Benjamin Wehnert
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Benjamin Wehnert has a total of 14 co-authors. Here are the top co-authors by number of shared publications:
- Brendan J. Floyd
Stanford Center for Inherited Cardiovascular Disease, Department of Medicine, Division of Cardiovascular Medicine, (Y.Y., K.C., D.S., A.F., B.J.F., C.C., L.W., Q.W., J.E.G., Y.H., F.B., R.H.W., A.S., A.T., R.A., M.T.W., M.M., E.A.A., V.N.P.), Stanford School of Medicine, Palo Alto, CA
1 shared publication - Brian Clarke
Division of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany
1 shared publication - Daniel Schraivogel
Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
1 shared publication - Edukondalu Mullapudi
European Molecular Biology Laboratory, Hamburg Unit, Notkestrasse 85, 22607 Hamburg, Germany
1 shared publication - Janosch Hennig
Department of Biochemistry IV – Biophysical Chemistry, University of Bayreuth, 95447 Bayreuth, Germany
1 shared publication - Julia Kornienko
DZHK (German Center for Cardiovascular Research), partner site Heidelberg/Mannheim, Heidelberg, Germany (J. Kornienko, D.L., K.F., L.K., M.M.G.v.d.H., L.M.S.).
1 shared publication
Latest Publications
- Open Access
Multimodal phenotyping defines variant-to-function maps for RBM20 in dilated cardiomyopathy
Multiplex assays of variant effects have linked thousands of genotypes to fitness effects, yet we lack profound understanding of how variants impact molecular phenotypes. Here, we introduce a deep mutational scanning framework that quantifies disease-determining molecular phenotypes in human cells, allowing readouts of protein localization and splicing regulatory function at scale. Applied to the dilated cardiomyopathy (DCM)-associated protein RBM20, we profiled ~4,300 amino acid substitutions across disease-linked protein domains. Complemented by structure-function investigations of RBM20 bound to its nuclear import receptor TNPO3, we discover new variant hotspots affecting protein function. Finally, we systematically probed nuclear relocalization to identify variants that may be amenable to this therapeutic strategy. Together, we create comprehensive variant-to-function maps that predict variant impact, enhance clinical interpretation, and stratify RBM20-mediated DCM into mechanistically distinct therapeutic classes.
Open AccessMultimodal phenotyping defines variant-to-function maps for RBM20 in dilated cardiomyopathy
Multiplex assays of variant effects have linked thousands of genotypes to fitness effects, yet we lack profound understanding of how variants impact molecular phenotypes. Here, we introduce a deep mutational scanning framework that quantifies disease-determining molecular phenotypes in human cells, allowing readouts of protein localization and splicing regulatory function at scale. Applied to the dilated cardiomyopathy (DCM)-associated protein RBM20, we profiled ~4,300 amino acid substitutions across disease-linked protein domains. Complemented by structure-function investigations of RBM20 bound to its nuclear import receptor TNPO3, we discover new variant hotspots affecting protein function. Finally, we systematically probed nuclear relocalization to identify variants that may be amenable to this therapeutic strategy. Together, we create comprehensive variant-to-function maps that predict variant impact, enhance clinical interpretation, and stratify RBM20-mediated DCM into mechanistically distinct therapeutic classes.