Normal Function
The TYMP gene (previously known as ECGF1) provides instructions for making an enzyme called thymidine phosphorylase. Thymidine is a molecule known as a nucleoside. After a chemical modification, thymidine is used as a building block of DNA. Thymidine phosphorylase converts thymidine into two smaller molecules, 2-deoxyribose 1-phosphate and thymine. By breaking down thymidine, this chemical reaction helps regulate the level of nucleosides in cells.
Thymidine phosphorylase plays an important role in maintaining the appropriate amount of thymidine in cell structures called mitochondria. Mitochondria convert the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA, called mitochondrial DNA or mtDNA. Mitochondria use nucleosides, including thymidine, to build new molecules of mtDNA.
Health Conditions Related to Genetic Changes
Mitochondrial neurogastrointestinal encephalopathy disease
About 50 variants (also called mutations) in the TYMP gene have been identified in people with mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease. This condition affects several parts of the body, particularly the digestive system and nervous system.
TYMP gene variants greatly reduce or eliminate the activity of thymidine phosphorylase. A shortage of this enzyme allows thymidine to build up to very high levels in the body. This extra thymidine can damage mtDNA, disrupting its usual maintenance and repair processes. As a result, variants can accumulate in mtDNA, causing it to become unstable. In people with MNGIE disease, mitochondria may also have less mtDNA than usual (mtDNA depletion). These genetic changes impair the normal function of mitochondria. Although mtDNA abnormalities underlie the digestive and neurological problems that are characteristic of MNGIE disease, it is unclear how defective mitochondria cause the specific features of the disorder.
More About This Health ConditionOther Names for This Gene
- ECGF1
- endothelial cell growth factor 1 (platelet-derived)
- gliostatin
- hPD-ECGF
- MNGIE
- PD-ECGF
- PDECGF
- TdRPase
- TP
- TYPH_HUMAN
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Hirano M, Marti R, Spinazzola A, Nishino I, Nishigaki Y. Thymidine phosphorylase deficiency causes MNGIE: an autosomal recessive mitochondrial disorder. Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1217-25. doi: 10.1081/NCN-200027485. Citation on PubMed
- Hirano M, Nishigaki Y, Marti R. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a disease of two genomes. Neurologist. 2004 Jan;10(1):8-17. doi: 10.1097/01.nrl.0000106919.06469.04. Citation on PubMed
- Lara MC, Valentino ML, Torres-Torronteras J, Hirano M, Marti R. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): biochemical features and therapeutic approaches. Biosci Rep. 2007 Jun;27(1-3):151-63. doi: 10.1007/s10540-007-9043-2. Citation on PubMed
- Marti R, Nishigaki Y, Vila MR, Hirano M. Alteration of nucleotide metabolism: a new mechanism for mitochondrial disorders. Clin Chem Lab Med. 2003 Jul;41(7):845-51. doi: 10.1515/CCLM.2003.128. Citation on PubMed
- Marti R, Spinazzola A, Nishino I, Andreu AL, Naini A, Tadesse S, Oliver JA, Hirano M. Mitochondrial neurogastrointestinal encephalomyopathy and thymidine metabolism: results and hypotheses. Mitochondrion. 2002 Nov;2(1-2):143-7. doi: 10.1016/s1567-7249(02)00036-3. Citation on PubMed
- Nishino I, Spinazzola A, Hirano M. MNGIE: from nuclear DNA to mitochondrial DNA. Neuromuscul Disord. 2001 Jan;11(1):7-10. doi: 10.1016/s0960-8966(00)00159-0. Citation on PubMed
- Nishino I, Spinazzola A, Hirano M. Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science. 1999 Jan 29;283(5402):689-92. doi: 10.1126/science.283.5402.689. Citation on PubMed
- Nishino I, Spinazzola A, Papadimitriou A, Hammans S, Steiner I, Hahn CD, Connolly AM, Verloes A, Guimaraes J, Maillard I, Hamano H, Donati MA, Semrad CE, Russell JA, Andreu AL, Hadjigeorgiou GM, Vu TH, Tadesse S, Nygaard TG, Nonaka I, Hirano I, Bonilla E, Rowland LP, DiMauro S, Hirano M. Mitochondrial neurogastrointestinal encephalomyopathy: an autosomal recessive disorder due to thymidine phosphorylase mutations. Ann Neurol. 2000 Jun;47(6):792-800. Citation on PubMed
- Valentino ML, Marti R, Tadesse S, Lopez LC, Manes JL, Lyzak J, Hahn A, Carelli V, Hirano M. Thymidine and deoxyuridine accumulate in tissues of patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). FEBS Lett. 2007 Jul 24;581(18):3410-4. doi: 10.1016/j.febslet.2007.06.042. Epub 2007 Jun 27. Citation on PubMed or Free article on PubMed Central
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