Fig. 1: Distribution of disease-causing variants across GNAI1.

(a) Schematic showing the pathogenic and likely pathogenic variants identified in GNAI1, including one previously reported variant (*) (Kaplanis et al.²). Variants cluster within the first guanine nucleotide-binding ___domain (green box). Missense variants are represented as brown diamonds, coding deletion variants as blue circles, and the truncating frameshift variant as a yellow star. Each symbol represents one individual. (b) 3D structure of Gαi1. The left figure shows the structure of Gαi1 as part of the trimeric G-protein complex (PDB accession 6crk); Gαi1 is shown as a cyan ribbon, except for positions of novel variants which are colored as follows: missense, magenta; in-frame deletions, yellow; frameshifting insertion at Ile278, light green; bound GDP is shown as space-filling spheres, colored by atom type (white, carbon; blue, nitrogen; red, oxygen; orange, phosphorus); the molecular surface is shown for the βγ dimer, with the β1 and γ2 chains colored dark green and orange respectively. The right figure shows Gαi1 only, rotated around the vertical axis; Gly45 is obscured by the GDP ligand in this view. In both parts, labeling in bold font indicates residues making direct contact with GDP (Gly45, Thr48, Lys270, Ala326).