DPYS dihydropyrimidinase [Homo sapiens (human)] - Gene

Summary

Official Symbol: DPYSprovided by HGNC
Official Full Name: dihydropyrimidinaseprovided by HGNC
Primary source: HGNC:HGNC:3013
See related: Ensembl:ENSG00000147647 MIM:613326; AllianceGenome:HGNC:3013
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; DHPase
Summary: Dihydropyrimidinase catalyzes the conversion of 5,6-dihydrouracil to 3-ureidopropionate in pyrimidine metabolism. Dihydropyrimidinase is expressed at a high level in liver and kidney as a major 2.5-kb transcript and a minor 3.8-kb transcript. Defects in the DPYS gene are linked to dihydropyrimidinuria. [provided by RefSeq, Jul 2008]
Expression: Biased expression in liver (RPKM 34.3) and kidney (RPKM 29.7) See more
Orthologs: mouse all
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Genomic context

Location:: 8q22.3

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (104379431..104467055, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (105506922..105594550, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (105391659..105479283, complement)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The burden of rare variants in DPYS gene is a novel predictor of the risk of developing severe fluoropyrimidine-related toxicity.
Title: The burden of rare variants in DPYS gene is a novel predictor of the risk of developing severe fluoropyrimidine-related toxicity.
Functional Characterization of 12 Dihydropyrimidinase Allelic Variants in Japanese Individuals for the Prediction of 5-Fluorouracil Treatment-Related Toxicity.
Title: Functional Characterization of 12 Dihydropyrimidinase Allelic Variants in Japanese Individuals for the Prediction of 5-Fluorouracil Treatment-Related Toxicity.
This study defines dihydropyrimidines as potentially cytotoxic metabolites that may offer an opportunity for therapeutic-targeting of dihydropyrimidinase activity in solid tumors.
Title: Dihydropyrimidinase protects from DNA replication stress caused by cytotoxic metabolites.
4 newly identified DHP deficient patients presented with strongly elevated levels of 5,6-dihydrouracil and 5,6-dihydrothymine in urine and a highly variable clinical presentation, ranging from asymptomatic to infantile spasm and reduced white matter and brain atrophy. Analysis of the DHP gene (DPYS) showed the presence of 8 variants including 4 novel/rare missense variants and one novel deletion.
Title: Dihydropyrimidinase deficiency in four East Asian patients due to novel and rare DPYS mutations affecting protein structural integrity and catalytic activity.
Two unrelated pediatric DPYS deficiency cases are being described as compound heterozygotes for a novel intronic mutation c.1443+5G>A in intron 8 and a previously described missense mutation c.1001A>G (p.Q334R) in exon 6.
Title: Altered Pre-mRNA Splicing Caused by a Novel Intronic Mutation c.1443+5G>A in the Dihydropyrimidinase (DPYS) Gene.
Stepwise Cox regression modelling suggested that the methylation of genes HSPB1, CCND2 and DPYS contributed objective prognostic information to Gleason score and PSA with respect to prostate cancer-related death.
Title: DNA methylation gene-based models indicating independent poor outcome in prostate cancer.
Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
Title: Analysis of copy number variation in 8,842 Korean individuals reveals 39 genes associated with hepatic biomarkers AST and ALT.
The p.S379R and p.L7V mutations were likely to cause structural destabilization and protein misfolding. Four mutations were identified in multiple unrelated DHP patients, indicating that DHP deficiency may be more common than anticipated.
Title: Dihydropyrimidinase deficiency: Phenotype, genotype and structural consequences in 17 patients.
Results indicate that missense and nonsense variants in DPYS are infrequent, however, the development of serious primarily gastrointestinal toxicity could be influenced by non-coding DPYS sequence variants c.-1T>C and IVS1-58T>C.
Title: Contribution of dihydropyrimidinase gene alterations to the development of serious toxicity in fluoropyrimidine-treated cancer patients.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Contribution of dihydropyrimidinase gene alterations to the development of serious toxicity in fluoropyrimidine-treated cancer patients.

Submit: New GeneRIF Correction See all GeneRIFs (13)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Dihydropyrimidinase deficiency MedGen: C0342803 OMIM: 222748 GeneReviews: Not available	Compare labs

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

RH80723 (e-PCR)
- UniSTS:91393

D8S1459 (e-PCR)
- UniSTS:18690

RH12824 (e-PCR)
- UniSTS:74092

D8S1738 (e-PCR)
- UniSTS:39282

RH80769 (e-PCR)
- UniSTS:85677

SHGC-112121 (e-PCR)
- UniSTS:168879

G59856 (e-PCR)
- UniSTS:137140

RH45444 (e-PCR)
- UniSTS:43745

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables dihydropyrimidinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables dihydropyrimidinase activity	IDA Inferred from Direct Assay more info	PubMed
enables dihydropyrimidinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables identical protein binding	ISS Inferred from Sequence or Structural Similarity more info
enables phosphoprotein binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables zinc ion binding	NAS Non-traceable Author Statement more info	PubMed

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 dCMP catabolic process	IEA Inferred from Electronic Annotation more info
involved_in dUMP catabolic process	IEA Inferred from Electronic Annotation more info
involved_in pyrimidine nucleobase catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in pyrimidine nucleobase catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in thymine catabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in uracil catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in uracil catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed

General protein information

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Preferred Names: dihydropyrimidinase

Names: dihydropyrimidine amidohydrolase; hydantoinase

NP_001376.1

EC 3.5.2.2

XP_005250875.1

EC 3.5.2.2

XP_006716581.1

EC 3.5.2.2

XP_011515205.1

EC 3.5.2.2

XP_016868656.1

EC 3.5.2.2

XP_047277371.1

EC 3.5.2.2

XP_047277372.1

EC 3.5.2.2

XP_047277374.1

EC 3.5.2.2

XP_047277375.1

EC 3.5.2.2

XP_054215878.1

EC 3.5.2.2

XP_054215879.1

EC 3.5.2.2

XP_054215880.1

EC 3.5.2.2

XP_054215881.1

EC 3.5.2.2

XP_054215882.1

EC 3.5.2.2

XP_054215883.1

EC 3.5.2.2

XP_054215884.1

EC 3.5.2.2

XP_054215885.1

EC 3.5.2.2

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_008840.2 RefSeqGene

Range

4995..92619

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001385.3 → NP_001376.1 dihydropyrimidinase

See identical proteins and their annotated locations for NP_001376.1

Status: REVIEWED

Source sequence(s)

AP002847, BC034395, D78011

Consensus CDS

CCDS6302.1

UniProtKB/Swiss-Prot

Q14117

Related

ENSP00000276651.2, ENST00000351513.7

Conserved Domains (1) summary

cd01314
Location:7 → 460

D-HYD; D-hydantoinases (D-HYD) also called dihydropyrimidases (DHPase) and related proteins; DHPases are a family of enzymes that catalyze the reversible hydrolytic ring opening of the amide bond in five- or six-membered cyclic diamides, like dihydropyrimidine ...

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_000008.11 Reference GRCh38.p14 Primary Assembly

Range

104379431..104467055 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047421418.1 → XP_047277374.1 dihydropyrimidinase isoform X5
XM_006716518.4 → XP_006716581.1 dihydropyrimidinase isoform X3

Conserved Domains (1) summary

cd01314
Location:7 → 443

D-HYD; D-hydantoinases (D-HYD) also called dihydropyrimidases (DHPase) and related proteins; DHPases are a family of enzymes that catalyze the reversible hydrolytic ring opening of the amide bond in five- or six-membered cyclic diamides, like dihydropyrimidine ...
XM_005250818.4 → XP_005250875.1 dihydropyrimidinase isoform X1

Conserved Domains (1) summary

cd01314
Location:7 → 496

D-HYD; D-hydantoinases (D-HYD) also called dihydropyrimidases (DHPase) and related proteins; DHPases are a family of enzymes that catalyze the reversible hydrolytic ring opening of the amide bond in five- or six-membered cyclic diamides, like dihydropyrimidine ...
XM_047421415.1 → XP_047277371.1 dihydropyrimidinase isoform X1
XM_011516903.4 → XP_011515205.1 dihydropyrimidinase isoform X2

Conserved Domains (2) summary

cd01314
Location:7 → 496

D-HYD; D-hydantoinases (D-HYD) also called dihydropyrimidases (DHPase) and related proteins; DHPases are a family of enzymes that catalyze the reversible hydrolytic ring opening of the amide bond in five- or six-membered cyclic diamides, like dihydropyrimidine ...

pfam07969
Location:50 → 408

Amidohydro_3; Amidohydrolase family
XM_047421416.1 → XP_047277372.1 dihydropyrimidinase isoform X4
XM_047421419.1 → XP_047277375.1 dihydropyrimidinase isoform X7
XM_017013167.3 → XP_016868656.1 dihydropyrimidinase isoform X6