CASP2

Chr 7AR

caspase 2

ENSG00000106144 UniProt: P42575 OMIM: 600639

The protein is a cysteine-aspartic acid protease (caspase) that regulates apoptosis by forming the PIDDosome complex with PIDD1 and CRADD, which triggers cell death in response to DNA damage and other cellular stress. Biallelic mutations cause autosomal recessive intellectual developmental disorder with variant lissencephaly, affecting brain development and cognitive function. The gene is highly constrained against loss-of-function variants (LOEUF 0.658), indicating intolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Is a regulator of the cascade of caspases responsible for apoptosis execution (PubMed:11156409, PubMed:15073321, PubMed:8087842). Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival (PubMed:15073321). Associates with PIDD1 and CRADD to form the PIDDosome, a complex that activates CASP2 and triggers apoptosis in response to genotoxic stress (PubMed:15073321)

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 80, with variant lissencephalyMIM #620653

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.66

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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