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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TTK
TTK protein kinase
Chromosome 6 · 6q14.1
NCBI Gene: 7272Ensembl: ENSG00000112742.11HGNC: HGNC:12401UniProt: P33981
225PubMed Papers
20Diseases
2Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneKinase
RESEARCH IMPACT
Trending
CLINICAL
Early Pipeline
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytoplasmprotein serine/threonine kinase activitymembraneprotein bindingneurodegenerative diseaseAlzheimer diseaselysosomal storage diseaseParkinson disease
✦AI Summary

TTK (TTK protein kinase) is a serine/threonine kinase primarily known for its role in mitotic spindle assembly checkpoint signaling and kinetochore-spindle microtubule attachment repair 123. TTK phosphorylates multiple checkpoint regulators including MAD1L1, CDCA8/Borealin, SKA3, and KNL1 to coordinate proper chromosome 6 12. Beyond mitotic functions, recent evidence reveals TTK's dysregulation in multiple cancers. In bladder cancer, TTK promotes proliferation and inhibits apoptosis by enhancing mitophagy through ULK1 phosphorylation, preventing mitochondrial apoptosis 4. In esophageal squamous cell carcinoma, the ANXA2/TTK complex activates Akt/mTOR signaling to drive epithelial-mesenchymal transition and metastasis 5. TTK is also transcriptionally upregulated through histone lactylation in pancreatic cancer, establishing a positive feedback loop with glycolysis that promotes oncogenesis 6. In T-cell lymphoma, TTK phosphorylates p38α to suppress AMPK/mTOR-mediated autophagy, and TTK inhibition restores anti-tumor immunity 7. TTK inhibitors like OSU13 induce DNA damage, trigger STING-mediated innate immunity, and synergize with anti-PD-1 immunotherapy 8. These findings establish TTK as both a critical cell cycle regulator and an emerging multi-cancer therapeutic target.

Sources cited
1
TTK phosphorylates MAD1L1 and CDCA8/Borealin in mitotic spindle assembly checkpoint signaling
PMID: 18243099
2
TTK phosphorylates SKA3, KNL1, and KNTC1 to regulate kinetochore-microtubule attachment and checkpoint signaling
PMID: 28441529
3
TTK phosphorylates MAD1L1 to promote mitotic spindle assembly checkpoint
PMID: 29162720
4
TTK phosphorylates ULK1 at Ser477 and SRSF3 at Ser108 to promote mitophagy and inhibit mitochondrial apoptosis in bladder cancer
PMID: 40269198
5
ANXA2/TTK complex activates Akt/mTOR signaling pathway and drives EMT in esophageal squamous cell carcinoma
PMID: 38658569
6
TTK is transcriptionally activated by histone lactylation (H3K18la) and phosphorylates LDHA at Y239 to create a positive feedback loop with glycolysis in pancreatic cancer
PMID: 38711083
7
TTK phosphorylates p38α at Thr180/Tyr182 to suppress AMPK/mTOR pathway in T-cell lymphoma; TTK inhibition promotes anti-tumor immunity
PMID: 39836493
8
TTK inhibitor OSU13 induces DNA damage and STING activation, promoting T cell recruitment and synergizing with anti-PD-1 immunotherapy
PMID: 38900577
9
TTK is upregulated in bladder cancer and promotes proliferation, migration, and epithelial-mesenchymal transition
PMID: 31949560
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.55Moderate
Alzheimer diseaseOpen Targets
0.38Weak
lysosomal storage diseaseOpen Targets
0.38Weak
multiple sclerosisOpen Targets
0.38Weak
Parkinson diseaseOpen Targets
0.38Weak
radius fractureOpen Targets
0.31Weak
ulna fractureOpen Targets
0.31Weak
breast cancerOpen Targets
0.12Weak
hepatocellular carcinomaOpen Targets
0.12Weak
neoplasmOpen Targets
0.11Weak
glioblastoma multiformeOpen Targets
0.11Weak
triple-negative breast cancerOpen Targets
0.11Weak
alcohol drinkingOpen Targets
0.11Weak
gastric cancerOpen Targets
0.10Weak
colorectal carcinomaOpen Targets
0.10Suggestive
non-small cell lung carcinomaOpen Targets
0.10Suggestive
ovarian cancerOpen Targets
0.09Suggestive
cancerOpen Targets
0.09Suggestive
lung cancerOpen Targets
0.09Suggestive
liver cancerOpen Targets
0.09Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets2
BAY-1161909Phase I
Dual specificity protein kinase TTK inhibitor
BAY-1217389Phase I
Dual specificity protein kinase TTK inhibitor
cancer
Related Genes
NCAPGProtein interaction100%CEP55Protein interaction100%ZCWPW1Protein interaction99%ZCWPW2Protein interaction99%BUB1BProtein interaction98%CENPEProtein interaction98%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
28%
Lung
1%
Heart
1%
Liver
0%
Ovary
0%
Gene Interaction Network
Click a node to explore
TTKNCAPGCEP55ZCWPW1ZCWPW2BUB1BCENPE
PROTEIN STRUCTURE
Preparing viewer…
PDB4H7Y · 1.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.67LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.53 [0.42–0.67]
RankingsWhere TTK stands among ~20K protein-coding genes
  • #1,813of 20,598
    Most Researched225 · top 10%
  • #4,888of 17,882
    Most Constrained (LOEUF)0.67
Genes detectedTTK
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Positive feedback regulation between glycolysis and histone lactylation drives oncogenesis in pancreatic ductal adenocarcinoma.
PMID: 38711083
Mol Cancer · 2024
1.00
2
Integrative analysis of T cell-mediated tumor killing-related genes reveals KIF11 as a novel therapeutic target in esophageal squamous cell carcinoma.
PMID: 39966857
J Transl Med · 2025
0.90
3
TTK promotes mitophagy by regulating ULK1 phosphorylation and pre-mRNA splicing to inhibit mitochondrial apoptosis in bladder cancer.
PMID: 40269198
Cell Death Differ · 2025
0.80
4
Annexin A2 combined with TTK accelerates esophageal cancer progression via the Akt/mTOR signaling pathway.
PMID: 38658569
Cell Death Dis · 2024
0.70
5
LncRNA938/ TAF9/TTK axis promotes EMT and serves as a therapeutic target in hepatoblastoma.
PMID: 40841910
J Transl Med · 2025
0.68