DPYD
  • 30
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
DPYD (HGNC:3012) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
dihydropyrimidine dehydrogenase
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
DPD, DHPDHase
%HI
1.82(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0(Read more about gnomAD pLI score)
LOEUF
1.09(Read more about gnomAD LOEUF score)
Cytoband
1p21.3
Genomic Coordinates
GRCh37/hg19: chr1:97543299-98386615 NCBI Ensembl UCSC
GRCh38/hg38: chr1:97077743-97921059 NCBI Ensembl UCSC
MANE Select Transcript
NM_000110.4 ENST00000370192.8 (Read more about MANE Select)
Function
Involved in pyrimidine base degradation (PubMed:1512248). Catalyzes the reduction of uracil and thymine (PubMed:1512248). Also involved the degradation of the chemotherapeutic drug 5-fluorouracil (PubMed:1512248). {ECO:0000269|PubMed:1512248}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-22079
ClinGen Curation ID:
CCID:007030
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Gene Associated with Autosomal Recessive Phenotype (30)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
01/24/2018

Haploinsufficiency (HI) Score Details

HI Score:
30
HI Evidence Strength:
Gene Associated with Autosomal Recessive Phenotype (Disclaimer)
HI Disease:
  • dihydropyrimidine dehydrogenase deficiency Monarch
HI Evidence Comments:
Homozygous or compound heterozygous mutation in the DPYD cause Dihydropyrimidine dehydrogenase deficiency (OMIM: 274270). Asymptomatic individuals with biallelic variants have also been reported, suggesting reduced penetrance (PMID: 9254861, 12668826). Carter 2010 has reported a maternally inherited heterozygous exon 6 deletion in a patient with autism spectrum disorder, however the mother is healthy with no history of academic or social difficulties. (PMID:21114665). Xu 2013 reported de novo missense and nonsense variants in 2 individuals in a schizophrenia cohort. DPYD deficiency was also confirmed in the missense variant carrier. However, neither of these individuals have intellectual disability or autistic features (PMID:23042115). Other de novo deletions involving DPYD gene in the literature are all larger than 1 Mb (PMID:21114665, 24038936), therefore not informative for this evaluation. Taken together, there is not enough evidence from the literature to support dosage sensitivity of DPYD gene at this time. In addition, homozygous and heterozygous mutation carriers are at increased risk of developing adverse reactions after the administration of the antineoplastic drug 5-fluorouracil (5FU), which is also catabolized by the DPYD enzyme (PMID:23988873, Clinical Pharmacogenetics Implementation Consortium Guidelines). Homozygotes may have higher risk while risk in heterozygotes may be lower. The Guideline provides dosing recommendations based on DPYD genotype.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000001.10) (NC_000001.11)