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Normal Function
The DPYD gene provides instructions for making an enzyme called dihydropyrimidine dehydrogenase, which is involved in the breakdown of molecules called uracil and thymine when they are not needed. Uracil and thymine are pyrimidines, which are one type of nucleotide. Nucleotides are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell.
Dihydropyrimidine dehydrogenase is involved in the first step of the breakdown of pyrimidines. This enzyme converts uracil to another molecule called 5,6-dihydrouracil and converts thymine to 5,6-dihydrothymine. The molecules created when pyrimidines are broken down are excreted by the body or used in other cellular processes.
Health Conditions Related to Genetic Changes
Dihydropyrimidine dehydrogenase deficiency
More than 50 mutations in the DPYD gene have been identified in people with dihydropyrimidine dehydrogenase deficiency. DPYD gene mutations interfere with the breakdown of uracil and thymine and result in excess quantities of these molecules in the blood, urine, and the fluid that surrounds the brain and spinal cord (cerebrospinal fluid). It is unclear how the excess uracil and thymine are related to the specific neurological problems that affect some people with dihydropyrimidine dehydrogenase deficiency.
Mutations in the DPYD gene also interfere with the breakdown of drugs with structures similar to the pyrimidines, such as the cancer drugs 5-fluorouracil and capecitabine. As a result, these drugs accumulate in the body and cause the severe reactions that can occur in people with dihydropyrimidine dehydrogenase deficiency.
More About This Health ConditionOther Names for This Gene
- DHP
- DHPDHASE
- dihydropyrimidine dehydrogenase [NADP+]
- dihydrothymine dehydrogenase
- dihydrouracil dehydrogenase
- DPD
- DPYD_HUMAN
- MGC132008
- MGC70799
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Al-Sanna'a NA, Van Kuilenburg AB, Atrak TM, Abdul-Jabbar MA, Van Gennip AH. Dihydropyrimidine dehydrogenase deficiency presenting at birth. J Inherit Metab Dis. 2005;28(5):793-6. doi: 10.1007/s10545-005-4218-0. Citation on PubMed
- Ciccolini J, Gross E, Dahan L, Lacarelle B, Mercier C. Routine dihydropyrimidine dehydrogenase testing for anticipating 5-fluorouracil-related severe toxicities: hype or hope? Clin Colorectal Cancer. 2010 Oct;9(4):224-8. doi: 10.3816/CCC.2010.n.033. Citation on PubMed
- Mattison LK, Fourie J, Desmond RA, Modak A, Saif MW, Diasio RB. Increased prevalence of dihydropyrimidine dehydrogenase deficiency in African-Americans compared with Caucasians. Clin Cancer Res. 2006 Sep 15;12(18):5491-5. doi: 10.1158/1078-0432.CCR-06-0747. Citation on PubMed
- Saif MW, Mattison L, Carollo T, Ezzeldin H, Diasio RB. Dihydropyrimidine dehydrogenase deficiency in an Indian population. Cancer Chemother Pharmacol. 2006 Sep;58(3):396-401. doi: 10.1007/s00280-005-0174-5. Epub 2006 Jan 19. Citation on PubMed
- van Kuilenburg AB, De Abreu RA, van Gennip AH. Pharmacogenetic and clinical aspects of dihydropyrimidine dehydrogenase deficiency. Ann Clin Biochem. 2003 Jan;40(Pt 1):41-5. doi: 10.1258/000456303321016150. Citation on PubMed
- van Kuilenburg AB, Dobritzsch D, Meinsma R, Haasjes J, Waterham HR, Nowaczyk MJ, Maropoulos GD, Hein G, Kalhoff H, Kirk JM, Baaske H, Aukett A, Duley JA, Ward KP, Lindqvist Y, van Gennip AH. Novel disease-causing mutations in the dihydropyrimidine dehydrogenase gene interpreted by analysis of the three-dimensional protein structure. Biochem J. 2002 May 15;364(Pt 1):157-63. doi: 10.1042/bj3640157. Citation on PubMed or Free article on PubMed Central
- van Kuilenburg AB, Meijer J, Mul AN, Hennekam RC, Hoovers JM, de Die-Smulders CE, Weber P, Mori AC, Bierau J, Fowler B, Macke K, Sass JO, Meinsma R, Hennermann JB, Miny P, Zoetekouw L, Vijzelaar R, Nicolai J, Ylstra B, Rubio-Gozalbo ME. Analysis of severely affected patients with dihydropyrimidine dehydrogenase deficiency reveals large intragenic rearrangements of DPYD and a de novo interstitial deletion del(1)(p13.3p21.3). Hum Genet. 2009 Jun;125(5-6):581-90. doi: 10.1007/s00439-009-0653-6. Epub 2009 Mar 19. Citation on PubMed
- Van Kuilenburg AB, Vreken P, Abeling NG, Bakker HD, Meinsma R, Van Lenthe H, De Abreu RA, Smeitink JA, Kayserili H, Apak MY, Christensen E, Holopainen I, Pulkki K, Riva D, Botteon G, Holme E, Tulinius M, Kleijer WJ, Beemer FA, Duran M, Niezen-Koning KE, Smit GP, Jakobs C, Smit LM, Van Gennip AH, et al. Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency. Hum Genet. 1999 Jan;104(1):1-9. doi: 10.1007/pl00008711. Citation on PubMed
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