Nucleotide metabolism disorders

Gene: DPYD

Green List (high evidence)

DPYD (dihydropyrimidine dehydrogenase)
EnsemblGeneIds (GRCh38): ENSG00000188641
EnsemblGeneIds (GRCh37): ENSG00000188641
OMIM: 612779, Gene2Phenotype
DPYD is in 11 panels

2 reviews

Bryony Thompson (Royal Melbourne Hospital)

Green List (high evidence)

Well-established gene-disease association (see OMIM entry). Dihydropyrimidine dehydrogenase deficiency is classified as a metabolic disorder by the NIH GARD (https://rarediseases.info.nih.gov/diseases/diseases-by-category/14/metabolic-disorders), and is an inborn error of pyrimidine metabolism.
Sources: NHS GMS
Created: 4 Feb 2021, 12:09 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Dihydropyrimidine dehydrogenase deficiency MIM#274270; 5-fluorouracil toxicity MIM#274270; Disorders of pyrimidine metabolism

Publications

Variants in this GENE are reported as part of current diagnostic practice

Elena Savva (Victorian Clinical Genetics Services)

Green List (high evidence)

Some individuals with the enzyme deficiency are asymptomatic (OMIM).

5-FU is a common chemotherapy drug. Toxicity is based on haplotypes not single variants.
A list of genotype-phenotype predicted outcomes can be found here: (https://cpicpgx.org/guidelines/guideline-for-fluoropyrimidines-and-dpyd/)
A useful database: https://www.pharmgkb.org/gene/PA145/variantAnnotation

It is important to note that there are conflicting reports regarding patients' true response to 5-FU and their genotype + supposed predicted reaction

Dihydropyrimidine dehydrogenase deficiency - is a clinically heterogenous AR disorder showing wide variablity of clinical presentations, ranging from no symptoms to severe convulsive disorders w/ motor and mental retardation. (PMID 29152729)
Created: 17 Apr 2020, 4:39 a.m. | Last Modified: 17 Apr 2020, 4:39 a.m.
Panel Version: 0.2301

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
5-fluorouracil toxicity 274270; Dihydropyrimidine dehydrogenase deficiency 274270

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert Review Green
  • NHS GMS
Phenotypes
  • Dihydropyrimidine dehydrogenase deficiency MONDO:0010130
  • Disorders of pyrimidine metabolism
OMIM
612779
Clinvar variants
Variants in DPYD
Penetrance
None
Publications
Panels with this gene

History Filter Activity

20 May 2024, Gel status: 3

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Bryony Thompson (Royal Melbourne Hospital)

gene: DPYD was added gene: DPYD was added to Nucleotide metabolism disorders. Sources: Expert Review Green Mode of inheritance for gene: DPYD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DPYD were set to 8051923; 29152729 Phenotypes for gene: DPYD were set to Dihydropyrimidine dehydrogenase deficiency MONDO:0010130; Disorders of pyrimidine metabolism