Skip to main content
. 2026 Jul 9;6(5):100507. doi: 10.1016/j.xjidi.2026.100507

Figure 3.

Figure 3

In silico characterization of MHY9 variants. (a) Cartoon representation of AlphaFold-predicted Myosin-9 structure, with domains color coded as in Figure 2a. The boxed region within the head/motor domain is shown enlarged in the middle panel. Residues previously altered in patients with MALTA syndrome are shown as green spheres. The bottom panels display the AlphaMissense pathogenicity heatmap for the amino acid region surrounding the wild-type residue (highlighted by a red box in the top sequence). The corresponding mutated substitution is indicated by a dashed white box. Unlike mutations in the tail domain that received low pathogenicity scores (Arg1497Gln: 0.126 and Ile1626Val: 0.086), residues Ser232Asn, Gly236Cys, Gly455Ser, Lys651Thr, and Cys671Tyr showed high pathogenicity scores (0.999, 0.998, 0.997, 0.983, and 1.000, respectively), supporting the interpretation that these variants likely disrupt MYH9 function. The heatmap color gradient represents AlphaMissense pathogenicity scores, ranging from blue (low probability of pathogenicity, score near 0) to red (high probability of pathogenicity, score near 1). (b) DynaMut2 predictions of the thermodynamic impact of various MYH9 sequence variants. The table shows ΔΔG values, with sequence variants identified in this study highlighted in red. The bottom panels display surface and stick models of residue interactions (hydrogen bonds, polar, and Van der Waals forces) surrounding wild-type Gly455 (top) and mutant Ser455 (bottom), revealing local structural disruptions. Notably, Ser455 but not Gly455 can form a hydrogen bond with Ser176. Additional changes in nearby interactions, including those involving Asn473 and Ile453, suggest a broader effect on the local structural environment owing to the Gly455Ser substitution.