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

Summary

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

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_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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).
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.
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.
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.
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.
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.
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	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 EBI GWAS CatalogPubMed
Duffy-null-associated low neutrophil counts influence HIV-1 susceptibility in high-risk South African black women. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis identifies 13 new risk loci for schizophrenia. EBI GWAS Catalog EBI GWAS CatalogPubMed
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 EBI GWAS CatalogPubMed
Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

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

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

EC 1.3.1.2

NP_001153773.1

EC 1.3.1.2

XP_005270619.2

EC 1.3.1.2

XP_006710460.1

EC 1.3.1.2

XP_016855996.1

EC 1.3.1.2

XP_047304032.1

EC 1.3.1.2

XP_047304033.1

EC 1.3.1.2

XP_054190775.1

EC 1.3.1.2

XP_054190776.1

EC 1.3.1.2

XP_054190777.1

EC 1.3.1.2

XP_054190778.1

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), LRG_722

mRNA and Protein(s)

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
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

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

97077743..97921059 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047448077.1 → XP_047304033.1 dihydropyrimidine dehydrogenase [NADP(+)] isoform X4
XM_017000507.2 → XP_016855996.1 dihydropyrimidine dehydrogenase [NADP(+)] isoform X1
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
XM_047448076.1 → XP_047304032.1 dihydropyrimidine dehydrogenase [NADP(+)] isoform X3
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

XR_001737014.2 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060925.1 Alternate T2T-CHM13v2.0

Range

96925834..97768903 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054334802.1 → XP_054190777.1 dihydropyrimidine dehydrogenase [NADP(+)] isoform X4
XM_054334800.1 → XP_054190775.1 dihydropyrimidine dehydrogenase [NADP(+)] isoform X1
XM_054334801.1 → XP_054190776.1 dihydropyrimidine dehydrogenase [NADP(+)] isoform X2
XM_054334803.1 → XP_054190778.1 dihydropyrimidine dehydrogenase [NADP(+)] isoform X5