Valyl-tRNA synthetase 2, mitochondrial (VARS2)

Valyl-tRNA synthetase 2, mitochondrial (VARS2), is an enzyme localized to mitochondria that catalyzes the attachment of the amino acid valine to its corresponding mitochondrial tRNA(Val), a key step in mitochondrial protein synthesis required for the proper assembly and function of the oxidative phosphorylation complexes. Mutations in VARS2 severely disrupt this process, leading to combined oxidative phosphorylation deficiency and a spectrum of mitochondrial diseases, with early-onset neurological impairment and frequently cardiomyopathy[1][2][5][7][10]. VARS2 is part of the aminoacyl-tRNA synthetase enzyme family and is essential for cellular energy production, especially in tissues with high metabolic demand. There are no drugs that directly target VARS2, but its genetic variants serve as biomarkers for certain mitochondrial disorders, and deficiency in this protein raises significant therapeutic challenges due to the critical role it plays in mitochondrial function[1][2][7][10].

Other names

Valine--tRNA ligase, mitochondrialVARS2KIAA1885VARS2LVARSLValRSDKFZP434L1435G7aValyl-tRNA synthetaseValyl-tRNA synthetase-likevaline tRNA ligase 2, mitochondrialCOXPD20VALRS

Not drugged directly; conceptually, inhibition or mutation leads to loss of aminoacylation of mitochondrial tRNA(Val), impairing mitochondrial translation and energy metabolism