UPP1 Gene: Uridine Phosphorylase 1 – Function, Disease Relevance, and Expression
Comprehensive biomedical overview of UPP1 (uridine phosphorylase 1), including genomic context, protein function, tissue expression, mutations, and clinical significance.
Gene Information Card
| Symbol | UPP1 |
|---|---|
| Full Name | Uridine phosphorylase 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 7p12.3 |
| NCBI Gene ID | 7378 ncbi.nlm.nih.gov/gene/7378 |
| Ensembl ID | ENSG00000183696 |
| UniProt ID | Q16831 |
| OMIM ID | 191730 |
| HGNC ID | 12576 |
| Aliases | UPase1, UP, UPP |
Description
UPP1 encodes uridine phosphorylase 1, an enzyme that catalyzes the reversible phosphorolysis of uridine and deoxyuridine to uracil and ribose-1-phosphate (or deoxyribose-1-phosphate). This reaction is a key step in the pyrimidine salvage pathway, regulating intracellular nucleoside pools and influencing nucleic acid synthesis. UPP1 is involved in the metabolism of chemotherapeutic nucleoside analogs, such as 5-fluorouracil (5-FU) and capecitabine, and its expression has been linked to drug sensitivity and resistance in various cancers. The gene is located on chromosome 7p12.3 and is expressed in multiple tissues, with highest levels in the liver, kidney, and gastrointestinal tract.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | UPP1 expression is associated with 5-FU metabolism; high expression may enhance activation of 5-FU to cytotoxic metabolites, but also correlates with tumor progression. | PMID: 12679347 (via NCBI Gene, COSMIC) |
| Hepatocellular carcinoma | UPP1 is overexpressed in liver cancer and may contribute to pyrimidine salvage, supporting rapid cell proliferation. | PMID: 21761190 (via NCBI Gene, COSMIC) |
| Pancreatic cancer | UPP1 expression is linked to gemcitabine resistance; altered nucleoside metabolism affects drug efficacy. | PMID: 23327944 (via NCBI Gene, COSMIC) |
| Thymidine phosphorylase deficiency (mitochondrial neurogastrointestinal encephalomyopathy, MNGIE) | UPP1 is not the primary cause, but its activity can modulate thymidine levels; mutations in TYMP cause MNGIE, while UPP1 variants may influence phenotype. | OMIM: 191730 (UPP1), OMIM: 603041 (TYMP) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 25.3 | High |
| Kidney | 18.7 | High |
| Small intestine | 15.2 | High |
| Colon | 12.8 | High |
| Lung | 8.4 | Medium |
| Spleen | 6.1 | Medium |
| Brain | 2.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 22.5 | High expression; consistent with liver tissue |
| A549 (lung) | 9.8 | Moderate expression |
| MCF7 (breast) | 4.2 | Low expression |
| K562 (leukemia) | 3.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.215C>T (p.Pro72Leu) | Missense | Rare (MAF <0.01) | Reduced enzyme activity in vitro; potential impact on nucleoside metabolism. |
| c.469G>A (p.Gly157Ser) | Missense | Rare (MAF <0.01) | Altered substrate affinity; clinical significance uncertain. |
| c.742A>G (p.Thr248Ala) | Missense | Rare (MAF <0.01) | No significant functional change reported. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in UPP1 are rare and may lead to reduced uridine phosphorylase activity, potentially affecting pyrimidine salvage and drug metabolism. No germline disease is directly attributed to UPP1 loss, but somatic alterations may influence cancer therapy response.
Gain of Function (GOF)
Gain-of-function mutations are not well documented; overexpression of UPP1 in tumors is more common than activating mutations, leading to increased nucleoside metabolism and drug activation.
Dominant Negative (DN)
No dominant-negative mutations have been reported for UPP1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Pyrimidine metabolism (KEGG: hsa00240)
• Pyrimidine salvage pathway (Reactome: R-HSA-73621)
• 5-Fluorouracil metabolism (Reactome: R-HSA-9749778)
Protein Summary
Uridine phosphorylase 1 (UPP1) is a homodimeric enzyme that catalyzes the reversible phosphorolysis of uridine and deoxyuridine to uracil and ribose-1-phosphate. It plays a central role in pyrimidine salvage, regulating nucleotide pools for DNA/RNA synthesis. UPP1 is also critical for the activation of fluoropyrimidine drugs like 5-FU and capecitabine, converting them to cytotoxic metabolites. The protein is expressed in various tissues, with high levels in the liver and gastrointestinal tract. Altered UPP1 expression is observed in multiple cancers, influencing drug sensitivity and tumor progression. Structural studies reveal a dimeric arrangement with a catalytic site that binds uridine and phosphate.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UPP1 Knockout HEK293 Cell Line | EDJ-KQ2442 | Human | 7378 | Details Get a Quote |
| UPP1 Knockout A-549 Cell Line | EDJ-KQ22954 | Human | 7378 | Details Get a Quote |
| UPP1 Knockout HCT 116 Cell Line | EDJ-KQ22955 | Human | 7378 | Details Get a Quote |
| UPP1 Knockout HeLa Cell Line | EDJ-KQ22956 | Human | 7378 | Details Get a Quote |
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