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Gene Review

TKTL1  -  transketolase-like 1

Homo sapiens

Synonyms: TK 2, TKR, TKT2, Transketolase 2, Transketolase-like protein 1, ...
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Disease relevance of TKTL1


High impact information on TKTL1


Biological context of TKTL1

  • The mutations within the TKTL1 gene caused a mutant transketolase enzyme with an altered substrate specificity and reaction modus [3].
  • During the evolution of the vertebrate genome, mutations in this transketolase gene (TKTL1) have led to tissue-specific transcripts different in size, which encode an enzymatically active transketolase protein as well as different smaller protein isoforms [3].
  • Comparison with known transketolases (TK) demonstrated a TKR-specific deletion mutating one thiamine binding site [8].
  • Human thymidine kinase 2 (TK2) is critical for the nucleotide salvage pathway and phosphorylation of nucleoside analog prodrugs in vivo; however, it remains poorly studied because of difficulties in expressing it heterologously [9].
  • Total knee arthroplasty (TKR) using a medial capsular approach gives worse results in arthritic knees with valgus deformity than in those in varus, usually because of swelling, poor wound healing and stiffness, instability, recurrent valgus deformity and poor patellar tracking [10].

Anatomical context of TKTL1

  • The tractive forces during the rolling motion at the knee joint were analyzed to determine which factors cause these forces to increase in TKR [11].
  • For TKR design, a continuous patella contact up to high flexion could be obtained by extending the trochlea 15 mm posterior to the intercondylar notch [12].
  • In this study, the consequences of a reduced thymidine kinase 2 (TK2) activity were measured in proliferating HeLa cells, on both whole-cell as well as mitochondrial dNTP levels [13].
  • Our results suggest that import of cytosolic dNTPs in mitochondria of proliferating cells can compensate a TK2 induced imbalance of the mitochondrial dNTP pool [13].

Associations of TKTL1 with chemical compounds

  • We propose that TKTL1 upregulation is a common phenomenon in GC and cancer of the GEJ leading to an enhanced, oxygen-independent glucose usage which might contribute to a more aggressive tumor growth [2].
  • TK2 is strictly pyrimidine-specific, whereas its phylogenetic relative, the Drosophila melanogaster deoxyribonucleoside kinase (DmdNK), shows higher activity and broader specificity towards both pyrimidines and purines [9].
  • METHODS: TKR/THR patients treated with a 21-day low-dose warfarin protocol were followed via a consecutive observational design [5].
  • The spread of TKS-MRSA in our hospital since 1996 may relate to the "total use threshold", as the level of tobramycin/amikacin use is below that required for selection of TKR-MRSA [14].
  • Epidural sufentanil for TKR-respiratory depression [15]?

Analytical, diagnostic and therapeutic context of TKTL1

  • Molecular cloning of tissue-specific transcripts of a transketolase-related gene: implications for the evolution of new vertebrate genes [8].
  • METHODS: Fifty-three consecutive postarthroplasty patients (30 THR, 23 TKR) (16 women, 37 men; mean age 71 yr; range 52-85 yr) underwent scintigraphic scanning with 99mTc-rt-PA and contrast venography, on the operated leg, in order to assess the accuracy of this new technique in these asymptomatic patients [16].
  • There is no convincing evidence that the well-tried and tested prostheses have a significantly greater overall rate of failure than TKR [17].
  • OBJECTIVE: To evaluate the rate of symptomatic VTE after TKR and THR surgery using a low-dose (INR 1.5-2.5) warfarin protocol started the evening before surgery compared with a literature cohort treated with enoxaparin [5].
  • Corresponding THR and TKR groups in each phase were comparable with respect to age, gender, length of stay, operating surgeon, pre- and lowest postoperative hemoglobin, reason for and timing of transfusion [18].


  1. Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted. Langbein, S., Zerilli, M., Zur Hausen, A., Staiger, W., Rensch-Boschert, K., Lukan, N., Popa, J., Ternullo, M.P., Steidler, A., Weiss, C., Grobholz, R., Willeke, F., Alken, P., Stassi, G., Schubert, P., Coy, J.F. Br. J. Cancer (2006) [Pubmed]
  2. Expression of the mutated transketolase TKTL1, a molecular marker in gastric cancer. Staiger, W.I., Coy, J.F., Grobholz, R., Hofheinz, R.D., Lukan, N., Post, S., Schwarzbach, M.H., Willeke, F. Oncol. Rep. (2006) [Pubmed]
  3. Mutations in the transketolase-like gene TKTL1: clinical implications for neurodegenerative diseases, diabetes and cancer. Coy, J.F., Dressler, D., Wilde, J., Schubert, P. Clin. Lab. (2005) [Pubmed]
  4. Overall cancer incidence not increased after prosthetic knee replacement: 14,551 patients followed for 66,622 person-years. Lewold, S., Olsson, H., Gustafson, P., Rydholm, A., Lidgren, L. Int. J. Cancer (1996) [Pubmed]
  5. Low-dose warfarin for prevention of symptomatic thromboembolism after orthopedic surgery. Enyart, J.J., Jones, R.J. The Annals of pharmacotherapy. (2005) [Pubmed]
  6. Four deoxynucleoside kinase activities from Drosophila melanogaster are contained within a single monomeric enzyme, a new multifunctional deoxynucleoside kinase. Munch-Petersen, B., Piskur, J., Sondergaard, L. J. Biol. Chem. (1998) [Pubmed]
  7. Identification of a gene within the tandem array of red and green color pigment genes. Hanna, M.C., Platts, J.T., Kirkness, E.F. Genomics (1997) [Pubmed]
  8. Molecular cloning of tissue-specific transcripts of a transketolase-related gene: implications for the evolution of new vertebrate genes. Coy, J.F., Dübel, S., Kioschis, P., Thomas, K., Micklem, G., Delius, H., Poustka, A. Genomics (1996) [Pubmed]
  9. Mutagenesis of non-conserved active site residues improves the activity and narrows the specificity of human thymidine kinase 2. Gerth, M.L., Lutz, S. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  10. Replacement arthroplasty of the valgus knee. A modified lateral capsular approach with repositioning of vastus lateralis. Fiddian, N.J., Blakeway, C., Kumar, A. The Journal of bone and joint surgery. British volume. (1998) [Pubmed]
  11. Tractive forces during rolling motion of the knee: implications for wear in total knee replacement. Wimmer, M.A., Andriacchi, T.P. Journal of biomechanics. (1997) [Pubmed]
  12. Relative positions of the contacts on the cartilage surfaces of the knee joint. Walker, P.S., Yildirim, G., Sussman-Fort, J., Klein, G.R. Knee (2006) [Pubmed]
  13. The Role of Mitochondrial dNTP Levels in Cells with Reduced TK2 Activity. Desler, C., Munch-Petersen, B., Rasmussen, L.J. Nucleosides Nucleotides Nucleic Acids (2006) [Pubmed]
  14. Antibiotic susceptibility and genotypic characterization of methicillin-resistant Staphylococcus aureus strains in eastern France. Bertrand, X., Thouverez, M., Talon, D. J. Hosp. Infect. (2000) [Pubmed]
  15. Epidural sufentanil for TKR-respiratory depression? Johnson, M.D. Regional anesthesia. (1990) [Pubmed]
  16. Detection of postoperative deep-venous thrombosis using technetium-99m-labeled tissue plasminogen activator. Butler, S.P., Rahman, T., Boyd, S.J., Parkes, S.L., Quinn, R.J. J. Nucl. Med. (1997) [Pubmed]
  17. Medial compartment arthroplasty of the knee. Ackroyd, C.E. The Journal of bone and joint surgery. British volume. (2003) [Pubmed]
  18. Do we really need to routinely crossmatch blood before primary total knee or hip arthroplasty? Mundy, G.M., Hardiment, K., Revill, J., Birtwistle, S.J., Power, R.A. Acta orthopaedica Scandinavica. (2004) [Pubmed]
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