Reviewed November 2012
What is the official name of the KRIT1 gene?
The official name of this gene is “KRIT1, ankyrin repeat containing.”
KRIT1 is the gene's official symbol. The KRIT1 gene is also known by other names, listed below.
What is the normal function of the KRIT1 gene?
The KRIT1 gene (also known as CCM1) provides instructions for making a protein that strengthens the interactions between cells that form blood vessels and limits leakage from the vessels. The KRIT1 protein 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, the KRIT1 protein 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.
Does the KRIT1 gene share characteristics with other genes?
The KRIT1 gene belongs to a family of genes called ANKRD (ankyrin repeat domain containing).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.
How are changes in the KRIT1 gene related to health conditions?
- cerebral cavernous malformation - caused by mutations in the KRIT1 gene
More than 100 KRIT1 gene mutations 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. Virtually all of these mutations place a premature stop signal in the instructions for making the KRIT1 protein, preventing adequate KRIT1 protein production. 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 KRIT1 gene account for up to 50 percent of all familial cerebral cavernous malformation cases. One particular mutation is responsible for up to 70 percent of cases in people of Hispanic heritage. This mutation changes a single DNA building block (nucleotide) at position 1363 in the KRIT1 gene, written as 1363C>T.
Where is the KRIT1 gene located?
Cytogenetic Location: 7q21.2
Molecular Location on chromosome 7: base pairs 92,198,968 to 92,246,127
The KRIT1 gene is located on the long (q) arm of chromosome 7 at position 21.2.
More precisely, the KRIT1 gene is located from base pair 92,198,968 to base pair 92,246,127 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 KRIT1?
You and your healthcare professional may find the following resources about KRIT1 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%28CCM1%5BTIAB%5D%29%20OR%20%28cerebral%20cavernous%20malformations%201%5BTIAB%5D%29%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/604214)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_KRIT1.html)
- HGNC Gene Family: Ankyrin repeat domain containing (http://www.genenames.org/cgi-bin/genefamilies/set/403)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=1573)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/889)
What other names do people use for the KRIT1 gene or gene products?
- ankyrin repeat-containing protein Krit1
- cerebral cavernous malformations 1
- krev interaction trapped 1
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 KRIT1?
cerebral hemorrhage ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Cavé-Riant F, Denier C, Labauge P, Cécillon M, Maciazek J, Joutel A, Laberge-Le Couteulx S, Tournier-Lasserve E. Spectrum and expression analysis of KRIT1 mutations in 121 consecutive and unrelated patients with Cerebral Cavernous Malformations. Eur J Hum Genet. 2002 Nov;10(11):733-40. (http://www.ncbi.nlm.nih.gov/pubmed/12404106?dopt=Abstract)
- Glading A, Han J, Stockton RA, Ginsberg MH. KRIT-1/CCM1 is a Rap1 effector that regulates endothelial cell cell junctions. J Cell Biol. 2007 Oct 22;179(2):247-54. (http://www.ncbi.nlm.nih.gov/pubmed/17954608?dopt=Abstract)
- Gunel M, Laurans MS, Shin D, DiLuna ML, Voorhees J, Choate K, Nelson-Williams C, Lifton RP. KRIT1, a gene mutated in cerebral cavernous malformation, encodes a microtubule-associated protein. Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10677-82. Epub 2002 Jul 24. (http://www.ncbi.nlm.nih.gov/pubmed/12140362?dopt=Abstract)
- Guzeloglu-Kayisli O, Kayisli UA, Amankulor NM, Voorhees JR, Gokce O, DiLuna ML, Laurans MS, Luleci G, Gunel M. Krev1 interaction trapped-1/cerebral cavernous malformation-1 protein expression during early angiogenesis. J Neurosurg. 2004 May;100(5 Suppl Pediatrics):481-7. (http://www.ncbi.nlm.nih.gov/pubmed/15287459?dopt=Abstract)
- OMIM: KREV INTERACTION TRAPPED 1 (http://omim.org/entry/604214)
- Laberge-le Couteulx S, Jung HH, Labauge P, Houtteville JP, Lescoat C, Cecillon M, Marechal E, Joutel A, Bach JF, Tournier-Lasserve E. Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas. Nat Genet. 1999 Oct;23(2):189-93. (http://www.ncbi.nlm.nih.gov/pubmed/10508515?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/889)
- 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)
- 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, Davenport WJ, Stefan H, Sure U, Siegel AM, Rouleau GA. Cerebral cavernous malformations: mutations in Krit1. Neurology. 2002 Mar 26;58(6):853-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11914398?dopt=Abstract)
- Verlaan DJ, Laurent SB, Sure U, Bertalanffy H, Andermann E, Andermann F, Rouleau GA, Siegel AM. CCM1 mutation screen of sporadic cases with cerebral cavernous malformations. Neurology. 2004 Apr 13;62(7):1213-5. (http://www.ncbi.nlm.nih.gov/pubmed/15079030?dopt=Abstract)
- Whitehead KJ, Plummer NW, Adams JA, Marchuk DA, Li DY. Ccm1 is required for arterial morphogenesis: implications for the etiology of human cavernous malformations. Development. 2004 Mar;131(6):1437-48. (http://www.ncbi.nlm.nih.gov/pubmed/14993192?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.