Fig. 2

A Whole exome sequencing of the GNAI3 heterozygous c.140G > A variant (indicated in a red box). B Sanger sequencing of the GNAI3 heterozygous c.140G > A variant (indicated by a red arrow). C Evaluation of the amino acid conservation by Ugene. Each residue in alignment is assigned a color according to the ClustalX color scheme. The Ser47 of Gαi3 (indicated in a red box) is highly conserved accross various species. D In silico prediction of the GNAI3 c.140G > A variant by PolyPhen, MutationTaster, PROVEAN, and SIFT. E The three dimensional molecular structure of Gαi3 and the guanosine diphosphate (GDP) ligand by SWISS-MODEL and Swiss-PdbViewer. The overview (left panel) and magnified views of the wild-type Ser47 (middle panel) and mutant Asn47 (right panel) are shown accordingly. The H-bonds to GDP are shown as green dashed lines, with H-bond distances (Å) shown in green numbers. F Schematic representation of all the identified mutations in the GNAI3 gene (NM_0064). Five guanine nucleotide-binding sites (G1–G5) are indicated by gray boxes. The novel missense mutation in the present report is shown in red