A p.N92K variant of the GTPase RAC3 disrupts cortical neuron migration and axon elongation.

ABSTRACT: RAC3 encodes a small GTPase of the Rho family, crucial for actin cytoskeleton organization and signaling pathways. De novo deleterious variants in RAC3 cause neurodevelopmental disorder with structural brain anomalies and dysmorphic facies (NEDBAF). Disease-causing variants thus far reported are thought to impact key conserved regions within RAC3, such as the P-loop, switch I/II, and G boxes, which are essential for the interaction with regulatory proteins and effectors. Recently, however, a novel variant, c.276T > A, p.N92K, was identified in a prenatal case with complex brain malformations. This variant, located outside the core functional regions, represents a unique class of RAC3 pathogenic mutations. We investigated the variant's effects using in vitro, in silico, and in vivo approach

SUBMITTER: Sugawara R 

PROVIDER: S-EPMC11968283 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature