CDC42 missense mutations and human diseases: from neurodevelopmental disorders to autoinflammation.

Abstract

Cdc42 is a member of the Rho family of small GTPases that controls various cellular responses by interacting with more than 45 effector proteins. Recent advances in genomic analysis reveal that Cdc42 missense variants cause various pathological phenotypes, including severe autoinflammation, suggesting previously unknown involvement of Cdc42 in innate immunity. This review aims to update our understanding of how CDC42 mutations are involved in human diseases, with emphasis on early-onset autoinflammation associated with mutations located at the carboxyl-terminus. Further analysis is required to elucidate the complex inflammatory mechanisms induced by various Cdc42 variants, leading to development of therapies that inhibit inflammatory pathologies.