Asparaginyl-tRNA synthetase (NARS1) variants implicated in dominant neurological phenotypes display dominant-negative properties.

ABSTRACT: Aminoacyl-tRNA synthetases (ARSs) are essential, ubiquitously expressed enzymes that ligate amino acids to cognate tRNAs in the cytoplasm and mitochondria. To date, seven dimeric ARS enzymes have been implicated in dominant inherited neuropathy, suggesting that tRNA charging-exacerbated by a dominant-negative effect-is a component of the peripheral nervous system (PNS) phenotype. Interestingly, heterozygosity for missense and protein-truncating variants in the gene encoding dimeric, cytoplasmic asparaginyl-tRNA synthetase (NARS1) have been associated with distinct clinical phenotypes where patients present with either an isolated PNS neuropathy or with a complex phenotype that includes both PNS and central nervous system (CNS) features. Thus, NARS1 variants are associated with a spectrum o

SUBMITTER: Peeples SM 

PROVIDER: S-EPMC12513288 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature