Cardiac Action of Dapagliflozin In Advanced Heart Failure Patients on Heart Transplant Waiting List

RECRUITING
NCT06868797Phase NACentral Hospital, Nancy, FranceStarted 2025-08-29
Biological sample for the measurement of suPAR levels.
Sphingosine Phosphate Lyase Insufficiency Syndrome (SPLIS)

Natural History of Sphingosine Phosphate Lyase Insufficiency Syndrome (SPLIS)

RECRUITING
NCT06669949University of California, San FranciscoStarted 2025-04-22
no intervention
Focal Segmental Glomerulosclerosis

A Study to Find Out if BI 764198 Helps Adults and Adolescents With a Kidney Condition Called Focal Segmental Glomerulosclerosis (FSGS)

RECRUITING
NCT07220083Phase PHASE3Boehringer IngelheimStarted 2026-02-16
BI 764198Placebo
Chronic Kidney DiseasesMAFLD

Pathogenesis of Chronic Kidney Disease Associated With Metabolic Dysfunction- Associated Fatty Liver Disease (MAFLD) and Treatment Response of Oral Semaglutide.

NOT YET RECRUITING
NCT07391267Phase NAInstitute of Liver and Biliary Sciences, IndiaStarted 2026-02-01
Semaglutide Oral TabletPlaceboStandard medical treatment

External Resources

Links to major genomics databases and tools