Functional characterization of two DYRK1B variants causative of AOMS3.

Autor: Detro-Dassen S; Institute of Pharmacology and Toxicology, RWTH Aachen University, Aachen, Germany., Sternberg A; Institute of Molecular and Cellular Anatomy, RWTH Aachen University, Aachen, Germany., Lehmann SM; Institute of Molecular and Cellular Anatomy, RWTH Aachen University, Aachen, Germany., Schwandt K; Institute of Pharmacology and Toxicology, RWTH Aachen University, Aachen, Germany., Düsterhöft S; Institute of Molecular Pharmacology, RWTH Aachen University, Aachen, Germany., Becker W; Institute of Pharmacology and Toxicology, RWTH Aachen University, Aachen, Germany. wbecker@ukaachen.de.
Jazyk: angličtina
Zdroj: Orphanet journal of rare diseases [Orphanet J Rare Dis] 2024 Jun 12; Vol. 19 (1), pp. 233. Date of Electronic Publication: 2024 Jun 12.
DOI: 10.1186/s13023-024-03183-0
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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