DPYS Gene

Name	dihydropyrimidinase
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Dihydropyrimidinase, encoded by the "}, {"type": "b", "children": [{"type": "t", "text": "DPYS"}]}, {"type": "t", "text": " gene, is a key enzyme in the pyrimidine degradation pathway that catalyzes the ring‐opening of 5,6‐dihydrouracil and 5,6‐dihydrothymine. Its normal function is essential for maintaining balanced pyrimidine catabolism, and genetic variation in DPYS has been shown to affect this metabolic process.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of cancer chemotherapy, several studies have demonstrated that polymorphisms in DPYS, along with related genes such as DPYD, can serve as pharmacogenetic markers predicting fluoropyrimidine toxicity. For example, patients carrying certain DPYS sequence variants are at increased risk for severe adverse reactions—such as gastrointestinal toxicity and mucositis—even when dihydropyrimidine dehydrogenase (DPD) activity is normal."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its impact on drug metabolism, inactivating mutations in DPYS lead to dihydropyrimidinase deficiency, a rare inborn error of pyrimidine metabolism. Such deficiency results in the accumulation of dihydrouracil and dihydrothymine in body fluids, and has been associated with a spectrum of clinical presentations ranging from neurological impairments to developmental delays."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, differential methylation and other epigenetic alterations of the DPYS gene have been correlated with tumor aggressiveness and prognosis in cancers such as prostate and ovarian carcinoma, suggesting that DPYS may also serve as a biomarker for disease outcome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, regulatory variants affecting DPYS expression have been identified in bone tissue, highlighting its broader involvement in tissue-specific metabolic processes and potential contributions to disorders such as Paget’s disease of bone."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the multifaceted role of DPYS: it is vital for proper pyrimidine catabolism, influences the toxicity profile of chemotherapeutic agents, and its dysregulation through genetic or epigenetic mechanisms can contribute to metabolic disorders and cancer progression.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "A Loganayagam, M Arenas Hernandez, A Corrigan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pharmacogenetic variants in the DPYD, TYMS, CDA and MTHFR genes are clinically significant predictors of fluoropyrimidine toxicity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Cancer (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/bjc.2013.262"}], "href": "https://doi.org/10.1038/bjc.2013.262"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23736036"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23736036"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Holly R Thomas, Hany H Ezzeldin, Vincenzo Guarcello, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic regulation of dihydropyrimidinase and its possible implication in altered uracil catabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharmacogenet Genomics (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/FPC.0b013e3282f01788"}], "href": "https://doi.org/10.1097/FPC.0b013e3282f01788"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18075467"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18075467"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Julie Fidlerova, Petra Kleiblova, Matej Bilek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Contribution of dihydropyrimidinase gene alterations to the development of serious toxicity in fluoropyrimidine-treated cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Chemother Pharmacol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00280-009-1071-0"}], "href": "https://doi.org/10.1007/s00280-009-1071-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19649633"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19649633"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "André B P van Kuilenburg, Doreen Dobritzsch, Judith Meijer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dihydropyrimidinase deficiency: Phenotype, genotype and structural consequences in 17 patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbadis.2010.03.013"}], "href": "https://doi.org/10.1016/j.bbadis.2010.03.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20362666"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20362666"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "André B P van Kuilenburg, Judith Meijer, Doreen Dobritzsch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical, biochemical and genetic findings in two siblings with a dihydropyrimidinase deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2007.02.008"}], "href": "https://doi.org/10.1016/j.ymgme.2007.02.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17383919"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17383919"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yoko Nakajima, Judith Meijer, Doreen Dobritzsch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dihydropyrimidinase deficiency in four East Asian patients due to novel and rare DPYS mutations affecting protein structural integrity and catalytic activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2017.10.003"}], "href": "https://doi.org/10.1016/j.ymgme.2017.10.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29054612"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29054612"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yoko Nakajima, Judith Meijer, Chunhua Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered Pre-mRNA Splicing Caused by a Novel Intronic Mutation c.1443+5G>A in the Dihydropyrimidinase (DPYS) Gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms17010086"}], "href": "https://doi.org/10.3390/ijms17010086"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26771602"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26771602"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Nataša Vasiljević, Amar S Ahmad, Mangesh A Thorat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA methylation gene-based models indicating independent poor outcome in prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2407-14-655"}], "href": "https://doi.org/10.1186/1471-2407-14-655"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25193387"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25193387"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Linda E Kelemen, Kathryn L Terry, Marc T Goodman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Nutr Food Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mnfr.201400068"}], "href": "https://doi.org/10.1002/mnfr.201400068"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25066213"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25066213"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Ying-Li Lin, Qiu-Kui Deng, Yu-Hao Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aberrant Protocadherin17 (PCDH17) Methylation in Serum is a Potential Predictor for Recurrence of Early-Stage Prostate Cancer Patients After Radical Prostatectomy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Med Sci Monit (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.12659/msm.896763"}], "href": "https://doi.org/10.12659/msm.896763"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26683656"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26683656"}]}]}]}
Synonyms	DHPASE
Proteins	DPYS_HUMAN
NCBI Gene ID	1807
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DPYS has 3,874 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 115 datasets.

Click the + buttons to view associations for DPYS from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

DPYS Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by DPYS gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of DPYS gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of DPYS gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of DPYS gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of DPYS gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of DPYS gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of DPYS gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of DPYS gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of DPYS gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of DPYS gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of DPYS gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of DPYS gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with DPYS gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of DPYS gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DPYS gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of DPYS gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with DPYS gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with DPYS gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of DPYS gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DPYS protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing DPYS protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with DPYS protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with DPYS protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of DPYS gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DPYS gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with DPYS gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with DPYS gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with DPYS gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by DPYS gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving DPYS gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with DPYS gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with DPYS gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with DPYS gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with DPYS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DPYS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at DPYS gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of DPYS gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DPYS gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing DPYS from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with DPYS gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.