Fig. 5: Structural modeling missense variants in novel hearing impairment candidate genes.

a Homology model of INPP4B. The mutated residues (I424T and Q616H) are represented with a sphere model. The NHR and dual phosphate domains are indicated with red and orange colors, respectively. b, c The electrostatic potential surface of wild-type and mutant protein is highlighted in the circle zoom-up view showing different patches (indicated by the arrow) around the mutated residue. d Three-dimensional structure of MYO19 showing the mutated residue, A317, in a sphere model. The actin-binding pocket, myosin motor, and IQ domain are represented by green, red, and yellow colors, respectively. e The superposed structure of the WT (gray) and mutant (orange) structure of MYO19 shows the root-mean-square deviation. f The electrostatic potential surface of wild-type and mutant protein is highlighted in a circle zoom-up view showing different patches (indicated by the arrow) around the mutated residue. g Three-dimensional structure of DNAH11 showing the N-terminal stem (blue), stalk (yellow), and the mutated residue Q4323 (sphere model) of the AAA domain (red). The difference in the interaction network due to the mutation is highlighted in the bottom panel. The residue is represented with a stick model and the distance between the residues is labeled in angstrom. h Predicted structure of CCDC141 showing the mutated residues in a sphere model. The bottom row represents the zoom-up view of WT (gray) and mutant type structures displaying the different orientations of residues (stick model). i Three-dimensional structure of PAX8. j The superposed structure of WT (gray) and mutant (orange) structure showing the difference in overall conformation due to the P323R mutation. k Predicted structure of POTEI showing the wild-type and mutated residues in a stick model in the right panel.