CDKL5

cyclin dependent kinase like 5

Ensembl:
ENSG00000008086
UniProt:
O76039
OMIM:
300203
Synonyms:
CFAP247, EIEE2, STK9

Cilia effects upon perturbation of CDKL5

Loss-of-function effect:
Longer cilia
Overexpression effect:
Shorter cilia

Ciliogenesis screen results (4 screens)

  • Kim2016: Not Reported
  • Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-2.94) PMID:26167766
  • Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
  • Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Phenotypes

Mouse phenotype:
decreased respiratory quotient
Human ciliopathy phenotype:
CDKL5 Deficiency Disorder (CDD): epileptic encephalopathy affecting young children.

Ciliopathy associations

  • Intellectual Developmental Disorder with Epilepsy

Subcellular localization

basal body, cilia, nucleus

Functional category

  • Ciliary assembly/disassembly
  • Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
  • Neurogenesis & migration

Function

Regulate cilium length, has a potential role in ciliogenesis, facilitates dendritic spine and excitatory sy pse formation (29420175). C. elegans CDKL-1, most closely related to CDKL1.CDKL-1/CDKL5 show dosage-sensitive control of cilium length — too little = long cilia, too much = short or defective ciliogenesis. Overexpression of CDKL5 specifically reduces the percentage of ciliated cells, indicating an effect on ciliogenesis initiation, not just length (PMID: 29420175).

Model organism evidence

Mus musculus (1 reference)

Activation of the ciliary kinase CDKL5 is mediated by the cyclin-dependent kinase CDK20/LF2 to control flagellar length.

PMIDs: 41385589

Drosophila (1 reference)

Our phylogenetic studies revealed that ancestral CDKLs were present in all major eukaryotic clades and had ciliary/flagellar functions, which may have diversified throughout evolution.

PMIDs: 40371392

C. elegans (2 references)

The conserved CCRK, RCK, and CDKL5 kinases regulate cilia length in diverse organisms.

elegans CDKL-1, related to the human CDKL kinase family (CDKL1/CDKL2/CDKL3/CDKL4/CDKL5), specifically controls the length of the proximal segment, a ciliary subdomain conserved in evolution from Tetrahymena motile cilia to C.

PMIDs: 35996689, 33857430