More specifically, while Gs activity is mainly accounted by higher GNAS levels (Fig. 4b), lower Gi/o levels are seemingly caused by a diminished expression of either Gi/o-proteins or their coupled receptors (Figs. S10, S11), which are more frequently affected by deleterious mutations (i.e., stop gains, frameshifts or non-synonymous mutations at highly conserved domain positions; see Methods) in multiple cancers (Fig. 4a; grey in middle panel). The gene discussed is GNAS; the disease is cancer.