CDKL1

Cilia effects upon perturbation of CDKL1

Loss-of-function effect:

Longer cilia

Overexpression effect:

Shorter cilia

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: No effect 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 locomotor activity, decreased heart weight, increased anxiety-related response

Human ciliopathy phenotype:

Thoracic aortic aneurysm and dissection (TAAD): 6 patients from 3 families with heterozygous CDKL1 missense variants [p.(Cys143Arg), p.(Ser206Leu), p.(Thr135Met)]. Patient fibroblasts show defective cilia formation and length; CDKL1 expressed in vascular smooth muscle cells in normal and diseased human aortic wall tissue (Nauth et al. 2025, PMID 41056017).

Ciliopathy associations

• Thoracic Aortic Aneurysm and Dissection

References: PMID:41056017, PMID:29420175

Subcellular localization

cilia, nucleus, transition zone

References: PMID:41056017, PMID:29420175

Functional category

• Ciliary assembly/disassembly
• Transition zone

Function

Serine/threonine protein kinase of the CDKL family controlling primary cilium length and formation. C. elegans CDKL-1 and human CDKL1/CDKL5 show dosage-sensitive control of cilium length - too little = long cilia, too much = short or defective ciliogenesis (PMID: 29420175). Heterozygous CDKL1 variants cause thoracic aortic aneurysm and dissection (TAAD) through defects in primary cilia of vascular smooth muscle cells; zebrafish cdkl1 KO produces intersomitic vessel malformations and aortic dilation rescued by wild-type but not variant CDKL1 RNA (PMID: 41056017).