In order to further understand the C9ORF72 potential synergistic effects with other ALS-related genes, the C. elegans model carrying mutative TDP-43 A315T or FUSΔUS5 combined with the null alfa-1 mutation were established, which showed that the null alfa-1 expression decreases and the paralytic phenotypes exacerbates but does not change the toxic of mutative FUS protein, which suggests that the mutative C9ORF72 gene exerts a synergistic effect with the mutative TDP-43 gene in the same MNs toxic pathway but not the mutative FUS gene. This evidence concerns the gene C9orf72 and amyotrophic lateral sclerosis.