RARS2

The RARS2 gene provides instructions for making an enzyme called mitochondrial arginyl-tRNA synthetase. This enzyme is active in cell structures called mitochondria. Each cell contains hundreds or thousands of mitochondria, which convert the energy from food into a form that cells can use.

Within mitochondria, mitochondrial arginyl-tRNA synthetase interacts with a molecule called transfer RNA (tRNA). This molecule, which is a chemical cousin of DNA, helps assemble protein building blocks called amino acids into functioning proteins. To build new proteins, tRNA must collect different amino acids and then attach them to one another in the correct order. Mitochondrial arginyl-tRNA synthetase is one of several enzymes that link amino acids to tRNA. Specifically, this enzyme links the amino acid arginine to the tRNA molecule, which then incorporates it into new proteins in mitochondria.

pontocerebellar hypoplasia - caused by mutations in the RARS2 gene

At least one mutation in the RARS2 gene has been found to cause pontocerebellar hypoplasia type 6 (PCH6). This mutation, which is written as IVS2+5A-G, disrupts the way the gene's instructions are used to make mitochondrial arginyl-tRNA synthetase. As a result, cells produce an abnormally short, nonfunctional version of this enzyme. A shortage of functional mitochondrial arginyl-tRNA synthetase prevents the normal assembly of new proteins within mitochondria. However, it is unclear how these changes disrupt normal brain development in people with PCH6.