On this page
PEX7
peroxisomal biogenesis factor 7
The *PEX7* gene provides instructions for producing peroxisomal biogenesis factor 7, a protein crucial for transporting enzymes into peroxisomes, which are vital cellular compartments. The *PEX7* gene encodes a protein called peroxisomal biogenesis factor 7, which is essential for the proper function of peroxisomes within cells.
PEX7 is located on the long (q) arm of chromosome 6, at band 6q23.3. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 6 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The *PEX7* gene, also known as peroxisomal biogenesis factor 7, is integral to the formation and function of peroxisomes. Peroxisomes are membrane-bound organelles found in almost all eukaryotic cells, playing crucial roles in various metabolic processes, including the breakdown of fatty acids and detoxification of harmful substances.
Disruptions in *PEX7* function can lead to severe inherited disorders that affect multiple organ systems, highlighting its importance in human health.
What the gene does
The protein encoded by the *PEX7* gene, peroxisomal biogenesis factor 7, is a member of the peroxisomal assembly (PEX) protein family. Its primary function involves importing specific enzymes into peroxisomes, which are cellular compartments responsible for diverse metabolic activities. These imported enzymes are essential for the normal assembly and function of peroxisomes.
One critical enzyme transported by PEX7 is alkylglycerone phosphate synthase, which is necessary for the synthesis of plasmalogens, a type of specialised lipid molecule abundant in cell membranes throughout the body. PEX7 also facilitates the transport of phytanoyl-CoA hydroxylase, an enzyme involved in processing phytanic acid, a fatty acid obtained from the diet. Without sufficient activity of these enzymes, peroxisomes cannot effectively break down certain substances or produce essential lipids, leading to metabolic dysfunction.
Video: Genetics 101
Chromosome location
The *PEX7* gene is located on chromosome 6 at position 6q23.3. This genomic address specifies its precise physical location on the long arm (q) of chromosome 6.
Protein structure
The peroxisomal biogenesis factor 7 protein consists of 323 amino acids. Its structure includes six WD repeats, which are common protein motifs typically involved in protein-protein interactions. These domains are sequentially arranged as follows: WD 1 (Repeat) spans amino acids 65-96, WD 2 (Repeat) from amino acids 109-141, WD 3 (Repeat) from amino acids 153-184, WD 4 (Repeat) from amino acids 196-227, WD 5 (Repeat) from amino acids 240-271, and WD 6 (Repeat) from amino acids 284-315.
Key variants
Variants within the *PEX7* gene can alter the function of the peroxisomal biogenesis factor 7 protein. These genetic changes can range from single nucleotide substitutions to larger deletions or insertions, and their impact varies depending on the specific alteration. Pathogenic variants can lead to a reduction in protein activity, a completely non-functional protein, or even prevent the protein from being produced at all.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.218_231del | p.Val73fs | Pathogenic/Likely pathogenic | ★★☆☆ | Peroxisome biogenesis disorder |
c.283T>G | p.Trp95Gly | Pathogenic | ★★☆☆ | Peroxisome biogenesis disorder 9B |
c.370_396del | p.Gly124_Ser132del | Pathogenic/Likely pathogenic | ★★☆☆ | PEX7-related disorder |
c.4_10dup | p.Val4fs | Pathogenic/Likely pathogenic | ★★☆☆ | Rhizomelic chondrodysplasia punctata |
c.45_52del | p.Gly16fs | Pathogenic | ★★☆☆ | Peroxisome biogenesis disorder 9B |
c.488G>A | p.Trp163Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Peroxisome biogenesis disorder 9B |
c.513del | p.Phe171fs | Pathogenic/Likely pathogenic | ★★☆☆ | Peroxisome biogenesis disorder 9B |
c.517del | p.Ser173fs | Pathogenic/Likely pathogenic | ★★☆☆ | Peroxisome biogenesis disorder 9B |
c.523_526dup | p.Gly176fs | Pathogenic | ★★☆☆ | Peroxisome biogenesis disorder |
c.549G>A | p.Trp183Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Peroxisome biogenesis disorder 9B |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the *PEX7* gene are primarily associated with a spectrum of peroxisomal disorders, including Rhizomelic Chondrodysplasia Punctata and a small percentage of cases of Refsum disease (infantile). These conditions are inherited in an autosomal recessive manner, meaning an individual must inherit two affected copies of the gene (one from each parent) to develop the disorder. The severity of these conditions can vary, often correlating with the residual function of the PEX7 protein.
- Refsum disease (infantile) Dedicated page coming soon
- Rhizomelic chondrodysplasia punctata Dedicated page coming soon
Inheritance pattern
Conditions caused by pathogenic PEX7 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The *PEX7* gene is included in several NHS Genomic Medicine Service national test panels. These panels cover a range of conditions, including Arthrogryposis, Bilateral congenital or childhood onset cataracts, Chondrodysplasia punctata, Foetal anomalies, Foetal hydrops, Hereditary neuropathy or pain disorder, Intellectual disability, Leukodystrophy (adult onset), Likely inborn error of metabolism, Peroxisomal disorders, Retinal disorders, Skeletal dysplasia, and Undiagnosed metabolic disorders, all of which are designated green within PanelApp, indicating strong evidence for gene-disease association.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the role of peroxisomes in the body?
Peroxisomes are vital cellular organelles involved in a wide array of metabolic processes. They are essential for breaking down fatty acids, synthesising lipids, and detoxifying certain compounds, contributing significantly to overall cellular health and function.
How is a condition caused by a *PEX7* gene variant inherited?
Conditions linked to *PEX7* variants, such as Rhizomelic Chondrodysplasia Punctata, are inherited in an autosomal recessive pattern. This means an individual must inherit two copies of the altered gene, one from each parent, to develop the condition. Parents who carry one altered copy of the gene are typically unaffected.
What are plasmalogens and why are they important?
Plasmalogens are a special type of lipid found in cell membranes throughout the body. They are particularly abundant in nerve and immune cells and play crucial roles in membrane integrity, cell signalling, and protection against oxidative stress. Their synthesis relies on enzymes transported by the PEX7 protein.
References
- Wanders RJ, Komen JC. Peroxisomes, Refsum's disease and the alpha- and omega-oxidation of phytanic acid. Biochemical Society transactions. 2007. PMID: 17956234
- van den Brink DM, Wanders RJ. Phytanic acid: production from phytol, its breakdown and role in human disease. Cellular and molecular life sciences : CMLS. 2006. PMID: 16799769
- Jansen GA, Waterham HR, Wanders RJ. Molecular basis of Refsum disease: sequence variations in phytanoyl-CoA hydroxylase (PHYH) and the PTS2 receptor (PEX7). Human mutation. 2004. PMID: 14974078
- Van den Brink DM, Brites P, Haasjes J. Identification of PEX7 as the second gene involved in Refsum disease. Advances in experimental medicine and biology. 2003. PMID: 14713215
- Motley AM, Brites P, Gerez L. Mutational spectrum in the PEX7 gene and functional analysis of mutant alleles in 78 patients with rhizomelic chondrodysplasia punctata type 1. American journal of human genetics. 2002. PMID: 11781871
- Braverman N, Chen L, Lin P. Mutation analysis of PEX7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype. Human mutation. 2002. PMID: 12325024
- Braverman N, Steel G, Lin P. PEX7 gene structure, alternative transcripts, and evidence for a founder haplotype for the frequent RCDP allele, L292ter. Genomics. 2000. PMID: 10673331
- Braverman N, Steel G, Obie C. Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata. Nature genetics. 1997. PMID: 9090381
- Adam MP, Bick S, Mirzaa GM. PEX7-Related Rhizomelic Chondrodysplasia Punctata. 1993. PMID: 20301447
- Adam MP, Bick S, Mirzaa GM. Adult Refsum Disease. 1993. PMID: 20301527