DPYS (dihydropyrimidinase)

Gene

• Entrez ID: 1807
• Gene name: Dihydropyrimidinase
• Gene symbol: DPYS
• Synonyms (NCBI Gene): DHP, DHPase
• Chromosome: 8
• Chromosome location: 8q22.3
• 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs61758444	G>A	Pathogenic	Coding sequence variant, genic downstream transcript variant, stop gained, non coding transcript variant
rs79080341	G>-	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, genic downstream transcript variant, non coding transcript variant, frameshift variant
rs201258823	G>T	Likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs267606773	C>T	Pathogenic	Non coding transcript variant, missense variant, genic downstream transcript variant, coding sequence variant
rs267606774	C>A	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs546700169	G>A	Likely-pathogenic	Intron variant, coding sequence variant, stop gained, non coding transcript variant
rs879851088	C>G,T	Pathogenic	Splice acceptor variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004157	Function	Dihydropyrimidinase activity	IBA
GO:0004157	Function	Dihydropyrimidinase activity	IDA	9718352, 10410956
GO:0004157	Function	Dihydropyrimidinase activity	IEA
GO:0004157	Function	Dihydropyrimidinase activity	IMP	18075467
GO:0005515	Function	Protein binding	IPI	32296183, 32814053
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IBA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	ISS
GO:0005829	Component	Cytosol	TAS
GO:0006208	Process	Pyrimidine nucleobase catabolic process	IBA
GO:0006208	Process	Pyrimidine nucleobase catabolic process	IDA	9718352
GO:0006210	Process	Thymine catabolic process	ISS
GO:0006212	Process	Uracil catabolic process	IDA	10410956
GO:0006212	Process	Uracil catabolic process	IMP	18075467
GO:0006248	Process	CMP catabolic process	IEA
GO:0006249	Process	DCMP catabolic process	IEA
GO:0008270	Function	Zinc ion binding	NAS	9718352
GO:0016787	Function	Hydrolase activity	IEA
GO:0016810	Function	Hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	IEA
GO:0042802	Function	Identical protein binding	ISS
GO:0046050	Process	UMP catabolic process	IEA
GO:0046079	Process	DUMP catabolic process	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0051219	Function	Phosphoprotein binding	IEA
GO:0070062	Component	Extracellular exosome	HDA	19056867

Other IDs

• MIM: 613326
• HGNC: 3013
• e!Ensembl: ENSG00000147647

Protein

• UniProt ID: Q14117
• Protein name: Dihydropyrimidinase (DHP) (DHPase) (EC 3.5.2.2) (Dihydropyrimidine amidohydrolase) (Hydantoinase)
• Protein function: Catalyzes the second step of the reductive pyrimidine degradation, the reversible hydrolytic ring opening of dihydropyrimidines. Can catalyze the ring opening of 5,6-dihydrouracil to N-carbamyl-alanine and of 5,6-dihydrothymine to N-carbamyl-ami
• PDB: 2VR2
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01979	Amidohydro_1	58 → 447	Amidohydrolase family	Domain

• Tissue specificity: TISSUE SPECIFICITY: Liver and kidney.
• Sequence:

  MAAPSRLLIRGGRVVNDDFSEVADVLVEDGVVRALGHDLLPPGGAPAGLRVLDAAGKLVL
  PGGIDTHTHMQFPFMGSRSIDDFHQGTKAALSGGTTMIIDFAIPQKGGSLIEAFETWRSW
  ADPKVCCDYSLHVAVTWWSDQVKEEMKILVQDKGVNSFKMFMAYKDLYMVTDLELYEAFS
  RCKEIGAIAQVHAENGDLIAEGAKKMLALGITGPEGHELCRPEAVEAEATLRAITIASAV
  NCPLYIVHVMSKSAAKVIADARRDGKVVYGEPIAASLGTDGTHYWNKEWHHAAHHVMGPP
  LRPDPSTPDFLMNLLANDDLTTTGTDNCTFNTCQKALGKDDFTKIPNGVNGVEDRMSVIW
  EKGVHSGKMDENRFVAVTSTNAAKIFNLYPRKGRIAVGSDADIVIWDPKGTRTISAKTHH
  QAVNFNIFEGMVCHGVPLVTISRGKVVYEAGVFSVTAGDGKFIPRKPFAEYIYKRIKQRD
  RTCTPTPVERAPYKGEVATLKSRVTKEDATAGTRKQAHP

• Sequence length: 519

Pathways

KEGG:

Pyrimidine metabolism
beta-Alanine metabolism
Pantothenate and CoA biosynthesis
Drug metabolism - other enzymes
Metabolic pathways

Reactome:

Pyrimidine catabolism

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Dihydropyrimidinase deficiency	Likely pathogenic; Pathogenic	rs142574766, rs771160155, rs770063251, rs121964923, rs267606773, rs121964924, rs267606774, rs1020872387, rs2537826958, rs376965972, rs2537770775, rs756733436, rs201258823, rs61758444, rs200913682, rs201280871, rs189448963, rs1321466782	RCV001330587 RCV004699508 RCV005863609 RCV000000207 RCV000000208 RCV000000209 RCV000000210 RCV003485818 RCV003480014 RCV003486531 RCV003486540 RCV004786966 RCV000779549 RCV001783010 RCV000778155 RCV001330586 RCV001160988 RCV001248855
DPYS-related disorder	Likely pathogenic; Pathogenic	rs879851088, rs189448963	RCV003422194 RCV004756182
Hepatocellular carcinoma	Likely pathogenic	rs756733436	RCV005871209

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
See cases	Conflicting classifications of pathogenicity	rs79080341	RCV002251978

Associations from Text Mining
Disease Name	Relationship Type	References
Breast Neoplasms	Associate	18446232
Colorectal Neoplasms	Associate	18446232, 25915935
Death	Associate	25193387
Dihydropyrimidinase Deficiency	Inhibit	20362666
Dihydropyrimidinase Deficiency	Associate	20362666, 25915935, 26771602
Dihydropyrimidine Dehydrogenase Deficiency	Associate	20797317
Drug Related Side Effects and Adverse Reactions	Associate	25915935, 32619063, 37946254
Immunologic Deficiency Syndromes	Associate	32600357
Neoplasms	Associate	27733154, 32619063
Papillon Lefevre Disease	Associate	20797317
Prostatic Neoplasms	Associate	18446232, 21694441, 27708246, 34777331
Uterine Cervical Dysplasia	Stimulate	24508839