CRADD

Chr 12AR

CARD and death domain containing adaptor protein

Also known as: MRT34, RAIDD

NCBI Gene: 8738 ENSG00000169372 UniProt: P78560 OMIM: 603454

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.431 OMIM phenotype

Clinical Summary— CRADD

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Gene-Disease Validity (ClinGen)

syndromic intellectual disability · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.88) — some intolerance to loss-of-function variants.

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