On this page
PEX1
peroxisomal biogenesis factor 1
The PEX1 gene encodes a protein essential for the formation and proper function of peroxisomes, cellular compartments involved in metabolising fatty acids and other compounds. PEX1 provides instructions for making peroxisomal biogenesis factor 1 (Pex1p), a protein vital for peroxisome development and activity.
PEX1 is located on the long (q) arm of chromosome 7, at band 7q21.2. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 7 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The PEX1 gene provides the genetic blueprint for a protein called peroxisomal biogenesis factor 1 (Pex1p). This protein is a member of a group known as peroxins, all of which are fundamental for the creation and normal operation of peroxisomes within cells. Peroxisomes are specialised compartments that house enzymes responsible for breaking down a range of substances, including certain toxic compounds and fatty acids. They also play a significant part in generating fats (lipids) that are important for both digestion and the nervous system.
What the gene does
The Pex1p protein, encoded by the PEX1 gene, is instrumental in the formation of peroxisomes. It helps establish the membrane that separates these organelles from the rest of the cell's interior. Beyond structural formation, Pex1p facilitates the import of essential enzymes into the peroxisome. This process is critical for peroxisomes to perform their functions, which include metabolising fatty acids and detoxification. Without properly functioning Pex1p, the biogenesis of peroxisomes is impaired, leading to their dysfunction and an inability to process crucial cellular components effectively.
Video: Genetics 101
Chromosome location
The PEX1 gene is located on chromosome 7, specifically at position 7q21.2. This genomic address specifies its exact position on the long arm of chromosome 7. The gene spans a significant region of the chromosome, containing the genetic instructions for its corresponding protein.
Protein structure
The PEX1 protein comprises 1283 amino acids. Its structure includes several key regions. Notably, there are two identified disordered regions: one spanning amino acids 346-367 and another located at the C-terminus, from amino acids 1260-1283. These disordered regions suggest areas of structural flexibility, which can be important for protein interactions and function.
Key variants
Variants in the PEX1 gene can alter the normal function of the Pex1p protein. These genetic changes can range from single nucleotide substitutions to larger deletions or insertions within the gene sequence. The impact of a variant depends on its specific nature and location, potentially leading to a non-functional or improperly functioning protein. Many different variants have been identified, contributing to a spectrum of associated health conditions.
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.1239G>A | p.Trp413Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Zellweger spectrum disorders |
c.1422_1425del | p.Thr475fs | Pathogenic/Likely pathogenic | ★★☆☆ | Zellweger spectrum disorders |
c.1671_1672del | - | Pathogenic | ★★☆☆ | Heimler syndrome 1 |
c.2146C>T | p.Gln716Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Zellweger spectrum disorders |
c.2308C>T | p.Gln770Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Heimler syndrome 1 |
c.2480del | p.Arg827fs | Pathogenic | ★★☆☆ | Peroxisome biogenesis disorder 1B |
c.466C>T | p.Gln156Ter | Pathogenic/Likely pathogenic | ★★☆☆ | PEX1-related disorder |
c.556G>T | p.Glu186Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Zellweger spectrum disorders |
c.794G>A | p.Trp265Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Zellweger spectrum disorders |
c.821_824del | p.Lys274fs | Pathogenic/Likely pathogenic | ★★☆☆ | Zellweger spectrum disorders |
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 PEX1 gene are primarily associated with Zellweger spectrum disorder. This is a group of related conditions characterised by overlapping symptoms and varying severity, affecting multiple organ systems. The features of Zellweger spectrum disorder can include developmental delays, weak muscle tone (hypotonia), and issues with vision and hearing. PEX1 variants are the most common genetic cause of this disorder.
- Zellweger spectrum disorder Dedicated page coming soon
Inheritance pattern
Conditions caused by pathogenic PEX1 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
In the UK, the PEX1 gene is included in several NHS England Genomic Medicine Service national panels via PanelApp. It is rated 'green' on panels such as Amelogenesis imperfecta (R340), Arthrogryposis (R83), Bilateral congenital or childhood onset cataracts (R31), and Zellweger spectrum disorder. This indicates that there is strong evidence supporting a gene-disease association for these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary role of the PEX1 gene?
The PEX1 gene provides instructions for the Pex1p protein, which is essential for the proper formation and function of peroxisomes, cellular compartments that break down fatty acids and toxic compounds.
What health conditions are associated with PEX1 gene variants?
Variants in the PEX1 gene are predominantly associated with Zellweger spectrum disorder, a group of conditions impacting multiple body systems, often resulting in developmental, vision, and hearing difficulties.
How does PEX1 relate to peroxisomes?
PEX1 encodes a protein that is a key component in the biogenesis of peroxisomes, helping to form their membrane and import necessary enzymes for their metabolic activities.
References
- Ebberink MS, Mooijer PA, Gootjes J. Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder. Human mutation. 2011. PMID: 21031596
- Fujiki Y, Miyata N, Matsumoto N. Dynamic and functional assembly of the AAA peroxins, Pex1p and Pex6p, and their membrane receptor Pex26p involved in shuttling of the PTS1 receptor Pex5p in peroxisome biogenesis. Biochemical Society transactions. 2008. PMID: 18208396
- Rosenkranz K, Birschmann I, Grunau S. Functional association of the AAA complex and the peroxisomal importomer. The FEBS journal. 2006. PMID: 16911527
- Thoms S, Erdmann R. Peroxisomal matrix protein receptor ubiquitination and recycling. Biochimica et biophysica acta. 2006. PMID: 17028012
- Wanders RJ, Waterham HR. Peroxisomal disorders I: biochemistry and genetics of peroxisome biogenesis disorders. Clinical genetics. 2005. PMID: 15679822
- Crane DI, Maxwell MA, Paton BC. PEX1 mutations in the Zellweger spectrum of the peroxisome biogenesis disorders. Human mutation. 2005. PMID: 16086329
- Rosewich H, Ohlenbusch A, Gärtner J. Genetic and clinical aspects of Zellweger spectrum patients with PEX1 mutations. Journal of medical genetics. 2005. PMID: 16141001
- Adam MP, Bick S, Mirzaa GM. Zellweger Spectrum Disorder. 1993. PMID: 20301621