CDKN3: Cyclin Dependent Kinase Inhibitor 3
A dual-function phosphatase regulating cell cycle progression and tumor suppression
Gene Information Card
| Symbol | CDKN3 |
|---|---|
| Full Name | Cyclin Dependent Kinase Inhibitor 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q22.1 |
| NCBI Gene ID | 1033 ncbi.nlm.nih.gov/gene/1033 |
| Ensembl ID | ENSG00000100526 |
| UniProt ID | Q16667 |
| OMIM ID | 600064 |
| HGNC ID | 1791 |
| Aliases | KAP, CDI1, CDKN3, cyclin-dependent kinase interactor 1 |
Description
CDKN3 (Cyclin Dependent Kinase Inhibitor 3) encodes a dual-specificity phosphatase that dephosphorylates cyclin-dependent kinases (CDKs), particularly CDK2, thereby regulating cell cycle progression. It also interacts with cyclins and plays a role in G1/S transition. The gene is frequently altered in various cancers, with both tumor-suppressive and oncogenic roles reported depending on context.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | CDKN3 overexpression promotes cell proliferation and invasion; loss of function may also contribute to genomic instability | PMID: 25642768; COSMIC |
| Breast cancer | CDKN3 mutations and altered expression linked to poor prognosis; phosphatase activity affects CDK2 regulation | PMID: 23431141; ClinVar |
| Prostate cancer | CDKN3 downregulation associated with aggressive disease; epigenetic silencing observed | PMID: 20628033; COSMIC |
| Lung cancer | CDKN3 copy number alterations and expression changes correlate with tumor progression | PMID: 25231345; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | Medium |
| Lymph node | 8.7 | Medium |
| Bone marrow | 6.5 | Low |
| Brain | 2.1 | Low |
| Liver | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line; high expression |
| MCF7 | 9.8 | Breast cancer cell line; moderate expression |
| A549 | 7.4 | Lung cancer cell line; moderate expression |
| HepG2 | 11.1 | Hepatocellular carcinoma cell line; high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.236C>T (p.Pro79Leu) | Missense | <1% | Reduced phosphatase activity; potential loss of function |
| c.412G>A (p.Glu138Lys) | Missense | <1% | Altered substrate binding; reported in COSMIC |
| c.544_545insA | Frameshift | <0.5% | Truncated protein; loss of function |
| c.1A>G (p.Met1Val) | Start loss | <0.1% | No protein expression; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift mutations that reduce or abolish phosphatase activity, impairing CDK dephosphorylation and cell cycle control.
Gain of Function (GOF)
Not well established; some overexpression studies suggest oncogenic potential but no clear gain-of-function mutations reported.
Dominant Negative (DN)
Not documented for CDKN3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cell Cycle (KEGG hsa04110)
• p53 signaling pathway (KEGG hsa04115)
• G1 to S cell cycle control (Reactome R-HSA-69278)
Protein Summary
CDKN3 is a 212-amino acid dual-specificity phosphatase localized to the nucleus. It dephosphorylates CDK2 at Thr160, inhibiting CDK2-cyclin A/E activity and blocking G1/S progression. The protein contains a conserved PTP (protein tyrosine phosphatase) domain. CDKN3 also interacts with cyclin A and PCNA, linking it to DNA replication and repair. Its expression is tightly regulated during the cell cycle, peaking in G2/M. Altered expression or mutation contributes to oncogenesis in multiple tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CDKN3 Knockout HEK293 Cell Line | EDJ-KQ3332 | Human | 1033 | Details Get a Quote |
| CDKN3 Knockout A-549 Cell Line | EDJ-KQ24959 | Human | 1033 | Details Get a Quote |
| CDKN3 Knockout HCT 116 Cell Line | EDJ-KQ24960 | Human | 1033 | Details Get a Quote |
| CDKN3 Knockout HeLa Cell Line | EDJ-KQ24961 | Human | 1033 | Details Get a Quote |
