TYMP (Thymidine Phosphorylase) Gene
Key regulator of pyrimidine metabolism and angiogenesis; mutations cause Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE) syndrome
Gene Information Card
| Symbol | TYMP |
|---|---|
| Full Name | Thymidine Phosphorylase |
| Gene Type | Protein coding |
| Chromosomal Location | 22q13.33 |
| NCBI Gene ID | 1890 ncbi.nlm.nih.gov/gene/1890 |
| Ensembl ID | ENSG00000100299 |
| UniProt ID | P19971 |
| OMIM ID | 131222 |
| HGNC ID | 12418 |
| Aliases | ECGF1, PDECGF, TP, MNGIE, gliostatin |
Description
The TYMP gene encodes thymidine phosphorylase (TP), an enzyme that catalyzes the reversible phosphorolysis of thymidine to thymine and 2-deoxy-D-ribose-1-phosphate. This enzyme plays a critical role in pyrimidine salvage and homeostasis. Additionally, TP functions as a platelet-derived endothelial cell growth factor (PD-ECGF) and gliostatin, promoting angiogenesis and inhibiting glial cell proliferation. Loss-of-function mutations in TYMP cause Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE) syndrome, a rare autosomal recessive disorder characterized by severe gastrointestinal dysmotility, peripheral neuropathy, leukoencephalopathy, and mitochondrial DNA abnormalities.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE) syndrome | Loss-of-function mutations in TYMP lead to thymidine phosphorylase deficiency, causing accumulation of thymidine and deoxyuridine. This imbalance disrupts mitochondrial nucleotide pools, resulting in multiple mitochondrial DNA deletions and depletion, particularly in post-mitotic tissues. | ClinVar, OMIM |
| Thymidine phosphorylase deficiency | Biallelic pathogenic variants in TYMP abolish enzyme activity, leading to systemic accumulation of thymidine and deoxyuridine, which are toxic to mitochondria. | OMIM, NCBI |
| Cancer (angiogenesis-related) | Overexpression of TYMP (as PD-ECGF) in solid tumors promotes angiogenesis and correlates with poor prognosis in colorectal, breast, and gastric cancers. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Small intestine | 10.8 | Medium |
| Lung | 8.3 | Medium |
| Spleen | 7.1 | Low |
| Brain | 2.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 15.2 | High expression |
| A549 (lung) | 9.8 | Medium expression |
| MCF7 (breast) | 6.5 | Low expression |
| HeLa (cervical) | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.866G>A (p.Gly289Asp) | Missense | Common in MNGIE | Loss of thymidine phosphorylase activity |
| c.457G>A (p.Glu153Lys) | Missense | Reported in MNGIE | Loss of function |
| c.1120C>T (p.Arg374*) | Nonsense | Rare | Premature truncation, loss of function |
| c.215delG (p.Gly72Valfs*12) | Frameshift | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations in TYMP cause thymidine phosphorylase deficiency, leading to MNGIE syndrome. These include missense, nonsense, frameshift, and splice-site variants that reduce or abolish enzyme activity.
Gain of Function (GOF)
Not reported for TYMP. Overexpression in tumors is due to transcriptional upregulation, not activating mutations.
Dominant Negative (DN)
Not described. MNGIE is autosomal recessive; heterozygous carriers are asymptomatic.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Pyrimidine metabolism (Reactome: R-HSA-500753)
• Pyrimidine salvage (Reactome: R-HSA-73621)
• Mitochondrial nucleotide metabolism (Reactome: R-HSA-159447)
Protein Summary
Thymidine phosphorylase (TP) is a homodimeric enzyme encoded by TYMP. Each subunit binds a phosphate ion and catalyzes the reversible phosphorolysis of thymidine. TP also acts as a growth factor (PD-ECGF) stimulating endothelial cell migration and angiogenesis. In MNGIE, TP deficiency leads to toxic accumulation of thymidine and deoxyuridine, causing mitochondrial DNA instability. The protein is predominantly cytosolic and highly expressed in liver, intestine, and lung.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TYMP Knockout HEK293 Cell Line | EDJ-KQ2212 | Human | 1890 | Details Get a Quote |
| TYMP Knockout A-549 Cell Line | EDJ-KQ22468 | Human | 1890 | Details Get a Quote |
| TYMP Knockout HCT 116 Cell Line | EDJ-KQ22469 | Human | 1890 | Details Get a Quote |
| TYMP Knockout HeLa Cell Line | EDJ-KQ22470 | Human | 1890 | Details Get a Quote |
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