YARS

The YARS gene provides instructions for making an enzyme called tyrosyl-tRNA synthetase. This enzyme is found in all cells, where it plays an important role in the production (synthesis) of proteins. During protein synthesis, building blocks (amino acids) are connected together in a specific order, creating the chain of amino acids that makes up the protein. Tyrosyl-tRNA synthetase plays a role in adding the amino acid tyrosine at the proper place in a protein's chain of amino acids.

In addition to its role in protein synthesis, tyrosyl-tRNA synthetase appears to have other functions. Under certain conditions, such as inflammation, this enzyme is cut (cleaved) into two fragments called mini-tyrRS and C-tyrRS. Research indicates that mini-tyrRS promotes the growth of new blood vessels (angiogenesis). Both fragments appear to stimulate the movement of particular cells, such as white blood cells that help fight infection.

Charcot-Marie-Tooth disease - caused by mutations in the YARS gene

At least three mutations in the YARS gene cause a form of Charcot-Marie-Tooth disease known as dominant intermediate C. One mutation replaces the amino acid glycine with the amino acid arginine at protein position 41 of the tyrosyl-tRNA synthetase enzyme (written as Gly41Arg or G41R). Another mutation replaces the amino acid glutamic acid with the amino acid lysine at protein position 196 (written as Glu196Lys or E196K). A third YARS gene mutation results in an altered version of the tyrosyl-tRNA synthetase enzyme that is missing four amino acids. Mutations in the YARS gene probably reduce the activity of tyrosyl-tRNA synthetase, which could affect the synthesis of any protein that contains tyrosine. It is unclear how these mutations lead to the dominant intermediate C form of Charcot-Marie-Tooth disease.