PEX1

The PEX1 gene provides instructions for making a protein called peroxisomal biogenesis factor 1 (Pex1p), which is part of a group of proteins called peroxins. Peroxins are essential for the formation and normal functioning of cell structures called peroxisomes. Peroxisomes are sac-like compartments that contain enzymes needed to break down many different substances, including fatty acids and certain toxic compounds. They are also important for the production of fats (lipids) used in digestion and in the nervous system. Peroxins assist in the formation (biogenesis) of peroxisomes by producing the membrane that separates the peroxisome from the rest of the cell and by importing enzymes into the peroxisome. Pex1p enables other peroxins to bring enzymes into the peroxisome.

Zellweger spectrum - caused by mutations in the PEX1 gene

At least 67 mutations in the PEX1 gene have been identified in people with the Zellweger spectrum. Mutations in this gene are the most common cause of the Zellweger spectrum and are found in nearly 70 percent of affected individuals.

There are two common PEX1 gene mutations found in people with the Zellweger spectrum. One mutation replaces the protein building block (amino acid) glycine with the amino acid aspartic acid at position 843 in the protein (written as Gly843Asp or G843D). This mutation leads to reduced levels of Pex1p. Individuals who have the G843D mutation tend to have signs and symptoms that are at the less severe end of the Zellweger spectrum. The other common mutation, which is known as the 1700fs mutation, leads to the production of an abnormally short, nonfunctional Pex1p. People who have the 1700fs mutation often have signs and symptoms that are at the severe end of the Zellweger spectrum.

Mutations in the PEX1 gene reduce or completely eliminate the activity of the Pex1p protein. Without enough functioning Pex1p, enzymes are not properly imported into peroxisomes. As a result, cells contain empty peroxisomes that cannot carry out their usual functions. The severe end of the Zellweger spectrum is caused by the absence of functional peroxisomes within cells. The less severe end of the Zellweger spectrum results from mutations that allow some peroxisomes to form.