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    DPYD dihydropyrimidine dehydrogenase [ Homo sapiens (human) ]

    Gene ID: 1806, updated on 27-Nov-2024

    Summary

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    Official Symbol
    DPYDprovided by HGNC
    Official Full Name
    dihydropyrimidine dehydrogenaseprovided by HGNC
    Primary source
    HGNC:HGNC:3012
    See related
    Ensembl:ENSG00000188641 MIM:612779; AllianceGenome:HGNC:3012
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    DHP; DPD; DYPD; DHPDHASE
    Summary
    The protein encoded by this gene is a pyrimidine catabolic enzyme and the initial and rate-limiting factor in the pathway of uracil and thymidine catabolism. Mutations in this gene result in dihydropyrimidine dehydrogenase deficiency, an error in pyrimidine metabolism associated with thymine-uraciluria and an increased risk of toxicity in cancer patients receiving 5-fluorouracil chemotherapy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]
    Expression
    Ubiquitous expression in gall bladder (RPKM 9.2), lung (RPKM 8.2) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See DPYD in Genome Data Viewer
    Location:
    1p21.3
    Exon count:
    26
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (97077743..97921059, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (96925834..97768903, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (97543299..98386615, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr1:97180360-97181288 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr1:97181289-97182216 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1107 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1108 Neighboring gene RN7SK pseudogene 270 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr1:97227285-97227992 Neighboring gene polypyrimidine tract binding protein 2 Neighboring gene NANOG hESC enhancer GRCh37_chr1:97580130-97580999 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1355 Neighboring gene VISTA enhancer hs671 Neighboring gene DPYD antisense RNA 1 Neighboring gene uncharacterized LOC105378867 Neighboring gene uncharacterized LOC124904226 Neighboring gene NANOG hESC enhancer GRCh37_chr1:97907396-97908033 Neighboring gene uncharacterized LOC124904225 Neighboring gene SEC63 homolog, protein translocation regulator pseudogene 1 Neighboring gene ribosomal protein L26 pseudogene 9 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1356 Neighboring gene MIA SH3 domain ER export factor 2 pseudogene Neighboring gene DPYD antisense RNA 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1109 Neighboring gene uncharacterized LOC124904227 Neighboring gene long intergenic non-protein coding RNA 1930

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Clinical relevance of different dihydropyrimidine dehydrogenase gene single nucleotide polymorphisms on 5-fluorouracil tolerance. Morel A, et al. Mol Cancer Ther, 2006 Nov. PMID 17121937
    2. Methylation of the DPYD promoter: an alternative mechanism for dihydropyrimidine dehydrogenase deficiency in cancer patients. Ezzeldin HH, et al. Clin Cancer Res, 2005 Dec 15. PMID 16361556
    3. The relationship between survival and the expression of dihydropyrimidine dehydrogenase in patients with colorectal cancer. Hotta T, et al. Oncol Rep, 2006 Jul. PMID 16786143
    4. High expression of dihydropyrimidine dehydrogenase in lung adenocarcinoma is associated with mutations in epidermal growth factor receptor: implications for the treatment of non--small-cell lung cancer using 5-fluorouracil. Mochinaga K, et al. Clin Lung Cancer, 2014 Mar. PMID 24405586
    5. Deficient expression of the DPD gene is caused by epigenetic modification in biliary tract cancer cells, and induces high sensitivity to 5-FU treatment. Sato K, et al. Int J Oncol, 2006 Aug. PMID 16820886

    See all (268) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. MIR27A Gene Polymorphism Modifies the Effect of Common DPYD Gene Variants on Severe Toxicity in Patients with Gastrointestinal Tumors Treated with Fluoropyrimidine-Based Anticancer Therapy.
      Title: MIR27A Gene Polymorphism Modifies the Effect of Common DPYD Gene Variants on Severe Toxicity in Patients with Gastrointestinal Tumors Treated with Fluoropyrimidine-Based Anticancer Therapy.
    2. DPYD genetic polymorphisms in non-European patients with severe fluoropyrimidine-related toxicity: a systematic review.
      Title: DPYD genetic polymorphisms in non-European patients with severe fluoropyrimidine-related toxicity: a systematic review.
    3. Lethal Capecitabine Toxicity in Patients With Complete Dihydropyrimidine Dehydrogenase Deficiency Due to Ultra-Rare DPYD Variants.
      Title: Lethal Capecitabine Toxicity in Patients With Complete Dihydropyrimidine Dehydrogenase Deficiency Due to Ultra-Rare DPYD Variants.
    4. Germline cis variant determines epigenetic regulation of the anti-cancer drug metabolism gene dihydropyrimidine dehydrogenase (DPYD).
      Title: Germline cis variant determines epigenetic regulation of the anti-cancer drug metabolism gene dihydropyrimidine dehydrogenase (DPYD).
    5. Common dihydropyrimidinase (DPYS) genetic variations do not predict fluoropyrimidine-related chemotherapy toxicity in a Canadian cohort.
      Title: Common dihydropyrimidinase ( DPYS ) genetic variations do not predict fluoropyrimidine-related chemotherapy toxicity in a Canadian cohort.
    6. MIR27A rs895819 TC genotype increases risk of fluoropyrimidine-induced severe toxicity independently of DPYD variations.
      Title: MIR27A rs895819 TC genotype increases risk of fluoropyrimidine-induced severe toxicity independently of DPYD variations.
    7. Integrating rare genetic variants into DPYD pharmacogenetic testing may help preventing fluoropyrimidine-induced toxicity.
      Title: Integrating rare genetic variants into DPYD pharmacogenetic testing may help preventing fluoropyrimidine-induced toxicity.
    8. Genetic Variation in miR-27a Is Associated with Fluoropyrimidine-Associated Toxicity in Patients with Dihydropyrimidine Dehydrogenase Variants after Genotype-Guided Dose Reduction.
      Title: Genetic Variation in miR-27a Is Associated with Fluoropyrimidine-Associated Toxicity in Patients with Dihydropyrimidine Dehydrogenase Variants after Genotype-Guided Dose Reduction.
    9. Allelic Frequency of DPYD Genetic Variants in Patients With Cancer in Spain: The PhotoDPYD Study.
      Title: Allelic Frequency of DPYD Genetic Variants in Patients With Cancer in Spain: The PhotoDPYD Study.
    10. DPYD and TYMS polymorphisms as predictors of 5 fluorouracil toxicity in colorectal cancer patients.
      Title: DPYD and TYMS polymorphisms as predictors of 5 fluorouracil toxicity in colorectal cancer patients.
    Submit: New GeneRIF Correction See all GeneRIFs (199)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Capecitabine response
    MedGen: CN077963 GeneReviews: Not available
    		not available
    Dihydropyrimidine dehydrogenase deficiency
    MedGen: C1959620 OMIM: 274270 GeneReviews: Not available
    		not available
    Fluoropyrimidine response
    MedGen: CN184090 GeneReviews: Not available
    		not available
    Tegafur response
    MedGen: C1852514 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    Biological insights from 108 schizophrenia-associated genetic loci.
    EBI GWAS Catalog
    Duffy-null-associated low neutrophil counts influence HIV-1 susceptibility in high-risk South African black women.
    EBI GWAS Catalog
    Genome-wide association analysis identifies 13 new risk loci for schizophrenia.
    EBI GWAS Catalog
    Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder.
    EBI GWAS Catalog
    Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.
    EBI GWAS Catalog
    Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC70799, MGC132008

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 4 iron, 4 sulfur cluster binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables NADP binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables NADP binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables dihydropyrimidine dehydrogenase (NADP+) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables dihydropyrimidine dehydrogenase (NADP+) activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables dihydropyrimidine dehydrogenase (NADP+) activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables dihydropyrimidine dehydrogenase (NADP+) activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables flavin adenine dinucleotide binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein homodimerization activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables uracil binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in CMP catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in UMP catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in beta-alanine biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in dCMP catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in dUMP catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in purine nucleobase catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in pyrimidine nucleobase catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in pyrimidine nucleobase catabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in thymidine catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in thymine catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in thymine catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in uracil catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in uracil catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    dihydropyrimidine dehydrogenase [NADP(+)]
    Names
    dihydrothymine dehydrogenase
    dihydrouracil dehydrogenase
    NP_000101.2
    NP_001153773.1
    XP_005270619.2
    XP_006710460.1
    XP_016855996.1
    XP_047304032.1
    XP_047304033.1
    XP_054190775.1
    XP_054190776.1
    XP_054190777.1
    XP_054190778.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_008807.2 RefSeqGene

      Range
      5001..848317
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_722

    mRNA and Protein(s)

    1. NM_000110.4 → NP_000101.2  dihydropyrimidine dehydrogenase [NADP(+)] isoform 1

      See identical proteins and their annotated locations for NP_000101.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AI124948, DA721123, U20938
      Consensus CDS
      CCDS30777.1
      UniProtKB/Swiss-Prot
      A2RRQ2, A2RRQ3, A8K5A2, A8MWG9, B1AN21, E9PFN1, Q12882, Q16694, Q16761, Q32NB0, Q96HL6, Q96TH1
      Related
      ENSP00000359211.3, ENST00000370192.8
      Conserved Domains (6) summary
      PRK08318
      Location:532 → 1007
      PRK08318; dihydropyrimidine dehydrogenase subunit B; Validated
      PRK11749
      Location:53 → 513
      PRK11749; dihydropyrimidine dehydrogenase subunit A; Provisional
      cd02940
      Location:532 → 834
      DHPD_FMN; Dihydropyrimidine dehydrogenase (DHPD) FMN-binding domain. DHPD catalyzes the first step in pyrimidine degradation: the NADPH-dependent reduction of uracil and thymine to the corresponding 5,6-dihydropyrimidines. DHPD contains two FAD, two FMN, and ...
      pfam13187
      Location:953 → 997
      Fer4_9; 4Fe-4S dicluster domain
      pfam13450
      Location:194 → 238
      NAD_binding_8; NAD(P)-binding Rossmann-like domain
      pfam14691
      Location:56 → 168
      Fer4_20; Dihydroprymidine dehydrogenase domain II, 4Fe-4S cluster

    2. NM_001160301.1 → NP_001153773.1  dihydropyrimidine dehydrogenase [NADP(+)] isoform 2

      See identical proteins and their annotated locations for NP_001153773.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 3' UTR and coding sequence compared to variant 1. The resulting isoform (2) has a shorter and distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AC138135, BC008379, DA721123
      Consensus CDS
      CCDS53346.1
      UniProtKB/Swiss-Prot
      Q12882
      Related
      ENSP00000307107.5, ENST00000306031.5
      Conserved Domains (1) summary
      pfam14691
      Location:56 → 162
      Fer4_20; Dihydroprymidine dehydrogenase domain II, 4Fe-4S cluster

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      97077743..97921059 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047448077.1 → XP_047304033.1  dihydropyrimidine dehydrogenase [NADP(+)] isoform X4

    2. XM_017000507.2 → XP_016855996.1  dihydropyrimidine dehydrogenase [NADP(+)] isoform X1

    3. XM_005270562.3 → XP_005270619.2  dihydropyrimidine dehydrogenase [NADP(+)] isoform X2

      Conserved Domains (6) summary
      PRK11749
      Location:53 → 508
      PRK11749; dihydropyrimidine dehydrogenase subunit A; Provisional
      cd02940
      Location:509 → 762
      DHPD_FMN; Dihydropyrimidine dehydrogenase (DHPD) FMN-binding domain. DHPD catalyzes the first step in pyrimidine degradation: the NADPH-dependent reduction of uracil and thymine to the corresponding 5,6-dihydropyrimidines. DHPD contains two FAD, two FMN, and ...
      pfam13187
      Location:881 → 925
      Fer4_9; 4Fe-4S dicluster domain
      pfam13450
      Location:194 → 238
      NAD_binding_8; NAD(P)-binding Rossmann-like domain
      pfam14691
      Location:56 → 168
      Fer4_20; Dihydroprymidine dehydrogenase domain II, 4Fe-4S cluster
      pfam14697
      Location:874 → 932
      Fer4_21; 4Fe-4S dicluster domain

    4. XM_047448076.1 → XP_047304032.1  dihydropyrimidine dehydrogenase [NADP(+)] isoform X3

    5. XM_006710397.4 → XP_006710460.1  dihydropyrimidine dehydrogenase [NADP(+)] isoform X5

      Conserved Domains (5) summary
      TIGR01037
      Location:533 → 846
      pyrD_sub1_fam; dihydroorotate dehydrogenase (subfamily 1) family protein
      PRK11749
      Location:53 → 513
      PRK11749; dihydropyrimidine dehydrogenase subunit A; Provisional
      cd02940
      Location:532 → 834
      DHPD_FMN; Dihydropyrimidine dehydrogenase (DHPD) FMN-binding domain. DHPD catalyzes the first step in pyrimidine degradation: the NADPH-dependent reduction of uracil and thymine to the corresponding 5,6-dihydropyrimidines. DHPD contains two FAD, two FMN, and ...
      pfam13450
      Location:194 → 238
      NAD_binding_8; NAD(P)-binding Rossmann-like domain
      pfam14691
      Location:56 → 168
      Fer4_20; Dihydroprymidine dehydrogenase domain II, 4Fe-4S cluster

    RNA

    1. XR_001737014.2 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      96925834..97768903 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054334802.1 → XP_054190777.1  dihydropyrimidine dehydrogenase [NADP(+)] isoform X4

    2. XM_054334800.1 → XP_054190775.1  dihydropyrimidine dehydrogenase [NADP(+)] isoform X1

    3. XM_054334801.1 → XP_054190776.1  dihydropyrimidine dehydrogenase [NADP(+)] isoform X2

    4. XM_054334803.1 → XP_054190778.1  dihydropyrimidine dehydrogenase [NADP(+)] isoform X5

    RNA

    1. XR_008485944.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q12882.2 GenPept UniProtKB/Swiss-Prot:Q12882

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