Alternative titles; symbols
HGNC Approved Gene Symbol: TKTL1
Cytogenetic location: Xq28 Genomic coordinates (GRCh38): X:154,295,795-154,330,350 (from NCBI)
Transketolase (TKT; 606781) is a thiamine-dependent enzyme that links the pentose phosphate pathway with the glycolytic pathway. As part of a systematic search for differentially expressed genes, Coy et al. (1996) isolated a novel transketolase-related gene, TKTL1, which they called TKR. They isolated transcripts encoding tissue-specific protein isoforms. Comparison with known transketolases demonstrated a TKR-specific deletion mutating 1 thiamine-binding site.
Coy et al. (1996) mapped the TKR gene between the green color vision pigment gene (300821) and the actin-binding protein-280 filamin gene (300017) on Xq28.
Genomic sequencing of the TKR gene by Coy et al. (1996) revealed the presence of a pseudoexon, as well as the acquisition of a tissue-specific spliced exon, compared to the TKT gene, which maps to 3p14.3. Coy et al. (1996) speculated that, since it had been postulated that the vertebrate genome arose by 2 cycles of tetraploidization from a cephalochordate genome, the finding of the pseudoexon and spliced exon could reflect the modulation of the function of a preexisting transketolase gene by gene duplication.
A variant transketolase enzyme has been proposed to be associated with Wernicke-Korsakoff syndrome (277730); however, no mutations have been found in the transketolase gene cloned from these patients (McCool et al., 1993). The findings of Coy et al. (1996) raised the possibility that variation in the X-linked TKT gene may be responsible for the genetic predisposition to the development of Wernicke-Korsakoff syndrome.
Coy, J. F., Dubel, S., Kioschis, P., Thomas, K., Micklem, G., Delius, H., Poustka, A. Molecular cloning of tissue-specific transcripts of a transketolase-related gene: implications for the evolution of new vertebrate genes. Genomics 32: 309-316, 1996. [PubMed: 8838793] [Full Text: https://doi.org/10.1006/geno.1996.0124]
McCool, B. A., Plonk, S. G., Martin, P. R., Singleton, C. K. Cloning of human transketolase cDNAs and comparison of the nucleotide sequence of the coding region in Wernicke-Korsakoff and non-Wernicke-Korsakoff individuals. J. Biol. Chem. 268: 1397-1404, 1993. [PubMed: 8419340]