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| Verfasst von: | Gregor, Anne [VerfasserIn]  |
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| | Meerbrei, Tanja [VerfasserIn] |
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| | Gerstner, Thorsten [VerfasserIn] |
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| | Toutain, Annick [VerfasserIn] |
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| | Lynch, Sally Ann [VerfasserIn] |
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| | Stals, Karen [VerfasserIn] |
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| | Maxton, Caroline [VerfasserIn] |
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| | Lemke, Johannes R. [VerfasserIn] |
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| | Bernat, John A. [VerfasserIn] |
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| | Bombei, Hannah M. [VerfasserIn] |
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| | Foulds, Nicola [VerfasserIn] |
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| | Hunt, David [VerfasserIn] |
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| | Kuechler, Alma [VerfasserIn] |
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| | Beygo, Jasmin [VerfasserIn] |
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| | Stobe, Petra [VerfasserIn] |
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| | Bouman, Arjan [VerfasserIn] |
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| | Palomares-Bralo, Maria [VerfasserIn] |
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| | Santos-Simarro, Fernando [VerfasserIn] |
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| | Garcia-Minaur, Sixto [VerfasserIn] |
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| | Pacio-Miguez, Marta [VerfasserIn] |
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| | Popp, Bernt [VerfasserIn] |
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| | Vasileiou, Georgia [VerfasserIn] |
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| | Hebebrand, Moritz [VerfasserIn] |
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| | Reis, Andre [VerfasserIn] |
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| | Schuhmann, Sarah [VerfasserIn] |
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| | Krumbiegel, Mandy [VerfasserIn] |
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| | Brown, Natasha J. [VerfasserIn] |
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| | Sparber, Peter [VerfasserIn] |
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| | Melikyan, Lyusya [VerfasserIn] |
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| | Bessonova, Liudmila [VerfasserIn] |
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| | Cherevatova, Tatiana [VerfasserIn] |
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| | Sharkov, Artem [VerfasserIn] |
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| | Shcherbakova, Natalia [VerfasserIn] |
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| | Dabir, Tabib [VerfasserIn] |
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| | Kini, Usha [VerfasserIn] |
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| | Schwaibold, Eva [VerfasserIn] |
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| | Haack, Tobias B. [VerfasserIn] |
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| | Bertoli, Marta [VerfasserIn] |
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| | Hoffjan, Sabine [VerfasserIn] |
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| | Falb, Ruth [VerfasserIn] |
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| | Shinawi, Marwan [VerfasserIn] |
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| | Sticht, Heinrich [VerfasserIn] |
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| | Zweier, Christiane [VerfasserIn] |
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| Titel: | De novo missense variants in FBXO11 alter its protein expression and subcellular localization |
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| Verf.angabe: | Anne Gregor, Tanja Meerbrei, Thorsten Gerstner, Annick Toutain, Sally Ann Lynch, Karen Stals, Caroline Maxton, Johannes R. Lemke, John A. Bernat, Hannah M. Bombei, Nicola Foulds, David Hunt, Alma Kuechler, Jasmin Beygo, Petra Stobe, Arjan Bouman, Maria Palomares-Bralo, Fernando Santos-Simarro, Sixto Garcia-Minaur, Marta Pacio-Miguez, Bernt Popp, Georgia Vasileiou, Moritz Hebebrand, Andre Reis, Sarah Schuhmann, Mandy Krumbiegel, Natasha J. Brown, Peter Sparber, Lyusya Melikyan, Liudmila Bessonova, Tatiana Cherevatova, Artem Sharkov, Natalia Shcherbakova, Tabib Dabir, Usha Kini, Eva M. C. Schwaibold, Tobias B. Haack, Marta Bertoli, Sabine Hoffjan, Ruth Falb, Marwan Shinawi, Heinrich Sticht, Christiane Zweier |
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| E-Jahr: | 2022 |
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| Jahr: | Feb 3 2022 |
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| Umfang: | 15 S. |
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| Fussnoten: | Published Feb 3 2022 ; Gesehen am 23.01.2023 |
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| Titel Quelle: | Enthalten in: Human molecular genetics |
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| Ort Quelle: | Oxford : Oxford Univ. Press, 1992 |
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| Jahr Quelle: | 2022 |
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| Band/Heft Quelle: | 31(2022), 3, Seite 440-454 |
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| ISSN Quelle: | 1460-2083 |
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| Abstract: | Recently, others and we identified de novo FBXO11 (F-Box only protein 11) variants as causative for a variable neurodevelopmental disorder (NDD). We now assembled clinical and mutational information on 23 additional individuals. The phenotypic spectrum remains highly variable, with developmental delay and/or intellectual disability as the core feature and behavioral anomalies, hypotonia and various facial dysmorphism as frequent aspects. The mutational spectrum includes intragenic deletions, likely gene disrupting and missense variants distributed across the protein. To further characterize the functional consequences of FBXO11 missense variants, we analyzed their effects on protein expression and localization by overexpression of 17 different mutant constructs in HEK293 and HeLa cells. We found that the majority of missense variants resulted in subcellular mislocalization and/or reduced FBXO11 protein expression levels. For instance, variants located in the nuclear localization signal and the N-terminal F-Box domain lead to altered subcellular localization with exclusion from the nucleus or the formation of cytoplasmic aggregates and to reduced protein levels in western blot. In contrast, variants localized in the C-terminal Zn-finger UBR domain lead to an accumulation in the cytoplasm without alteration of protein levels. Together with the mutational data, our functional results suggest that most missense variants likely lead to a loss of the original FBXO11 function and thereby highlight haploinsufficiency as the most likely disease mechanism for FBXO11-associated NDDs. |
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| DOI: | doi:10.1093/hmg/ddab265 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1093/hmg/ddab265 |
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| | Volltext: https://www.webofscience.com/api/gateway?GWVersion=2&SrcAuth=DynamicDOIArticle&SrcApp=WOS&KeyAID=10.1093%2Fhmg%2Fddab265 ... |
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| | DOI: https://doi.org/10.1093/hmg/ddab265 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | deficiency |
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| | delay |
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| | disorder |
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| | encephalopathy |
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| | gene |
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| | humans |
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| | intellectual-disability |
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| | mutations |
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| | sequence |
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| | ubiquitin ligase |
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| K10plus-PPN: | 1831821710 |
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| Verknüpfungen: | → Zeitschrift |
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De novo missense variants in FBXO11 alter its protein expression and subcellular localization / Gregor, Anne [VerfasserIn]; Feb 3 2022 (Online-Ressource)
