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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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CDKL2
cyclin dependent kinase like 2
Chromosome 4 Β· 4q21.1
NCBI Gene: 8999Ensembl: ENSG00000138769.11HGNC: HGNC:1782UniProt: A0A140VJG1
26PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
nucleoplasmprotein bindingnucleusprotein serine/threonine kinase activitytype 2 diabetes mellitusgastrointestinal diseasepolypovarian neoplasm
✦AI Summary

CDKL2 (cyclin-dependent kinase-like 2) is a serine-threonine kinase belonging to the CDKL family 1. Functionally, CDKL2 regulates ciliary architecture by controlling the length of the ciliary proximal segment through association with intraflagellar transport machinery and influencing kinesin motor distribution 2. At the cellular level, CDKL2 phosphorylates EB2 substrate and can partially compensate for CDKL5 function in the brain, suggesting functional overlap within the CDKL kinase family 3. Clinically, CDKL2 is implicated in both neurodevelopmental and malignant disorders. De novo CDKL2 variants act as dominant-negative alleles causing developmental delay, intellectual disability, childhood-onset epilepsy, dyspraxia, and speech deficits 1. In cancer, CDKL2 promotes epithelial-mesenchymal transition and breast cancer progression via ZEB1/E-cadherin signaling, with elevated expression associated with shorter disease-free survival 4. Conversely, CDKL2 shows tumor-suppressive roles in hepatocellular carcinoma and clear cell renal cell carcinoma, where hypermethylation-induced downregulation and low expression respectively correlate with poor prognosis 56. In gastric cancer, CDKL2 expression correlates with HER2 status and overall survival 7. These findings indicate CDKL2 has context-dependent roles as either an oncogene or tumor suppressor.

Sources cited
1
De novo CDKL2 variants cause neurodevelopmental symptoms including developmental delay, intellectual disability, epilepsy, dyspraxia, and speech deficits through dominant-negative mechanisms
PMID: 40088891
2
CDKL-1 (CDKL family member) regulates ciliary proximal segment length through interaction with intraflagellar transport machinery
PMID: 33857430
3
CDKL2 phosphorylates EB2 substrate and can compensate for CDKL5 function in the brain
PMID: 38326557
4
CDKL2 promotes epithelial-mesenchymal transition and breast cancer progression via ZEB1/E-cadherin signaling; elevated expression associates with shorter disease-free survival
PMID: 25333262
5
CDKL2 promoter hypermethylation is increased in hepatocellular carcinoma and associated with poor prognosis; functions as potential diagnostic biomarker
PMID: 30292871
6
CDKL2 expression is decreased in clear cell renal cell carcinoma and low expression predicts poor prognosis; correlates with immune infiltration
PMID: 35096961
7
CDKL2 protein expression and gene copy number correlate with HER2 status and overall survival in gastric cancer
PMID: 33178818
Disease Associationsβ“˜20
type 2 diabetes mellitusOpen Targets
0.40Moderate
gastrointestinal diseaseOpen Targets
0.28Weak
polypOpen Targets
0.26Weak
ovarian neoplasmOpen Targets
0.21Weak
Testicular Germ Cell TumorOpen Targets
0.14Weak
neurodegenerative diseaseOpen Targets
0.14Weak
gastric cancerOpen Targets
0.09Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.06Suggestive
autosomal recessive hypophosphatemic ricketsOpen Targets
0.04Suggestive
gliomaOpen Targets
0.04Suggestive
Alzheimer diseaseOpen Targets
0.04Suggestive
hypoparathyroidism, familial isolated, 2Open Targets
0.03Suggestive
Liddle syndrome 2Open Targets
0.03Suggestive
Liddle syndrome 3Open Targets
0.03Suggestive
hepatocellular carcinomaOpen Targets
0.03Suggestive
autosomal dominant hypophosphatemic ricketsOpen Targets
0.03Suggestive
glioblastoma multiformeOpen Targets
0.03Suggestive
Liddle syndrome 1Open Targets
0.03Suggestive
Pathogenic Variants1
NM_001330724.2(CDKL2):c.643A>T (p.Met215Leu)Likely pathogenic
CDKL2-related condition
β˜…β˜†β˜†β˜†2025β†’ Residue 215
View on ClinVar β†—
Related Genes
CDKL4Shared pathway50%MRFAP1L2Shared pathway50%CABLES2Shared pathway50%DMRTA1Shared pathway50%DMRTA2Shared pathway50%DMRTB1Shared pathway50%
Tissue Expression6 tissues
Brain
100%
Lung
31%
Ovary
25%
Heart
19%
Bone Marrow
2%
Liver
2%
Gene Interaction Network
Click a node to explore
CDKL2CDKL4MRFAP1L2CABLES2DMRTA1DMRTA2DMRTB1
PROTEIN STRUCTURE
Preparing viewer…
PDB4AAA Β· 1.53 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.22LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.90 [0.67–1.22]
RankingsWhere CDKL2 stands among ~20K protein-coding genes
  • #12,748of 20,598
    Most Researched26
  • #5,295of 5,498
    Most Pathogenic Variants1
  • #12,882of 17,882
    Most Constrained (LOEUF)1.22
Genes detectedCDKL2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
De novo variants in CDKL1 and CDKL2 are associated with neurodevelopmental symptoms.
PMID: 40088891
Am J Hum Genet Β· 2025
1.00
2
CDKL kinase regulates the length of the ciliary proximal segment.
PMID: 33857430
Curr Biol Β· 2021
0.90
3
Clinical significance of aberrant cyclin-dependent kinase-like 2 methylation in hepatocellular carcinoma.
PMID: 30292871
Gene Β· 2019
0.80
4
Cell type-specific expression, regulation and compensation of CDKL5 activity in mouse brain.
PMID: 38326557
Mol Psychiatry Β· 2024
0.70
5
CDKL2 Is Associated with HER2 Status and Overall Survival in Gastric Cancer: Comparative Analysis of CDKL2 Protein Expression and Gene Copy Number.
PMID: 33178818
Biomed Res Int Β· 2020
0.60