CDKL3

Chr 5

cyclin dependent kinase like 3

Also known as: NKIAMRE

NCBI Gene: 51265ENSG00000006837UniProt: Q8IVW4

The protein encoded by this gene is a member of cyclin-dependent protein kinase (CDK) family. CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression. This gene was identified as a gene absent in leukemic patients with chromosome 5q deletion. This loss may be an important determinant of dysmyelopoiesis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

103
ClinVar variants
16
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CDKL3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 81 VUS of 103 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.15LOEUF
pLI 0.000
Z-score 0.97
OE 0.80 (0.56–1.15)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.39Z-score
OE missense 0.93 (0.84–1.04)
245 obs / 262.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.80 (0.56–1.15)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.84–1.04)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.85
0≤1.21.6
LoF obs/exp: 21 / 26.4Missense obs/exp: 245 / 262.7Syn Z: 1.07

ClinVar Variant Classifications

103 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic1
VUS81
Likely Benign4
Benign2
15
Pathogenic
1
Likely Pathogenic
81
VUS
4
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
1
0
1
VUS
0
77
4
0
81
Likely Benign
0
3
1
0
4
Benign
0
0
0
2
2
Total080212103

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CDKL3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
CDKL3 is a targetable regulator of cell cycle progression in cancers.
Zhang H et al.·J Clin Invest
2024
Clear cell renal carcinoma essentially requires CDKL3 for oncogenesis.
Ma L et al.·Proc Natl Acad Sci U S A
2025
CDKL3 Targets ATG5 to Exacerbate the Progression of Malignant Melanoma.
Chen Q et al.·Mol Carcinog
2025
Bone marrow mesenchymal stem cells-secreted exosomal microRNA-205-5p exerts inhibitory effect on the progression of liver cancer through regulating CDKL3.
Sun Q et al.·Pathol Res Pract
2021
Inactivation of the CDKL3 gene at 5q31.1 by a balanced t(X;5) translocation associated with nonspecific mild mental retardation.
Dubos A et al.·Am J Med Genet A
2008
CircTP53 promotes colorectal cancer by acting as a miR-876-3p sponge to increase cyclin-dependent kinase-like 3 expression.
Yan S et al.·Cell Signal
2021
MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone.
Li C et al.·PLoS Biol
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools