TYMP
HGNC:3148 GeneID:1890 MIM.131222
Definition: TYMP encodes a thymidine phosphorylase. It is an angiogenic factor which promotes angiogenesis in vivo and stimulates the in vitro growth of a variety of endothelial cells. It has a highly restricted target cell specificity acting only on endothelial cells.
Function
TYMP (or Platelet-derived endothelial cell growth factor; PD-ECGF) is a novel angiogenic factor distinct from the previously described endothelial cell mitogens of the fibroblast growth factor family.
TYMP is stored in platelets as a 45-kD single polypeptide chain. It has a highly restricted target cell specificity acting only on endothelial cells.
It promotes angiogenesis in vivo and stimulates the in vitro growth of a variety of endothelial cells.
In addition to its function in angiogenesis, PDECFG is also known as thymidine phosphorylase and as gliostatin, because it limits glial cell proliferation.
Pathology
Mutations in TYMP gene have been associated with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) (MIM.603041). Multiple alternatively spliced variants, encoding the same protein, have been identified.
Several homozygous and compound heterozygous TYMP mutations have been identified mitochondrial neurogastrointestinal encephalomyopathy (MNGIE; MIM.603041).
MNGIE is characterized by multiple deletions of mtDNA. Most patients tested had multiple mtDNA deletions.
TP activity in leukocytes from MNGIE patients was less than 5 percent of controls, indicating that loss-of-function mutations in TP cause MNGIE.
Aberrant thymidine metabolism leads to impaired replication or maintenance of mtDNA, or both.
References
Gamez, J., Ferreiro, C., Accarino, M. L., Guarner, L., Tadesse, S., Marti, R. A., Andreu, A. L., Raguer, N., Cervera, C., Hirano, M. Phenotypic variability in a Spanish family with MNGIE. Neurology 59: 455-457, 2002. [PubMed: #12177387#]
Hagiwara, K., Stenman, G., Honda, H., Sahlin, P., Andersson, A., Miyazono, K., Heldin, C. H., Ishikawa, F., Takaku, F. Organization and chromosomal localization of the human platelet-derived endothelial cell growth factor gene. Molec. Cell. Biol. 11: 2125-2132, 1991. [PubMed: #2005900#]
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Lopez, L. C., Akman, H. O., Garcia-Cazorla, A., Dorado, B., Marti, R., Nishino, I., Tadesse, S., Pizzorno, G., Shungu, D., Bonilla, E., Tanji, K., Hirano, M. Unbalanced deoxynucleotide pools cause mitochondrial DNA instability in thymidine phosphorylase-deficient mice. Hum. Molec. Genet. 18: 714-722, 2009. [PubMed: #19028666#]
Marti, R., Verschuuren, J. J. G. M., Buchman, A., Hirano, I., Tadesse, S., van Kuilenburg, A. B. P., van Gennip, A. H., Poorthuis, B. J. H. M., Hirano, M. Late-onset MNGIE due to partial loss of thymidine phosphorylase activity. Ann. Neurol. 58: 649-652, 2005. [PubMed: #16178026#]
Nishino, I., Spinazzola, A., Hirano, M. Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science 283: 689-692, 1999. [PubMed: #9924029#]
Stenman, G., Sahlin, P., Dumanski, J. P., Hagiwara, K., Ishikawa, F., Miyazono, K., Collins, V. P., Heldin, C.-H. Regional localization of the human platelet-derived endothelial cell growth factor (ECGF1) gene to chromosome 22q13. Cytogenet. Cell Genet. 59: 22-23, 1992. [PubMed: #1733667#]
Szigeti, K., Wong, L.-J. C., Perng, C.-L., Saifi, G. M., Eldin, K., Adesina, A. M., Cass, D. L., Hirano, M., Lupski, J. R., Scaglia, F. MNGIE with lack of skeletal muscle involvement and a novel TP splice site mutation. J. Med. Genet. 41: 125-129, 2004. [PubMed: #14757860#]