About: DIHYDROPYRIMIDINE DEHYDROGENASE; DPYD [omim:612779]   Goto Sponge  NotDistinct  Permalink

An Entity of Type : http://bio2rdf.org/omim_vocabulary:Gene, within Data Space : virtuoso:8890 associated with source document(s)

  • The DPYD gene encodes dihydropyrimidine dehydrogenase ({EC}), the initial and rate-limiting enzyme in the catabolism of the pyrimidine bases uracil and thymine ({10:Van Kuilenburg et al., 1999}).
  • omim:612779
Bio2RDF identifier
  • 612779
Bio2RDF namespace
  • omim
Bio2RDF uri
identifiers.org URI
alternative title ...lternative-title]
  • DPD
article [omim_vocabulary:article]
chromosome [omim_vocabulary:chromosome]
cloning [omim_vocabulary:cloning]
  • {19:Yokota et al. (1994)} cloned and sequenced pig and human DPD cDNAs. The pig and human enzymes contain 1,025 amino acids and have a calculated molecular mass of 111 kD. The sequence of the gene suggested that DPD has at least 3 distinct domains: a possible NADPH binding site and FAD-binding site in the N terminus, 2 motifs of putative iron/sulfur-binding sites near the C terminus, and a central peptide domain corresponding to the uracil-binding site. Expression of the pig enzyme in E. coli catalyzed the reduction of uracil, thymine, and 5-fluorouracil (5FU) with kinetics approximating those published for the enzyme purified from mammalian liver.
cytolocation [omim...ary:cytolocation]
  • 1p22
gene function [omi...ry:gene-function]
  • {9:Van Kuilenburg et al. (1999)} studied the expression of DPD in various blood cell components. They demonstrated that the highest level of DPD was found in monocytes followed by that in lymphocytes, granulocytes, and platelets, whereas no significant activity of DPD could be detected in erythrocytes. The activity of DPD in peripheral blood mononuclear cells was intermediate between that observed in monocytes and lymphocytes. {9:Van Kuilenburg et al. (1999)} also observed a profound positive correlation between the DPD activity of these cells and the percentage of monocytes, thus introducing a large inter- and intrapatient variability in the activity of DPD. By cDNA microarray, Western blot analysis, and luciferase reporter assay, {20:Yoo et al. (2009)} identified the transcription factor LSF (TFCP2; {189889}) as a positive regulator of DPYD.
gene name [omim_vocabulary:gene-name]
  • Dihydropyrimidine dehydrogenase
gene structure [om...y:gene-structure]
  • {17:Wei et al. (1998)} characterized the structure of the DPYD gene and determined that it contains 23 exons spanning about 950 kb.
gene symbol [omim_...lary:gene-symbol]
mapping [omim_vocabulary:mapping]
  • Using somatic cell hybrid strategies, {19:Yokota et al. (1994)} mapped the DPYD gene to the centromeric region of chromosome 1 between 1p22 and 1q21. By fluorescence in situ hybridization, {6:Takai et al. (1994)} assigned the DPYD gene to 1p22.
mapping method [om...y:mapping-method]
molecular genetics...lecular-genetics]
  • In a Dutch patient with dihydropyrimidine dehydrogenase deficiency ({274270}) reported by {7:Van Gennip et al. (1994)}, {4:Meinsma et al. (1995)} identified homozygosity for a mutation in the DPYD gene (IVS14+1G-A; {612779.0001}). Both unaffected parents and 1 unaffected sib were heterozygous for the mutation. {18:Wei et al. (1996)} identified heterozygosity for the IVS14+1G-A mutation in a British cancer patient with partial DPD deficiency and severe toxicity after 5-fluorouracil treatment (see {274270}). {13:Vreken et al. (1997)} identified a 4-bp deletion in the DPYD gene ({612779.0003}) in affected members of a Dutch consanguineous family with DPD deficiency. Among a group of 22 patients from 17 families with complete DPD deficiency, {10:Van Kuilenburg et al. (1999)} identified 7 different mutations in the DPYD gene. The most common mutation by far, accounting for 52% of mutant alleles, was the IVS14+1G-A. There were no genotype/phenotype correlations. {8:Van Kuilenburg et al. (2009)} identified intragenic deletions of the DPYD gene in 4 patients with severe DPD deficiency in whom no point mutations were found. Three patients had a homozygous 13.8-kb deletion of exon 12, and 1 had a homozygous 122-kb deletion of exons 14 through 16 of the DPYD gene. All of these patients were born of consanguineous parents. A fifth patient was compound heterozygous for a 4-bp deletion ({612779.0003}) in the DPYD gene and a de novo 14-Mb deletion of chromosome 1p21.3-p13.3, including DPYD and several other genes, which likely contributed to severe psychomotor retardation and unusual craniofacial features in this patient. Overall, the study found genomic deletions affecting the DPYD gene in 7% (5 of 72) of DPD-deficient patients. These patients had a severe form of the disorder, with psychomotor retardation, epilepsy, hypotonia, and dysmorphic features, suggesting that gross deletions have a particularly detrimental effect.
mouse gene symbol ...ouse-gene-symbol]
nomenclature [omim...ary:nomenclature]
  • To standardize DPYD allele nomenclature and to conform with the international human gene nomenclature guidelines, {3:McLeod et al. (1998)} described an alternative to the existing arbitrary system. Based on recommendations for human genome nomenclature, they proposed that each distinct allele be designed by DPYD followed by an asterisk and an arabic numeral. Criteria for classification as a distinct allele were also presented.
preferred title [o...:preferred-title]
refers to [omim_vocabulary:refers-to]
variant [omim_vocabulary:variant]
x ensembl [omim_vocabulary:x-ensembl]
x flybase [omim_vocabulary:x-flybase]
x gi [omim_vocabulary:x-gi]
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