Extended Data Fig. 1. Meta-analysis of effects of ICL3 mutagenesis on receptor function (See Methods, Supplementary Table 1 for details).

a. Influence of mutagenized ICL3 position and b. size of ICL3 mutation on agonist binding affinity (pK_d) (N = 228 mutations, 32 receptors, 62 studies). (c-d) compare the same effects on signaling, potency (pEC₅₀) (N = 146 mutations, 18 receptors, 30 studies), (e-f) on maximum signaling output (Emax) (N = 258 mutations, 27 receptors, 58 studies), and (g-h) on signaling efficacy (log(E_max/EC₅₀) (N = 145 mutations, 17 receptors, 29 studies). WT, wild-type receptor. Large points reflect mean ± standard deviation of mutagenizing each site in ICL3. Small, translucent points reflect individual experimental data points, colored by receptor identity.