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Updated: Jun 24, 2025

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Functional characterization of two DYRK1B variants causative of AOMS3
Silvia Detro-Dassen1, Anna Sternberg2, Sonja Maria Lehmann2
1Institute of Pharmacology and Toxicology, RWTH Aachen University, Aachen, Germany.
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.
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