Mutations in genes encoding for histone methylation proteins are associated with several developmental disorders. Among them, KDM6A is the disease causative gene of type 2 Kabuki Syndrome, a rare multisystem disease. While nonsense mutations and short insertions/deletions are known to trigger pathogenic mechanisms, the functional effects of missense mutations are still uncharacterized. In this study, we demonstrate that a selected set of missense mutations significantly hamper the interaction between KDM6A and the histone H3, by modifying the dynamics of the linker domain, and then causing a loss of function effect.
Petrizzelli, F., Biagini, T., Barbieri, A., Parca, L., Panzironi, N., Castellana, S., et al. (2020). Mechanisms of pathogenesis of missense mutations on the KDM6A-H3 interaction in type 2 Kabuki Syndrome. COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL, 18, 2033-2042 [10.1016/j.csbj.2020.07.013].
Mechanisms of pathogenesis of missense mutations on the KDM6A-H3 interaction in type 2 Kabuki Syndrome
Vescovi A. L.;
2020
Abstract
Mutations in genes encoding for histone methylation proteins are associated with several developmental disorders. Among them, KDM6A is the disease causative gene of type 2 Kabuki Syndrome, a rare multisystem disease. While nonsense mutations and short insertions/deletions are known to trigger pathogenic mechanisms, the functional effects of missense mutations are still uncharacterized. In this study, we demonstrate that a selected set of missense mutations significantly hamper the interaction between KDM6A and the histone H3, by modifying the dynamics of the linker domain, and then causing a loss of function effect.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
