We found that M3 (R385C) and M4 (R385H) FBXW7β mutants, which are most highly mutated in several data sets (Supplementary Fig. 2a–e), have lost their activity in attenuating steady-state expression of FASN, increasing the ubiquitination of FASN, reducing BODIPY staining, and inhibiting cell growth when compared with wild type (wt) FBXW7β (Fig. 3s–v), suggesting that FBXW7β mutations in several hot spots leads to deregulation of lipogenesis in colon cancer. Here, FASN is linked to malignant colon neoplasm.