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

Gene ID: 6792, updated on 12-Aug-2018
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; Vega:OTTHUMG00000021214
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
See CDKL5 in Genome Data Viewer
Location:
Xp22.13
Exon count:
23
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) X NC_000023.11 (18425605..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 transfer RNA-Val (TAC) 1-2 Neighboring gene PPEF1 antisense RNA 1 Neighboring gene retinoschisin 1 Neighboring gene protein phosphatase with EF-hand domain 1

Go to nucleotide: Graphics FASTA GenBank

  • 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 Jun 15 11:32:44 2016

Related articles in PubMed

  1. CDKL Family Kinases Have Evolved Distinct Structural Features and Ciliary Function. Canning P, et al. Cell Rep, 2018 Jan 23. PMID 29420175, Free PMC Article
  2. Novel mutations in the CDKL5 gene in complex genotypes associated with West syndrome with variable phenotype: First description of somatic mosaic state. Jdila MB, et al. Clin Chim Acta, 2017 Oct. PMID 28780406
  3. Functional abilities in children and adults with the CDKL5 disorder. Fehr S, et al. Am J Med Genet A, 2016 Nov. PMID 27528505
  4. A novel CDKL5 mutation in a Japanese patient with atypical Rett syndrome. Christianto A, et al. Clin Chim Acta, 2016 Aug 1. PMID 27265524
  5. Turkish cases of early infantile epileptic encephalopathy: two novel mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene. Gökben S, et al. Turk J Pediatr, 2015 May-Jun. PMID 26701947

See all (86) citations in PubMed

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

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

  1. mutations in the CDKL5 gene in complex genotypes associated with West syndrome with variable phenotype
    Title: Novel mutations in the CDKL5 gene in complex genotypes associated with West syndrome with variable phenotype: First description of somatic mosaic state.
  2. The genetic etiology of Rett syndrome (RTT) without MECP2, CDKL5, and FOXG1 mutations is heterogeneous, overlaps with other NDDs, and complicated by a high mutation burden. Dysregulation of chromatin structure and abnormal excitatory synaptic signaling may form two common pathological bases of RTT.
    Title: Enrichment of mutations in chromatin regulators in people with Rett syndrome lacking mutations in MECP2.
  3. Although abilities were markedly impaired for the majority with the CDKL5 disorder, some females and a few males had better functional abilities. This variability may be related to underlying gene variants, with females with a late truncating variant having better levels of ability than those with no functional protein.
    Title: Functional abilities in children and adults with the CDKL5 disorder.
  4. We have characterised the predominant brain isoform of CDKL5, a 9.7 kb transcript comprised of 18 exons with a large 6.6 kb 3'-untranslated region (UTR), which we name hCDKL5_1. In addition we describe new exonic regions and a range of novel splice and UTR isoforms
    Title: Characterisation of CDKL5 Transcript Isoforms in Human and Mouse.
  5. In the asymptomatic mother, the mutated copy of the CDKL5 gene was inactivated in 90% of blood cells. We also identified a premature stop codon (p.Arg926*) in IQSEC2 in a patient with a Rett-like phenotype. Finally, exome sequencing enabled us to characterize a heterozygous de novo missense (p.Val408Ala) in KCNA2 in a girl with infantile-onset seizures variant of Rett syndrome (RTT)
    Title: Rett-like phenotypes: expanding the genetic heterogeneity to the KCNA2 gene and first familial case of CDKL5-related disease.
  6. The results suggested the mutant CDKL5 was responsible for the Rett syndrome disease.
    Title: A novel CDKL5 mutation in a Japanese patient with atypical Rett syndrome.
  7. Rett syndrome with early epilepsy and the congenital variant are mainly due to variations in the CDKL5 and FOXG1 genes, respectively
    Title: [Molecular basis of Rett syndrome: A current look].
  8. Mutations in exon 8 of cyclin-dependent kinase-like 5 gene were determined to be disease-causing in epileptic encephalopathy.
    Title: Turkish cases of early infantile epileptic encephalopathy: two novel mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene.
  9. study presents the genotype of 2 sisters, a CDKL5 mutation c. 283-3_290del, but different phenotype
    Title: Two Siblings With a CDKL5 Mutation: Genotype and Phenotype Evaluation.
  10. Data suggest that the increased dosage of cyclin dependent kinase like 5 protein(CDKL5) might have affected interactions of this kinase with its substrates, leading to perturbation of neurodevelopmental and neurobehavioral abnormalities.
    Title: Neurodevelopmental and neurobehavioral characteristics in males and females with CDKL5 duplications.
Submit: New GeneRIF Correction See all GeneRIFs (67)

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: C1839333 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

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Products Interactant Other Gene Complex Source Pubs Description

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
  
kinase activity IDA
Inferred from Direct Assay
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 
protein phosphorylation TAS
Traceable Author Statement
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 EXP
Inferred from Experiment
more info
 PubMed 
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 
cytosol IDA
Inferred from Direct Assay
more info
  
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 EXP
Inferred from Experiment
more info
 PubMed 
glutamatergic synapse IDA
Inferred from Direct Assay
more info
 PubMed 
glutamatergic synapse IMP
Inferred from Mutant Phenotype
more info
 PubMed 
nucleoplasm IDA
Inferred from Direct Assay
more info
  
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
  
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

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_001037343.1 → 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, OTTHUMP00000023002, ENST00000379989.6, OTTHUMT00000055945
    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_001323289.1 → 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, OTTHUMP00000278131, ENST00000623535.1, OTTHUMT00000479617
    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_003159.2 → 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, OTTHUMP00000023003, ENST00000379996.7, OTTHUMT00000055946
    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 Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000023.11 Reference GRCh38.p12 Primary Assembly

    Range
    18425605..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

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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