CCM2: Cerebral Cavernous Malformation 2 Gene
Key regulator of endothelial cell junction stability and angiogenesis
Gene Information Card
| Symbol | CCM2 |
|---|---|
| Full Name | cerebral cavernous malformation 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 7p13 |
| NCBI Gene ID | 83605 ncbi.nlm.nih.gov/gene/83605 |
| Ensembl ID | ENSG00000106560 |
| UniProt ID | Q9BSQ5 |
| OMIM ID | 603284 |
| HGNC ID | 2174 |
| Aliases | malcavernin, CCM2, PP10187, MGC4067 |
Description
CCM2 encodes malcavernin, a scaffold protein that assembles a signaling complex critical for endothelial cell-cell junction integrity. Loss-of-function mutations in CCM2 lead to cerebral cavernous malformations (CCM), characterized by dilated, leaky capillaries in the central nervous system. The protein interacts with CCM1 (KRIT1) and CCM3 (PDCD10) to regulate RhoA signaling and adherens junction stability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cerebral cavernous malformation 2 (CCM2) | Loss-of-function mutations disrupt endothelial junction integrity, leading to vascular leak and cavernoma formation | OMIM #603284; ClinVar pathogenic variants |
| Cerebral cavernous malformations (familial) | Heterozygous germline mutations in CCM2 predispose to multiple cavernous angiomas | NCBI Gene; multiple case studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Medium |
| Heart | 6.7 | Low |
| Liver | 4.2 | Low |
| Kidney | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (endothelial) | 15.2 | High expression; relevant to vascular function |
| HEK293 | 9.8 | Moderate expression |
| HeLa | 7.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.30_31delAG | Frameshift | Rare | Loss of function; associated with CCM |
| c.97C>T (p.Arg33*) | Nonsense | Rare | Premature truncation; loss of function |
| c.286G>A (p.Gly96Arg) | Missense | Rare | Likely loss of function; disrupts protein interaction |
Mutation functional classification
Loss of Function (LOF)
Majority of CCM2 mutations are loss-of-function (nonsense, frameshift, splice-site), leading to haploinsufficiency or complete loss of malcavernin protein.
Gain of Function (GOF)
No gain-of-function mutations reported in CCM2.
Dominant Negative (DN)
Some missense mutations may act via dominant-negative mechanism by interfering with CCM1/CCM3 complex assembly, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • cell-cell junction (GO:0005911) | • signal transduction (GO:0007165) |
| • small GTPase mediated signal transduction (GO:0007264) | • plasma membrane (GO:0005886) |
| • lamellipodium (GO:0030027) |
Pathways
• CCM signaling pathway (Reactome: R-HSA-9013405)
• Rho GTPase cycle (Reactome: R-HSA-194840)
Protein Summary
Malcavernin (CCM2) is a 444-amino acid scaffold protein containing a phosphotyrosine-binding (PTB) domain. It forms a ternary complex with CCM1 (KRIT1) and CCM3 (PDCD10) at endothelial cell junctions. This complex negatively regulates RhoA activity, promoting stable adherens junctions and barrier function. Loss of CCM2 leads to increased RhoA signaling, actin stress fiber formation, and endothelial permeability, culminating in cavernous malformations.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CCM2 Knockout HEK293 Cell Line | EDJ-KQ3705 | Human | 83605 | Details Get a Quote |
| CCM2L Knockout HEK293 Cell Line | EDJ-KQ9804 | Human | 140706 | Details Get a Quote |
| CCM2 Knockout A-549 Cell Line | EDJ-KQ25725 | Human | 83605 | Details Get a Quote |
| CCM2 Knockout HCT 116 Cell Line | EDJ-KQ25726 | Human | 83605 | Details Get a Quote |
| CCM2 Knockout HeLa Cell Line | EDJ-KQ25727 | Human | 83605 | Details Get a Quote |
| CCM2L Knockout HeLa Cell Line | EDJ-KQ58452 | Human | 140706 | Details Get a Quote |
| CCM2L Knockout A-549 Cell Line | EDJ-KQ66938 | Human | 140706 | Details Get a Quote |
| CCM2L Knockout HCT 116 Cell Line | EDJ-KQ75340 | Human | 140706 | Details Get a Quote |
