Fig. 4

Protein structural analysis and DNA interaction of PAX2 missense variants. A Locations of missense variants stratified by phenotype. The structural analysis of PAX2 was performed using crystallographic structure of PAX5 in complex with DNA (PDB accession 1k78). The sequence of the paired domain of PAX5 differs from that of PAX2 by just three residues (97,122 and 123), all relatively far from those affected by the variants, so that the generation of a homology model was not necessary. Residues caused by pathogenic variants in individuals with renal coloboma syndrome (RCS) were shown in red, residues associated with variants in individuals with isolated CAKUT were shown in yellow, and residues associated with variants in individuals with nephrosis were shown in cornflower blue. Cartoon representation showing both N- and C-terminal domains. The fig was done with the molecular visualization software Pymol. B Schematic view of the distribution of PAX2 variants and the energy results predicted by FoldX. The residues are color coded according to its change in stability. Residues with two colors represent the results for different variants in the same position. Residue numbering throughout the article is based on the Uniprot numbering (Q02962-1, Isoform 1). Protein structure was indicated on base of PAX5 in complex with DNA (PDB accession 1k78) with α-helices shaded in gray cylindrical and β-sheets shaded in gray arrow