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26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TK1
thymidine kinase 1
Chromosome 17 · 17q25.3
NCBI Gene: 7083Ensembl: ENSG00000167900.13HGNC: HGNC:11830UniProt: A0A384MDV9
176PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneKinase
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
thymidine kinase activityprotein bindingzinc ion bindingidentical protein bindingCOVID-19neurodegenerative diseasecancerhepatocellular carcinoma
✦AI Summary

TK1 (thymidine kinase 1) is a cell-cycle-regulated enzyme catalyzing the first step of thymidine salvage, converting thymidine to thymidine monophosphate 1. Expression is transcriptionally limited to S phase, coinciding with dTTP oscillations. Beyond nucleotide metabolism, TK1 plays critical roles in telomere maintenance—TK1 deletion decreases telomere length, while thymidine supplementation drives telomerase-mediated telomere elongation 2. TK1 also activates anticancer and antiviral nucleoside analogs including AraC and AZT 1. In cancer biology, TK1 is significantly overexpressed across multiple malignancies and serves as a prognostic biomarker 3. TK1 promotes tumor progression through multiple mechanisms: it enhances cellular proliferation by regulating G0/G1 phase arrest 4, mediates replication stress in pancreatic cancer via dTTP accumulation 5, and coordinates tumor immune evasion by modulating Th2 cell polarization via CCL5 chemokine signaling 4. In lung adenocarcinoma and triple-negative breast cancer, TK1 knockdown impairs proliferation, migration, and invasion while restoring immune function 67. TK1 mRNA stability is enhanced through m5C methylation-dependent mechanisms 8. Clinically, TK1 represents a promising CAR T-cell immunotherapy target and biomarker for predicting immunotherapy response and overall survival across cancer types.

Sources cited
1
TK1 catalyzes thymidine to thymidine monophosphate conversion and activates anticancer/antiviral nucleoside analogs
PMID: 22385435
2
TK1-mediated thymidine salvage is essential for telomere length maintenance and telomerase activity
PMID: 36959362
3
Serum TK1 activity serves as biomarker for prognosis and therapy monitoring across multiple malignancies
PMID: 36201558
4
TK1 promotes tumor progression through cell proliferation and Th2 cell polarization via CCL5 signaling
PMID: 39343871
5
TK1 stabilization increases dTTP levels and mediates replication stress in pancreatic cancer
PMID: 40155654
6
TK1 knockdown impairs TNBC cell proliferation, migration, invasion and is associated with poor prognosis
PMID: 37767092
7
TK1 is a functional oncogenic driver in lung adenocarcinoma regulating proliferation and immune evasion
PMID: 40830974
8
TK1 mRNA stability is controlled through m5C methylation-dependent mechanisms in bladder cancer
PMID: 36806253
Disease Associationsⓘ20
COVID-19Open Targets
0.35Weak
neurodegenerative diseaseOpen Targets
0.27Weak
cancerOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.11Weak
neoplasmOpen Targets
0.10Weak
posterior cortical atrophyOpen Targets
0.10Weak
breast cancerOpen Targets
0.10Suggestive
lung adenocarcinomaOpen Targets
0.09Suggestive
non-small cell lung carcinomaOpen Targets
0.09Suggestive
gliomaOpen Targets
0.08Suggestive
lymphomaOpen Targets
0.08Suggestive
oral squamous cell carcinomaOpen Targets
0.08Suggestive
thyroid carcinomaOpen Targets
0.08Suggestive
prostate cancerOpen Targets
0.08Suggestive
systemic lupus erythematosusOpen Targets
0.08Suggestive
acute lymphoblastic leukemiaOpen Targets
0.07Suggestive
cervical squamous intraepithelial neoplasiaOpen Targets
0.07Suggestive
renal cell carcinomaOpen Targets
0.06Suggestive
esophageal squamous cell carcinomaOpen Targets
0.06Suggestive
triple-negative breast cancerOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CDC45Protein interaction100%ADAT3Protein interaction100%CEP55Protein interaction100%ASPMProtein interaction99%CENPFProtein interaction98%RRM1Protein interaction96%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
21%
Lung
17%
Liver
13%
Heart
3%
Ovary
2%
Gene Interaction Network
Click a node to explore
TK1CDC45ADAT3CEP55ASPMCENPFRRM1
PROTEIN STRUCTURE
Preparing viewer…
PDB1W4R · 1.83 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.01LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.61 [0.39–1.01]
RankingsWhere TK1 stands among ~20K protein-coding genes
  • #2,492of 20,598
    Most Researched176 · top quartile
  • #9,907of 17,882
    Most Constrained (LOEUF)1.01
Genes detectedTK1
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
Thymidine nucleotide metabolism controls human telomere length.
PMID: 36959362
Nat Genet · 2023
1.00
2
Regulatory T cells are associated with the tumor immune microenvironment and immunotherapy response in triple-negative breast cancer.
PMID: 37767092
Front Immunol · 2023
0.90
3
m
PMID: 36806253
Cell Death Dis · 2023
0.80
4
A sensitive and kinetically defined radiochemical assay for canine and human serum thymidine kinase 1 (TK1) to monitor canine malignant lymphoma.
PMID: 22516918
Vet J · 2012
0.72
5
Coordinating oncogenesis and immune evasion: KPNA2, GOLM1, and TK1 as novel CAR T-cell targets in lung adenocarcinoma.
PMID: 40830974
Eur J Med Res · 2025
0.70