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FLASH GENE
Symbol DPYD contributors: SGE - updated : 03-05-2010
HGNC name dihydropyrimidine dehydrogenase
HGNC id 3012
Corresponding disease
DPYD dihydropyrimidine dehydrogenase (DPD) deficiency
Location 1p21.3      Physical location : 97.543.301 - 98.386.615
Synonym name
  • dihydrothymine dehydrogenase
  • dihydrouracil dehydrogenase2
    • Synonym symbol(s) DPD, DHP, MGC132008, MGC70799, DHPDHase
    EC.number 1.3.1.2
    DNA
    TYPE functioning gene
    STRUCTURE 843.32 kb     23 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    cytosine-phosphate-guanine/HTF
    Binding site   transcription factor
    text structure
  • three consensus Sp protein binding sites (SpA, SpB and SpC)
  • Sp1 and Sp3 binding sites (Sp1 is a strong activator)
    • MAPPING cloned Y linked N status confirmed
    Physical map
    HSU15552 1p22.1 acidic 82 kDa protein mRNA GCLM 1p22.1 glutamate-cysteine ligase, modifier subunit ABCA4 1p22.1 ATP-binding cassette, sub-family A (ABC1), member 4 PARG1 1p22.1 PTPL1-associated RhoGAP 1 LOC391057 1 similar to uracil DNA glycosylase ABCD3 1p22.1-p21.3 ATP-binding cassette, sub-family D (ALD), member 3 F3 1p22.1-p21 coagulation factor III (thromboplastin, tissue factor) MGC45474 1p22.1 hypothetical protein MGC45474 CNN3 1p21 calponin 3, acidic MGC19780 1p22.1 hypothetical protein MGC19780 FLJ31842 1p22.1 hypothetical protein FLJ31842 RWDD3 1p22.1 RWD domain containing 3 LOC388652 1 LOC388652 LOC284555 1p22.1 hypothetical LOC284555 LOC284556 1p22.1 similar to eukaryotic translation elongation factor 1 alpha 1; CTCL tumor antigen; translation elongation factor 1 alpha 1-like 14; prostate tumor-inducing protein 1; EF1a-like protein; glucocorticoid receptor AF-1 specific elongati PTBP2 1p22.11-p21.3 polypyrimidine tract binding protein 2 DPYD 1p22 dihydropyrimidine dehydrogenase SNX7 1p21.2 sorting nexin 7 LOC388653 1 LOC388653 LOC391058 1 similar to 60S ribosomal protein L5 PRG1 10q22.1 proteoglycan 1, secretory granule PALMD 1p22-p21 palmdelphin LOC391059 1 similar to Stromal cell derived factor receptor 2 AGL 1p21 amylo-1, 6-glucosidase, 4-alpha-glucanotransferase (glycogen debranching enzyme, glycogen storage disease type III) SLC35A3 1p21 solute carrier family 35 (UDP-N-acetylglucosamine (UDP-GlcNAc) transporter), member A3 HIAT1 1p21.3 hippocampus abundant transcript 1 DKFZp761A078 1p21.3 hypothetical protein DKFZp761A078 FLJ10287 1pter-q31.3 hypothetical protein FLJ10287 MGC14816 1p21.3 hypothetical protein MGC14816 DBT 1p31 dihydrolipoamide branched chain transacylase (E2 component of branched chain keto acid dehydrogenase complex; maple syrup urine disease) RTCD1 1p21.1 RTC domain containing 1 CDC14A 1p22 CDC14 cell division cycle 14 homolog A (S. cerevisiae)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    23 - 4451 - 1025 - 1994 8083224
    6 - 1789 - 173 - -
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  highly
     liver   highly
    Endocrineneuroendocrinepituitary  highly
    Nervousnerve   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticgranulocyte
    Blood/Hematopoieticmonocyte
    Blood/Hematopoieticplatelet
    Lymphoid/Immunelymphocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a pyridine nucleotide-disulphide oxidoreductase domain
  • dihydroorotate dehydrogenase domain
  • binding sites for NADPH, FAD/FMN, uracil and two iron-sulfur motifs
    • conjugated FlavoP , PhosphoP
    mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to C.elegans C25F6-3
    homolog to rattus Dpyd (89.2pc)
    homolog to murine Dpyd (89.6pc)
    Homologene
    FAMILY
  • dihydropyrimidine dehydrogenase family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • initial and rate-limiting enzyme in the catabolism of the pyrimidine bases uracil and thymine
  • dihydropyrimidine dehydrogenase implicated in pyrimidine catabolic pathway, in degradation of chemotherapeutic drug 5-fluorouracil, inhibiting thymidylate synthase
    • CELLULAR PROCESS nucleotide
    PHYSIOLOGICAL PROCESS circadian
    text circadian variation of expression
    PATHWAY
    metabolism aminoacid , purine/pyrimidine
    signaling
    amino acid biosynthesis
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding, cofactor,
  • binding two FAD
  • binding two FMN
  • binding two 4Fe-S clusters
  • containing 33 irons atoms per molecule
    • protein
    cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) DPYD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    disturbance of circadian expression in advanced gastric carcinoma, may be relevant for chronomodulated 5-fluoro-uracil-chemo therapy
    constitutional   deletion    
    hemizygous deletions in autism spectrum disorder with severe speech delay
    Susceptibility to developing severe 5FU-associated toxicity
    Variant & Polymorphism SNP , other
  • mutation with increased risk of developing severe 5FU-associated toxicity
  • variant c1796T>C is potentially pathogenic whereas DPYD IVS14+ 17A>G is suggested as a variant without clinical significance (Ofverholm 2010)
    • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivecolon
    HPLC assay could be available for routine clinical use before deficiency assesment in colorectal cancer patients prior to 5-FU administration
    ANIMAL & CELL MODELS