Valyl-tRNA synthetase 1 (VARS1)

Valyl-tRNA synthetase 1 (VARS1) is a cytoplasmic enzyme that catalyzes the attachment of the amino acid valine to its corresponding tRNA (tRNA^Val), a critical process in protein biosynthesis. It belongs to the class I family of aminoacyl-tRNA synthetases and ensures that valine is correctly incorporated during translation via a "double-sieve" mechanism to discriminate against structurally similar amino acids such as isoleucine and threonine. Mutations in the VARS1 gene lead to markedly reduced enzymatic activity, resulting in disorders like developmental delay, seizures, microcephaly, and progressive neurodegeneration. The enzyme is essential for cellular viability and accurate genetic code translation. There are currently no known drugs that directly target VARS1, but it is essential in disease pathology when mutated, making it of therapeutic and diagnostic interest in rare pediatric neurodevelopmental diseases. The VARS1 gene is not to be confused with VARS2, its paralog, which encodes the mitochondrial isoform. VARS1 acts as the only known cytoplasmic valine-tRNA ligase in humans. The enzyme’s activity is vital for nervous system development, which is illustrated by its role in a spectrum of severe pediatric neurological disorders upon loss of function.

Other names

Valyl-tRNA synthetaseValine--tRNA ligase 1, cytoplasmicVARSVARS2ValRSProtein G7aG7ANDMSCASYVCvalyl-tRNA synthetase 2valRSvaline tRNA ligase 1, cytoplasmic