CASP3

Chr 4

caspase 3

Also known as: CPP32, CPP32B, SCA-1

NCBI Gene: 836 ENSG00000164305 UniProt: P42574 OMIM: 600636

The protein is a cysteine protease that serves as a major effector caspase in the execution phase of apoptosis, cleaving numerous cellular proteins including PARP1, huntingtin, and other caspases to mediate programmed cell death. Mutations cause a severe neurodevelopmental disorder with intellectual disability, microcephaly, and seizures, inherited in an autosomal recessive pattern. The gene shows moderate tolerance to loss-of-function variants (pLI 0.10, LOEUF 0.69), consistent with the recessive inheritance pattern observed clinically.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

1051

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.69

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — CASP3

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.69LOEUF

pLI 0.100

Z-score 2.37

OE 0.30 (0.15–0.69)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.66Z-score

OE missense 0.63 (0.53–0.74)

99 obs / 157.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.30 (0.15–0.69)

0≤0.351.4

Missense OE?0.63 (0.53–0.74)

0≤0.61.4

Synonymous OE?0.77

0≤1.21.6

LoF obs/exp: 4 / 13.3Missense obs/exp: 99 / 157.6Syn Z: 1.31

ClinVar Variant Classifications

0 submitted variants in ClinVar

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

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — CASP3

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

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

Metastatic Malignant Solid NeoplasmMetastatic Pancreatic AdenocarcinomaStage III Pancreatic Cancer AJCC v8

Testing the Safety and Tolerability of the Anti-cancer Drugs Trastuzumab Deruxtecan and Neratinib for Cancers With Changes in the HER2 Gene

RECRUITING

NCT05372614Phase PHASE1National Cancer Institute (NCI)Started 2022-10-05

Biopsy ProcedureBiospecimen CollectionComputed Tomography

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

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

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

Spinocerebellar Ataxia Type 1Spinocerebellar Ataxia Type 2Spinocerebellar Ataxia Type 3

Natural History Study of and Genetic Modifiers in Spinocerebellar Ataxias

RECRUITING

NCT01060371Lauren MooreStarted 2010-04

Genetic TestingBlood CollectionMagnetic Resonance Imaging (MRI) Scan

Breast Cancer

Impact of CASP3 Gene in Chemoresistance

NOT YET RECRUITING

NCT06195371Gehad Salah El-Din shakerStarted 2024-05-01

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

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

Cancer

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

RECRUITING

NCT06644560Phase NAUniversity of ArizonaStarted 2025-11-13

Prehabilitation Intervention

Clinical Literature

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