Fig. 8: Applying COSMIS to custom-built oligomeric structural models facilitates interpretation of potassium channel variants.
From: The 3D mutational constraint on amino acid sites in the human proteome
a COSMIS score distributions for interface and non-interface amino acid sites in 41 oligomeric potassium ion channels. Overall, interface sites (n = 4762) involved in oligomerization (making more 3D contacts in oligomers than in monomers) have a significantly lower COSMIS scores than non-interface sites (n = 14,331) (median −1.3 vs. −1.1, \(p=1.3\times {10}^{-16}\), two-sided Mann–Whitney U test). b COSMIS scores of interface sites computed based on oligomers are generally lower than those computed based on monomers (median difference −0.13, \(p=8.1\times {10}^{-8}\), two-sided Mann–Whitney U test). c COSMIS score performs well (AUROC 0.854) at predicting the pathogenicity of 111 benign and 489 pathogenic potassium channel missense variants curated from ClinVar. AUROC area under the receiver operating characteristic. Source data are provided as a Source Data file.
