(A) Conservation of variant residues in SSBP1 from Homo sapiens (Hs) through Rattus norvegicus (Rn), Xenopus laevis (Xl), Drosophila melanogaster (Dm), and Saccharomyces cerevisiae (Sc). (*) perfect alignment; (:) strong similarity; (.) weak similarity. (B) Surface rendering of the SSBP1 tetramer (based on PBDID: 3ULL) with each monomer indicated, along with a simplified representation that will appear throughout this report. (C) Locations of the SSBP1 residues effected by disease mutations. Coordinates of S141 were not present in the reference crystal structure [9]. (D) Breakdown of all possible combinations of WT and variant monomers in SSBP1 tetramers in heterozygous patients, including ratios of all WT : single variant : double variant : triple variant : all variant tetramer systems (left) and WT : compromised tetramer systems (right). White indicates WT monomers; black indicates variant monomers. (E) Representation of 32 tetramer systems modeled in molecular dynamics simulations.