Mechanisms of pathogenesis of missense mutations on the KDM6A-H3 interaction in type 2 Kabuki Syndrome

Francesco Petrizzelli, Tommaso Biagini, Alessandro Barbieri, Luca Parca, Noemi Panzironi, Stefano Castellana, Viviana Caputo, Angelo Luigi Vescovi, Massimo Carella, Tommaso Mazza

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2033-2042
Number of pages10
JournalComputational and Structural Biotechnology Journal
Volume18
DOIs
StatePublished - 2020

Keywords

  • Computational biology
  • Histone demethylation
  • KDM6A
  • Kabuki Syndrome
  • Molecular dynamics simulation

ASJC Scopus subject areas

  • Biotechnology
  • Biophysics
  • Structural Biology
  • Biochemistry
  • Genetics
  • Computer Science Applications

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