CCM2

Chr 7AD

CCM2 scaffold protein

Also known as: C7orf22, OSM, PP10187

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.662 OMIM phenotypes
Clinical SummaryCCM2
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Gene-Disease Validity (ClinGen)
cerebral cavernous malformation 2 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.66LOEUF
pLI 0.009
Z-score 2.68
OE 0.35 (0.200.66)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.52Z-score
OE missense 0.91 (0.821.01)
244 obs / 267.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.35 (0.200.66)
00.351.4
Missense OE0.91 (0.821.01)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 7 / 19.9Missense obs/exp: 244 / 267.9Syn Z: -0.96

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CCM2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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