Defective kinase activity of IKKα leads to combined immunodeficiency and disruption of immune tolerance in humans.

ABSTRACT: IKKα is a multifunctional serine/threonine kinase that controls various biological processes, either dependent on or independent of its kinase activity. However, the importance of the kinase function of IKKα in human physiology remains unknown since no biallelic variants disrupting its kinase activity have been reported. In this study, we present a homozygous germline missense variant in the kinase domain of IKKα, which is present in three children from two Turkish families. This variant, referred to as IKKα^G167R, is in the activation segment of the kinase domain and affects the conserved (DF/LG) motif responsible for coordinating magnesium atoms for ATP binding. As a result, IKKα^G167R abolishes the kinase activity of IKKα, leading to impaired activation of the non-ca

SUBMITTER: Cildir G 

PROVIDER: S-EPMC11569180 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature