Severe WR mutants show large residual activity that is uninhibited by warfarin. Inhibition curves of strong WR mutants (> 5-fold resistance) in GSH (left) are similar to those in the cell-based assay (right), indicating that redox state is essential. The largest warfarin-uninhibited activity is observed for Ala26Pro, Trp59Arg, and Leu128Arg; patients carrying these mutations exhibit severe WR, and warfarin therapy is often aborted (Table 1). All error bars are from 3 replicates.