Figure 3.
Graphical overview of the molecular phenotyping of the 38 selected missense variants. Area under the curve (AUC) of the dose–response curves, maximal response (Emax), and LogEC50 between mutant and wildtype glucagon receptor in cAMP accumulation (wildtype n = 33; variants n = 3–6) and β-arrestin1/2 recruitment (wildtype n = 31; variants n = 3–5). Variants are sorted by their number of statistically significant (ordinary one-way ANOVA p < 0.05) alterations and clustered into four groups based on displaying wildtype-like signaling and their number of cross-pathway significant alterations. In total, 15 variants display altered signaling in at least one pathway measured endpoint. Individual parameters are Z-score normalized to compare between endpoints. AUC and Emax of variants were normalized to the wildtype glucagon receptor. ND (gray background) indicates nondetectable potency windows at 10 nM glucagon (for cAMP accumulation) and 10 μM glucagon (for the β-arrestin recruitment). ∗p < 0.05; ∗∗p < 0.005; ∗∗∗p < 0.0005.