Fig. 1From: The role of small in-frame insertions/deletions in inherited eye disorders and how structural modelling can help estimate their pathogenicityIntegrative protein structure modeling for four variants identified in individuals with childhood cataracts. Affected amino acids are highlighted in red. a, b Models of the CRYBA1 c.272_274del, p. (Gly91del) (a) and CRYBA4 c.136_156del, p. (Ser46_Gly52del) (b) variants. The CRYBA1 and CRYBA4 proteins exhibit significant sequence similarity and the template with pdb code 3LWK (human β-crystallin A4) was used on both occasions. The main chain backbone atoms (white/grey lines) and the hydrogen bond network (brown lines) of the affected protein regions are shown. Both sequence alterations involve deleting residues located in β-sheets. c Homology model of the BFSP2 c.697_699del, p. (Glu233del) variant. BFSP2 forms parallel coiled-coil dimers that interact with one another in the form of a symmetrical anti-parallel dimer. The main chain backbone atoms (white/yellow lines) and the side chains that comprise the interaction interface (green) of the affected protein region are shown. The wild-type protein is presented on the left hand-side image. Notably, the affected amino acid is located in an α-helical region (highlighted in red). The right hand-side image shows a model of the mutant protein; the deletion shifts the position of the interacting side chains resulting in disruption of the dimer structure and exposure of the hydrophobic interface residues to the protein surface. d Model of the PITX2 c.429_431del, p. (Arg144del) variant. The main chain backbone atoms of the protein (white/grey lines) complexed with an interacting DNA double helix (brown chain) are shown. The mutated residue (highlighted in red) makes direct contact with the phosphate backbone of DNA, forming a salt bridgeBack to article page