Valine--tRNA ligase

Valine–tRNA ligase (VARS1) is an aminoacyl-tRNA synthetase that catalyzes the attachment of valine to tRNA(Val), a fundamental step in translation initiation and elongation (UniProt: P26640). The enzyme is essential for accurate protein synthesis across all cellular compartments.

In addition to its housekeeping role in translation, VARS1 is associated with neurodevelopmental disease. Biallelic VARS1 mutations cause neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy (NDMSCA, MIM 617802), an autosomal recessive condition marked by severe developmental delay, intellectual disability, microcephaly, and cortical atrophy (UniProt: P26640).

VARS1 is tagged for Alzheimer's disease relevance in this dataset. However, proteomics analysis of post-mortem AD brain across four subcellular fractions shows an ambiguous directional pattern, with a mean log2 fold-change of 0.055 relative to age-matched controls (Chaparral AD proteomics). This minimal change near baseline suggests no consistent dysregulation of VARS1 in AD pathology across the examined fractions.