The PHYH gene provides instructions for making an enzyme called phytanoyl-CoA hydroxylase. This enzyme is critical for the normal function of cell structures called peroxisomes. These sac-like compartments contain enzymes needed to break down many different substances, including fatty acids and certain toxic compounds.
One substance that is broken down in peroxisomes is phytanic acid, a type of fatty acid obtained from the diet (particularly from beef and dairy products). Phytanoyl-CoA hydroxylase is responsible for one of the first steps in breaking down phytanic acid as part of a process known as alpha-oxidation. In subsequent steps, additional enzymes in peroxisomes and other parts of the cell further process this compound into smaller molecules that the body can use for energy.
Researchers suspect that phytanoyl-CoA hydroxylase may have other functions in addition to its role in breaking down phytanic acid. For example, this enzyme appears to help determine the number of peroxisomes within cells and is involved in regulating their activity.
Health Conditions Related to Genetic Changes
Mutations in the PHYH gene have been found to cause more than 90 percent of all cases of Refsum disease. About 30 mutations in this gene have been identified. These mutations alter the structure or production of phytanoyl-CoA hydroxylase, which reduces the enzyme's activity. A shortage of this enzyme disrupts the breakdown of phytanic acid in peroxisomes. As a result, phytanic acid and related compounds build up in the body's tissues. The accumulation of phytanic acid is toxic to cells, although it is unclear how an excess of this substance affects vision and smell and causes the other specific features of Refsum disease.More About This Health Condition
Other Names for This Gene
- phytanic acid oxidase
- phytanoil-CoA alpha hydroxylase
- phytanoyl-CoA 2 oxoglutarate dioxygenase
- phytanoyl-CoA alpha-hydroxylase
- phytanoyl-CoA dioxygenase, peroxisomal
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Jansen GA, Hogenhout EM, Ferdinandusse S, Waterham HR, Ofman R, Jakobs C, Skjeldal OH, Wanders RJ. Human phytanoyl-CoA hydroxylase: resolution of the gene structure and the molecular basis of Refsum's disease. Hum Mol Genet. 2000 May 1;9(8):1195-200. doi: 10.1093/hmg/9.8.1195. Citation on PubMed
- Jansen GA, Ofman R, Ferdinandusse S, Ijlst L, Muijsers AO, Skjeldal OH, Stokke O, Jakobs C, Besley GT, Wraith JE, Wanders RJ. Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene. Nat Genet. 1997 Oct;17(2):190-3. doi: 10.1038/ng1097-190. Citation on PubMed
- Jansen GA, Wanders RJ, Watkins PA, Mihalik SJ. Phytanoyl-coenzyme A hydroxylase deficiency -- the enzyme defect in Refsum's disease. N Engl J Med. 1997 Jul 10;337(2):133-4. doi: 10.1056/NEJM199707103370215. No abstract available. Citation on PubMed
- Jansen GA, Waterham HR, Wanders RJ. Molecular basis of Refsum disease: sequence variations in phytanoyl-CoA hydroxylase (PHYH) and the PTS2 receptor (PEX7). Hum Mutat. 2004 Mar;23(3):209-18. doi: 10.1002/humu.10315. Citation on PubMed
- McDonough MA, Kavanagh KL, Butler D, Searls T, Oppermann U, Schofield CJ. Structure of human phytanoyl-CoA 2-hydroxylase identifies molecular mechanisms of Refsum disease. J Biol Chem. 2005 Dec 9;280(49):41101-10. doi: 10.1074/jbc.M507528200. Epub 2005 Sep 25. Citation on PubMed
- Mihalik SJ, Morrell JC, Kim D, Sacksteder KA, Watkins PA, Gould SJ. Identification of PAHX, a Refsum disease gene. Nat Genet. 1997 Oct;17(2):185-9. doi: 10.1038/ng1097-185. Citation on PubMed
- Mukherji M, Chien W, Kershaw NJ, Clifton IJ, Schofield CJ, Wierzbicki AS, Lloyd MD. Structure-function analysis of phytanoyl-CoA 2-hydroxylase mutations causing Refsum's disease. Hum Mol Genet. 2001 Sep 1;10(18):1971-82. doi: 10.1093/hmg/10.18.1971. Citation on PubMed
- van den Brink DM, Wanders RJ. Phytanic acid: production from phytol, its breakdown and role in human disease. Cell Mol Life Sci. 2006 Aug;63(15):1752-65. doi: 10.1007/s00018-005-5463-y. Citation on PubMed
- Wanders RJ, Komen JC. Peroxisomes, Refsum's disease and the alpha- and omega-oxidation of phytanic acid. Biochem Soc Trans. 2007 Nov;35(Pt 5):865-9. doi: 10.1042/BST0350865. Citation on PubMed
- Waterham HR, Wanders RJA, Leroy BP. Adult Refsum Disease. 2006 Mar 20 [updated 2021 Sep 30]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from http://www.ncbi.nlm.nih.gov/books/NBK1353/ Citation on PubMed
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