Reviewed November 2012
What is the official name of the CCM2 gene?
The official name of this gene is “cerebral cavernous malformation 2.”
CCM2 is the gene's official symbol. The CCM2 gene is also known by other names, listed below.
What is the normal function of the CCM2 gene?
The CCM2 gene provides instructions for making a protein called malcavernin, which strengthens the interactions between cells that form blood vessels and limits leakage from the vessels. Malcavernin interacts with a number of other proteins to form a complex that is found in the junctions that connect neighboring cells. As part of this complex, malcavernin helps turn off (suppress) a signaling molecule known as RhoA-GTPase. This molecule plays a role in regulating the actin cytoskeleton, which is a network of fibers that makes up the cell's structural framework. When turned on, RhoA-GTPase stimulates the formation of actin fibers, which has been linked to weakened junctions between cells and increased leakage from blood vessels.
Malcavernin is also involved in a process called angiogenesis, which is the formation of new blood vessels.
How are changes in the CCM2 gene related to health conditions?
- cerebral cavernous malformation - caused by mutations in the CCM2 gene
Dozens of mutations in the CCM2 gene have been identified in families with cerebral cavernous malformations, which are collections of blood vessels in the brain that are weak and prone to leakage. Most of these mutations result in an abnormally short or malformed malcavernin protein that does not function. A shortage of this protein likely impairs the function of the complex. As a result, RhoA-GTPase signaling is turned on abnormally, weakening cellular junctions and increasing the permeability of blood vessel walls. The increased leakage into the brain can cause health problems such as headaches, seizures, and bleeding in the brain (cerebral hemorrhage) in some people with cerebral cavernous malformations.
Mutations in the CCM2 gene are involved in approximately 15 percent of all familial cerebral cavernous malformation cases.
Where is the CCM2 gene located?
Cytogenetic Location: 7p13
Molecular Location on chromosome 7: base pairs 44,999,746 to 45,076,470
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/83605))
The CCM2 gene is located on the short (p) arm of chromosome 7 at position 13.
More precisely, the CCM2 gene is located from base pair 44,999,746 to base pair 45,076,470 on chromosome 7.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about CCM2?
You and your healthcare professional may find the following resources about CCM2 helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28%28CCM2%5BALL%5D%29%20OR%20%28cerebral%20cavernous%20malformation%202%5BALL%5D%29%20OR%20%28CCM2%20gene%5BALL%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/607929)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_CCM2.html)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=21708)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/83605)
What other names do people use for the CCM2 gene or gene products?
- chromosome 7 open reading frame 22
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding CCM2?
cerebral hemorrhage ;
open reading frame ;
You may find definitions for these and many other terms in the Genetics Home Reference
- OMIM: CCM2 GENE (http://omim.org/entry/607929)
- Craig HD, Günel M, Cepeda O, Johnson EW, Ptacek L, Steinberg GK, Ogilvy CS, Berg MJ, Crawford SC, Scott RM, Steichen-Gersdorf E, Sabroe R, Kennedy CT, Mettler G, Beis MJ, Fryer A, Awad IA, Lifton RP. Multilocus linkage identifies two new loci for a mendelian form of stroke, cerebral cavernous malformation, at 7p15-13 and 3q25.2-27. Hum Mol Genet. 1998 Nov;7(12):1851-8. (http://www.ncbi.nlm.nih.gov/pubmed/9811928?dopt=Abstract)
- Denier C, Goutagny S, Labauge P, Krivosic V, Arnoult M, Cousin A, Benabid AL, Comoy J, Frerebeau P, Gilbert B, Houtteville JP, Jan M, Lapierre F, Loiseau H, Menei P, Mercier P, Moreau JJ, Nivelon-Chevallier A, Parker F, Redondo AM, Scarabin JM, Tremoulet M, Zerah M, Maciazek J, Tournier-Lasserve E; Société Française de Neurochirurgie. Mutations within the MGC4607 gene cause cerebral cavernous malformations. Am J Hum Genet. 2004 Feb;74(2):326-37. Epub 2004 Jan 22. (http://www.ncbi.nlm.nih.gov/pubmed/14740320?dopt=Abstract)
- Dupré N, Verlaan DJ, Hand CK, Laurent SB, Turecki G, Davenport WJ, Acciarri N, Dichgans J, Ohkuma A, Siegel AM, Rouleau GA. Linkage to the CCM2 locus and genetic heterogeneity in familial cerebral cavernous malformation. Can J Neurol Sci. 2003 May;30(2):122-8. (http://www.ncbi.nlm.nih.gov/pubmed/12774951?dopt=Abstract)
- Liquori CL, Berg MJ, Siegel AM, Huang E, Zawistowski JS, Stoffer T, Verlaan D, Balogun F, Hughes L, Leedom TP, Plummer NW, Cannella M, Maglione V, Squitieri F, Johnson EW, Rouleau GA, Ptacek L, Marchuk DA. Mutations in a gene encoding a novel protein containing a phosphotyrosine-binding domain cause type 2 cerebral cavernous malformations. Am J Hum Genet. 2003 Dec;73(6):1459-64. Epub 2003 Nov 17. (http://www.ncbi.nlm.nih.gov/pubmed/14624391?dopt=Abstract)
- Liquori CL, Berg MJ, Squitieri F, Leedom TP, Ptacek L, Johnson EW, Marchuk DA. Deletions in CCM2 are a common cause of cerebral cavernous malformations. Am J Hum Genet. 2007 Jan;80(1):69-75. Epub 2006 Nov 14. (http://www.ncbi.nlm.nih.gov/pubmed/17160895?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/83605)
- Plummer NW, Zawistowski JS, Marchuk DA. Genetics of cerebral cavernous malformations. Curr Neurol Neurosci Rep. 2005 Sep;5(5):391-6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16131422?dopt=Abstract)
- Seker A, Pricola KL, Guclu B, Ozturk AK, Louvi A, Gunel M. CCM2 expression parallels that of CCM1. Stroke. 2006 Feb;37(2):518-23. Epub 2005 Dec 22. (http://www.ncbi.nlm.nih.gov/pubmed/16373645?dopt=Abstract)
- Stockton RA, Shenkar R, Awad IA, Ginsberg MH. Cerebral cavernous malformations proteins inhibit Rho kinase to stabilize vascular integrity. J Exp Med. 2010 Apr 12;207(4):881-96. doi: 10.1084/jem.20091258. Epub 2010 Mar 22. (http://www.ncbi.nlm.nih.gov/pubmed/20308363?dopt=Abstract)
- Verlaan DJ, Laurent SB, Rochefort DL, Liquori CL, Marchuk DA, Siegel AM, Rouleau GA. CCM2 mutations account for 13% of cases in a large collection of kindreds with hereditary cavernous malformations. Ann Neurol. 2004 May;55(5):757-8. (http://www.ncbi.nlm.nih.gov/pubmed/15122722?dopt=Abstract)
- Whitehead KJ, Chan AC, Navankasattusas S, Koh W, London NR, Ling J, Mayo AH, Drakos SG, Jones CA, Zhu W, Marchuk DA, Davis GE, Li DY. The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases. Nat Med. 2009 Feb;15(2):177-84. doi: 10.1038/nm.1911. Epub 2009 Jan 18. Erratum in: Nat Med. 2009 Apr;15(4):462. Jones, Christopher A [added]; Zhu, Weiquan [added]. (http://www.ncbi.nlm.nih.gov/pubmed/19151728?dopt=Abstract)
- Zawistowski JS, Stalheim L, Uhlik MT, Abell AN, Ancrile BB, Johnson GL, Marchuk DA. CCM1 and CCM2 protein interactions in cell signaling: implications for cerebral cavernous malformations pathogenesis. Hum Mol Genet. 2005 Sep 1;14(17):2521-31. Epub 2005 Jul 21. (http://www.ncbi.nlm.nih.gov/pubmed/16037064?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.