CLCC1 and amyotrophic lateral sclerosis: However, we noticed that heterozygous or homozygous mice for ALS-associated S263R and W267R mutations did not display ALS-like phenotypes and pathologies (Fig. 6d) but decreased CLCC1 expression and activation of ER UPR (Fig. 6a, b; Supplementary information, Fig. S21), suggesting that a subthreshold ER stress occurs in these mice.