TK1
Chr 17thymidine kinase 1
The protein encoded by this gene is a cytosolic enzyme that catalyzes the addition of a gamma-phosphate group to thymidine. This creates dTMP and is the first step in the biosynthesis of dTTP, which is one component required for DNA replication. The encoded protein, whose levels fluctuate depending on the cell cycle stage, can act as a low activity dimer or a high activity tetramer. High levels of this protein have been used as a biomarker for diagnosing and categorizing many types of cancers. [provided by RefSeq, Oct 2016]
Clinical Summary— TK1
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Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
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ClinVar Variants
13 Pathogenic / Likely Pathogenic· 35 VUS of 51 total submissions
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.78LOEUF
pLI 0.137
Z-score 2.04
OE 0.30 (0.14–0.78)
Typical tolerance to LoF variation
Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.31Z-score
OE missense 0.69 (0.59–0.82)
101 obs / 145.5 exp
Mild missense constraint
Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.30 (0.14–0.78)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.69 (0.59–0.82)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.89
0≤1.21.6
LoF obs/exp: 3 / 9.9Missense obs/exp: 101 / 145.5Syn Z: 0.64
ClinVar Variant Classifications
51 submitted variants in ClinVar
Classification Summary
Pathogenic13
VUS35
Likely Benign2
Benign1
13
Pathogenic
35
VUS
2
Likely Benign
1
Benign
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 13 | 0 | 13 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 1 | 33 | 1 | 0 | 35 |
Likely Benign | 0 | 1 | 1 | 0 | 2 |
Benign | 0 | 0 | 0 | 1 | 1 |
| Total | 1 | 34 | 15 | 1 | 51 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TK1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
OMIM — Genotype-Phenotype Relationships
1 OMIM entry
THYMIDINE KINASE, SOLUBLE; TK1
MIM #188300 · *
External Resources
Links to major genomics databases and tools
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
LncRNA SNHG4 promotes prostate cancer cell survival and resistance to enzalutamide through a let-7a/RREB1 positive feedback loop and a ceRNA network.
Dong Q et al.·J Exp Clin Cancer Res
2023
Coordinating oncogenesis and immune evasion: KPNA2, GOLM1, and TK1 as novel CAR T-cell targets in lung adenocarcinoma.
Liu W et al.·Eur J Med Res
2025
Circ_IGF2BP1/miR-885-3p/TK1 axis regulates the malignant phenotype and chemotherapeutic resistance of lung adenocarcinoma cells via DNA damage and apoptosis.
Wang K et al.·Int J Biol Macromol
2025
Thymidine kinase 1 (TK1) as a proteomic biomarker in cancer.
Samuel VP et al.·Clin Chim Acta
2026Review
KAT7-acetylated YBX1 promotes hepatocellular carcinoma proliferation by reprogramming nucleotide metabolism.
Huang H et al.·BMC Cancer
2025
Clinical Value Analysis of Serum TK1, SCC-Ag, and MUC-1 in the Diagnosis and Prognosis Evaluation of Cervical Cancer.
Zhang M et al.·Altern Ther Health Med
2023
Serum TK1 protein and C-reactive protein correlate to treatment response and predict survival in dogs with hematologic malignancies.
Saellström S et al.·Res Vet Sci
2022
A comprehensive analysis and experimental validation of TK1 in uterine corpus endometrial carcinoma.
Sun Y et al.·Sci Rep
2024
A comprehensive review and in silico analysis of the role of survivin (BIRC5) in hepatocellular carcinoma hallmarks: A step toward precision.
Mohamed NM et al.·Int J Biol Macromol
2025Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
A novel APE1-assisted cycling amplification for rapid and ultrasensitive SERS detection of TK1 mRNA in human serum.
Du C et al.·Anal Methods
2026
Combination of prostate cancer antigen 3 (PCA3), sarcosine, glypican-1 (GPC1), urokinase plasminogen activator receptor (uPAR), and thymidine kinase 1 (TK1), and T2WI and DWI radiomics model for distinguishing benign prostatic hyperplasia, prostate cancer, and prostatitis.
Yang F et al.·J Med Biochem
2025Open AccessFunctional
Simultaneous Knockout of Tk1-SST and Tk1-FFT via CRISPR/Cas9 Enhances the Natural Rubber Accumulation in Taraxacum kok-saghyz.
Qin B et al.·Plant Biotechnol J
2025Open Access
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
Identification of Novel Immune Cell-Relevant Therapeutic Targets and Validation of Roles of TK1 in BMSCs of Systemic Lupus Erythematosus
Chen F et al.·Front Mol Biosci
2022
Thymidine Kinase 1 Drives Skin Cutaneous Melanoma Malignant Progression and Metabolic Reprogramming
Zuo S et al.·Front Oncol
2022
Prediction of Overall Survival by Thymidine Kinase 1 Combined with Prostate-Specific Antigen in Men with Prostate Cancer
Tribukait B et al.·Int J Mol Sci
2023
Serum thymidine kinase 1 concentration as a predictive biomarker in prostate cancer
Lundgren PO et al.·Prostate
2022
Molecular characterization of equine thymidine kinase 1 and preliminary evaluation of its suitability as a serum biomarker for equine lymphoma
Wang L et al.·BMC Mol Cell Biol
2021
Feline thymidine kinase 1: molecular characterization and evaluation of its serum form as a diagnostic biomarker
Wang L et al.·BMC Vet Res
2021
Selection of human single domain antibodies (sdAb) against thymidine kinase 1 and their incorporation into sdAb-Fc antibody constructs for potential use in cancer therapy
Velazquez EJ et al.·PLoS One
2022
Use of thymidine kinase 1 autoantibody, thymidine kinase antigen, extracellular protein kinase A autoantibody, and C-reactive protein for early detection of malignant tumors in dogs
Kim Y et al.·J Vet Intern Med
2025
Thymidine kinase 1 indicates resistance to immune checkpoint plus tyrosine kinase inhibition in renal cell carcinoma
Wang J et al.·Cell Oncol (Dordr)
2025
Top 9 full-text resultsSearch PubTator3 ↗
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools