DPYD dihydropyrimidine dehydrogenase [Homo sapiens (human)] - Gene

Summary

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Official Symbol: DPYDprovided by HGNC
Official Full Name: dihydropyrimidine dehydrogenaseprovided by HGNC
Primary source: HGNC:3012
See related: Ensembl:ENSG00000188641; HPRD:02036; MIM:612779; Vega:OTTHUMG00000039683
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; 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]

Genomic context

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Location :: 1p22

Sequence :: Chromosome: 1; NC_000001.10 (97543299..98386615, complement)

See DPYD in Epigenomics, MapViewer

Chromosome 1 - NC_000001.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

More than 30 mutations of DPYD gene have been identified in patients with cancer. A large number of them limits introduction of simple genetic test, which could be used for detection of DPD deficiency.
Title: [Review of methods for determination of dihydropyrimidine dehydrogenase and possible application in screening previous chemotheraphy with 5-fluorouracil].
The expression level of DPD was correlated to differentiation levels of pancreatic cancer and TNM staging.
Title: [Expression of dihydropyrimidine dehydrogenase negatively correlated with the prognosis of pancreatic ductal adenocarcinoma].
TYMP and TYMS mRNA and protein expression levels were significantly higher in epithelial ovarian cancer, and DPYD mRNA and protein expression levels were significantly lower.
Title: Relationship between the expression of thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase and survival in epithelial ovarian cancer.
DPYD gene expression is regulated by miR-27a, miR-27b, miR-134, and miR-582-5p.
Title: Dihydropyrimidine dehydrogenase (DPD) expression is negatively regulated by certain microRNAs in human lung tissues.
No clear correlation was observed between the dihydropyrimidine dehydrogenase mRNA expression and any clinicopathological variable in gallbladder carcinoma.
Title: Role of thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expressions in gallbladder carcinoma.
The radiosensitizing effect of DPYD depletion plus CPT was the additive effect of DPYD depletion and CPT.
Title: Effects of depletion of dihydropyrimidine dehydrogenase on focus formation and RPA phosphorylation.
The organs in which metastases of colorectal cancer arise may be controlled by the expression of dihydropyrimidine dehydrogenase.
Title: Expression of dihydropyrimidine dehydrogenase, orotate phosphoribosyl transferase and thymidylate synthase in patients with primary colorectal cancer, and associations with site of first metastasis.
mRNA expression of TYMS, DPYD, and TYMP is associated with distinct characteristics and may be useful for predicting survival in patients with stage IV colorectal cancer.
Title: Expression levels of thymidylate synthase, dihydropyrimidine dehydrogenase, and thymidine phosphorylase in patients with colorectal cancer.
Results suggest that polymorphisms of rs1801159 in DPYD may be used as valuable predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in the Chinese population.
Title: Polymorphisms of dihydropyrimidine dehydrogenase gene and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population.
High TS and DPD mRNA levels on FFPE specimens may predict distant recurrence of rectal cancer treated with 5-FU-based preoperative CRT followed by surgery.
Title: TS and DPD mRNA levels on formalin-fixed paraffin-embedded specimens as predictors for distant recurrence of rectal cancer treated with preoperative chemoradiotherapy.

Submit: New GeneRIF Correction See all (98)

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

Dihydropyrimidine dehydrogenase deficiency

MIM: 274270

Genetic Testing Registry

NHGRI GWAS Catalog

Duffy-null-associated low neutrophil counts influence HIV-1 susceptibility in high-risk South African black women.

Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder.

Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description
BioGRID:108140	BioGRID:138943	CHAC2		BioGRID	PubMed	Co-fractionation
BioGRID:108140	BioGRID:113164	UBC		BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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Drug metabolism - other enzymes, organism-specific biosystem (from KEGG)
Drug metabolism - other enzymes, organism-specific biosystem
Drug metabolism - other enzymes
Drug metabolism - other enzymes, conserved biosystem (from KEGG)
Drug metabolism - other enzymes, conserved biosystem
Drug metabolism - other enzymes
Fluoropyrimidine Activity, organism-specific biosystem (from WikiPathways)
Fluoropyrimidine Activity, organism-specific biosystemThe main mechanism of 5-FU activation is conversion to fluorodeoxyuridine monophosphate (FdUMP) which inhibits the enzyme thymidylate synthase (TYMS), an important part of the folate-homocysteine cyc...
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of nucleotides, organism-specific biosystem (from REACTOME)
Metabolism of nucleotides, organism-specific biosystemNucleotides and their derivatives are used for short-term energy storage (ATP, GTP), for intra- and extra-cellular signaling (cAMP; adenosine), as enzyme cofactors (NAD, FAD), and for the synthesis o...
Pantothenate and CoA biosynthesis, organism-specific biosystem (from KEGG)
Pantothenate and CoA biosynthesis, organism-specific biosystem
Pantothenate and CoA biosynthesis
Pantothenate and CoA biosynthesis, conserved biosystem (from KEGG)
Pantothenate and CoA biosynthesis, conserved biosystem
Pantothenate and CoA biosynthesis
Pyrimidine catabolism, organism-specific biosystem (from REACTOME)
Pyrimidine catabolism, organism-specific biosystemIn parallel sequences of three reactions each, thymine is converted to beta-aminoisobutyrate and uracil is converted to beta-alanine. Both of these molecules are excreted in human urine and appear to...
Pyrimidine degradation, uracil => beta-alanine, thymine => 3-aminoisobutanoate, organism-specific biosystem (from KEGG)
Pyrimidine degradation, uracil => beta-alanine, thymine => 3-aminoisobutanoate, organism-specific biosystemPathway module; Nucleotide and amino acid metabolism; Pyrimidine metabolism
Pyrimidine degradation, uracil => beta-alanine, thymine => 3-aminoisobutanoate, conserved biosystem (from KEGG)
Pyrimidine degradation, uracil => beta-alanine, thymine => 3-aminoisobutanoate, conserved biosystemPathway module; Nucleotide and amino acid metabolism; Pyrimidine metabolism
Pyrimidine metabolism, organism-specific biosystem (from REACTOME)
Pyrimidine metabolism, organism-specific biosystemThe events of human pyrimidine metabolism are conveniently, if somewhat arbitrarily, grouped into four pathways: de novo synthesis of the pyrimidine ring and its conversion to uridine 5'-monophosphat...
Pyrimidine metabolism, organism-specific biosystem (from KEGG)
Pyrimidine metabolism, organism-specific biosystem
Pyrimidine metabolism
Pyrimidine metabolism, conserved biosystem (from KEGG)
Pyrimidine metabolism, conserved biosystem
Pyrimidine metabolism
beta-Alanine metabolism, organism-specific biosystem (from KEGG)
beta-Alanine metabolism, organism-specific biosystem
beta-Alanine metabolism
beta-Alanine metabolism, conserved biosystem (from KEGG)
beta-Alanine metabolism, conserved biosystem
beta-Alanine metabolism
superpathway of pyrimidine ribonucleosides degradation, organism-specific biosystem (from BIOCYC)
superpathway of pyrimidine ribonucleosides degradation, organism-specific biosystem
superpathway of pyrimidine ribonucleosides degradation
thymine degradation, organism-specific biosystem (from BIOCYC)
thymine degradation, organism-specific biosystemGeneral Background Pyrimidines can be catabolized through two different pathways. This pathway and : PWY-3982 uracil degradation, in which pyrimidines are reduced to beta-amino acids, : CARBON-DIOXI...
uracil degradation I (reductive), organism-specific biosystem (from BIOCYC)
uracil degradation I (reductive), organism-specific biosystemGeneral Background Pyrimidines can be catabolized through two different pathways. This pathway and : PWY-6430 thymine degradation) in which pyrimidines are reduced to beta-amino acids, : CARBON-DIOX...

General gene information

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Markers

SHGC-105236 (e-PCR)
- UniSTS:169232

SHGC-80046 (e-PCR)
- UniSTS:101655

SHGC-84442 (e-PCR)
- UniSTS:104740

AL009678 (e-PCR)
- UniSTS:21798

AL009912 (e-PCR)
- UniSTS:79925

RH121366 (e-PCR)
- UniSTS:134212

AL034211 (e-PCR)
- UniSTS:94037

AL034016 (e-PCR)
- UniSTS:93530

SHGC-75193 (e-PCR)
- UniSTS:19559

AL034057 (e-PCR)
- UniSTS:93819

RH80889 (e-PCR)
- UniSTS:91516

G59961 (e-PCR)
- UniSTS:137098

G30582 (e-PCR)
- UniSTS:77460

RH66034 (e-PCR)
- UniSTS:38040

RH17430 (e-PCR)
- UniSTS:68254

SHGC-107533 (e-PCR)
- UniSTS:170400

SHGC-132118 (e-PCR)
- UniSTS:170657

SHGC-83640 (e-PCR)
- UniSTS:95907

SHGC-80794 (e-PCR)
- UniSTS:102317

AL009994 (e-PCR)
- UniSTS:52141

G34876 (e-PCR)
- UniSTS:73143

AL009925 (e-PCR)
- UniSTS:78008

RH103958 (e-PCR)
- UniSTS:98283

G54618 (e-PCR)
- UniSTS:117751

SHGC-12941 (e-PCR)
- UniSTS:57599

Genotypes

See DPYD SNP Geneview Report
See DPYD SNP Genotype Report
See DPYD SNP Variation Viewer Report

Homology

Homologs of the DPYD gene: The DPYD gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, A.thaliana, and rice.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
4 iron, 4 sulfur cluster binding	IEA Inferred from Electronic Annotation more info
NADP binding	ISS Inferred from Sequence or Structural Similarity more info
dihydroorotate oxidase activity	IEA Inferred from Electronic Annotation more info
dihydropyrimidine dehydrogenase (NADP+) activity	IDA Inferred from Direct Assay more info	PubMed
dihydropyrimidine dehydrogenase (NADP+) activity	IMP Inferred from Mutant Phenotype more info	PubMed
dihydropyrimidine dehydrogenase (NADP+) activity	ISS Inferred from Sequence or Structural Similarity more info
dihydropyrimidine dehydrogenase (NADP+) activity	TAS Traceable Author Statement more info
flavin adenine dinucleotide binding	ISS Inferred from Sequence or Structural Similarity more info
metal ion binding	IEA Inferred from Electronic Annotation more info
protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
protein homodimerization activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
UMP biosynthetic process	IEA Inferred from Electronic Annotation more info
beta-alanine biosynthetic process	IEA Inferred from Electronic Annotation more info
nucleobase-containing small molecule metabolic process	TAS Traceable Author Statement more info
purine nucleobase catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
pyrimidine nucleobase catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
pyrimidine nucleobase catabolic process	ISS Inferred from Sequence or Structural Similarity more info
pyrimidine nucleobase metabolic process	TAS Traceable Author Statement more info
pyrimidine nucleoside catabolic process	TAS Traceable Author Statement more info
small molecule metabolic process	TAS Traceable Author Statement more info
thymidine catabolic process	IDA Inferred from Direct Assay more info	PubMed
thymine catabolic process	IDA Inferred from Direct Assay more info	PubMed
uracil catabolic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	IDA Inferred from Direct Assay more info	PubMed
cytosol	TAS Traceable Author Statement more info

General protein information

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Preferred Names: dihydropyrimidine dehydrogenase [NADP(+)]

Names: dihydropyrimidine dehydrogenase [NADP(+)]; dihydrouracil dehydrogenase; dihydrothymine dehydrogenase

NP_000101.2

EC 1.3.1.2

NP_001153773.1

EC 1.3.1.2

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

NG_008807.2 RefSeqGene

Range

5001..848317

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000110.3 → NP_000101.2 dihydropyrimidine dehydrogenase [NADP(+)] isoform 1

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

Q12882

Related

ENSP00000359211, OTTHUMP00000037640, ENST00000370192, OTTHUMT00000095698

Conserved Domains (5) summary

COG0167
Location:532 – 848
Blast Score: 546

PyrD; Dihydroorotate dehydrogenase [Nucleotide transport and metabolism]

cd02940
Location:532 – 834
Blast Score: 1271

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 ...

PRK11749
Location:53 – 513
Blast Score: 884

PRK11749; dihydropyrimidine dehydrogenase subunit A; Provisional

pfam13237
Location:948 – 997
Blast Score: 137

Fer4_10; 4Fe-4S dicluster domain

pfam13450
Location:194 – 238
Blast Score: 121

NAD_binding_8; NAD(P)-binding Rossmann-like domain
NM_001160301.1 → NP_001153773.1 dihydropyrimidine dehydrogenase [NADP(+)] isoform 2

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, OTTHUMP00000037641, ENST00000306031, OTTHUMT00000095699

Conserved Domains (1) summary

PRK11749
Location:53 – 162
Blast Score: 332

PRK11749; dihydropyrimidine dehydrogenase subunit A; Provisional

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000001.10 Reference GRCh37.p10 Primary Assembly

Range

97543299..98386615, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000133.1 Alternate HuRef

Range

95664181..96508076, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018912.1 Alternate CHM1_1.0

Range

97566863..98410153, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01045471.1 (719..2245)	None
genomic	ABBA01045472.1	None
genomic	ABBA01045473.1	None
genomic	ABBA01045474.1	None
genomic	ABBA01045475.1	None
genomic	ABBA01045476.1	None
genomic	ABBA01045477.1	None
genomic	AC091608.2 (95974..125305)	None
genomic	AC093576.3 (2001..185461)	None
genomic	AC099787.2	None
genomic	AC114878.2 (1752..157405)	None
genomic	AC138135.2 (2001..111000)	None
genomic	AL356457.25 (2001..120510)	None
genomic	AL645494.6 (2001..14500)	None
genomic	AMYH01000816.1 (314900..440597)	None
genomic	AMYH01000817.1	None
genomic	AMYH01000818.1	None
genomic	AMYH01000819.1	None
genomic	BX908805.1 (2001..59492)	None
genomic	CH471097.2	EAW73002.1
		EAW73003.1
genomic	U57655.1	AAB07049.1
genomic	X95670.1	CAA64973.1
mRNA	AB003063.1	BAA89789.1
mRNA	AI124948.1	None
mRNA	AK291217.1	BAF83906.1
mRNA	AK297515.1	BAG59923.1
mRNA	BC008379.1	AAH08379.1
mRNA	BC064027.1	AAH64027.1
mRNA	BC108742.1	AAI08743.1
mRNA	BC131777.1	AAI31778.1
mRNA	BC131778.1	AAI31779.1
mRNA	BT006740.1	AAP35386.1
mRNA	DA721123.1	None
mRNA	U09178.1	AAA57474.1
mRNA	U20938.1	AAB51366.1