Human disease-causing missense genetic variants are enriched in the evolutionarily ancient domains of the cytosolic aminoacyl-tRNA synthetase proteins.

ABSTRACT: All life depends on accurate and efficient protein synthesis. The aminoacyl-tRNA synthetases (aaRSs) are a family of proteins that play an essential role in protein translation, as they catalyze the esterification reaction that charges a transfer RNA (tRNA) with its cognate amino acid. However, new domains added to the aaRSs over the course of evolution in eukaryotes confer novel functions unrelated to protein translation. To date, damaging variants that affect aaRS-encoding genes have been linked to over 50 human diseases. In this study, we leverage the evolutionary history of the aaRS proteins to better understand the distribution of disease-causing missense variants in human cytosolic aaRSs. We hypothesized that disease-causing missense variants in human aaRSs were more likely to be loc

SUBMITTER: Turvey AK 

PROVIDER: S-EPMC11664165 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature