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	[1]	[2]

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.

Mutations

CDKL5 is sometimes associated with Rett syndrome (though much less frequently than MECP2). 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.

Mutations in the CDKL5 gene also cause a disorder called X-linked infantile spasm syndrome (ISSX) or West syndrome. 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.

Location

CDKL5 in X-chromosome

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 18,443,724 to base pair 18,671,748 on the X chromosome.

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

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

See also

• Cyclin-dependent kinase
• Rett syndrome
• West syndrome

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