Histidine--tRNA ligase, cytoplasmic

Histidine--tRNA ligase, cytoplasmic (HARS1) is an aminoacyl-tRNA synthetase that catalyzes the ATP-dependent ligation of histidine to its cognate tRNA, forming an aminoacyl-adenylate intermediate (UniProt: P12081). Beyond its canonical role in translation, the protein also participates in axon guidance processes.

HARS1 is primarily recognized for its involvement in protein synthesis across tissues. UniProt documentation associates HARS1 mutations with two neurological disorders: Usher syndrome 3B (USH3B), characterized by progressive hearing and vision loss, and Charcot-Marie-Tooth disease type 2W (CMT2W), an autosomal dominant peripheral axonal neuropathy affecting distal muscles and sensory function.

HARS1 is curated in this dataset for Alzheimer's Disease relevance (Chaparral AD proteomics). Analysis of post-mortem AD brain tissue versus age-matched controls using TMT-labeled proteomics across four subcellular fractions shows an ambiguous direction of change, with a mean log2 fold-change of 0.4613. This modest elevation lacks consistency across fractions, precluding a clear directional assignment in AD pathology.