KRIT1

Chr 7AD

KRIT1 ankyrin repeat containing

Also known as: CAM, CCM1

NCBI Gene: 889 ENSG00000001631 UniProt: O00522 OMIM: 604214

The KRIT1 protein is a crucial regulator of heart and vessel formation that maintains endothelial junction integrity, regulates angiogenesis, and controls cellular reactive oxygen species homeostasis. Mutations cause cerebral cavernous malformations, which are vascular lesions in the brain and spinal cord that can present with seizures, headaches, or neurological deficits. The condition follows autosomal dominant inheritance with reduced penetrance and variable expressivity.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein containing four ankyrin repeats, a band 4.1/ezrin/radixin/moesin (FERM) domain, and multiple NPXY sequences. The encoded protein is localized in the nucleus and cytoplasm. It binds to integrin cytoplasmic domain-associated protein-1 alpha (ICAP1alpha), and plays a critical role in beta1-integrin-mediated cell proliferation. It associates with junction proteins and RAS-related protein 1A (Rap1A), which requires the encoded protein for maintaining the integrity of endothelial junctions. It is also a microtubule-associated protein and may play a role in microtubule targeting. Mutations in this gene result in cerebral cavernous malformations. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cavernous malformations of CNS and retinaMIM #116860

Cerebral cavernous malformations-1MIM #116860

Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformationsMIM #116860

Clinical highlights

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

—

P/LP missense

0.50

LOEUF

LOF

Mechanism· G2P

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GeneReview available — KRIT1