Missense Variant of Endoplasmic Reticulum Region of WFS1 Gene Causes Autosomal Dominant Hearing Loss without Syndromic Phenotype

Figure 5

3D protein modeling of WFS1 variants at amino acid residue 674 leading to hearing loss or Wolfram syndrome. (a) Wild type has a hydrogen bond between Gly674 and Thr663; (b) p.Gly674Glu. The variant alters the interaction between Glu674 and Thr663 and increases two hydrogen bonds between Glu674 and Arg676, a hydrogen bond between Glu674 and Cys673, and a hydrogen bond between Gln668 and Pro675; (c) p.Gly674Val. The variant increases a hydrogen bond between Val674 and Cys673, and a hydrogen bond between Gln668 and Pro675; (d) p.Gly674Trp. The variant increases a hydrogen bond and two arene interactions between Trp674 and Cys673 and a hydrogen bond between Gln668 and Pro675; (e) p.Gly674Arg. The variant increases a hydrogen bond between Gln668 and Leu672 and two hydrogen bonds between Gly674 and Cys673.

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