Supplementary Figure 2: Serpentine plot of human MC4R

Mutations found in obese patients are indicated by a black arrow from the mutated amino-acid to the colored circle that indicates the amino-acid in the mutant protein. Red arrows indicate frameshift mutations. Most patients were heterozygous for one mutation. Amino-acid changes causing severe effects on MC4R membrane expression are in red. Such mutations are expected to alter membrane and cilia localization as well as ligand response. Mutations in blue lead to decreased agonist activation (blue) or decreased constitutive activity (purple). Whether these mutations also alter cilia localization has not been tested. Mutations tested in Fig. 3a are in yellow. Mutations leading specifically to decreased ciliary expression are indicated by a green arrow.