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CDKL5 cyclin dependent kinase like 5 [ Homo sapiens (human) ]

Gene ID: 6792, updated on 18-Aug-2020

Summary

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Official Symbol
CDKL5provided by HGNC
Official Full Name
cyclin dependent kinase like 5provided by HGNC
Primary source
HGNC:HGNC:11411
See related
Ensembl:ENSG00000008086 MIM:300203
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
ISSX; STK9; EIEE2; CFAP247
Summary
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]
Expression
Broad expression in brain (RPKM 11.1), lung (RPKM 3.0) and 18 other tissues See more
Orthologs
mouse all

Genomic context

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See CDKL5 in Genome Data Viewer
Location:
Xp22.13
Exon count:
23
Annotation release Status Assembly Chr Location
109.20200815 current GRCh38.p13 (GCF_000001405.39) X NC_000023.11 (18425608..18653629)
105 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (18443725..18671749)

Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene BEN domain containing 2 Neighboring gene Scm polycomb group protein like 2 Neighboring gene thymosin beta 10 pseudogene 2 Neighboring gene gap junction protein alpha 6, pseudogene Neighboring gene tRNA-Val (anticodon TAC) 1-2 Neighboring gene PPEF1 antisense RNA 1 Neighboring gene retinoschisin 1 Neighboring gene protein phosphatase with EF-hand domain 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Gene replacement ameliorates deficits in mouse and human models of cyclin-dependent kinase-like 5 disorder. Gao Y, et al. Brain, 2020 Mar 1. PMID 32125365
  2. Artificial escape from XCI by DNA methylation editing of the CDKL5 gene. Halmai JANM, et al. Nucleic Acids Res, 2020 Mar 18. PMID 31925439, Free PMC Article
  3. Clinical evolution and epilepsy outcome in three patients with CDKL5-related developmental encephalopathy. Bernardo P, et al. Epileptic Disord, 2019 Jun 1. PMID 31225800
  4. Cyclin-Dependent Kinase-Like 5 Deficiency Disorder: Clinical Review. Olson HE, et al. Pediatr Neurol, 2019 Aug. PMID 30928302, Free PMC Article
  5. A framework for understanding quality of life domains in individuals with the CDKL5 deficiency disorder. Tangarorang J, et al. Am J Med Genet A, 2019 Feb. PMID 30561084

See all (104) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. study provides the first evidence that gene therapy mediated by Adenovirus vectors can be used for treating CDKL5 disorder.
    Title: Gene replacement ameliorates deficits in mouse and human models of cyclin-dependent kinase-like 5 disorder.
  2. Pathogenic variants include deletions, truncations, splice variants, and missense variants. Pathogenic missense variants occur exclusively within the kinase domain or affect splice sites. The CDKL5 protein is widely expressed in the brain, predominantly in neurons, with roles in cell proliferation, neuronal migration, axonal outgrowth, dendritic morphogenesis, and synapse development. Review.
    Title: Cyclin-Dependent Kinase-Like 5 Deficiency Disorder: Clinical Review.
  3. Targeting of CDKL5 promoter causes significant reactivation of the inactive allele affected by X chromosome inactivation; this change is associated with removal of methyl groups from CpG dinucleotides.
    Title: Artificial escape from XCI by DNA methylation editing of the CDKL5 gene.
  4. the evolution and molecular features of MeCP2, CDKL5, and FOXG1 and their binding partners, were analyzed.
    Title: In Silico Study of Rett Syndrome Treatment-Related Genes, <i>MECP2</i>, <i>CDKL5</i>, and <i>FOXG1</i>, by Evolutionary Classification and Disordered Region Assessment.
  5. we showed that selective cortical deletion of CDKL5 from excitatory cells is sufficient to produce abnormalities of visual cortical responses, demonstrating that the normal function of cortical circuits is dependent on CDKL5.
    Title: Site-specific abnormalities in the visual system of a mouse model of CDKL5 deficiency disorder.
  6. Twenty-five parents of individuals registered in the International CDKL5 Disorder Database participated in semi-structured telephone interviews to explore areas that supported or challenged their child's QOL
    Title: A framework for understanding quality of life domains in individuals with the CDKL5 deficiency disorder.
  7. that CDKL5 mutations likely play a direct role in psychomotor development, whereas epilepsy is one of the clinical features associated with this complex disorder
    Title: Clinical evolution and epilepsy outcome in three patients with CDKL5-related developmental encephalopathy.
  8. CDKL5 is a gene identified as causative genes in atypical forms of Rett syndrome.
    Title: Epilepsy and genetic in Rett syndrome: A review.
  9. These data reveal the first cellular substrates of CDKL5, which may represent important biomarkers in the diagnosis and treatment of CDKL5 disorder, and illuminate the functions of this poorly characterized kinase.
    Title: Phosphoproteomic screening identifies physiological substrates of the CDKL5 kinase.
  10. new consensus for evaluating CDKL5/STK9-dependent signalling mechanisms.
    Title: A new consensus for evaluating CDKL5/STK9-dependent signalling mechanisms.
Submit: New GeneRIF Correction See all GeneRIFs (81)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Angelman syndrome-like
MedGen: CN128785 GeneReviews: Not available
Compare labs
Early infantile epileptic encephalopathy 2
MedGen: C4750718 OMIM: 300672 GeneReviews: Not available
Compare labs

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated (2012-07-12)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated (2012-07-12)

ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IDA
Inferred from Direct Assay
more info
 PubMed 
Rac GTPase binding ISS
Inferred from Sequence or Structural Similarity
more info
  
cyclin-dependent protein serine/threonine kinase activity IEA
Inferred from Electronic Annotation
more info
  
kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
protein kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
protein serine/threonine kinase activity TAS
Traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
neuron migration ISS
Inferred from Sequence or Structural Similarity
more info
  
positive regulation of GTPase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
positive regulation of axon extension IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
positive regulation of axon extension ISS
Inferred from Sequence or Structural Similarity
more info
  
positive regulation of dendrite morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
  
positive regulation of dendritic spine development IEA
Inferred from Electronic Annotation
more info
  
protein autophosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
protein phosphorylation IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
regulation of cell cycle IEA
Inferred from Electronic Annotation
more info
  
regulation of cilium assembly IMP
Inferred from Mutant Phenotype
more info
 PubMed 
regulation of dendrite development IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
regulation of dendrite development ISS
Inferred from Sequence or Structural Similarity
more info
  
regulation of postsynapse organization IDA
Inferred from Direct Assay
more info
 PubMed 
regulation of postsynapse organization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
centrosome IDA
Inferred from Direct Assay
more info
 PubMed 
ciliary basal body IDA
Inferred from Direct Assay
more info
 PubMed 
ciliary tip IDA
Inferred from Direct Assay
more info
 PubMed 
dendrite cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
dendrite cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
  
dendritic growth cone ISS
Inferred from Sequence or Structural Similarity
more info
  
glutamatergic synapse IDA
Inferred from Direct Assay
more info
 PubMed 
glutamatergic synapse IMP
Inferred from Mutant Phenotype
more info
 PubMed 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
perinuclear region of cytoplasm IEA
Inferred from Electronic Annotation
more info
  
postsynaptic density, intracellular component IEA
Inferred from Electronic Annotation
more info
  
colocalizes_with ruffle membrane ISS
Inferred from Sequence or Structural Similarity
more info
  

General protein information

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Preferred Names
cyclin-dependent kinase-like 5
Names
cyclin dependent kinase 5 transcript
serine/threonine kinase 9
serine/threonine-protein kinase 9
NP_001032420.1
NP_001310218.1
NP_003150.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008475.1 RefSeqGene

    Range
    5001..233025
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001037343.2 → NP_001032420.1  cyclin-dependent kinase-like 5 isoform 1

    See identical proteins and their annotated locations for NP_001032420.1

    Status: REVIEWED

    Source sequence(s)
    AI286150, AL704691, AY217744, BC036091
    Consensus CDS
    CCDS14186.1
    UniProtKB/Swiss-Prot
    O76039
    Related
    ENSP00000369325.3, ENST00000379989.6
    Conserved Domains (2) summary
    smart00220
    Location:13 → 297
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd07848
    Location:11 → 297
    STKc_CDKL5; Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5

  2. NM_001323289.2 → NP_001310218.1  cyclin-dependent kinase-like 5 isoform 2

    Status: REVIEWED

    Source sequence(s)
    AL109798, AW452901, HQ171445, Z92542
    Consensus CDS
    CCDS83458.1
    UniProtKB/Swiss-Prot
    O76039
    Related
    ENSP00000485244.1, ENST00000623535.2
    Conserved Domains (1) summary
    cd07848
    Location:11 → 297
    STKc_CDKL5; Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5

  3. NM_003159.3 → NP_003150.1  cyclin-dependent kinase-like 5 isoform 1

    See identical proteins and their annotated locations for NP_003150.1

    Status: REVIEWED

    Source sequence(s)
    AI286150, AY217744, BC010966
    Consensus CDS
    CCDS14186.1
    UniProtKB/Swiss-Prot
    O76039
    Related
    ENSP00000369332.3, ENST00000379996.7
    Conserved Domains (2) summary
    smart00220
    Location:13 → 297
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd07848
    Location:11 → 297
    STKc_CDKL5; Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20200815

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000023.11 Reference GRCh38.p13 Primary Assembly

    Range
    18425608..18653629
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O76039.1 GenPept UniProtKB/Swiss-Prot:O76039

Gene LinkOut

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