FRG1 and myopathy: Although DUX4 gene de-repression is now considered the primary insult underlying FSHD, several other candidate genes have been tested in cells and mice over the years, including FRG1. FRG1 is an evolutionarily conserved protein located in the 4q35 region that causes a severe myopathy when overexpressed at high levels in mouse muscle (Gabellini et al., 2006; Wallace et al., 2011).