DPYS

dihydropyrimidinase, the group of M38 metallopeptidases

Basic information

Region (hg38): 8:104330324-104467055

Links

ENSG00000147647 ∙ NCBI:1807 ∙ OMIM:613326 ∙ HGNC:3013 ∙ Uniprot:Q14117 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dihydropyrimidinuria (Strong), mode of inheritance: AR
• dihydropyrimidinuria (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dihydropyriminidase deficiency	AR	Pharmacogenomic	Affected individuals could theoretically have severe toxicity with 5-fluorouracil; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic	1770794; 9323563; 9266350; 9718352; 17383919; 20362666; 29054612

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DPYS gene.

• not provided (9 variants)
• Dihydropyrimidinase deficiency (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DPYS gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	24	8	37
missense	1	7	90	3	1	102
nonsense	3	2				5
start loss			1			1
frameshift	5	1		1		7
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region		1	3			4
non coding			7	11	6	24
Total	9	11	103	39	15

Highest pathogenic variant AF is 0.0000460

Variants in DPYS

This is a list of pathogenic ClinVar variants found in the DPYS region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-104348556-G-C		not specified	Uncertain significance (Mar 31, 2023)
8-104348607-G-A		not specified	Uncertain significance (Mar 19, 2024)
8-104348676-A-C		not specified	Uncertain significance (Jul 19, 2023)
8-104348747-G-T		not specified	Uncertain significance (Oct 25, 2022)
8-104348755-C-A		not specified	Uncertain significance (Sep 21, 2023)
8-104348773-G-T		not specified	Uncertain significance (Dec 20, 2021)
8-104348774-C-G		not specified	Uncertain significance (Mar 20, 2024)
8-104348778-A-G		not specified	Uncertain significance (May 05, 2023)
8-104348862-G-A		not specified	Uncertain significance (Oct 26, 2021)
8-104348868-G-A		not specified	Uncertain significance (Aug 08, 2023)
8-104348883-G-A		not specified	Uncertain significance (Mar 19, 2024)
8-104348914-T-G		not specified	Uncertain significance (Apr 27, 2022)
8-104348962-A-G		not specified	Uncertain significance (Dec 21, 2023)
8-104349070-T-C		not specified	Uncertain significance (May 14, 2024)
8-104349106-A-G		not specified	Uncertain significance (Aug 07, 2024)
8-104349138-G-A		not specified	Likely benign (Feb 10, 2023)
8-104349177-T-C		not specified	Uncertain significance (Nov 29, 2021)
8-104349223-T-C		not specified	Uncertain significance (Jul 31, 2024)
8-104349289-A-G		not specified	Uncertain significance (Jan 23, 2024)
8-104349304-T-A		not specified	Uncertain significance (May 13, 2024)
8-104349361-A-G		not specified	Likely benign (Apr 18, 2024)
8-104349406-C-T		not specified	Likely benign (May 11, 2022)
8-104349438-T-C		not specified	Uncertain significance (May 20, 2024)
8-104349496-A-T		not specified	Uncertain significance (Mar 01, 2023)
8-104349520-C-T		not specified	Uncertain significance (Sep 09, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DPYS	protein_coding	protein_coding	ENST00000351513	9	136730

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.78e-11	0.269	125457	3	288	125748	0.00116

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.335	272	288	0.944	0.0000154	3369
Missense in Polyphen		124	137.09	0.90448		1589
Synonymous	-0.604	115	107	1.07	0.00000623	1036
Loss of Function	0.921	19	23.9	0.797	0.00000144	256

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00769	0.00765
Ashkenazi Jewish	0.00	0.00
East Asian	0.00109	0.00109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000766	0.000756
Middle Eastern	0.00109	0.00109
South Asian	0.00101	0.00101
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Function: 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-amino isobutyrate.
• Disease: DISEASE: Dihydropyrimidinase deficiency (DPYSD) [MIM:222748]: An autosomal recessive disorder of pyrimidine metabolism characterized by dihydropyrimidinuria. It is associated with a variable clinical phenotype characterized by epileptic or convulsive attacks, dysmorphic features and severe developmental delay, and congenital microvillous atrophy. Most patients are, however, asymptomatic. {ECO:0000269|PubMed:9718352}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Pyrimidine metabolism - Homo sapiens (human);beta-Alanine metabolism - Homo sapiens (human);Pantothenate and CoA biosynthesis - Homo sapiens (human);Drug metabolism - other enzymes - Homo sapiens (human);Fluoropyrimidine Pathway, Pharmacokinetics;Carnosinuria, carnosinemia;Ureidopropionase deficiency;GABA-Transaminase Deficiency;Pyrimidine Metabolism;Beta-Alanine Metabolism;UMP Synthase Deiciency (Orotic Aciduria);MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy);Beta Ureidopropionase Deficiency;Dihydropyrimidinase Deficiency;Fluoropyrimidine Activity;pyrimidine ribonucleosides degradation;Pyrimidine metabolism;Pyrimidine catabolism;Nucleobase catabolism;Metabolism of nucleotides;Metabolism;uracil degradation;thymine degradation;Pyrimidine nucleotides nucleosides metabolism (Consensus)

Recessive Scores

• pRec: 0.303

Intolerance Scores

• loftool: 0.267
• rvis_EVS: -1.04
• rvis_percentile_EVS: 7.71

Haploinsufficiency Scores

• pHI: 0.145
• hipred: Y
• hipred_score: 0.528
• ghis: 0.448

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.857

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dpys

Gene ontology

• Biological process: pyrimidine nucleobase catabolic process;thymine catabolic process;uracil catabolic process;beta-alanine metabolic process;pyrimidine nucleoside catabolic process;protein homotetramerization
• Cellular component: cytosol;extracellular exosome
• Molecular function: uracil binding;thymine binding;dihydropyrimidinase activity;zinc ion binding;amino acid binding;phosphoprotein binding