Our findings were further substantiated in cell lines derived from a murine liver cancer model system, in which we observed paralog synthetic lethality for simultaneous Cas9 and/or shRNA-mediated MFRN1/2 perturbation (Additional file 1: Fig. S7a–f) and pronounced tumor growth retardation in xenograft tumors upon inducible MFRN2 knockdown only in the setting of MFRN1 loss (Additional file 1: Fig. S7g). Here, SLC25A28 is linked to neoplasm.