Affinage

TK2

Thymidine kinase 2, mitochondrial · UniProt O00142

Length
265 aa
Mass
31.0 kDa
Annotated
2026-06-10
58 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TK2 is a homodimeric mitochondrial pyrimidine deoxynucleoside kinase that phosphorylates thymidine and deoxycytidine to their 5'-monophosphates with Michaelis-Menten kinetics for deoxycytidine, negative cooperativity for thymidine, and feedback inhibition by dTTP and dCTP, supplying the mitochondrial dNTP pool required for mtDNA replication and maintenance (PMID:11812127). Its activity directly controls mtDNA copy number and respiratory chain biogenesis: cardiac overexpression doubles mtDNA abundance and increases complex I subunits, cristae density, and succinate dehydrogenase activity (PMID:17322372). TK2 cooperates with CMPK2 in a physically associated two-enzyme complex in the mitochondrial matrix that channels thymidine phosphorylation, with CMPK2 immediately converting TK2-generated TMP to TDP so that exogenous TMP cannot serve as a TTP precursor in intact mitochondria (PMID:40967432). Loss-of-function mutations at conserved residues abolish TK2 activity and cause mtDNA depletion and respiratory dysfunction preferentially in skeletal muscle, a tissue specificity explained by intrinsically low basal mitochondrial TK activity and high dependence on salvage for dTTP (PMID:16504786, PMID:12765840, PMID:32345222). Disease onset is gated by postnatal downregulation of cytosolic TK1, which unmasks TK2 deficiency, while spared organs compensate through hENT1-mediated nucleoside import, MTERF3 downregulation that boosts mitochondrial transcription, or upregulation of cytosolic TK1/dCK (PMID:20940150, PMID:19265691, PMID:31383553, PMID:34070501). Because TK2 also phosphorylates pyrimidine nucleoside analogues, it mediates mitochondrial activation of NRTIs and antineoplastic deoxycytidine analogues, accounting for both NRTI mitochondrial toxicity and a role in gemcitabine sensitivity (PMID:17322372, PMID:26087398, PMID:10478487); loss of TK2 additionally activates the cGAS-STING pathway and couples mitochondrial dysfunction to neuroinflammation (PMID:41500441).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 High

    Establishing that TK2 has substrate and inhibitor specificity distinct from cytosolic TK1 was needed to define it as a separate salvage enzyme and a selective drug target.

    Evidence In vitro phosphorylation and inhibition kinetics with purified human TK2 and TK1, identifying TK2-selective substrate analogues and inhibitors

    PMID:10478487

    Open questions at the time
    • Did not establish in vivo substrate flux or physiological dNTP contribution
    • No structural basis for selectivity
  2. 2002 High

    Defining TK2's core enzymology resolved how it phosphorylates pyrimidine deoxynucleosides and is regulated, anchoring its role in dNTP pool control.

    Evidence In vitro kinetics with purified recombinant enzymes, oligomeric state determination, and dNTP feedback inhibition assays

    PMID:11812127

    Open questions at the time
    • Feedback regulation characterized in vitro, not in the mitochondrial matrix context
    • No partner enzymes identified at this stage
  3. 2003 Medium

    Identifying non-nucleoside reversible inhibitors of TK2 and the biochemical/tissue basis of muscle-restricted disease connected enzyme activity to tissue-specific pathology.

    Evidence In vitro inhibition kinetics with mode-of-action analysis; biochemical TK2 activity, deoxynucleotide carrier, and mtDNA measurements across patient tissues

    PMID:12527796 PMID:12765840

    Open questions at the time
    • Tissue correlation did not exclude developmental TK1 contributions
    • Inhibitor work did not address in vivo target engagement
  4. 2006 Medium

    Linking specific conserved-residue mutations to abolished enzyme activity and muscle mtDNA depletion established TK2 deficiency as an enzymatic loss-of-function disease.

    Evidence Patient mutation sequencing with biochemical TK2 activity measurement in affected tissues

    PMID:16504786

    Open questions at the time
    • Single lab, limited families
    • Did not explain why muscle is selectively vulnerable
  5. 2007 High

    Demonstrating that TK2 gain-of-function increases mtDNA and respiratory capacity, and that NRTIs abrogate this, proved TK2 activity directly sets mitochondrial dNTP supply and mediates NRTI toxicity.

    Evidence Transgenic cardiac TK2 overexpression with mtDNA, OXPHOS protein, ultrastructure readouts and NRTI treatment

    PMID:17322372

    Open questions at the time
    • Cardiac overexpression model may not reflect physiological muscle dosage
    • NRTI specificity for individual analogues not fully resolved
  6. 2008 High

    Defining TK2-selective nucleoside substrates (FMAU, BvdU) provided tools to measure TK2 activity and image mitochondrial salvage in cells and tissues.

    Evidence Radiochemical and in vitro phosphorylation assays with TK2 inhibition controls and HPLC metabolite analysis

    PMID:18265975 PMID:18600552

    Open questions at the time
    • Imaging correlates do not measure mtDNA outcome directly
    • Probe behavior in TK2-deficient tissue not tested
  7. 2009 High

    Identifying hENT1 upregulation as a compensatory route in TK2-deficient cells revealed that nucleoside import can bypass TK2 to maintain mtDNA, explaining tissue sparing.

    Evidence Real-time PCR, western blot, and siRNA knockdown of hENT1 vs TK1 with mtDNA quantification in patient fibroblasts

    PMID:19265691

    Open questions at the time
    • Mechanism by which imported nucleosides reach the matrix not detailed
    • Generalizability across tissues untested in this system
  8. 2010 High

    Showing that postnatal TK1 downregulation unmasks TK2 deficiency, and that MTERF3 downregulation compensates in spared organs, explained the temporal and tissue gating of disease onset.

    Evidence Tk2 H126N knockin mouse with developmental TK1/TK2 activity assays, mtDNA and transcript quantification, and biogenesis regulator profiling

    PMID:20940150

    Open questions at the time
    • Trigger for postnatal TK1 downregulation not identified
    • MTERF3 compensation mechanism only correlative
  9. 2015 Medium

    Demonstrating that TK2 knockdown sensitizes tumor cells to gemcitabine via dCTP depletion extended TK2 function to chemotherapeutic deoxycytidine analogue metabolism.

    Evidence siRNA knockdown with dNTP pool, dCK activity, and mitochondrial function readouts, controlled against TK1/TS knockdown

    PMID:26087398

    Open questions at the time
    • Single lab, two cell lines
    • In vivo relevance to gemcitabine resistance not established
  10. 2019 High

    Placing cytosolic TK1 and dCK as determinants of deoxynucleoside therapy efficacy clarified why treatment response is tissue- and time-specific and informed therapeutic design.

    Evidence Tk2 H126N mouse deoxynucleoside therapy with tissue dNTP/mtDNA measurements, activity assays, and human muscle expression analysis

    PMID:31383553

    Open questions at the time
    • Brain therapeutic failure mechanism beyond TK1 loss not fully resolved
    • Long-term human efficacy data limited
  11. 2020 Medium

    Quantifying tissue TK activity and detecting a cytosolic TK2 isoform reinforced that low total salvage capacity in skeletal muscle underlies its selective vulnerability.

    Evidence Mitochondrial/cytosolic fractionation of rat tissues with substrate-specific TK activity, thymidylate synthase, and p53R2 measurements

    PMID:32345222

    Open questions at the time
    • Function and origin of the cytosolic TK2 isoform unresolved
    • Rat tissue data require human confirmation
  12. 2021 Medium

    Profiling autopsy tissue from a TK2-deficient patient showed diaphragm as most severely affected with compensatory TK1 overexpression across tissues, linking salvage compensation to human disease severity.

    Evidence Postmortem mtDNA, OXPHOS western blot, MALDI-TOF proteomics, and TK1 immunohistochemistry across multiple muscles

    PMID:34070501

    Open questions at the time
    • Single patient case
    • Causality of compensatory TK1 not experimentally tested
  13. 2025 High

    Identifying a physical TK2-CMPK2 channeling complex resolved how matrix compartmentalization enforces sequential thymidine to TDP phosphorylation and explains why exogenous TMP is not a usable precursor.

    Evidence Perfused hearts and isolated mitochondria with AZT block, intact vs broken mitochondria, proximity labeling, immunofluorescence, and fractionation

    PMID:40967432

    Open questions at the time
    • Stoichiometry and structural interface of the complex undefined
    • Whether the complex extends to deoxycytidine arm not addressed
  14. 2025 Medium

    Linking TK2 loss to cGAS-STING activation and increased seizure susceptibility connected mitochondrial dysfunction to neuroinflammation, broadening TK2 pathophysiology beyond mtDNA depletion.

    Evidence Proteomics of epileptogenic human brain, two seizure mouse models, and cGAS-STING/inflammatory gene validation

    PMID:41500441

    Open questions at the time
    • No direct TK2 knockout rescue of the inflammatory phenotype
    • Mechanism connecting mtDNA depletion to cGAS sensing not directly shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The atomic structure of the TK2-CMPK2 channeling complex and the molecular trigger linking mitochondrial dysfunction to cGAS-STING activation remain undefined.
  • No structural model of the matrix two-enzyme complex
  • Causal step from mtDNA depletion to innate immune activation unresolved
  • Cytosolic TK2 isoform function unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0140096 catalytic activity, acting on a protein 2 GO:0140657 ATP-dependent activity 2
Localization
GO:0005739 mitochondrion 3
Pathway
R-HSA-69306 DNA Replication 3 R-HSA-1430728 Metabolism 2 R-HSA-1643685 Disease 2
Partners
CMPK2
Complex memberships
TK2-CMPK2 mitochondrial phosphorylation complex

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Human TK2 (and its orthologs) are pyrimidine deoxynucleoside kinases that display Michaelis-Menten kinetics with deoxycytidine and negative cooperativity with thymidine as substrates; they are homodimers and are subject to feedback inhibition by thymidine triphosphate and deoxycytidine triphosphate in a complex, substrate-dependent pattern. In vitro enzyme kinetics assays with purified recombinant enzymes; gel filtration/sedimentation for oligomeric state; feedback inhibition assays with dNTPs Journal of molecular biology High 11812127
1999 Human TK2 phosphorylates pyrimidine nucleoside analogues with modified sugar moieties; alpha-dT is a substrate of TK2 (Ki ~30 µM); several 5'-substituted dC analogues act as non-substrate inhibitors of TK2; substrate/inhibitor specificities differ substantially between TK1 and TK2, with 3'-hexanoylamino-2',3'-dideoxythymidine being an excellent TK2-selective inhibitor (Ki ~0.1 µM vs ~600 µM for TK1). In vitro phosphorylation assays with purified human TK2 and TK1 from leukemic spleen; kinetic analysis Nucleosides & nucleotides High 10478487
2003 Non-nucleoside inhibitors (5'-O-trityl derivatives, notably KIN-52) act as reversible uncompetitive inhibitors of TK2 with respect to ATP (Ki = 0.50 µM), whereas substrate analogue BVDU behaves as a noncompetitive (alternative substrate) inhibitor; these compounds represent the first non-nucleoside-specific inhibitors of TK2. In vitro enzyme inhibition kinetics with purified TK2, HSV-1 TK, and Dm-dNK; competitive inhibition analysis vs. thymidine and ATP; computer-assisted molecular modeling Molecular pharmacology High 12527796
2003 Low basal TK2 activity combined with high requirement for mitochondrially encoded respiratory chain proteins in skeletal muscle underlies the tissue specificity of TK2 deficiency; other tissues (liver, brain, heart, skin) with lower dependence on TK2 activity remain unaffected. Biochemical measurement of TK2 enzyme activity, mitochondrial deoxynucleotide carrier expression, and mtDNA content across multiple tissues from patients and controls Molecular genetics and metabolism Medium 12765840
2006 TK2 mutations at conserved residues (A181V, C108W, L257P) abolish or severely reduce TK2 enzymatic activity, causing mtDNA depletion and respiratory chain dysfunction specifically in muscle. Patient mutation identification by sequencing; biochemical measurement of TK2 activity in affected tissues Pediatric neurology Medium 16504786
2007 Transgenic cardiac overexpression of TK2 (300-fold increased activity) doubles mtDNA abundance and increases mitochondrial complex I subunit levels, cristae density, and succinate dehydrogenase activity, demonstrating that TK2 activity directly controls mitochondrial dNTP supply and mtDNA copy number; NRTIs abrogate these effects, establishing TK2-mediated NRTI phosphorylation as the mechanism of mitochondrial toxicity. Transgenic mouse overexpression; echocardiography; TK activity assays; mtDNA quantification; immunohistochemistry; electron microscopy; NRTI treatment experiments The American journal of pathology High 17322372
2008 FMAU (a fluoropyrimidine PET tracer) is preferentially phosphorylated by mitochondrial TK2, not cytosolic TK1; TK2 inhibition decreases FMAU retention and phosphorylation; FMAU retention correlates with TK2 activity (r²=0.87) and mitochondrial mass (r²=0.88) under cellular stress conditions. Radiochemical phosphorylation assays; TK2 inhibition experiments; HPLC metabolite analysis; flow cytometry for mitochondrial mass; correlation analysis across stress conditions European journal of nuclear medicine and molecular imaging High 18265975
2008 5-Bromovinyl-2'-deoxyuridine (BvdU) at 2.5 µM is phosphorylated by TK2 at a 500-fold higher rate than by TK1, enabling selective measurement of TK2 activity in crude tissue extracts. In vitro phosphorylation assays with purified human TK2 and TK1; substrate specificity ratio determination Nucleosides, nucleotides & nucleic acids Medium 18600552
2009 In TK2-deficient fibroblasts, the human equilibrative nucleoside transporter 1 (hENT1) is upregulated at both mRNA and protein levels; siRNA knockdown of hENT1 (but not TK1) induces mtDNA depletion in TK2-deficient fibroblasts, demonstrating that hENT1 compensates for TK2 deficiency by facilitating nucleoside import to maintain mtDNA levels. Real-time PCR; western blotting; siRNA knockdown of hENT1 and TK1 with subsequent mtDNA quantification by PCR Experimental cell research High 19265691
2010 In Tk2 H126N knockin mice, disease onset correlates with postnatal downregulation of cytosolic TK1 activity (between days 8 and 13), which unmasks TK2 deficiency and triggers mtDNA depletion in brain and heart; organs spared from pathology (heart) compensate by downregulating mitochondrial transcriptional terminator MTERF3, thereby increasing mitochondrial transcript levels relative to mtDNA content without altering PGC-1α, NRF1/2, or TFAM/B1/B2. Tk2 H126N knockin mouse model; TK1/TK2 activity assays across development; mtDNA quantification by PCR; RT-PCR for mitochondrial transcripts; western blotting for mitochondrial proteins; expression analysis of biogenesis regulators Human molecular genetics High 20940150
2015 siRNA knockdown of TK2 sensitizes human tumor cells (MCF7, HeLa) to gemcitabine by decreasing dCTP levels, increasing dCK activity, and causing mitochondrial damage (reduced redox status, mtDNA content, and mitochondrial activity); knockdown of TK1 or thymidylate synthase did not sensitize cells to gemcitabine, indicating a specific role for TK2 in gemcitabine resistance. siRNA knockdown; cell viability assays; dNTP pool measurement; dCK activity assays; mitochondrial function assays (redox status, mtDNA quantification, respiratory activity) Oncotarget Medium 26087398
2019 The cytosolic pyrimidine salvage enzymes TK1 and dCK are critical for the therapeutic efficacy of deoxynucleoside (dCyd + dThd) therapy in TK2 deficiency: down-regulation of TK1 correlates with temporal- and tissue-specific failure of response (e.g., brain), and human infant/adult muscle expresses TK1 and dCK which account for long-term therapeutic efficacy. Tk2 H126N knockin mouse model; parenteral vs. oral deoxynucleoside treatment; tissue-level dNTP/nucleoside measurement; mtDNA quantification; TK1 and dCK activity assays; expression analysis in human muscle samples EBioMedicine High 31383553
2020 In adult rat tissues, a cytosolic isoform of TK2 with similar substrate specificity to mitochondrial TK2 was detected; skeletal muscle mitochondria have the lowest total TK activity of any tissue examined and are likely dependent on both salvage and de novo synthesis pathways for dTTP, explaining why TK2 deficiency preferentially affects skeletal muscle. Mitochondrial and cytosolic fractionation of multiple rat tissues; TK activity assays with substrate specificity profiling; thymidylate synthase activity and protein level measurements; p53R2 protein quantification BMC molecular and cell biology Medium 32345222
2025 TK2 and CMPK2 (cytidine/uridine monophosphate kinase 2) physically associate in the mitochondrial matrix, creating a two-enzyme complex that channels thymidine phosphorylation: TK2 phosphorylates thymidine to TMP, and the proximity of CMPK2 allows immediate conversion of TMP to TDP, preventing TMP from diffusing away; this compartmentalization explains why exogenously supplied TMP cannot serve as a TTP precursor in intact mitochondria unless first dephosphorylated to thymidine. Perfused rat hearts and isolated mitochondria from multiple tissues (heart, liver, kidney, brain); azidothymidine block of TK2; radiolabeled TMP incubation with intact vs. broken mitochondria; proximity labeling; immunofluorescence microscopy; differential centrifugation fractionation The Journal of biological chemistry High 40967432
2025 Loss of Tk2 in human epileptic brain tissue and seizure mouse models activates the cGAS-STING innate immune pathway, upregulates inflammatory genes, and increases seizure susceptibility, demonstrating that TK2 couples mitochondrial dysfunction to neuroinflammation. Proteomic profiling of resected epileptogenic brain tissue; two seizure mouse models (pilocarpine, ferric chloride); Tk2 expression correlation with seizure frequency; mechanistic validation of cGAS-STING pathway activation by western blot and inflammatory gene expression assays Neuroscience Medium 41500441
2021 In an adult TK2-deficient patient, the diaphragm shows more profound loss of OXPHOS proteins, glycolytic enzymes (fructose-bisphosphate aldolase by MALDI-TOF), sarcomeric proteins, and antioxidant enzymes than other skeletal muscles; strong overexpression of TK1 is observed across all tissues with the highest levels in the diaphragm, indicating compensatory upregulation of the cytosolic thymidine salvage pathway. Postmortem tissue biochemistry; mtDNA quantification; OXPHOS subunit western blotting; MALDI-TOF/TOF mass spectrometry proteomics; TK1 immunohistochemistry across multiple tissues International journal of molecular sciences Medium 34070501

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Transcriptomic profiling of TK2 deficient human skeletal muscle suggests a role for the p53 signalling pathway and identifies growth and differentiation factor-15 as a potential novel biomarker for mitochondrial myopathies. BMC genomics 115 24484525
2003 mtDNA depletion myopathy: elucidation of the tissue specificity in the mitochondrial thymidine kinase (TK2) deficiency. Molecular genetics and metabolism 87 12765840
2006 New mutations in TK2 gene associated with mitochondrial DNA depletion. Pediatric neurology 53 16504786
2003 Mitochondrial myopathy of childhood associated with mitochondrial DNA depletion and a homozygous mutation (T77M) in the TK2 gene. Archives of neurology 52 12873860
2003 Reversion of mtDNA depletion in a patient with TK2 deficiency. Neurology 45 12682338
2012 Adult cases of mitochondrial DNA depletion due to TK2 defect: an expanding spectrum. Neurology 42 22345218
2008 Novel mutations in the TK2 gene associated with fatal mitochondrial DNA depletion myopathy. Neuromuscular disorders : NMD 39 18508266
2002 Deoxyribonucleoside kinases belonging to the thymidine kinase 2 (TK2)-like group vary significantly in substrate specificity, kinetics and feed-back regulation. Journal of molecular biology 35 11812127
2013 Molecular and clinical characterization of the myopathic form of mitochondrial DNA depletion syndrome caused by mutations in the thymidine kinase (TK2) gene. Molecular genetics and metabolism 34 23932787
2020 Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy. Scientific reports 32 32572108
2008 Tracking cellular stress with labeled FMAU reflects changes in mitochondrial TK2. European journal of nuclear medicine and molecular imaging 32 18265975
2010 Onset and organ specificity of Tk2 deficiency depends on Tk1 down-regulation and transcriptional compensation. Human molecular genetics 29 20940150
2013 TK2 mutation presenting as indolent myopathy. Neurology 27 23303857
2005 Novel mutations in the thymidine kinase 2 gene (TK2) associated with fatal mitochondrial myopathy and mitochondrial DNA depletion. Neuromuscular disorders : NMD 26 15907288
2007 Targeted transgenic overexpression of mitochondrial thymidine kinase (TK2) alters mitochondrial DNA (mtDNA) and mitochondrial polypeptide abundance: transgenic TK2, mtDNA, and antiretrovirals. The American journal of pathology 25 17322372
1999 Substrate/inhibitor properties of human deoxycytidine kinase (dCK) and thymidine kinases (TK1 and TK2) towards the sugar moiety of nucleosides, including O'-alkyl analogues. Nucleosides & nucleotides 24 10478487
2008 Structure, physiological role, and specific inhibitors of human thymidine kinase 2 (TK2): present and future. Medicinal research reviews 23 18459168
2013 Late-onset respiratory failure due to TK2 mutations causing multiple mtDNA deletions. Neurology 21 24198295
2019 Bioavailability and cytosolic kinases modulate response to deoxynucleoside therapy in TK2 deficiency. EBioMedicine 19 31383553
2003 Non-nucleoside inhibitors of mitochondrial thymidine kinase (TK-2) differentially inhibit the closely related herpes simplex virus type 1 TK and Drosophila melanogaster multifunctional deoxynucleoside kinase. Molecular pharmacology 18 12527796
2014 Clinical application of whole exome sequencing reveals a novel compound heterozygous TK2-mutation in two brothers with rapidly progressive combined muscle-brain atrophy, axonal neuropathy, and status epilepticus. Mitochondrion 17 25446393
2010 Hearing loss in a patient with the myopathic form of mitochondrial DNA depletion syndrome and a novel mutation in the TK2 gene. Pediatric research 17 20421844
2007 Selective muscle fiber loss and molecular compensation in mitochondrial myopathy due to TK2 deficiency. Journal of the neurological sciences 16 18021809
2024 Clinical and Genetic Analysis of Patients With TK2 Deficiency. Neurology. Genetics 14 38544965
2021 Complete genome sequencing of Bacillus sp. TK-2, analysis of its cold evolution adaptability. Scientific reports 14 33649356
2013 DPYD, TYMS, TYMP, TK1, and TK2 genetic expressions as response markers in locally advanced rectal cancer patients treated with fluoropyrimidine-based chemoradiotherapy. BioMed research international 14 24455740
2010 Application of oligonucleotide array CGH to the simultaneous detection of a deletion in the nuclear TK2 gene and mtDNA depletion. Molecular genetics and metabolism 14 19815440
2014 Mitochondrial DNA depletion in single fibers in a patient with novel TK2 mutations. Neuromuscular disorders : NMD 12 24953930
2012 Recent advances in thymidine kinase 2 (TK2) inhibitors and new perspectives for potential applications. Current pharmaceutical design 12 22571666
2024 Remarkable clinical improvement with oral nucleoside treatment in a patient with adult-onset TK2 deficiency: A case report. Mitochondrion 11 38599303
2022 Muscle MRI characteristic pattern for late-onset TK2 deficiency diagnosis. Journal of neurology 11 35286480
2006 N1-substituted thymine derivatives as mitochondrial thymidine kinase (TK-2) inhibitors. Journal of medicinal chemistry 11 17181158
2022 The impact of TK2 deficiency syndrome and its treatment by nucleoside therapy on quality of life. Mitochondrion 9 36374792
2015 siRNA knockdown of mitochondrial thymidine kinase 2 (TK2) sensitizes human tumor cells to gemcitabine. Oncotarget 9 26087398
2006 The role of mitochondrial dNTP levels in cells with reduced TK2 activity. Nucleosides, nucleotides & nucleic acids 9 17065084
2004 Synthesis and evaluation of thymine-derived carboxamides against mitochondrial thymidine kinase (TK-2) and related enzymes. Bioorganic & medicinal chemistry 9 15351391
2021 Preferent Diaphragmatic Involvement in TK2 Deficiency: An Autopsy Case Study. International journal of molecular sciences 8 34070501
2009 Altered gene transcription profiles in fibroblasts harboring either TK2 or DGUOK mutations indicate compensatory mechanisms. Experimental cell research 8 19265691
2008 5-Bromovinyl 2'-deoxyuridine phosphorylation by mitochondrial and cytosolic thymidine kinase (TK2 and TK1) and its use in selective measurement of TK2 activity in crude extracts. Nucleosides, nucleotides & nucleic acids 8 18600552
2020 Basic biochemical characterization of cytosolic enzymes in thymidine nucleotide synthesis in adult rat tissues: implications for tissue specific mitochondrial DNA depletion and deoxynucleoside-based therapy for TK2-deficiency. BMC molecular and cell biology 7 32345222
2017 Myopathic mtDNA Depletion Syndrome Due to Mutation in TK2 Gene. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 7 28812460
1987 A novel HLA class II alloantigen detected by an alloantiserum TK2. Human immunology 7 3494716
2016 Novel TK2 mutations as a cause of delayed muscle maturation in mtDNA depletion syndrome. Neurology. Genetics 5 27660820
1998 Substrate/inhibitor specificities of human deoxycytidine kinase (dCK) and thymidine kinases (TK1 and TK2). Advances in experimental medicine and biology 5 9598140
2025 Infantile TK2 Deficiency Causing Mitochondrial Encephalomyopathy With Migrating Focal Seizures. Neurology 3 40030095
2022 Pathological Features in Paediatric Patients with TK2 Deficiency. International journal of molecular sciences 3 36232299
2020 Mild myopathic phenotype in a patient with homozygous c.416C > T mutation in TK2 gene. Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology 3 32904881
2026 Exploring Outcome Measures for Mitochondrial Myopathies; Insights From a Longitudinal Study on TK2 Deficiency. Journal of inherited metabolic disease 1 41571587
2022 Case Report: Thymidine Kinase 2 (TK2) Deficiency: A Novel Mutation Associated With Childhood-Onset Mitochondrial Myopathy and Atypical Progression. Frontiers in neurology 1 35280287
2021 Generation of an induced pluripotent stem cell line from a compound heterozygous patient in TK2 gene. Stem cell research 1 34973561
2026 Tk2 deficiency-mediated mitochondrial dysfunction drives neuroinflammation and seizure frequency in epilepsy. Neuroscience 0 41500441
2026 Late-onset TK2 deficiency in adults: Long-term clinical outcomes of deoxynucleoside therapy. Mitochondrion 0 41771327
2026 First case of schizophrenia and OCD in TK2-related mitochondrial DNA depletion myopathy: a case report. BMC psychiatry 0 41808087
2025 Novel biallelic TK2 mutations cause mitochondrial DNA depletion syndrome with infantile early-onset lipid storage myopathy. Orphanet journal of rare diseases 0 40098049
2025 Compartmentalized thymidine phosphorylation by mitochondrial nucleotide kinases TK2 and CMPK2. The Journal of biological chemistry 0 40967432
2025 National diagnostic gaps for TK2 Deficiency in Italy: insights from the AIM Multicenter Survey. Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology 0 41199730
2024 Creatine kinase elevation in chronic hepatitis B patients with telbivudine therapy: influence of telbivudine plasma concentration and single nucleotide polymorphisms of TK2, RRM2B, and NME4. European journal of clinical pharmacology 0 38502357
2012 Biochemistry and biology of 2'-Fluoro-2'-deoxythymidine (FT), a putative highly selective substrate for thymidine kinase type 2 (TK2). Current radiopharmaceuticals 0 21864241

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