Extended Data Fig. 9: Relationships between the conformational properties of IDRs and the incidence of pathogenic missense and frameshift variants.
From: Conformational ensembles of the human intrinsically disordered proteome
a–c, Distributions of (a) the conformational entropy per residue, Sconf/N; (b) the pLDDT scores of the substituted residues; and (c) the scaling exponent, ν, for 11,173 benign (black line) and 1,656 pathogenic (grey bars) variants of IDRs without UniProt domain annotations (fdomain = 0). d,e, Distributions of the difference in (d) ΔSconf,SVR/N and (e) ΔνSVR between variant and wild type for benign (black line) and pathogenic (grey bars) variants of IDRs with fdomain = 0. g,h, Distributions of the difference in (g) ΔSconf,SVR/N and (h) ΔνSVR between variant and wild type for 5,039 benign (or of unknown significance, black line) and 637 pathogenic (grey bars) frameshift variants identified by Mensah et al.56. P values are estimated from one-sided Brunner–Munzel tests using t-distributions and the reported degrees of freedom (DoF). Standard errors of Cohen’s d values are estimated through 105 bootstraps. f, Average number of ClinVar missense variants per IDR. i, Average number of publications per IDR obtained from the “Find my Understudied Gene” tool59. Data in f and i are displayed as mean ± s.e.m. calculated over n = 25; 87; 498; 18,546; 8,864; and 32 IDRs.
