Fig. 4

Structure of human calcineurin, isoform (PDBID 1AUI) [23]. CnA (from PPP3CA) is shown in dark blue and CnB (from PPP3R1) in grey, with the catalytic iron ion as an orange sphere and the catalytic zinc ion as a pale blue sphere. Calcium ions bound to CnB are shown as grey spheres. The intrinsically disordered regulatory domain (RD) was generated using MODELLER [24]. The variant identified in this work, c.1324C>T (p.(Gln442Ter)), is shown in red, variants identified by Myers et al. [7] and Deciphering Developmental Disorders Study [20] are purple, those identified by Mizuguchi et al. [8] in yellow, and c.275A>G (p.(His92Arg)), reported by both the latter two groups, in green. The top inset shows variants that occur in the autoinhibitory domain (AID) and the bottom inset shows those clustered around the active site