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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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MKNK2
MAPK interacting serine/threonine kinase 2
Chromosome 19 · 19p13.3
NCBI Gene: 2872Ensembl: ENSG00000099875.17HGNC: HGNC:7111UniProt: B3KS07
53PubMed Papers
20Diseases
1Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
CLINICAL
Clinical Trials
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytosolnuclear bodyATP bindingprotein serine/threonine kinase activityneurodegenerative diseaseAlzheimer diseaseParkinson diseaselysosomal storage disease
✦AI Summary

MKNK2 (MAPK interacting serine/threonine kinase 2) is a serine/threonine protein kinase that regulates translation initiation through phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) 1. The gene produces two splice variants, MKNK2a and MKNK2b, which differ in their kinase activity levels and biological functions 2. MKNK2 functions as a downstream target of MAPK signaling pathways, particularly ERK and p38 1. In cancer biology, MKNK2 demonstrates context-dependent roles. In gastric cancer, decreased MKNK2 expression is associated with poor prognosis 3. Conversely, in colorectal cancer liver metastases, MKNK2 upregulation promotes tumor progression following insufficient radiofrequency ablation through the miR-1180-3p/MKNK2/CREB3 signaling axis 4. The MKNK2b isoform specifically acts as an oncogenic variant in colon cancer, where its expression is regulated by the splicing factor RBM25 and correlates with tumor growth 5. MKNK2 is also expressed in human dorsal root and trigeminal ganglia, suggesting potential roles in nociception 1. Additionally, MKNK2 participates in metabolic regulation, as its downregulation by rubusoside helps alleviate lipid metabolism disorders 6.

Sources cited
1
MKNK2 is a serine/threonine kinase that phosphorylates eIF4E and functions downstream of MAPK signaling
PMID: 36764601
2
MKNK2 has two splice variants (MKNK2a and MKNK2b) with different kinase activities
PMID: 11013076
3
Decreased MKNK2 expression is associated with poor prognosis in gastric cancer
PMID: 38404710
4
MKNK2 upregulation promotes colorectal cancer liver metastasis progression through miR-1180-3p/MKNK2/CREB3 axis
PMID: 40784570
5
MKNK2b isoform acts as oncogenic variant in colon cancer and is regulated by RBM25
PMID: 39110401
6
MKNK2 downregulation by rubusoside alleviates lipid metabolism disorders
PMID: 39508235
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.54Moderate
Alzheimer diseaseOpen Targets
0.27Weak
Parkinson diseaseOpen Targets
0.27Weak
lysosomal storage diseaseOpen Targets
0.27Weak
multiple sclerosisOpen Targets
0.27Weak
mathematical abilityOpen Targets
0.26Weak
carpal tunnel syndromeOpen Targets
0.26Weak
knee fractureOpen Targets
0.16Weak
non-small cell lung carcinomaOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
colorectal cancerOpen Targets
0.08Suggestive
triple-negative breast cancerOpen Targets
0.07Suggestive
lymphomaOpen Targets
0.07Suggestive
cancerOpen Targets
0.06Suggestive
glioblastomaOpen Targets
0.05Suggestive
acute myeloid leukemiaOpen Targets
0.04Suggestive
posterior cortical atrophyOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets1
TOMIVOSERTIBPhase II
MAP kinase-interacting serine/threonine-protein kinase 1/2 inhibitor
colorectal cancer
Related Genes
MAPK14Protein interaction100%MAPK3Protein interaction99%MAPK1Protein interaction98%EIF4E1BProtein interaction91%EIF4E2Protein interaction91%EIF4G1Protein interaction86%
Tissue Expression6 tissues
Lung
100%
Liver
51%
Bone Marrow
31%
Ovary
27%
Heart
24%
Brain
11%
Gene Interaction Network
Click a node to explore
MKNK2MAPK14MAPK3MAPK1EIF4E1BEIF4E2EIF4G1
PROTEIN STRUCTURE
Preparing viewer…
PDB2AC3 · 2.10 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.46LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.18 [0.96–1.46]
RankingsWhere MKNK2 stands among ~20K protein-coding genes
  • #8,455of 20,598
    Most Researched53
  • #14,948of 17,882
    Most Constrained (LOEUF)1.46
Genes detectedMKNK2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Human umbilical cord-derived mesenchymal stem cells not only ameliorate blood glucose but also protect vascular endothelium from diabetic damage through a paracrine mechanism mediated by MAPK/ERK signaling.
PMID: 35715841
Stem Cell Res Ther · 2022
1.00
2
Comprehensive integration of single-cell RNA and transcriptome RNA sequencing to establish a pyroptosis-related signature for improving prognostic prediction of gastric cancer.
PMID: 38404710
Comput Struct Biotechnol J · 2024
0.90
3
Identification of the human Mnk2 gene (MKNK2) through protein interaction with estrogen receptor beta.
PMID: 11013076
Genomics · 2000
0.80
4
The role and mechanisms of the microRNA-1180-3p/MKNK2/CREB3 signaling axis in tumor progression following insufficient radiofrequency ablation of colorectal cancer liver metastasis.
PMID: 40784570
Biochem Pharmacol · 2025
0.70
5
MNK1 and MNK2 Expression in the Human Dorsal Root and Trigeminal Ganglion.
PMID: 36764601
Neuroscience · 2023
0.60