PFKM

PEX7

PEX7 is a gene that encodes the peroxisomal targeting signal 2 receptor, a protein crucial for the import of specific enzymes into peroxisomes. Peroxisomes are small, membrane-bound organelles that play a key role in lipid metabolism and the detoxification of reactive oxygen species. The PEX7 protein is essential for the proper functioning of peroxisomes, and mutations in the PEX7 gene can lead to peroxisomal biogenesis disorders.

Function

The PEX7 protein is a cytosolic receptor that recognizes and binds to the peroxisomal targeting signal 2 (PTS2) found on certain peroxisomal matrix proteins. Once bound, PEX7 facilitates the transport of these proteins into the peroxisome by interacting with other peroxisomal import machinery components, such as PEX5 and PEX14. This import process is vital for maintaining peroxisomal function and cellular homeostasis.

Clinical Significance

Mutations in the PEX7 gene are associated with a spectrum of disorders known as rhizomelic chondrodysplasia punctata (RCDP). RCDP is characterized by skeletal abnormalities, cataracts, and profound developmental delays. The severity of the disorder can vary depending on the nature of the mutation and its impact on PEX7 function.

Rhizomelic Chondrodysplasia Punctata

RCDP is a rare genetic disorder that affects bone growth, leading to shortening of the proximal limbs (rhizomelia), as well as other systemic manifestations. The disorder is classified into different types based on the genetic cause, with PEX7 mutations being responsible for RCDP type 1. Diagnosis is typically confirmed through genetic testing and biochemical assays that demonstrate impaired peroxisomal function.

Molecular Biology

The PEX7 gene is located on chromosome 6q23.3 and consists of multiple exons. The protein product of PEX7 is approximately 323 amino acids in length and contains a WD40 repeat domain, which is involved in protein-protein interactions. The WD40 domain is crucial for the recognition of the PTS2 signal and the subsequent import of target proteins into the peroxisome.

Research Directions

Current research on PEX7 focuses on understanding the detailed mechanisms of peroxisomal protein import and the development of potential therapies for disorders caused by PEX7 mutations. Gene therapy and small molecule approaches are being explored to restore peroxisomal function in affected individuals.

Also see

• Peroxisome
• Peroxisomal biogenesis disorder
• Rhizomelic chondrodysplasia punctata
• PEX5
• PEX14