DPYD

dihydropyrimidine dehydrogenase

Basic information

Region (hg38): 1:97077742-97995000

Links

ENSG00000188641 ∙ NCBI:1806 ∙ OMIM:612779 ∙ HGNC:3012 ∙ Uniprot:Q12882 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dihydropyrimidine dehydrogenase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dihydropyrimidine dehydrogenase deficiency	AR	Pharmacogenomic	Homozygous/compound heterozygous variants can cause Dihydropyrimidine dehydrogenase deficiency; Severe toxicity can occur with certain medications (eg, 5-fluorouracil), and precautions may be beneficial	Biochemical; Neurologic	6488556; 2989687; 3335642; 8051923; 7832988; 9254861; 10027340; 10071185; 15303009; 19296131; 20544545; 20803296; 20920994; 21420945; 21553285; 21590448; 22410472; 22754590; 23042115

ClinVar

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

• Dihydropyrimidine dehydrogenase deficiency (259 variants)
• not provided (158 variants)
• Inborn genetic diseases (94 variants)
• not specified (42 variants)
• fluorouracil response - Other (14 variants)
• fluorouracil response - Toxicity (14 variants)
• capecitabine response - Toxicity (11 variants)
• DPYD-related condition (7 variants)
• tegafur response - Toxicity (3 variants)
• Fluorouracil response (2 variants)
• Neurodevelopmental delay (1 variants)
• Hirschsprung disease, susceptibility to, 1 (1 variants)
• See cases (1 variants)
• 22 conditions (1 variants)
• 5-fluorouracil response (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DPYD 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	30		35
missense		3	114	6	1	124
nonsense	2	29	2			33
start loss		2				2
frameshift	2	46	2			50
inframe indel						0
splice donor/acceptor (+/-2bp)	1	33	2			36
splice region			6	5		11
non coding			34	11	43	88
Total	5	113	159	47	44

Highest pathogenic variant AF is 0.000118

Variants in DPYD

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

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

Position	Type	Phenotype	Significance	ClinVar
1-97077787-C-T		Dihydropyrimidine dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)
1-97077823-T-C		Dihydropyrimidine dehydrogenase deficiency	Uncertain significance (Jan 12, 2018)
1-97077914-T-C		Dihydropyrimidine dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)
1-97077926-T-A		Dihydropyrimidine dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)
1-97077930-G-T		Dihydropyrimidine dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)
1-97077966-A-C		Dihydropyrimidine dehydrogenase deficiency	Uncertain significance (Jan 12, 2018)
1-97077976-T-C		Dihydropyrimidine dehydrogenase deficiency	Uncertain significance (Jan 12, 2018)
1-97078015-T-C			not provided (-)
1-97078065-T-C			not provided (-)
1-97078076-A-G		Dihydropyrimidine dehydrogenase deficiency	Likely benign (Jan 13, 2018)
1-97078124-G-A		Dihydropyrimidine dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)
1-97078193-C-A		Dihydropyrimidine dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)
1-97078196-G-A		Dihydropyrimidine dehydrogenase deficiency	Benign (Jan 13, 2018)
1-97078208-C-T		Dihydropyrimidine dehydrogenase deficiency	Benign (Jan 12, 2018)
1-97078240-T-A			not provided (-)
1-97078303-C-T		Dihydropyrimidine dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)
1-97078311-C-T		Dihydropyrimidine dehydrogenase deficiency	Uncertain significance (Jan 12, 2018)
1-97078341-A-T		Dihydropyrimidine dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)
1-97078350-C-T		Dihydropyrimidine dehydrogenase deficiency	Uncertain significance (Apr 27, 2017)
1-97078390-G-A		Dihydropyrimidine dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)
1-97078403-C-T		Dihydropyrimidine dehydrogenase deficiency	Benign (Jan 13, 2018)
1-97078473-T-A		Dihydropyrimidine dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)
1-97078500-C-T		Dihydropyrimidine dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)
1-97078518-A-T		Dihydropyrimidine dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)
1-97078544-A-T		Dihydropyrimidine dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DPYD	protein_coding	protein_coding	ENST00000370192	23	843307

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.37e-22	0.103	124125	10	1613	125748	0.00647

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.217	569	555	1.03	0.0000294	6700
Missense in Polyphen		220	215.85	1.0192		2598
Synonymous	-0.374	204	197	1.03	0.0000109	2024
Loss of Function	1.52	40	51.8	0.772	0.00000267	621

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00260	0.00260
Ashkenazi Jewish	0.00506	0.00507
East Asian	0.00245	0.00245
Finnish	0.0244	0.0244
European (Non-Finnish)	0.00633	0.00632
Middle Eastern	0.00245	0.00245
South Asian	0.00624	0.00616
Other	0.00441	0.00441

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine. Also involved the degradation of the chemotherapeutic drug 5-fluorouracil.
• 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;TYROBP Causal Network;Pyrimidine metabolism;Pyrimidine catabolism;Nucleobase catabolism;Metabolism of nucleotides;Metabolism;uracil degradation;thymine degradation;Pyrimidine nucleotides nucleosides metabolism (Consensus)

Recessive Scores

• pRec: 0.386

Intolerance Scores

• loftool: 0.110
• rvis_EVS: 1.43
• rvis_percentile_EVS: 95.02

Haploinsufficiency Scores

• pHI: 0.300
• hipred: Y
• hipred_score: 0.544
• ghis: 0.490

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.931

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dpyd
• Phenotype: reproductive system phenotype; skeleton phenotype

Gene ontology

• Biological process: purine nucleobase catabolic process;pyrimidine nucleobase catabolic process;thymine catabolic process;uracil catabolic process;thymidine catabolic process;beta-alanine biosynthetic process;pyrimidine nucleoside catabolic process;oxidation-reduction process
• Cellular component: cytoplasm;cytosol
• Molecular function: uracil binding;NADH dehydrogenase activity;dihydrouracil dehydrogenase (NAD+) activity;protein binding;dihydropyrimidine dehydrogenase (NADP+) activity;protein homodimerization activity;metal ion binding;flavin adenine dinucleotide binding;NADP binding;iron-sulfur cluster binding;4 iron, 4 sulfur cluster binding