A case in point is the molecular function of the yeast gene TUM1, an orthologue of the mammalian gene Tst that was proposed as a candidate obesity-resistance gene [7]: we show here that TUM1 and Tst are direct orthologues, yet the mammalian orthologue cannot replace the yeast gene. The gene discussed is MPST; the disease is obesity due to melanocortin 4 receptor deficiency.