Figure 1. Identification and location of RyR2 mutations associated with IVF and SCD.

(A) A schematic diagram of the linear sequence of RyR2. Major structural domains of RyR2 are depicted as solid blue boxes. The orange boxes indicate four disease-associated mutation clusters (mutation hotspots) in RyR2. IVF- and SCD-associated RyR2 mutations identified were listed underneath their corresponding domains. (B) Locations of RyR2 mutations in the three-dimensional structure of RyR2 (6JI0). The three-dimensional locations of RyR2 mutations, F2331S, G2337V, A3442E, I3476T, and R3570W have not been resolved and thus were not shown in the three-dimensional structure. The bindings sites for Ca²⁺, caffeine, and ATP are also shown.