Most rat resistances to anticoagulants have been associated with genetic mutations (single nucleotide polymorphisms, SNPs) at the vkorc1 gene. Many of the mutations locate at the top of the rat VKORC1 central cavity (Figure ). Most abundant European rat resistances, corresponded to Y139F, but other mutations are also abundant, such as Y139/C/S L120Q, L128Q and F63C (first letter corresponds to wild-type amino acid residues, number to the position and last letter to the mutant) . In 12 Spanish regions, our group has identified mutations located at S149I/T in urban (brown rat Rattus norvegicus) and E155K/Q in rural (black rat Rattus rattus) environments. These Spanish mutations map down the VKORC1 cavity nearby the cell membrane (Figure , orange spheres). These mutations cause a model displacement of their nearby α-helix by inducing an small 1-2 Å widening of the central cavity (not shown).