CDKL5 Gene

HGNC Family	Cyclin-dependent kinases (CDK)
Name	cyclin-dependent kinase-like 5
Description	This gene is a member of Ser/Thr protein kinase family and encodes a phosphorylated protein with protein kinase activity. Mutations in this gene have been associated with X-linked infantile spasm syndrome (ISSX), also known as X-linked West syndrome, and Rett syndrome (RTT). Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "t", "text": "<head>\n <meta charset=\"utf-8\">\n <title>CDKL5 Functional Summary</title>\n </head>\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n The X‐linked cyclin‐dependent kinase–like 5 (CDKL5) gene encodes a serine/threonine kinase that plays a pivotal role in brain development and function through both nuclear and cytoplasmic mechanisms."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n CDKL5 is widely expressed in neurons where it modulates essential processes—including neural precursor proliferation, neuronal migration, axonal outgrowth, dendritic morphogenesis, and synapse development—as well as activity‐dependent gene expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the nucleus, CDKL5 can phosphorylate key substrates such as methyl-CpG-binding protein 2 (MeCP2) and histone deacetylase 4 (HDAC4), thereby influencing transcriptional regulation and chromatin dynamics. In the cytoplasm, CDKL5 localizes at excitatory synapses where it phosphorylates proteins like NGL-1 to stabilize its association with postsynaptic density protein 95 (PSD95), contributing to proper dendritic spine structure and synaptic signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Functional studies in patients and mouse models demonstrate that loss-of-function mutations in CDKL5 cause early infantile epileptic encephalopathy and atypical Rett syndrome features. Affected individuals typically present with early-onset, intractable seizures, severe developmental delay, and hypotonia. Moreover, CDKL5 deficiency disrupts synaptic homeostasis by altering dendritic spine stabilization and postsynaptic receptor composition—for instance, by mislocalizing GluN2B-containing NMDA receptors—and perturbs downstream signal transduction pathways such as the AKT-mTOR cascade, ultimately leading to autistic-like behaviors, motor deficits, and cognitive impairments."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, CDKL5 functions as a multifunctional regulator that integrates nuclear and synaptic signaling. Through its kinase activity and interactions with a range of substrates, CDKL5 orchestrates neuronal maturation, synaptic organization, and activity-dependent gene expression. Dysfunction of CDKL5 therefore underlies a spectrum of severe neurodevelopmental disorders, establishing it as a critical component in the maintenance of normal brain structure and function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Linda S Weaving, John Christodoulou, Sarah L Williamson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations of CDKL5 cause a severe neurodevelopmental disorder with infantile spasms and mental retardation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/426462"}], "href": "https://doi.org/10.1086/426462"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15492925"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15492925"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Francesca Mari, Sara Azimonti, Ilaria Bertani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddi198"}], "href": "https://doi.org/10.1093/hmg/ddi198"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15917271"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15917271"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nadia Bahi-Buisson, Juliette Nectoux, Haydeé Rosas-Vargas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Key clinical features to identify girls with CDKL5 mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/brain/awn197"}], "href": "https://doi.org/10.1093/brain/awn197"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18790821"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18790821"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Laura Rusconi, Lisa Salvatoni, Laura Giudici, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CDKL5 expression is modulated during neuronal development and its subcellular distribution is tightly regulated by the C-terminal tail."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M804613200"}], "href": "https://doi.org/10.1074/jbc.M804613200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18701457"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18701457"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Heather E Olson, Scott T Demarest, Elia M Pestana-Knight, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cyclin-Dependent Kinase-Like 5 Deficiency Disorder: Clinical Review."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatr Neurol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.pediatrneurol.2019.02.015"}], "href": "https://doi.org/10.1016/j.pediatrneurol.2019.02.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30928302"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30928302"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Charlotte Kilstrup-Nielsen, Laura Rusconi, Paolo La Montanara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "What we know and would like to know about CDKL5 and its involvement in epileptic encephalopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neural Plast (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2012/728267"}], "href": "https://doi.org/10.1155/2012/728267"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22779007"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22779007"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sara Ricciardi, Federica Ungaro, Melanie Hambrock, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CDKL5 ensures excitatory synapse stability by reinforcing NGL-1-PSD95 interaction in the postsynaptic compartment and is impaired in patient iPSC-derived neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb2566"}], "href": "https://doi.org/10.1038/ncb2566"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22922712"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22922712"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Stefania Trazzi, Claudia Fuchs, Rocchina Viggiano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HDAC4: a key factor underlying brain developmental alterations in CDKL5 disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddw231"}], "href": "https://doi.org/10.1093/hmg/ddw231"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27466189"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27466189"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "H L Archer, J Evans, S Edwards, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2006.041467"}], "href": "https://doi.org/10.1136/jmg.2006.041467"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16611748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16611748"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Grazia Della Sala, Elena Putignano, Gabriele Chelini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dendritic Spine Instability in a Mouse Model of CDKL5 Disorder Is Rescued by Insulin-like Growth Factor 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Psychiatry (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopsych.2015.08.028"}], "href": "https://doi.org/10.1016/j.biopsych.2015.08.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26452614"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26452614"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Kosuke Okuda, Shizuka Kobayashi, Masahiro Fukaya, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CDKL5 controls postsynaptic localization of GluN2B-containing NMDA receptors in the hippocampus and regulates seizure susceptibility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Dis (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.nbd.2017.07.002"}], "href": "https://doi.org/10.1016/j.nbd.2017.07.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28688852"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28688852"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "I-Ting Judy Wang, Megan Allen, Darren Goffin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of CDKL5 disrupts kinome profile and event-related potentials leading to autistic-like phenotypes in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1216988110"}], "href": "https://doi.org/10.1073/pnas.1216988110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23236174"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23236174"}]}]}]}
Synonyms	ISSX, CFAP247, EIEE2, STK9
Proteins	CDKL5_HUMAN
NCBI Gene ID	6792
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CDKL5 has 5,988 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 126 datasets.

Click the + buttons to view associations for CDKL5 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CDKL5 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CDKL5 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CDKL5 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CDKL5 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CDKL5 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CDKL5 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CDKL5 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CDKL5 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CDKL5 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CDKL5 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CDKL5 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CDKL5 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with CDKL5 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CDKL5 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CDKL5 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CDKL5 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CDKL5 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with CDKL5 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with CDKL5 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CDKL5 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CDKL5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CDKL5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing CDKL5 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing CDKL5 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CDKL5 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CDKL5 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CDKL5 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CDKL5 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CDKL5 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CDKL5 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CDKL5 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving CDKL5 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving CDKL5 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CDKL5 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CDKL5 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CDKL5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CDKL5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CDKL5 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CDKL5 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CDKL5 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CDKL5 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.