The PEX7 gene provides instructions for making a protein called peroxisomal biogenesis factor 7, which is part of a group known as the peroxisomal assembly (PEX) proteins. Within cells, PEX proteins are responsible for importing certain enzymes into structures called peroxisomes. The enzymes in these sac-like compartments break down many different substances, including fatty acids and certain toxic compounds. They are also important for the production (synthesis) of fats (lipids) used in digestion and in the nervous system.
Peroxisomal biogenesis factor 7 transports several enzymes that are essential for the normal assembly and function of peroxisomes. The most important of these enzymes is alkylglycerone phosphate synthase (produced from the AGPS gene). This enzyme is required for the synthesis of specialized lipid molecules called plasmalogens, which are present in cell membranes throughout the body. Peroxisomal biogenesis factor 7 also transports the enzyme phytanoyl-CoA hydroxylase (produced from the PHYH gene). This enzyme helps process a type of fatty acid called phytanic acid, which is obtained from the diet. Phytanic acid is broken down through a multistep process into smaller molecules that the body can use for energy.
Health Conditions Related to Genetic Changes
Mutations in the PEX7 gene cause a small percentage of all cases of Refsum disease. The three mutations known to be responsible for this condition reduce the activity of peroxisomal biogenesis factor 7, which disrupts the import of several critical enzymes (including phytanoyl-CoA hydroxylase) into peroxisomes. Without enough of these enzymes, peroxisomes cannot break down fatty acids and other substances effectively.
In people with Refsum disease, a shortage of phytanoyl-CoA hydroxylase prevents peroxisomes from breaking down phytanic acid. Instead, this substance gradually builds up in the body's tissues. Over time, the accumulation of phytanic acid becomes toxic to cells. It is unclear, however, how an excess of this substance affects vision and smell and causes the other specific features of Refsum disease.More About This Health Condition
Rhizomelic chondrodysplasia punctata
More than three dozen mutations in the PEX7 gene have been found to cause rhizomelic chondrodysplasia punctata type 1 (RCDP1). These mutations tend to be more severe than the mutations that cause Refsum disease. The genetic changes associated with RCDP1 often lead to a completely nonfunctional version of peroxisomal biogenesis factor 7 or prevent cells from making any of this protein. The most common mutation responsible for RCDP1 replaces the amino acid leucine at protein position 292 with a premature stop signal in the instructions for making peroxisomal biogenesis factor 7 (written as Leu292Ter or L292X). This mutation leads to a nonfunctional version of the protein.
The PEX7 gene mutations responsible for RCDP1 prevent peroxisomal biogenesis factor 7 from transporting critical enzymes, particularly alkylglycerone phosphate synthase, into peroxisomes. A shortage of alkylglycerone phosphate synthase prevents the synthesis of plasmalogens. Problems with the production of these lipid molecules appear to cause the signs and symptoms of RCDP1. However, researchers are still working to determine how a lack of plasmalogens leads to skeletal abnormalities, intellectual disability, and the other features of this condition.More About This Health Condition
Other Names for This Gene
- peroxisomal PTS2 receptor
- peroxisome targeting signal 2 receptor
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Braverman N, Chen L, Lin P, Obie C, Steel G, Douglas P, Chakraborty PK, Clarke JT, Boneh A, Moser A, Moser H, Valle D. Mutation analysis of PEX7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype. Hum Mutat. 2002 Oct;20(4):284-97. Citation on PubMed
- Braverman N, Steel G, Lin P, Moser A, Moser H, Valle D. PEX7 gene structure, alternative transcripts, and evidence for a founder haplotype for the frequent RCDP allele, L292ter. Genomics. 2000 Jan 15;63(2):181-92. Citation on PubMed
- Braverman N, Steel G, Obie C, Moser A, Moser H, Gould SJ, Valle D. Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata. Nat Genet. 1997 Apr;15(4):369-76. Citation on PubMed
- Braverman NE, Steinberg SJ, Fallatah W, Duker A, Bober M. Rhizomelic Chondrodysplasia Punctata Type 1. 2001 Nov 16 [updated 2020 Jan 30]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from http://www.ncbi.nlm.nih.gov/books/NBK1270/ 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. Review. Citation on PubMed
- Motley AM, Brites P, Gerez L, Hogenhout E, Haasjes J, Benne R, Tabak HF, Wanders RJ, Waterham HR. Mutational spectrum in the PEX7 gene and functional analysis of mutant alleles in 78 patients with rhizomelic chondrodysplasia punctata type 1. Am J Hum Genet. 2002 Mar;70(3):612-24. Epub 2002 Jan 7. Citation on PubMed or Free article on PubMed Central
- Van den Brink DM, Brites P, Haasjes J, Wierzbicki AS, Mitchell J, Lambert-Hamill M, de Belleroche J, Jansen GA, Waterham HR, Wanders RJ. Identification of PEX7 as the second gene involved in Refsum disease. Adv Exp Med Biol. 2003;544:69-70. 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. Review. 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. Review. 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® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from http://www.ncbi.nlm.nih.gov/books/NBK1353/ Citation on PubMed