U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

DPYD dihydropyrimidine dehydrogenase [ Homo sapiens (human) ]

Gene ID: 1806, updated on 7-Apr-2024

Summary

Go to the top of the page Help
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
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
Location:
1p21.3
Exon count:
26
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (97077743..97921059, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (96925834..97768903, complement)
105.20220307 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

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • 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

Go to the top of the pageHelp

Related articles in PubMed

  1. Impact of renal impairment on dihydropyrimidine dehydrogenase (DPD) phenotyping. Royer B, et al. ESMO Open, 2023 Jun. PMID 37267808, Free PMC Article
  2. Dihydropyrimidine dehydrogenase phenotype in peripheral blood mononuclear cells is related to adverse events of fluoropyrimidine-therapy. Doornhof KR, et al. Eur J Clin Pharmacol, 2023 Apr. PMID 36757428
  3. DPYD Exon 4 Deletion Associated with Fluoropyrimidine Toxicity and Importance of Copy Number Variation. Wigle TJ, et al. Curr Oncol, 2023 Jan 4. PMID 36661700, Free PMC Article
  4. Poor association between dihydropyrimidine dehydrogenase (DPYD) genotype and fluoropyrimidine-induced toxicity in an Asian population. Kanai M, et al. Cancer Med, 2023 Apr. PMID 36524458, Free PMC Article
  5. Fluoropyrimidine-associated toxicity and DPYD variants c.85T>C, c.496A>G, and c.1236G>A: impact of haplotype. Medwid S, et al. Cancer Chemother Pharmacol, 2023 Jan. PMID 36357798

See all (256) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. Impact of renal impairment on dihydropyrimidine dehydrogenase (DPD) phenotyping.
    Title: Impact of renal impairment on dihydropyrimidine dehydrogenase (DPD) phenotyping.
  8. Poor association between dihydropyrimidine dehydrogenase (DPYD) genotype and fluoropyrimidine-induced toxicity in an Asian population.
    Title: Poor association between dihydropyrimidine dehydrogenase (DPYD) genotype and fluoropyrimidine-induced toxicity in an Asian population.
  9. Dihydropyrimidine dehydrogenase phenotype in peripheral blood mononuclear cells is related to adverse events of fluoropyrimidine-therapy.
    Title: Dihydropyrimidine dehydrogenase phenotype in peripheral blood mononuclear cells is related to adverse events of fluoropyrimidine-therapy.
  10. Dihydropyrimidine dehydrogenase (DPD) genotype and phenotype among Danish cancer patients: prevalence and correlation between DPYD-genotype variants and P-uracil concentrations.
    Title: Dihydropyrimidine dehydrogenase (DPD) genotype and phenotype among Danish cancer patients: prevalence and correlation between DPYD-genotype variants and P-uracil concentrations.
Submit: New GeneRIF Correction See all GeneRIFs (195)

Phenotypes

Go to the top of the page Help

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
Compare labs
Dihydropyrimidine dehydrogenase deficiency
MedGen: C1959620 OMIM: 274270 GeneReviews: Not available
Compare labs
Fluoropyrimidine response
MedGen: CN184090 GeneReviews: Not available
Compare labs
Tegafur response
MedGen: C1852514 GeneReviews: Not available
Compare labs

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

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

Go to the top of the page

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

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

Go to the top of the page Help
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)

Go to the top of the page Help

NEW Try the new Transcript table

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_2023_10

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

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Medical
Molecular Biology Databases
Research Materials
Tools
Miscellaneous