De novo variants in the KDM2A gene have been identified in ASD probands, including a de novo missense variant (p.Arg449Lys) in a proband from the Simons Simplex Collection (Iossifov et al., 2014; Yuen et al., 2016; Yuen et al., 2017; Turner et al., 2017; Satterstrom et al., 2020), while a germline missense variant in this gene was identified in brain tissue from an ASD brain donor from the Harvard Brain Tissue Resource Center (Woodbury-Smith et al., 2022). Functional assessment of the ASD-associated p.Arg449Lys missense variant in Drosophila using an rescue-based strategy in Macrogliese et al., 2020 demonstrated that humanized flies carrying the p.Arg449Lys mutation showed decreased time copulating compared to the humanized reference in a behavioral paradigm.
Molecular Function
This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class and, in addition to an F-box, contains at least six highly degenerated leucine-rich repeats. This family member plays a role in epigenetic silencing. It nucleates at CpG islands and specifically demethylates both mono- and di-methylated lysine-36 of histone H3.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
The contribution of de novo coding mutations to autism spectrum disorder
