ArticleAmerican journal of human genetics1997
Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families.
Article in American journal of human genetics, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
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- Both gene expression for orotate phosphoribosyltransferase and its ratio to dihydropyrimidine dehydrogenase influence outcome following fluoropyrimidine-based chemotherapy for metastatic colorectal cancer.British journal of cancer · 2003Trial
- Dynamic control of nucleotide metabolism in physiology and disease.Nature cell biology · 2026Review
- Structural and systems characterization of phosphorylation on metabolic enzymes identifies sex-specific metabolic reprogramming in obesity.Molecular cell · 2025Article
- A Facile Fluorometric Assay of Orotate Phosphoribosyltransferase Activity Using a Selective Fluorogenic Reaction for Orotic Acid.Sensors (Basel, Switzerland) · 2023Article
- Hereditary orotic aciduria identified by newborn screening.Frontiers in genetics · 2023Article
- Serum Orotidine: A Novel Biomarker of Increased CVD Risk in Type 2 Diabetes Discovered Through Metabolomics Studies.Diabetes care · 2022Article
- Role of pH in Regulating Cancer Pyrimidine Synthesis.Journal of xenobiotics · 2022Review
- Identification of critical genetic variants associated with metabolic phenotypes of the Japanese population.Communications biology · 2020Article
- An optimized chemical-genetic method for cell-specific metabolic labeling of RNA.Nature methods · 2020Article
- Modulating pyrimidine ribonucleotide levels for the treatment of cancer.Cancer & metabolism · 2020Review
- Genome wide analysis reveals heparan sulfate epimerase modulates TDP-43 proteinopathy.PLoS genetics · 2019Article
- Mild orotic aciduria in UMPS heterozygotes: a metabolic finding without clinical consequences.Journal of inherited metabolic disease · 2017Article
- Article
- Biallelic mutations in CAD, impair de novo pyrimidine biosynthesis and decrease glycosylation precursors.Human molecular genetics · 2015Article
- Pharmacogenetics research on chemotherapy resistance in colorectal cancer over the last 20 years.World journal of gastroenterology · 2014Review
- Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.The Journal of biological chemistry · 2013Article
- Transition-state inhibitors of purine salvage and other prospective enzyme targets in malaria.Future medicinal chemistry · 2013Review
- Novel mRNA isoforms and mutations of uridine monophosphate synthetase and 5-fluorouracil resistance in colorectal cancer.The pharmacogenomics journal · 2013Article
- Protein instability and functional defects caused by mutations of dihydro-orotate dehydrogenase in Miller syndrome patients.Bioscience reports · 2012Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Uridine monophosphate (UMP) synthase is a bifunctional enzyme catalyzing the last two steps of de novo pyrimidine biosynthesis, orotate phosphoribosyltransferase (OPRT) and orotidine-5'-monophosphate decarboxylase (ODC). Loss of either enzymatic activity results in hereditary orotic aciduria, a rare autosomal recessive disorder characterized by retarded growth, anemia, and excessive urinary excretion of orotic acid. We have isolated the UMP synthase chromosomal gene from a lambdaEMBL-3 human genomic library and report a single-copy gene spanning approximately 15 kb. The UMP synthase genomic structure encodes six exons ranging in size from 115 bp to 672 bp, and all splicing junctions adhere to the canonical GT/AG rule. Cognate promoter elements implicated in glucocorticoid- and cAMP-mediated regulation as well as in liver-, myeloid-, and lymphocyte-specific expression are located within the 5' flanking sequence. Molecular investigation of UMP synthase deficiency in a Japanese orotic aciduria patient revealed mutations R96G (A-to-G transition; nt 286) and G429R (G-to-C transversion; nt 1285) in one allele and V109G (T-to-G transversion; nt 326) in the other allele. Expression of human UMP synthase cDNAs containing these mutations in pyrimidine auxotrophic Escherichia coli and in recombinant baculovirus-infected Sf21 cells demonstrates impaired activity presumably associated with the urinary orotic acid substrate accumulations observed in vivo. We further establish the identity of two polymorphisms, G213A (v = .26) and 440Gpoly (v = .27) located in exons 3 and 6, respectively, which did not significantly compromise either OPRT or ODC function.
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9042911PMC1712531W1579173063What OpenQuestion holds
Registered trials
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