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Genetics of 5 families with <italic toggle='yes'>UNC45A</italic> deficiency and molecular characterization of UNC45A variants.(A) Pedigree of families with AR UNC45A deficiency (filled shapes indicate affected individuals). (B) Schematic representation of UNC45A protein showing location of the variants identified in this study. (C) Western blot analysis of UNC45A protein in HEK293T cells transfected with EV, WT, and mutant alleles (n = 2). (D) Ribbon representation of the human UNC45a model generated by MODELLER (based on the D. melanogaster and C. elegans UNC45 protein structures) showing its domain architecture. The variants were modeled in silico using Chimera. The location and a close-up view of each variant are shown. For the L237P and A838P mutations, hydrogen bonds are depicted by dark-blue dashed lines. For the T230R and E728K mutations, Van der Waals radii are represented for each atom and steric clashes occurring in the structure are shown with brown dashed lines. Coulombic surface representations are also shown. Red surface indicates the lowest electrostatic potential energy and blue the highest. Locations of the mutated residue are highlighted by a black circle. Distances are indicated using black dotted lines.
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