MYH9 Variant p.(Arg424Gly) Alters Nonmuscle Myosin IIA Contraction, Causing Atypical MYH9-related Disease

We identified a novel fully segregating <i>MYH9</i> variant causing <i>MYH9</i>-related disease. Based on biochemical findings, we report the first gain-of-function variant of <i>MYH9</i>. We propose that the enhanced intrinsic motor activity of the p.(Arg424Gly) variant is a key contributor to the disease mechanism. Incorporation of the p.(Arg424Gly) variant into nonmuscle myosin IIA filaments and higher-order actomyosin assemblies may, in principle, affect actomyosin dynamics.