CASP3

Chr 4

caspase 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]

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 0.69
Clinical SummaryCASP3
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
💊
Clinical Trials
9 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.69LOEUF
pLI 0.100
Z-score 2.37
OE 0.30 (0.150.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.66Z-score
OE missense 0.63 (0.530.74)
99 obs / 157.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.30 (0.150.69)
00.351.4
Missense OE?0.63 (0.530.74)
00.61.4
Synonymous OE?0.77
01.21.6
LoF obs/exp: 4 / 13.3Missense obs/exp: 99 / 157.6Syn Z: 1.31

This gene — mechanism propensity

DN
0.83top 10%
GOF
0.74top 25%
LOF
0.2289th %ile

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.

DNprediction above median
GOFprediction above median

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

CASP3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Colorectal CarcinomaUlcerative Colitis

Testing Atorvastatin to Lower Colon Cancer Risk in Longstanding Ulcerative Colitis

ACTIVE NOT RECRUITING
NCT04767984Phase PHASE2Northwestern UniversityStarted 2021-09-24
Atorvastatin CalciumBiopsy of ColonBiospecimen Collection
Head and Neck Squamous Cell CarcinomaSoft Tissue Sarcoma AdultTriple Negative Breast Cancer

A Phase 0 Multicenter Study of the Pharmacodynamic Effects of Intratumoral Microdose Administration of PBA-0111 in Patients With Solid Tumors

RECRUITING
NCT06700070Phase EARLY_PHASE1Pure Biologics S.A.Started 2025-03-27
PBA-0111
Rheumatoid ArthritisOsteoarthritisSarcopenia

Effect of Exercise Type on Muscle Quality in Patients With OA, SARC and RA: an Explorative Study

NOT YET RECRUITING
NCT06480643Phase NAAmsterdam UMC, location VUmcStarted 2024-12-01
High load exercise typeLow load exercise type
High-Risk CancerLocally Advanced Breast Cancer

Three Fraction Radiation to Induce Immuno-Oncologic Response

ACTIVE NOT RECRUITING
NCT03978663Phase NALondon Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sStarted 2020-09-02
Neoadjuvant radiotherapy
Time Restricted EatingObesityWeight Loss

Time-restricted Eating Versus Daily Continuous Calorie Restriction on Body Weight and Colorectal Cancer Risk Markers

ACTIVE NOT RECRUITING
NCT05114798Phase NAUniversity of Illinois at ChicagoStarted 2022-05-17
Time restricted eatingCalorie Restriction
Cancer

A Nutrition & Exercise Prehabilitation Intervention on Inflammatory Biomarkers in AI Cancer Patients

RECRUITING
NCT06644560Phase NAUniversity of ArizonaStarted 2025-11-13
Prehabilitation Intervention
Recurrent Ovarian High Grade Serous AdenocarcinomaRecurrent Platinum-Resistant Ovarian Carcinoma

Testing the Addition of Abemaciclib to Olaparib for Women With Recurrent Ovarian Cancer

RECRUITING
NCT04633239Phase PHASE1National Cancer Institute (NCI)Started 2021-07-02
AbemaciclibBiopsy ProcedureBiospecimen Collection
Lung DiseasesCarcinoma, Non-Small-Cell LungResectable Lung Non-Small Cell Carcinoma

Study of Treatment With Sacituzumab and Zimberelimab for Patients With Lung Cancer Confined to the Chest and Previously Operated on Who Were Not Disease-free.

RECRUITING
NCT06431633Phase PHASE3Fundación GECPStarted 2025-02-04
ZimberelimabSacituzumab govitecanCisplatin
Breast Cancer

Impact of CASP3 Gene in Chemoresistance

NOT YET RECRUITING
NCT06195371Gehad Salah El-Din shakerStarted 2024-05-01