CRKL

Chr 22

CRK like proto-oncogene, adaptor protein

NCBI Gene: 1399 ENSG00000099942 UniProt: P46109

The protein is an adaptor kinase containing SH2 and SH3 domains that activates RAS and JUN kinase signaling pathways and mediates intracellular signal transduction. Mutations cause autosomal dominant developmental disorders including intellectual disability, seizures, and craniofacial abnormalities, often as part of 22q11.2 deletion syndrome. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.64), suggesting some tolerance to haploinsufficiency.

ResearchSummary from RefSeq, UniProt

This gene encodes a protein kinase containing SH2 and SH3 (src homology) domains which has been shown to activate the RAS and JUN kinase signaling pathways and transform fibroblasts in a RAS-dependent fashion. It is a substrate of the BCR-ABL tyrosine kinase, plays a role in fibroblast transformation by BCR-ABL, and may be oncogenic.[provided by RefSeq, Jan 2009]

ResearchGenerating clinical summary…

Clinical highlights

Gene-disease validity (ClinGen)

congenital heart disease · UDNo Known Disease Relationshipno established gene-disease relationship

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.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.64

LOEUF

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Mechanism

Some data sources returned errors (1)

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