Functional characterization of two DYRK1B variants causative of AOMS3.

ABSTRACT

BACKGROUND: Two new missense variants (K68Q and R252H) of the protein kinase DYRK1B were recently reported to cause a monogenetic form of metabolic syndrome with autosomal dominant inheritance (AOMS3). RESULTS: Our in vitro functional analysis reveals that neither of these substitutions eliminates or enhances the catalytic activity of DYRK1B. DYRK1B-K68Q displays reduced nuclear translocation. CONCLUSION: The pathogenicity of DYRK1B variants does not necessarily correlate with the gain or loss of catalytic activity, but can be due to altered non-enzymatic characteristics such as subcellular localization.