Pharmacological rescue of mutant GnRHRs. Loci of fourteen reported point mutations of the human GnRHR (N10K, T32I, E90K, Q106R, A129D, R139H, S168R, C200Y, S217R, R262Q, L266R, C279Y, Y284C, and L314X) isolated from patients with hypogonadotropic hypogonadism, of which eleven were rescued with IN3. The two internal substitutions that cannot be rescued by IN3 are less than 20 angstroms apart; the red circle represents the site of truncation of the C-terminal deletion mutant. The range of loci of mutation from which rescue can be effected is remarkably broad.