CDKL5
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4BGQ
Identifiers
Aliases	CDKL5, EIEE2, ISSX, STK9, CFAP247, cyclin dependent kinase like 5, DEE2
External IDs	OMIM: 300203 MGI: 1278336 HomoloGene: 55719 GeneCards: CDKL5
Gene location (Human) Chr. X chromosome (human)[1] Band Xp22.13 Start 18,425,583 bp[1] End 18,653,629 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X F4|X 73.95 cM Start 159,554,919 bp[2] End 159,777,700 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in frontal pole Brodmann area 23 middle temporal gyrus endothelial cell palpebral conjunctiva superior frontal gyrus entorhinal cortex visceral pleura postcentral gyrus amniotic fluid Top expressed in medial dorsal nucleus medial geniculate nucleus primary motor cortex lateral geniculate nucleus cingulate gyrus piriform cortex Region I of hippocampus proper prefrontal cortex olfactory tubercle temporal lobe More reference expression data BioGPS n/a
Gene ontology Molecular function transferase activity protein kinase activity nucleotide binding kinase activity protein serine/threonine kinase activity ATP binding cyclin-dependent protein serine/threonine kinase activity Cellular component dendritic growth cone nucleoplasm ruffle membrane nucleus cytosol dendrite cytoplasm synapse perinuclear region of cytoplasm centrosome ciliary basal body ciliary tip cytoplasm microtubule organizing center cytoskeleton cell projection glutamatergic synapse postsynaptic density, intracellular component Biological process phosphorylation neuron migration protein phosphorylation positive regulation of GTPase activity positive regulation of dendrite morphogenesis protein autophosphorylation positive regulation of axon extension regulation of dendrite development positive regulation of dendritic spine development regulation of cilium assembly regulation of cell cycle regulation of postsynapse organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6792 382253 Ensembl ENSG00000008086 ENSMUSG00000031292 UniProt O76039 Q3UTQ8 RefSeq (mRNA) NM_001037343 NM_003159 NM_001323289 NM_001024624 RefSeq (protein) NP_001032420 NP_001310218 NP_003150 NP_001019795 Location (UCSC) Chr X: 18.43 – 18.65 Mb Chr X: 159.55 – 159.78 Mb PubMed search [3] [4]
Wikidata
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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. Mutations in the gene can cause deficiencies in the protein. The gene regulates neuronal morphology through cytoplasmic signaling and controlling gene expression.^[5] 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 are currently working to determine which proteins are targeted by the CDKL5 protein.^[6]

The CDKL5 protein acts as a kinase, which is an enzyme that modulates the activity of other proteins by adding a phosphate group to specific positions. The CDKL5 protein regulates neuronal morphology through cytoplasmic signaling and by controlling gene expression, playing a crucial role in the development and maintenance of the nervous system.

Studies have shown that the CDKL5 protein interacts with various signaling pathways and plays a role in controlling neurotransmitter release, synaptic plasticity, and cell survival. The CDKL5 protein has also been shown to regulate the activity of genes involved in neuronal development and the formation of synaptic connections.

Researchers are actively working to better understand the role of the CDKL5 protein in brain development and the underlying mechanisms of CDKL5 disorders. Further studies are needed to determine which proteins are targeted by the CDKL5 protein, as well as to develop effective treatments for individuals affected by CDKL5 disorders.

Mutations

Mutations in the CDKL5 gene cause CDKL5 deficiency disorder.^[7] CDKL5 deficiency disorder had, earlier, been thought of as a variant of Rett syndrome, due to some similarities in the clinical presentation.^[8] CDKL5 deficiency syndrome is now known to be an independent clinical entity caused by mutations in a distinct X-linked gene, and is considered separate from Rett Syndrome, rather than a variant of it.^[9] While CDKL5 is primarily found in girls, it has been seen in boys as well.^[10] 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 alter a single 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, nonfunctioning version of the protein. At least 50 disease-causing mutations in this gene have been discovered.^[11]

Further confirmation that CDKL5 is an independent disorder with its own characteristics is provided by a 2016 study which concluded that the clinical presentations of the two disorders were not identical.^[12] At one time, mutations in the CDKL5 gene were thought to cause a disorder called X-linked infantile spasm syndrome (ISSX),^[13][14] or West syndrome.^[15][16] Studies have established CDKL5 disorder as a distinct clinical entity.

Animal studies

GSK3β inhibitors in CDKL5 knockout (CDKL5 -/Y) mice permit normal hippocampal development and learning.^[17]

IGF-1 treatment in CDKL5 knockout mice restores synaptic function.^{[further explanation needed][18]}

Therapeutics

Anticonvulsants were the mainstay of treatment for most affected people. These have limited efficacy, pointing to a strong need to develop new treatment strategies for patients.^[19] Some treatments might show efficacy in a relevant proportion of patients, such as valproic acid, vigabatrin, clobazam or sodium channel blockers, as well as a ketogenic diet^[20][21]

A CDKL5 protein replacement therapy is in development.^[22]

Location

The CDKL5 gene is located on the short (p) arm of the X chromosome at position 22.^[23] More precisely, the CDKL5 gene is located from base pair 18,443,724 to base pair 18,671,748 on the X chromosome.^[6]

ICD-10

G40.42