These mutations lead to reduced metal ion content, decreased net charge (in some cases), disruption of the surface hydrogen bond network, increase in the hydrophobicity, changes in the flexibility, and alternations in the functional characteristics of SOD1, therefore play a crucial role in the formation of toxic aggregates and the pathology of ALS (Antonyuk et al., 2005; Khare and Dokholyan, 2006; Byström et al., 2010; Tompa and Kadhirvel, 2020; Mavadat et al., 2023a; Mavadat et al., 2023b). The gene discussed is SOD1; the disease is amyotrophic lateral sclerosis.