9epu

Structural highlights

Disease

CDKL5_HUMAN Note=Chromosomal aberrations involving CDKL5 are found in patients manifesting early-onset seizures and spams and psychomotor impairment. Translocation t(X;6)(p22.3;q14); translocation t(X;7)(p22.3;p15). Epileptic encephalopathy, early infantile, 2 (EIEE2) [MIM:300672: A severe form of epilepsy characterized by seizures or spasms beginning in infancy. Patients with epileptic encephalopathy early infantile type 2 manifest features resembling Rett syndrome such as microcephaly, lack of speech development, stereotypic hand movements. Note=The disease is caused by mutations affecting the gene represented in this entry.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13]}

Function

CDKL5_HUMAN Mediates phosphorylation of MECP2.^{[14] [15]}

References

1. ↑ 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. PMID:15917271 doi:10.1093/hmg/ddi198
2. ↑ 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. PMID:16935860 doi:10.1074/jbc.M606325200
3. ↑ Kalscheuer VM, Tao J, Donnelly A, Hollway G, Schwinger E, Kubart S, Menzel C, Hoeltzenbein M, Tommerup N, Eyre H, Harbord M, Haan E, Sutherland GR, Ropers HH, Gecz J. Disruption of the serine/threonine kinase 9 gene causes severe X-linked infantile spasms and mental retardation. Am J Hum Genet. 2003 Jun;72(6):1401-11. Epub 2003 May 7. PMID:12736870 doi:S0002-9297(07)60440-6
4. ↑ 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, Gecz 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. PMID:15492925 doi:S0002-9297(07)60075-5
5. ↑ Tao J, Van Esch H, Hagedorn-Greiwe M, Hoffmann K, Moser B, Raynaud M, Sperner J, Fryns JP, Schwinger E, Gecz J, Ropers HH, Kalscheuer VM. Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5/STK9) gene are associated with severe neurodevelopmental retardation. Am J Hum Genet. 2004 Dec;75(6):1149-54. PMID:15499549 doi:10.1086/426460
6. ↑ 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. PMID:15689447 doi:10.1136/jmg.2004.026237
7. ↑ Evans JC, Archer HL, Colley JP, Ravn K, Nielsen JB, Kerr A, Williams E, Christodoulou J, Gecz 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. PMID:16015284 doi:5201451
8. ↑ 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. PMID:16611748 doi:10.1136/jmg.2006.041467
9. ↑ Bahi-Buisson N, Nectoux J, Rosas-Vargas H, Milh M, Boddaert N, Girard B, Cances C, Ville D, Afenjar A, Rio M, Heron D, N'guyen Morel MA, Arzimanoglou A, Philippe C, Jonveaux P, Chelly J, Bienvenu T. Key clinical features to identify girls with CDKL5 mutations. Brain. 2008 Oct;131(Pt 10):2647-61. Epub 2008 Sep 12. PMID:18790821 doi:awn197
10. ↑ Rosas-Vargas H, Bahi-Buisson N, Philippe C, Nectoux J, Girard B, N'Guyen Morel MA, Gitiaux C, Lazaro L, Odent S, Jonveaux P, Chelly J, Bienvenu T. Impairment of CDKL5 nuclear localisation as a cause for severe infantile encephalopathy. J Med Genet. 2008 Mar;45(3):172-8. Epub 2007 Nov 9. PMID:17993579 doi:jmg.2007.053504
11. ↑ Elia M, Falco M, Ferri R, Spalletta A, Bottitta M, Calabrese G, Carotenuto M, Musumeci SA, Lo Giudice M, Fichera M. CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy. Neurology. 2008 Sep 23;71(13):997-9. PMID:18809835 doi:71/13/997
12. ↑ Sprovieri T, Conforti FL, Fiumara A, Mazzei R, Ungaro C, Citrigno L, Muglia M, Arena A, Quattrone A. A novel mutation in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene associated with a severe Rett phenotype. Am J Med Genet A. 2009 Feb 15;149A(4):722-5. PMID:19253388 doi:10.1002/ajmg.a.32711
13. ↑ Russo S, Marchi M, Cogliati F, Bonati MT, Pintaudi M, Veneselli E, Saletti V, Balestrini M, Ben-Zeev B, Larizza L. Novel mutations in the CDKL5 gene, predicted effects and associated phenotypes. Neurogenetics. 2009 Jul;10(3):241-50. Epub 2009 Feb 25. PMID:19241098 doi:10.1007/s10048-009-0177-1
14. ↑ 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. PMID:15917271 doi:10.1093/hmg/ddi198
15. ↑ 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. PMID:16935860 doi:10.1074/jbc.M606325200