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UMPS
UMPS Full Name
uridine monophosphate synthetase
UMPS Introduction
UMPS encodes uridine monophosphate synthetase, a single bifunctional protein that catalyzes the final two reactions of the de novo pyrimidine biosynthetic pathway. Its N-terminal domain acts as orotate phosphoribosyltransferase (OPRT), converting orotic acid and phosphoribosyl pyrophosphate into orotidine-5'-monophosphate, while its C-terminal domain functions as orotidine-5'-monophosphate decarboxylase (ODC), decarboxylating that intermediate into uridine monophosphate (UMP), the direct precursor of all other pyrimidines such as UDP, UTP, and CTP. Because pyrimidines are essential building blocks of DNA, RNA, and a host of sugar- and lipid-conjugated molecules, UMPS sits at a metabolic crossroads that every dividing cell depends on. The gene is broadly expressed across human tissues, and its single polypeptide is organized so that the two catalytic activities operate in sequence without releasing the intermediate into the cytosol, an elegant arrangement that improves efficiency and protects the cell from accumulating toxic orotic acid.
Figure 1. Schematic of the de novo pyrimidine synthesis pathway. (Source: Villa E, et al. 2019)
When UMPS is absent or severely impaired, the body cannot make enough pyrimidines, and orotic acid instead spills into the urine, the hallmark of hereditary orotic aciduria, a rare autosomal recessive disorder. Affected infants typically present with megaloblastic anemia that does not improve with iron or vitamin B12, along with failure to thrive, developmental delay, and immune problems; unlike urea-cycle defects, they do not show hyperammonemia. The condition is uniquely treatable: supplying uridine bypasses the blocked step and resolves the hematologic and neurologic manifestations. Beyond rare disease, UMPS has gained attention in oncology because it converts the widely used antimetabolite 5-fluorouracil (5-FU) into its active cytotoxic metabolites; mutations, isoform switching, and reduced expression of UMPS in colorectal tumors are now recognized as mechanisms of acquired 5-FU resistance, making the enzyme a candidate biomarker for chemotherapy response. Notably, heterozygous carriers of UMPS variants can also excrete mildly elevated orotic acid without developing overt disease, illustrating how gene dosage shapes the metabolic phenotype and broadening the differential diagnosis of orotic aciduria.
Alternate Names for UMPS
UMPS; uridine monophosphate synthetase; uridine 5-monophosphate synthase; orotate phosphoribosyl transferase and orotidine 5 decarboxylase; OPRTase; OMPdecase; UMP synthase; orotate phosphoribosyltransferase; orotidine 5-phosphate decarboxylase; OPRT;
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