Fig. 3: Protein robustness to stability effects of amino acid change with respect to functional constraint category. | Nature Communications

Fig. 3: Protein robustness to stability effects of amino acid change with respect to functional constraint category.

From: Functionally constrained human proteins are less prone to mutational instability from single amino acid substitutions

Fig. 3

In all boxplots, the central bar in each box represents the median value of each respective category, the bounds of each box are the interquartile range (IQR), whiskers extend 1.5*IQR from each box and the central notches (where present) represent an approximation of the 95% confidence interval of the median box value. a Observed range of Instability Heat Score (IHS) for all human proteins, grouped by Loss-of-Function Observed/Expected Upper Bound Fraction (LOEUF) functional constraint decile bins (bin 0 is most constrained and bin 9 is least constrained; bin 0 n = 1031, bin 1 n = 1035, bin 2 n = 1049, bin 3 n = 1083, bin 4 n = 1071, bin 5 n = 1053, bin 6 n = 1079, bin 8 n = 972, bin 9 n = 736), (b) observed range of IHS by LOEUF decile bins for all well-powered human proteins (bin 0 n = 1557, bin 1 n = 1601, bin 2 n = 11553, bin 3 n = 1505, bin 4 n = 1473, bin 5 n = 1479, bin 6 n = 1454, bin 8 n = 1210, bin 9 n = 803), (c) proportion of protein (AlphaFold2-model) with order greater than pLDDT > 0.7 by LOEUF functional constraint decile bin (bin 0 n = 671, bin 1 n = 716, bin 2 n = 795, bin 3 n = 834, bin 4 n = 901, bin 5 n = 864, bin 6 n = 913, bin 8 n = 778, bin 9 n = 555), (d) comparative range of IHS for well-powered human genes (defined from Chen et al.28; n = 13218) grouped by low- and high-pLi scores, with respective low (n = 10017) and high (n = 3201) functional constraint. The width of boxes in the upper plot indicates the relative number of genes present in each category, and (e) observed range of IHS for all human genes partitioned by Shet selection constraint categories (Extreme n = 1747, Strong n = 6485, Weak n = 1901, Neutral n = 7). Box widths are proportional to the number of genes included in each category, and (f) median B-factor for experimentally solved protein structures, grouped by LOEUF and Shet constraint categories. LOEUF constraint decile categories are grouped by Most (bins 0–2; n = 43), Intermediate (bins 3–6; n = 23) and Least (bins 7–9; n = 18). Shet categories are grouped by Extreme (n = 34), Strong (n = 19), Weak (n = 12) and Neutral (n = 18). Source data are provided as a Source Data file.

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