DPYD Gene (Dihydropyrimidine Dehydrogenase)
Key enzyme in pyrimidine catabolism; pharmacogenetic marker for fluoropyrimidine toxicity
Gene Information Card
| Symbol | DPYD |
|---|---|
| Full Name | Dihydropyrimidine Dehydrogenase |
| Gene Type | Protein coding |
| Chromosomal Location | 1p21.3 |
| NCBI Gene ID | 1806 ncbi.nlm.nih.gov/gene/1806 |
| Ensembl ID | ENSG00000188641 |
| UniProt ID | Q12882 |
| OMIM ID | 612779 |
| HGNC ID | 3012 |
| Aliases | DPD, DHPDHASE, MGC132008 |
Description
The DPYD gene encodes dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme in the catabolism of pyrimidines (uracil and thymine) and fluoropyrimidines (e.g., 5-fluorouracil). DPD deficiency, often due to loss-of-function variants in DPYD, leads to severe toxicity in patients treated with fluoropyrimidine chemotherapeutic agents. The gene spans approximately 950 kb and contains 23 exons.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dihydropyrimidine dehydrogenase deficiency | Loss-of-function mutations reduce DPD activity, causing accumulation of pyrimidines and severe fluoropyrimidine toxicity | ClinVar, OMIM |
| 5-Fluorouracil toxicity | Reduced DPD activity impairs clearance of 5-FU, leading to severe gastrointestinal, hematologic, and neurologic adverse effects | ClinVar, NCBI |
| Thymine-uraciluria | Deficient DPD activity results in elevated urinary excretion of thymine and uracil | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Small intestine | 8.3 | Medium |
| Kidney | 6.1 | Medium |
| Lung | 3.2 | Low |
| Spleen | 2.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 10.1 | Liver cancer cell line |
| Caco-2 | 7.4 | Colorectal adenocarcinoma |
| A549 | 3.5 | Lung carcinoma |
| MCF7 | 1.2 | Breast cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1905+1G>A (IVS14+1G>A) | Splice donor | Common in Caucasians (~1-2%) | Loss of function; increased 5-FU toxicity risk |
| c.1679T>G (p.Ile560Ser) | Missense | ~0.5-1% in Europeans | Reduced DPD activity |
| c.2846A>T (p.Asp949Val) | Missense | ~0.5-1% in Europeans | Moderate reduction in DPD activity |
| c.1129-5923C>G (HapB3) | Intronic | ~2-5% in Africans | Decreased DPD expression |
Mutation functional classification
Loss of Function (LOF)
Most DPYD variants (e.g., c.1905+1G>A, c.1679T>G) reduce or abolish DPD enzymatic activity, leading to impaired pyrimidine catabolism and increased risk of severe fluoropyrimidine toxicity.
Gain of Function (GOF)
No well-characterized gain-of-function variants reported in DPYD.
Dominant Negative (DN)
No dominant-negative mechanisms described for DPYD mutations; deficiency is typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • dihydropyrimidine dehydrogenase activity (GO:0004152) | • uracil catabolic process (GO:0006212) |
| • thymine catabolic process (GO:0006213) | • cytosol (GO:0005829) |
| • cytoplasm (GO:0005737) |
Pathways
• Pyrimidine metabolism (Reactome: R-HSA-73621)
• Beta-ureidopropionase pathway (KEGG: hsa00240)
Protein Summary
Dihydropyrimidine dehydrogenase (DPD) is a 1025-amino-acid homodimeric flavoprotein that catalyzes the first and rate-limiting step in pyrimidine degradation: the reduction of uracil and thymine to 5,6-dihydrouracil and 5,6-dihydrothymine, respectively. DPD also metabolizes the chemotherapeutic agent 5-fluorouracil (5-FU). The enzyme contains FMN, FAD, and [4Fe-4S] clusters as cofactors. Reduced DPD activity due to genetic variants is a major cause of severe 5-FU toxicity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DPYD Knockout HEK293 Cell Line | EDJ-KQ4478 | Human | 1806 | Details Get a Quote |
| DPYD Knockout A-549 Cell Line | EDJ-KQ27048 | Human | 1806 | Details Get a Quote |
| DPYD Knockout HCT 116 Cell Line | EDJ-KQ27049 | Human | 1806 | Details Get a Quote |
| DPYD Knockout HeLa Cell Line | EDJ-KQ27050 | Human | 1806 | Details Get a Quote |
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