Fig. 4

ARH3 predicted structure. a) structure modeling of the normal protein and superimposed structure modeling of the variated protein was based on a well-known template (PDB: 2FOZ); the variated site of p.Leu212 is highlighted in greenish-yellow color. The red sections are the affected parts that will be deleted because of the premature stop codon. A BLAST sequence search against the protein data bank (PDB) was performed to select the template structure with the most sequence similarity to the domain of ARH3. To further evaluate, we used “human ADP-ribosylhydrolase 3” as the favorite template (PDB ID: 2FOZ) [35]. To predict any impact of p.(Leu212fs) on the structure and function of ARH3, the Iterative Threading Assembly Refinement (I-TASSER) package (https://zhanglab.ccmb.med.umich.edu/I-TASSER/) was utilized in which the highest significant alignment regions of the templates were selected by considering the Z-score measurement. The protein structure and possible effects of the novel variant on protein structure were depicted by the PyMOL package (https://pymol.org/). b) the premature stop codon is shown, while the remained parts are exhibited in green. c) the remained parts after the deletion of amino acids are shown. d) two Mg²⁺ ions are indicated. α-Helices approximately perpendicular to the viewing plane are represented as circles, those oriented roughly horizontally in the viewing plane as rectangles. Because of the frameshift deletion, helixes from 13 to 19 will be deleted. This figure is redrawn from [35]. e) The amino acid sequence of ARH3 colored based on conservation scores derived from the ConSurf database; highly conserved regions are shown in purple, although weak conserved areas are indicated in blue. The highly conserve areas make the binding site and also an active domain of ARH3