CCM2

Chr 7

CCM2 scaffold protein

Also known as: C7orf22, OSM, PP10187

NCBI Gene: 83605 ENSG00000136280 UniProt: Q9BSQ5

The encoded protein functions as a scaffold in endothelial cell signaling pathways and is essential for maintaining normal blood vessel integrity and endothelial cell-cell junctions. Mutations cause cerebral cavernous malformations, a condition characterized by abnormal clusters of dilated blood vessels in the brain and spinal cord that can lead to seizures, headaches, and neurological deficits. This condition follows autosomal dominant inheritance with variable age of onset and clinical severity.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a scaffold protein that functions in the stress-activated p38 Mitogen-activated protein kinase (MAPK) signaling cascade. The protein interacts with SMAD specific E3 ubiquitin protein ligase 1 (also known as SMURF1) via a phosphotyrosine binding domain to promote RhoA degradation. The protein is required for normal cytoskeletal structure, cell-cell interactions, and lumen formation in endothelial cells. Mutations in this gene result in cerebral cavernous malformations. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2009]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCerebral cavernous malformations 2

Clinical highlights

Gene-disease validity (ClinGen)

cerebral cavernous malformation 2 · ADDefinitivesufficient evidence for diagnostic panels

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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