HARS1 and Charcot-Marie-Tooth disease: Interestingly, an analysis of multiple CMT-associated HARS1 variants revealed that each mutant protein had some degree of conformational opening compared to wildtype HisRS, and that the degree of structural opening correlated with disease severity (Bervoets et al., 2019), however, no specific abnormal protein interactions for mutant HisRS have yet been identified.