CASP3
Chr 4caspase 3
Also known as: CPP32, CPP32B, SCA-1
The protein encoded by this gene is a cysteine-aspartic acid protease that plays a central role in the execution-phase of cell apoptosis. The encoded protein cleaves and inactivates poly(ADP-ribose) polymerase while it cleaves and activates sterol regulatory element binding proteins as well as caspases 6, 7, and 9. This protein itself is processed by caspases 8, 9, and 10. It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease. [provided by RefSeq, Aug 2017]
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
143 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 | 96 | 0 | 96 |
Likely Pathogenic | 0 | 0 | 9 | 0 | 9 |
VUS | 1 | 13 | 13 | 0 | 27 |
Likely Benign | 0 | 2 | 1 | 2 | 5 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 1 | 15 | 120 | 2 | 138 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CASP3 · 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
Effect of Exercise Type on Muscle Quality in Patients With OA, SARC and RA: an Explorative Study
NOT YET RECRUITINGImpact of CASP3 Gene in Chemoresistance
NOT YET RECRUITINGStudy of Treatment With Sacituzumab and Zimberelimab for Patients With Lung Cancer Confined to the Chest and Previously Operated on Who Were Not Disease-free.
RECRUITINGSafety and Impact of Baricitinib on Cell Surivival Pathways, HIV-1 Reservoir and Inflamation in People With HIV-1
ACTIVE NOT RECRUITINGRMC-5552 Monotherapy in Adult Subjects With Recurrent Glioblastoma
RECRUITINGTesting Atorvastatin to Lower Colon Cancer Risk in Longstanding Ulcerative Colitis
ACTIVE NOT RECRUITINGA Nutrition & Exercise Prehabilitation Intervention on Inflammatory Biomarkers in AI Cancer Patients
RECRUITINGThree Fraction Radiation to Induce Immuno-Oncologic Response
ACTIVE NOT RECRUITINGTesting the Addition of Abemaciclib to Olaparib for Women With Recurrent Ovarian Cancer
RECRUITINGA Phase 0 Multicenter Study of the Pharmacodynamic Effects of Intratumoral Microdose Administration of PBA-0111 in Patients With Solid Tumors
RECRUITINGIdentification of Circulating microRNAs in Adolescent Idiopathic Scoliosis
RECRUITINGTime-restricted Eating Versus Daily Continuous Calorie Restriction on Body Weight and Colorectal Cancer Risk Markers
RECRUITINGExternal Resources
Links to major genomics databases and tools