CDKL5

Cyclin-dependent kinase-like 5
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4BGQ​
Identifiers
Symbols	CDKL5 ; EIEE2; ISSX; STK9
External IDs	OMIM: 300203 MGI: 1278336 HomoloGene: 55719 IUPHAR: 1986 ChEMBL: 1163112 GeneCards: CDKL5 Gene
EC number	2.7.11.22
Gene ontology Molecular function • protein kinase activity • protein serine/threonine kinase activity • cyclin-dependent protein serine/threonine kinase activity • ATP binding • kinase activity • Rac GTPase binding Cellular component • nucleus • nucleoplasm • cytoplasm • ruffle membrane • dendrite cytoplasm • dendritic growth cone Biological process • neuron migration • protein phosphorylation • positive regulation of GTPase activity • positive regulation of axon extension • protein autophosphorylation • regulation of dendrite development • positive regulation of dendrite morphogenesis • regulation of cell cycle Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6792	382253
Ensembl	ENSG00000008086	ENSMUSG00000031292
UniProt	O76039	Q3UTQ8
RefSeq (mRNA)	NM_001037343	NM_001024624
RefSeq (protein)	NP_001032420	NP_001019795
Location (UCSC)	Chr X: 18.43 – 18.65 Mb	Chr X: 160.77 – 160.99 Mb
PubMed search

CDKL5 is a gene that provides instructions for making a protein called cyclin-dependent kinase-like 5 also known as serine/threonine kinase 9 (STK9) that is essential for normal brain development. Although little is known about the protein's function, it may play a role in regulating the activity of other genes. 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. Researchers have not determined which proteins are targeted by the CDKL5 protein.^[1]

Mutations

CDKL5 is sometimes associated with Rett syndrome (though much less frequently than MECP2).^[2] At least 10 mutations in the CDKL5 gene have been identified in girls with an atypical form of Rett syndrome known as the early-onset seizure variant. While CDKL5 is primarily associated with girls, it has been seen in boys as well. This disorder includes many of the features of classic Rett syndrome (including developmental problems, loss of language skills, and repeated hand wringing or hand washing movements), but also causes recurrent seizures beginning in infancy. Some CDKL5 mutations 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 result in seizures and the characteristic features of Rett syndrome in affected children.^[1]

Mutations in the CDKL5 gene also cause a disorder called X-linked infantile spasm syndrome (ISSX)^[3][4] or West syndrome.^[5][6] Like the early-onset seizure variant of Rett syndrome, X-linked infantile spasm syndrome is characterized by recurrent seizures that begin in infancy. Children with this condition also have severe to profound intellectual disability and may have other brain abnormalities. The CDKL5 mutations responsible for X-linked infantile spasm syndrome lead to the production of an abnormally short, nonfunctional version of the CDKL5 protein. It remains uncertain how these defects cause seizures and intellectual disability.^[1]

Location

The CDKL5 gene is located on the short (p) arm of the X chromosome at position 22.^[7] More precisely, the CDKL5 gene is located from base pair 18,443,724 to base pair 18,671,748 on the X chromosome.^[1]

Cdkl5 Research

The online CDKL5 research community to share information and promote collaboration.

• CDKL5 Forum www.cdkl5forum.org

Charitable Organisations

North America

• CDKL5 America www.cdkl5.com
• CDKL5 Canada www.cdkl5canada.ca

Europe

There are a number of organisations in Europe working to raise awareness and funds for the CDKL5 research effort. These include:

• CDKL5 UK - www.curecdkl5.org
• CDKL5 Ireland - www.curecdkl5.ie
• CDKL5 Italy / CDKL5 Associazione di Volontariato ONLUS - www.cdkl5.org
• CDKL5 Germany - www.cdkl5.de
• CDKL5 Netherlands / Foundation cdkl-5 NL collaborates with foundations worldwide - www.cdkl-5.nl

For details of other CDKL5 charities in the Europe, visit CDKL5 Europe

See also

• Cyclin-dependent kinase
• Rett syndrome
• West syndrome

References

1. CDKL5 on Genetics Home Reference
2. Weaving LS, Ellaway CJ, Gécz J, Christodoulou J (January 2005). "Rett syndrome: clinical review and genetic update". J. Med. Genet. 42 (1): 1–7. doi:10.1136/jmg.2004.027730. PMC 1735910. PMID 15635068.
3. Infantile spasm syndrome, X-linked
4. Kalscheuer VM, Tao J, Donnelly A, Hollway G, Schwinger E, Kübart S, Menzel C, Hoeltzenbein M, Tommerup N, Eyre H, Harbord M, Haan E, Sutherland GR, Ropers HH, Gécz J (June 2003). "Disruption of the serine/threonine kinase 9 gene causes severe X-linked infantile spasms and mental retardation". Am. J. Hum. Genet. 72 (6): 1401–11. doi:10.1086/375538. PMC 1180301. PMID 12736870.
5. West Syndrome
6. Kato M (August 2006). "A new paradigm for West syndrome based on molecular and cell biology". Epilepsy Res. 70 Suppl 1: S87–95. doi:10.1016/j.eplepsyres.2006.02.008. PMID 16806828.
7. Montini E, Andolfi G, Caruso A, Buchner G, Walpole SM, Mariani M, Consalez G, Trump D, Ballabio A, Franco B (August 1998). "Identification and characterization of a novel serine-threonine kinase gene from the Xp22 region". Genomics 51 (3): 427–33. doi:10.1006/geno.1998.5391. PMID 9721213.

Further reading

• Ricciardi S, Kilstrup-Nielsen C, Bienvenu T; et al. (2009). "CDKL5 influences RNA splicing activity by its association to the nuclear speckle molecular machinery.". Hum. Mol. Genet. 18 (23): 4590–602. doi:10.1093/hmg/ddp426. PMID 19740913.
• Grosso S, Brogna A, Bazzotti S; et al. (2007). "Seizures and electroencephalographic findings in CDKL5 mutations: case report and review.". Brain Dev. 29 (4): 239–42. doi:10.1016/j.braindev.2006.09.001. PMID 17049193.
• Rosas-Vargas H, Bahi-Buisson N, Philippe C; et al. (2008). "Impairment of CDKL5 nuclear localisation as a cause for severe infantile encephalopathy.". J. Med. Genet. 45 (3): 172–8. doi:10.1136/jmg.2007.053504. PMID 17993579.
• Bahi-Buisson N, Kaminska A, Boddaert N; et al. (2008). "The three stages of epilepsy in patients with CDKL5 mutations.". Epilepsia 49 (6): 1027–37. doi:10.1111/j.1528-1167.2007.01520.x. PMID 18266744.
• Mei D, Marini C, Novara F; et al. (2010). "Xp22.3 genomic deletions involving the CDKL5 gene in girls with early onset epileptic encephalopathy.". Epilepsia 51 (4): 647–54. doi:10.1111/j.1528-1167.2009.02308.x. PMID 19780792.
• Bahi-Buisson N, Nectoux J, Rosas-Vargas H; et al. (2008). "Key clinical features to identify girls with CDKL5 mutations.". Brain 131 (Pt 10): 2647–61. doi:10.1093/brain/awn197. PMID 18790821.
• Nabbout R, Depienne C, Chipaux M; et al. (2009). "CDKL5 and ARX mutations are not responsible for early onset severe myoclonic epilepsy in infancy.". Epilepsy Res. 87 (1): 25–30. doi:10.1016/j.eplepsyres.2009.07.004. PMID 19734009.
• Rusconi L, Salvatoni L, Giudici L; et al. (2008). "CDKL5 expression is modulated during neuronal development and its subcellular distribution is tightly regulated by the C-terminal tail.". J. Biol. Chem. 283 (44): 30101–11. doi:10.1074/jbc.M804613200. PMC 2662074. PMID 18701457.
• Nemos C, Lambert L, Giuliano F; et al. (2009). "Mutational spectrum of CDKL5 in early-onset encephalopathies: a study of a large collection of French patients and review of the literature.". Clin. Genet. 76 (4): 357–71. doi:10.1111/j.1399-0004.2009.01194.x. PMID 19793311.
• Elia M, Falco M, Ferri R; et al. (2008). "CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy.". Neurology 71 (13): 997–9. doi:10.1212/01.wnl.0000326592.37105.88. PMID 18809835.
• Barbe L, Lundberg E, Oksvold P; et al. (2008). "Toward a confocal subcellular atlas of the human proteome.". Mol. Cell Proteomics 7 (3): 499–508. doi:10.1074/mcp.M700325-MCP200. PMID 18029348.
• Russo S, Marchi M, Cogliati F; et al. (2009). "Novel mutations in the CDKL5 gene, predicted effects and associated phenotypes.". Neurogenetics 10 (3): 241–50. doi:10.1007/s10048-009-0177-1. PMID 19241098.
• Li MR, Pan H, Bao XH; et al. (2009). "[Methyl-CpG-binding protein 2 gene and CDKL5 gene mutation in patients with Rett syndrome: analysis of 177 Chinese pediatric patients]". Zhonghua Yi Xue Za Zhi 89 (4): 224–9. PMID 19552836.
• Li MR, Pan H, Bao XH; et al. (2007). "MECP2 and CDKL5 gene mutation analysis in Chinese patients with Rett syndrome.". J. Hum. Genet. 52 (1): 38–47. doi:10.1007/s10038-006-0079-0. PMID 17089071.
• Fichou Y, Bieth E, Bahi-Buisson N; et al. (2009). "Re: CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy.". Neurology 73 (1): 77–8; author reply 78. doi:10.1212/01.wnl.0000349658.05677.d7. PMID 19564592.
• Pintaudi M, Baglietto MG, Gaggero R; et al. (2008). "Clinical and electroencephalographic features in patients with CDKL5 mutations: two new Italian cases and review of the literature.". Epilepsy Behav 12 (2): 326–31. doi:10.1016/j.yebeh.2007.10.010. PMID 18063413.
• Erez A, Patel AJ, Wang X; et al. (2009). "Alu-specific microhomology-mediated deletions in CDKL5 in females with early-onset seizure disorder.". Neurogenetics 10 (4): 363–9. doi:10.1007/s10048-009-0195-z. PMID 19471977.
• Psoni S, Willems PJ, Kanavakis E; et al. (2010). "A novel p.Arg970X mutation in the last exon of the CDKL5 gene resulting in late-onset seizure disorder.". Eur. J. Paediatr. Neurol. 14 (2): 188–91. doi:10.1016/j.ejpn.2009.03.006. PMID 19428276.
• Wu C, Ma MH, Brown KR; et al. (2007). "Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening.". Proteomics 7 (11): 1775–85. doi:10.1002/pmic.200601006. PMID 17474147.

External links

• CDKL5 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
• International Foundation for CDKL5 Research - based in the US
• CDKL5 UK - for UK families
• Supporting-CDKL5 - CDKL5 information and family support site
• Stichting-CDKL5 Netherlands - Dutch CDKL5 Foundation