The GNAI1 gene (NM_002069) contains 8 coding exons. The encoded protein GNAI1 functions as an intrinsic GTPase. It comprises several key structural and functional domains within which the reported mutations are predominantly clustered:
G1-G5 motifs 35-48 aa (G1), 173-181 aa (G2), 196-205 aa (G3), 265-272 aa (G4), 324-329 aa (G5)
binding sites 43-48 aa (GTP), 47aa (Mg2+), 151 aa (GTP), 175-181 aa (GTP), 181 aa (Mg2+), 200-204 aa (GTP), 269-272 aa (GTP), 326 aa (GTP).
The graphical visualization is placed below.
blue circles – deletion mutations, red circles – missense mutations, green circle – frameshift mutation
The graphical output visualizes reported pathogenic and likely pathogenic variants, which were adopted from UniProt entry P63096; Muir et al., 2021; Wayhelova et al., 2022; ClinVar.
G1-G5 motifs form a pocket which serves for GDP or GTP binding. The mutational clusters are located predominantly in these motifs, so their structural alterations may significantly affect the GDP or GTP binding or GDP hydrolysation (Muir et al., 2021).