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

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
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	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
DPYS-related disorder	Likely pathogenic; Pathogenic	rs879851088, rs189448963	RCV003422194 RCV004756182	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hepatocellular carcinoma	Likely pathogenic	rs756733436	RCV005871209	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
BILIRUBIN METABOLISM DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIHYDROPYRIMIDINURIA	—	ClinVar, Disgenet, Orphanet ClinVar, Disgenet, Orphanet ClinVar, Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER CIRRHOSIS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OTOSCLEROSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anus, Imperforate	Imperforate anus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar Disorder	BEFREE	27112918		★☆☆☆☆ Found in Text Mining only
Brain atrophy	Brain atrophy	BEFREE	29054612		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	18446232		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	18446232	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	BEFREE	29054612		★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	18446232, 25915935		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	18446232, 25915935	Associate	★☆☆☆☆ Found in Text Mining only
Congenital clubfoot	Congenital Clubfoot	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	28477411, 30613400		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	28477411, 30613400		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Insulin-Dependent	Diabetes Mellitus	BEFREE	30613400		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	30799197		★☆☆☆☆ Found in Text Mining only
Diabetic Nephropathy	Diabetic Nephropathy	BEFREE	30966785		★☆☆☆☆ Found in Text Mining only
Dihydropyrimidinase deficiency	Dihydropyrimidinase Deficiency	CLINVAR_DG	20362666, 23732435, 28642038		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Dihydropyrimidinase deficiency	Dihydropyrimidinase Deficiency	ORPHANET_DG	20362666, 9718352		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Dihydropyrimidinase Deficiency	Dihydropyrimidinase deficiency	Pubtator	20362666	Inhibit	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Dihydropyrimidinase Deficiency	Dihydropyrimidinase deficiency	Pubtator	20362666, 25915935, 26771602	Associate	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Dihydropyrimidinase deficiency	Dihydropyrimidinase Deficiency	BEFREE	29054612		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Dihydropyrimidinase deficiency	Dihydropyrimidinase Deficiency	UNIPROT_DG	9718352		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Dihydropyrimidinase deficiency	Dihydropyrimidinase Deficiency	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Dihydropyrimidine Dehydrogenase Deficiency	Dihydropyrimidine dehydrogenase deficiency	Pubtator	20797317	Associate	★☆☆☆☆ Found in Text Mining only
Dihydropyrimidinuria	Dihydropyrimidinuria	ORPHANET_DG	20362666, 9718352		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dihydropyrimidinuria	Dihydropyrimidinuria	BEFREE	20797317, 9718352		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dihydropyrimidinuria	Dihydropyrimidinuria	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Extrapyramidal dyskinesia	Extrapyramidal dyskinesia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Fibrosarcoma	Fibrosarcoma	BEFREE	30871041		★☆☆☆☆ Found in Text Mining only
Hypokalemic periodic paralysis	Hypokalemic Periodic Paralysis	BEFREE	10599760, 7650604, 7897626, 7959693, 7987325, 8004673, 8584443, 9132138, 9196905		★☆☆☆☆ Found in Text Mining only
Hypokalemic periodic paralysis type 1	Hypokalemic Periodic Paralysis	BEFREE	10599760, 9132138		★☆☆☆☆ Found in Text Mining only
Infantile Spasm	Infantile Spasms	BEFREE	29054612		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	30871041		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	18446232		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of liver	Liver Cancer	BEFREE	30203236		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	18446232		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	19649633, 31735158		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	18446232, 25915935		★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	BEFREE	7650604		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	31735158		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	24011394		★☆☆☆☆ Found in Text Mining only
Osteitis Deformans	Paget disease	GWASDB_DG	20436471, 21623375		★☆☆☆☆ Found in Text Mining only
Osteitis Deformans	Paget disease	GWASCAT_DG	21623375		★☆☆☆☆ Found in Text Mining only
Paget Disease	Paget disease	GWASDB_DG	20436471, 21623375		★☆☆☆☆ Found in Text Mining only
Papillon-Lefevre Disease	Papillon-Lefevre Disease	BEFREE	20797317		★☆☆☆☆ Found in Text Mining only
Plagiocephaly	Plagiocephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Post-Traumatic Stress Disorder	Stress Disorder	BEFREE	29727810, 30529908		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	18446232		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	18446232, 21694441, 27708246, 34777331	Associate	★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	27112918		★☆☆☆☆ Found in Text Mining only
Septicemia	Septicemia	BEFREE	28092497, 29478200, 30769293		★☆☆☆☆ Found in Text Mining only
Uterine Cervical Dysplasia	Uterine disease	Pubtator	24508839	Stimulate	★☆☆☆☆ Found in Text Mining only
West Syndrome	West Syndrome	BEFREE	29054612		★☆☆☆☆ Found in Text Mining only