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| DPYD | |
|---|---|
| Name | DPYD |
| Organism | Homo sapiens |
| Location | 1p21.3 |
| Aliases | DPD, DYPD |
DPYD
DPYD is a human gene encoding an enzyme central to pyrimidine catabolism and drug metabolism. The protein product catalyzes the rate-limiting step of uracil and thymine degradation and determines toxicity of fluoropyrimidine chemotherapies. DPYD links biochemical pathways that intersect with clinical oncology, pharmacology, and genetic medicine.
The enzyme product catalyzes reduction of uracil and thymine in a pathway connected to nucleotide salvage and energy metabolism, interacting with coenzymes and cellular redox systems characterized in studies from Max Planck Society, Harvard Medical School, Karolinska Institutet, Institut Pasteur, and University of Oxford. Biochemical analyses reference interactions with flavin adenine dinucleotide and iron-sulfur clusters described in work at Cold Spring Harbor Laboratory, ETH Zurich, Stanford University School of Medicine, Mayo Clinic, and Johns Hopkins University. Structural and kinetic investigations cite methods developed at European Molecular Biology Laboratory, Scripps Research, Massachusetts Institute of Technology, University of Cambridge, and National Institutes of Health. Enzymatic activity of the protein is modulated in pathways studied alongside enzymes characterized at Imperial College London, University of Tokyo, University of California, San Francisco, Yale School of Medicine, and UCLA David Geffen School of Medicine.
The DPYD locus on chromosome 1 was delineated using mapping approaches pioneered at Wellcome Trust Sanger Institute, Broad Institute, Genentech, Roche, and Novartis. Exon–intron organization and transcript variants were annotated in databases maintained by Ensembl, GenBank, UniProt, RefSeq, and GeneCards. Protein domain architecture and cofactor-binding motifs were resolved by crystallography efforts at Diamond Light Source, Argonne National Laboratory, Riken, Weizmann Institute of Science, and Max Planck Institute for Biochemistry. Comparative genomics placing DPYD among orthologs used pipelines developed at European Bioinformatics Institute, Cold Spring Harbor Laboratory Press, University of California, Berkeley, University of Edinburgh, and Purdue University.
Transcriptional control elements and promoter activity were defined in studies from NIH Clinical Center, University of Toronto, McGill University, University of Melbourne, and Seoul National University Hospital. Post-transcriptional regulation involving RNA-binding proteins and microRNA networks connects to research from Dana-Farber Cancer Institute, Fred Hutchinson Cancer Center, Karolinska University Hospital, Cleveland Clinic, and Mount Sinai Hospital (New York City). Tissue-specific expression patterns detected in liver and peripheral blood were mapped in projects led by GTEx Consortium, Human Protein Atlas, European Nucleotide Archive, National Center for Biotechnology Information, and Cancer Genome Atlas Research Network. Epigenetic modulation and chromatin interactions referencing methods from Broad Institute of MIT and Harvard, Cold Spring Harbor Laboratory, European Epigenome Atlas, Wellcome Sanger Institute, and Baylor College of Medicine influence expression under physiological and pathological states.
DPYD’s enzyme activity predicts severe toxicity to fluoropyrimidines such as 5-fluorouracil and capecitabine used in protocols from National Comprehensive Cancer Network, European Society for Medical Oncology, American Society of Clinical Oncology, World Health Organization, and Food and Drug Administration. Clinical pharmacogenetic guidelines referencing DPYD originate from Clinical Pharmacogenetics Implementation Consortium, PharmGKB, European Medicines Agency, Royal Marsden Hospital, and Mayo Clinic Proceedings. Case series and trials from MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center, Karolinska University Hospital, NCI, and Royal College of Physicians document dose adjustments, adverse event profiles, and outcome correlations.
Pathogenic and functional variants were cataloged in variant databases curated by ClinVar, dbSNP, HGMD, DECIPHER, and LOVD. Population genetics and allele frequency estimates derive from studies by 1000 Genomes Project, gnomAD consortium, HapMap Project, Human Genome Diversity Project, and UK Biobank. Associations between reduced enzyme function and treatment-related morbidity have been reported in cohorts at Vanderbilt University Medical Center, Sydney Cancer Centre, Seoul National University Hospital, Hospital Clínic de Barcelona, and Charité – Universitätsmedizin Berlin.
Genetic screening and phenotypic assays for DPYD deficiency are implemented in diagnostic workflows at Quest Diagnostics, LabCorp, Genome Medical, Invitae, and PathAI. Clinical algorithms integrating genotype-guided dosing reference protocols from Clinical Pharmacogenetics Implementation Consortium, European Society for Medical Oncology, NICE, French National Cancer Institute, and Dutch Pharmacogenetics Working Group. Therapeutic interventions, including dose reduction, alternative chemotherapy regimens, and uridine triacetate rescue, are described in practice at Johns Hopkins Hospital, Massachusetts General Hospital, Cleveland Clinic Foundation, St. Jude Children’s Research Hospital, and Royal Marsden.
Animal and cellular models used to study gene function include efforts from Jackson Laboratory, Zebrafish International Resource Center, European Mouse Mutant Archive, National Cancer Institute Mouse Repository, and Thermo Fisher Scientific Cell Culture Services. CRISPR and RNAi functional studies were performed at Broad Institute, CRG (Centre for Genomic Regulation), Genome Institute of Singapore, Cold Spring Harbor Laboratory, and Salk Institute. High-throughput screening and systems biology analyses linking DPYD to networks cite pipelines from Illumina, Agilent Technologies, PerkinElmer, Takeda Pharmaceutical Company, and GlaxoSmithKline. Translational research collaborations and consortia include Translational Genomics Research Institute, European Organisation for Research and Treatment of Cancer, ICGC, P4 Medicine Institute, and Cancer Research UK.
Category:Genes on human chromosome 1