Fig. 3: Mapping of all CLCN4 variants functionally investigated in this study.

A Schematic of the CLCN4 gene and ClC4-protein with position of variants from newly identified families with clearly affected males and females depicted above the schematic, and position of variants published to date shown below the schematic. B Position of the investigated missense variants in a CLC topology model. Altered residues are shown as circles and functional effects are color-coded as indicated in the figure. C Three-dimensional homology model of the human ClC-4 protein based on the structure of the CmClC homodimer (Protein Data Bank: 3ORG). The view from within the membrane delimited by dashed lines. The two subunits forming the homodimer are shown in dark and light grey. Mutated residues are shown as spheres colored as in B. Right 3D model viewed from the extracellular site.