CRADD

Chr 12

CARD and death domain containing adaptor protein

Also known as: MRT34, RAIDD

NCBI Gene: 8738 ENSG00000169372 UniProt: P78560

CRADD encodes an adapter protein that forms the PIDDosome complex with PIDD1 and caspase-2 to activate apoptosis, and also participates in TNF receptor-1 signaling pathways. Mutations cause autosomal recessive intellectual developmental disorder with variant lissencephaly, affecting both cognitive development and brain structure formation. The gene is highly constrained against loss-of-function variants (pLI 0.88, LOEUF 0.44), indicating that functional CRADD protein is essential for normal development.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein containing a death domain (DD) motif. This protein recruits caspase 2/ICH1 to the cell death signal transduction complex, which includes tumor necrosis factor receptor 1 (TNFR1A) and RIPK1/RIP kinase, and acts in promoting apoptosis. A mutation in this gene was associated with cognitive disability. A related pseudogene is found on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder, autosomal recessive 34, with variant lissencephaly

Clinical highlights

Gene-disease validity (ClinGen)

syndromic intellectual disability · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.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

0.43

LOEUF

LOF

Mechanism· G2P

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GeneReview available — CRADD