CDKL5

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Cyclin-dependent kinase-like 5
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CDKL5 ; EIEE2; ISSX; STK9
External IDs OMIM300203 MGI1278336 HomoloGene55719 ChEMBL: 1163112 GeneCards: CDKL5 Gene
EC number 2.7.11.22
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:
18.44 – 18.67 Mb
Chr X:
160.78 – 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.[1]

Mutations[edit]

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[edit]

CDKL5 in X-chromosome

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]

See also[edit]

References[edit]

  1. ^ a b c d 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[edit]

External links[edit]