Figure 3.

SOX11 variants identified in the current study. (A) Schematic diagram of SOX11 protein demonstrating location of three reported sequence variants. The p.S60P and p.Y116C variants reported by Tsurusaki et al⁸  are also shown, the structural effects of these mutations can be found in reference 8. (B and D) Models demonstrating alteration of SOX11 protein structure associated with the two missense variants. Green areas represent the wildtype residue while the red area indicates the structure adopted by the mutant amino acid. Both the missense variants were in the DNA binding domain of SOX11 and predicted to alter its structure, thus interfering with DNA binding. (C) Bar chart demonstrating that the twoSOX11 missense variants had reduce ability to activate the GDF5 promoter in an in vitro reporter system. The adjacent western blot confirms that the mutant proteins were stably expressed during the experiment.