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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NEK3
NIMA related kinase 3
Chromosome 13 · 13q14.3
NCBI Gene: 4752Ensembl: ENSG00000136098.20HGNC: HGNC:7746UniProt: P51956
31PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingprotein phosphorylationmitotic cell cyclenucleusneurodegenerative diseasecutaneous melanomabone fractureocular hypotension
✦AI Summary

NEK3 (NIMA-related kinase 3) is a serine/threonine protein kinase that functions in cell cycle regulation and cytoskeletal dynamics. As a member of the NIMA family of kinases, NEK3 is expressed preferentially in mitotically active tissues including testis, ovary, and brain 1. NEK3 regulates intracellular membrane fusion through phosphorylation of SNAP29 at serine 105, directing its membrane association and affecting focal adhesion formation and Golgi structure 2. In prolactin signaling, NEK3 acts as a key mediator of breast cancer cell motility by phosphorylating Vav2 and paxillin, thereby activating the small GTPase Rac1 and promoting cytoskeletal reorganization 34. NEK3 overexpression correlates with poor prognosis in gastric cancer, promoting tumor malignancy through enhanced migration and proliferation 5. Recent evidence demonstrates NEK3's role as a suppressor of cuproptosis; NEK3 depletion enhances copper-dependent cell death and synergizes with immunomodulatory effects by promoting M1 macrophage polarization in cervical cancer 6. These findings establish NEK3 as an important oncogenic kinase and potential therapeutic target across multiple cancer types.

Sources cited
1
NEK3 is a NIMA-related protein kinase with preferential expression in testis, ovary, and brain tissues
PMID: 12063396
2
NEK3 phosphorylates SNAP29 at serine 105 to regulate membrane association and intracellular membrane fusion processes
PMID: 29454964
3
NEK3 interacts with Vav2 in prolactin signaling and phosphorylates it to activate Rac1 and promote breast cancer cell signaling
PMID: 15618286
4
NEK3 regulates prolactin-mediated cytoskeletal reorganization, paxillin phosphorylation, and breast cancer cell migration and invasion
PMID: 17297458
5
NEK3 is overexpressed in gastric cancer and correlates with poor prognosis and tumor malignancy
PMID: 29504992
6
NEK3 suppresses cuproptosis and its knockdown enhances sensitivity to copper-dependent cell death while promoting M1 macrophage polarization in cervical cancer
PMID: 41483620
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.32Weak
cutaneous melanomaOpen Targets
0.27Weak
bone fractureOpen Targets
0.27Weak
ocular hypotensionOpen Targets
0.18Weak
placental retentionOpen Targets
0.17Weak
trauma complicationOpen Targets
0.13Weak
pericarditisOpen Targets
0.13Weak
cataractOpen Targets
0.12Weak
Hereditary breast and ovarian cancer syndromeOpen Targets
0.12Weak
hereditary breast ovarian cancer syndromeOpen Targets
0.12Weak
gastric cancerOpen Targets
0.08Suggestive
esophageal adenocarcinomaOpen Targets
0.04Suggestive
Alzheimer diseaseOpen Targets
0.03Suggestive
cancerOpen Targets
0.03Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.02Suggestive
breast cancerOpen Targets
0.02Suggestive
lymph node metastatic carcinomaOpen Targets
0.02Suggestive
hyperinsulinemic hypoglycemia, familial, 4Open Targets
0.01Suggestive
cervical cancerOpen Targets
0.01Suggestive
Fanconi renotubular syndromeOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TPTEProtein interaction79%MYBL2Shared pathway50%GLYCTKShared pathway50%ZNRD2Shared pathway50%PPP4R1Shared pathway50%NEDD1Shared pathway33%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
62%
Heart
51%
Lung
50%
Liver
45%
Brain
32%
Gene Interaction Network
Click a node to explore
NEK3TPTEMYBL2GLYCTKZNRD2PPP4R1NEDD1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt P51956
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.94LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.69 [0.52–0.94]
RankingsWhere NEK3 stands among ~20K protein-coding genes
  • #11,754of 20,598
    Most Researched31
  • #8,676of 17,882
    Most Constrained (LOEUF)0.94
Genes detectedNEK3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Molecular cloning and characterization of the human NIMA-related protein kinase 3 gene (NEK3).
PMID: 12063396
Cytogenet Cell Genet · 2001
1.00
2
The NEK family of serine/threonine kinases as a biomarker for cancer.
PMID: 35037094
Clin Exp Med · 2023
0.90
3
Novel association of Vav2 and Nek3 modulates signaling through the human prolactin receptor.
PMID: 15618286
Mol Endocrinol · 2005
0.80
4
NIMA-related kinases: isolation and characterization of murine nek3 and nek4 cDNAs, and chromosomal localization of nek1, nek2 and nek3.
PMID: 10393247
Gene · 1999
0.70
5
Multi-omics profiling reveals that targeting NEK3 synergizes with cuproptosis to promote M1 macrophage polarization in cervical cancer.
PMID: 41483620
Int Immunopharmacol · 2026
0.60