Reviewed December 2013
What is the official name of the CDKL5 gene?
The official name of this gene is “cyclin-dependent kinase-like 5.”
CDKL5 is the gene's official symbol. The CDKL5 gene is also known by other names, listed below.
What is the normal function of the CDKL5 gene?
The CDKL5 gene provides instructions for making a protein that is essential for normal brain development and function. The CDKL5 protein acts as a kinase, which is an enzyme that changes the activity of other proteins by adding a cluster of oxygen and phosphorus atoms (a phosphate group) at specific positions. One of the proteins targeted by the CDKL5 protein is MeCP2, which is produced from the MECP2 gene. The MeCP2 protein plays important roles in the function of nerve cells (neurons) and other brain cells and in the maintenance of connections (synapses) between neurons. Researchers have not determined which other proteins are targeted by the CDKL5 protein.
Does the CDKL5 gene share characteristics with other genes?
The CDKL5 gene belongs to a family of genes called CDK (cyclin-dependent kinases).
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 CDKL5 gene related to health conditions?
- X-linked infantile spasm syndrome - caused by mutations in the CDKL5 gene
Mutations in the CDKL5 gene can cause a disorder known as X-linked infantile spasm syndrome, which is characterized by recurrent seizures called infantile spasms that begin in the first year of life. Children with this condition also have intellectual disability. X-linked infantile spasm syndrome caused by CDKL5 gene mutations occurs more often in females, but it has been identified in a small number of males.
Some cases of X-linked infantile spasm syndrome are caused by a deletion involving part or all of the CDKL5 gene; others result from mutations that alter the function of the CDKL5 protein or prevent the production of any functional protein. It is unclear how defects in this protein cause seizures and intellectual disability.
- other disorders - caused by mutations in the CDKL5 gene
More than 10 mutations in the CDKL5 gene have been identified in females with a condition similar to Rett syndrome, which is a disorder whose characteristic features include developmental problems, loss of language skills, and repeated hand wringing or hand washing movements. Girls with CDKL5 gene mutations have many of the features of classic Rett syndrome. However, unlike girls with classic Rett syndrome, they also develop recurrent seizures beginning in infancy. Although this condition was previously described as an atypical form of Rett syndrome (often called the early-onset seizure variant), it is now usually considered to be a separate condition.
Some of the CDKL5 gene mutations that cause this condition change a single protein building block (amino acid) in a region of the CDKL5 protein that is critical for its kinase function. Other mutations lead to the production of an abnormally short, nonfunctional version of the protein. Researchers are working to determine how these changes impair brain development, resulting in seizures and features similar to Rett syndrome.
Where is the CDKL5 gene located?
Cytogenetic Location: Xp22
Molecular Location on the X chromosome: base pairs 18,425,604 to 18,653,628
The CDKL5 gene is located on the short (p) arm of the X chromosome at position 22.
More precisely, the CDKL5 gene is located from base pair 18,425,604 to base pair 18,653,628 on the X chromosome.
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 CDKL5?
You and your healthcare professional may find the following resources about CDKL5 helpful.
Educational resources - Information pages
- International Foundation for CDKL5 Research (http://www.cdkl5.com/)
- Jasper's Basic Mechanisms of the Epilepsies (fourth edition, 2012): The Monogenic Forms of Early Infantile Epileptic Encephalopathies (http://www.ncbi.nlm.nih.gov/books/NBK98182/)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for CDKL5 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=6792%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- OMIM - Genetic disorder catalog (http://omim.org/entry/300203)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_CDKL5.html)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=6792)
- HGNC Gene Family: Cyclin-dependent kinases (http://www.genenames.org/genefamilies/CDK)
- HGNC Gene Symbol Report (http://www.genenames.org/data/hgnc_data.php?hgnc_id=11411)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/6792)
What other names do people use for the CDKL5 gene or gene products?
- serine/threonine kinase 9
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 CDKL5?
amino acid ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Archer HL, Evans J, Edwards S, Colley J, Newbury-Ecob R, O'Callaghan F, Huyton M, O'Regan M, Tolmie J, Sampson J, Clarke A, Osborne J. CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients. J Med Genet. 2006 Sep;43(9):729-34. Epub 2006 Apr 12. (http://www.ncbi.nlm.nih.gov/pubmed/16611748?dopt=Abstract)
- Artuso R, Mencarelli MA, Polli R, Sartori S, Ariani F, Pollazzon M, Marozza A, Cilio MR, Specchio N, Vigevano F, Vecchi M, Boniver C, Dalla Bernardina B, Parmeggiani A, Buoni S, Hayek G, Mari F, Renieri A, Murgia A. Early-onset seizure variant of Rett syndrome: definition of the clinical diagnostic criteria. Brain Dev. 2010 Jan;32(1):17-24. doi: 10.1016/j.braindev.2009.02.004. Epub 2009 Apr 10. (http://www.ncbi.nlm.nih.gov/pubmed/19362436?dopt=Abstract)
- Bahi-Buisson N, Bienvenu T. CDKL5-Related Disorders: From Clinical Description to Molecular Genetics. Mol Syndromol. 2012 Apr;2(3-5):137-152. Epub 2011 Sep 13. (http://www.ncbi.nlm.nih.gov/pubmed/22670135?dopt=Abstract)
- Bertani I, Rusconi L, Bolognese F, Forlani G, Conca B, De Monte L, Badaracco G, Landsberger N, Kilstrup-Nielsen C. Functional consequences of mutations in CDKL5, an X-linked gene involved in infantile spasms and mental retardation. J Biol Chem. 2006 Oct 20;281(42):32048-56. Epub 2006 Aug 24. (http://www.ncbi.nlm.nih.gov/pubmed/16935860?dopt=Abstract)
- Evans JC, Archer HL, Colley JP, Ravn K, Nielsen JB, Kerr A, Williams E, Christodoulou J, Gécz J, Jardine PE, Wright MJ, Pilz DT, Lazarou L, Cooper DN, Sampson JR, Butler R, Whatley SD, Clarke AJ. Early onset seizures and Rett-like features associated with mutations in CDKL5. Eur J Hum Genet. 2005 Oct;13(10):1113-20. (http://www.ncbi.nlm.nih.gov/pubmed/16015284?dopt=Abstract)
- Kilstrup-Nielsen C, Rusconi L, La Montanara P, Ciceri D, Bergo A, Bedogni F, Landsberger N. What we know and would like to know about CDKL5 and its involvement in epileptic encephalopathy. Neural Plast. 2012;2012:728267. doi: 10.1155/2012/728267. Epub 2012 Jun 17. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22779007?dopt=Abstract)
- Liang JS, Shimojima K, Takayama R, Natsume J, Shichiji M, Hirasawa K, Imai K, Okanishi T, Mizuno S, Okumura A, Sugawara M, Ito T, Ikeda H, Takahashi Y, Oguni H, Imai K, Osawa M, Yamamoto T. CDKL5 alterations lead to early epileptic encephalopathy in both genders. Epilepsia. 2011 Oct;52(10):1835-42. doi: 10.1111/j.1528-1167.2011.03174.x. Epub 2011 Jul 19. (http://www.ncbi.nlm.nih.gov/pubmed/21770923?dopt=Abstract)
- Lin C, Franco B, Rosner MR. CDKL5/Stk9 kinase inactivation is associated with neuronal developmental disorders. Hum Mol Genet. 2005 Dec 15;14(24):3775-86. Epub 2005 Dec 5. (http://www.ncbi.nlm.nih.gov/pubmed/16330482?dopt=Abstract)
- Mari F, Azimonti S, Bertani I, Bolognese F, Colombo E, Caselli R, Scala E, Longo I, Grosso S, Pescucci C, Ariani F, Hayek G, Balestri P, Bergo A, Badaracco G, Zappella M, Broccoli V, Renieri A, Kilstrup-Nielsen C, Landsberger N. CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome. Hum Mol Genet. 2005 Jul 15;14(14):1935-46. Epub 2005 May 25. (http://www.ncbi.nlm.nih.gov/pubmed/15917271?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/6792)
- Scala E, Ariani F, Mari F, Caselli R, Pescucci C, Longo I, Meloni I, Giachino D, Bruttini M, Hayek G, Zappella M, Renieri A. CDKL5/STK9 is mutated in Rett syndrome variant with infantile spasms. J Med Genet. 2005 Feb;42(2):103-7. (http://www.ncbi.nlm.nih.gov/pubmed/15689447?dopt=Abstract)
- Weaving LS, Christodoulou J, Williamson SL, Friend KL, McKenzie OL, Archer H, Evans J, Clarke A, Pelka GJ, Tam PP, Watson C, Lahooti H, Ellaway CJ, Bennetts B, Leonard H, Gécz J. Mutations of CDKL5 cause a severe neurodevelopmental disorder with infantile spasms and mental retardation. Am J Hum Genet. 2004 Dec;75(6):1079-93. Epub 2004 Oct 18. (http://www.ncbi.nlm.nih.gov/pubmed/15492925?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.