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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CDKN3
cyclin dependent kinase inhibitor 3
Chromosome 14 · 14q22.2
NCBI Gene: 1033Ensembl: ENSG00000100526.21HGNC: HGNC:1791UniProt: G3V2J7
72PubMed Papers
21Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
regulation of cell cycleprotein serine/threonine phosphatase activityprotein tyrosine phosphatase activitycytosolMyasthenia gravishepatocellular carcinomaAbnormality of the skeletal systemInguinal hernia
✦AI Summary

CDKN3 (cyclin dependent kinase inhibitor 3) is a dual-specificity phosphatase that plays a complex role in cell cycle regulation. The protein exhibits both protein serine/threonine and tyrosine phosphatase activity, dephosphorylating CDK2 at Thr-160 in a cyclin-dependent manner 123. CDKN3 expression fluctuates during the cell cycle, peaking in mitosis, which explains its frequent overexpression in rapidly growing tumors 4. Contrary to its name suggesting an inhibitory function, CDKN3 demonstrates oncogenic properties across multiple cancer types. It is significantly upregulated in most human cancers and correlates with poor overall survival 56. In hepatocellular carcinoma, gastric cancer, cervical cancer, ovarian cancer, and pancreatic cancer, CDKN3 overexpression promotes cell proliferation, invasion, and tumor growth while inhibiting apoptosis 7891011. The protein's oncogenic effects appear mediated through regulation of cell cycle checkpoints, mitotic spindle checkpoint, and chromosome 14 pathways, with associations to P53 and PI3K-AKT signaling 6. CDKN3 also correlates with immune cell infiltration in tumor tissues, suggesting additional roles in tumor microenvironment regulation 5.

Sources cited
1
CDKN3 dephosphorylates CDK2 at Thr-160 in a cyclin-dependent manner
PMID: 7569954
2
CDKN3 has dual specificity phosphatase activity toward phosphotyrosine substrates
PMID: 8127873
3
CDKN3 has dual specificity phosphatase activity toward phosphoserine substrates
PMID: 8242750
4
CDKN3 expression fluctuates during cell cycle, peaking in mitosis, explaining overexpression in rapidly growing tumors
PMID: 28504190
5
CDKN3 is highly expressed in most tumors and has extensive tumor-promoting effects related to immune infiltration
PMID: 38380029
6
CDKN3 is significantly upregulated in most tumors, correlates with overall survival, and is associated with P53, PI3K-AKT, cell cycle checkpoints, and chromosome maintenance pathways
PMID: 38720365
7
CDKN3 identified as hub biomarker in hepatocellular carcinoma
PMID: 40169794
8
CDKN3 significantly upregulated in gastric carcinoma compared to control group
PMID: 35446856
9
CDKN3 upregulated and associated with low survival in cervical cancer patients
PMID: 25152075
10
CDKN3 silence inhibited ovarian cancer cell proliferation, decreased invasion and promoted apoptosis
PMID: 26191143
11
GID2 positively regulated CDKN3 expression and promoted pancreatic cancer progression
PMID: 36828188
Disease Associationsⓘ21
Myasthenia gravisOpen Targets
0.41Moderate
hepatocellular carcinomaOpen Targets
0.33Weak
Abnormality of the skeletal systemOpen Targets
0.32Weak
Inguinal herniaOpen Targets
0.28Weak
neurodegenerative diseaseOpen Targets
0.22Weak
myopiaOpen Targets
0.20Weak
Progressive visual lossOpen Targets
0.20Weak
refractive errorOpen Targets
0.19Weak
neoplasmOpen Targets
0.12Weak
cancerOpen Targets
0.10Weak
lung adenocarcinomaOpen Targets
0.10Suggestive
gastric cancerOpen Targets
0.10Suggestive
malignant pleural mesotheliomaOpen Targets
0.08Suggestive
Nijmegen breakage syndromeOpen Targets
0.08Suggestive
ovarian cancerOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
neuroblastomaOpen Targets
0.08Suggestive
pachyonychia congenitaOpen Targets
0.08Suggestive
squamous cell carcinomaOpen Targets
0.08Suggestive
thyroid cancerOpen Targets
0.08Suggestive
Hepatocellular carcinomaUniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TPX2Protein interaction100%CCNA1Protein interaction100%TP53Protein interaction100%PLK1Protein interaction100%CDC20Protein interaction100%CCNL2Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
35%
Heart
7%
Lung
2%
Ovary
2%
Liver
2%
Gene Interaction Network
Click a node to explore
CDKN3TPX2CCNA1TP53PLK1CDC20CCNL2
PROTEIN STRUCTURE
Preparing viewer…
PDB1FPZ · 2.00 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.12LoF Tolerant
pLIⓘ
0.39Tolerant
Observed/Expected LoF0.36 [0.14–1.12]
RankingsWhere CDKN3 stands among ~20K protein-coding genes
  • #6,534of 20,598
    Most Researched72
  • #11,587of 17,882
    Most Constrained (LOEUF)1.12
Genes detectedCDKN3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The role of Cyclin Dependent Kinase Inhibitor 3 (
PMID: 38380029
Heliyon · 2024
1.00
2
Integrating single-cell RNA sequencing, WGCNA, and machine learning to identify key biomarkers in hepatocellular carcinoma.
PMID: 40169794
Sci Rep · 2025
0.90
3
Targeting CDKN3 in cervical cancer.
PMID: 25152075
Expert Opin Ther Targets · 2014
0.80
4
Evaluation of gene expression of PLEKHS1, AADAC, and CDKN3 as novel genomic markers in gastric carcinoma.
PMID: 35446856
PLoS One · 2022
0.70
5
Expression and alternative splicing of the cyclin-dependent kinase inhibitor-3 gene in human cancer.
PMID: 28504190
Int J Biochem Cell Biol · 2017
0.60