KDM2Blysine demethylase 2B

Relevance to Autism

A number of de novo variants in the KDM2B gene, including two de novo missense variants, have been identified in ASD probands (Iossifov et al., 2014; Feliciano et al., 2019; Satterstrom et al., 2020). Gao et al., 2022 demonstrated that Kdm2b played a critical role in maintaining neural stem cells (NSCs) in the mouse brain, and that heterozygous adult Kdm2b mutant mice displayed both intellectual disability-like memory deficits and core autistic-like behaviors. van Jaarsveld et al., 2022 described a cohort of 21 individuals with heterozygous and likely pathogenic variants in KDM2B presenting with a neurodevelopmental syndrome characterized by developmental delay and/or intellectual disability, autism, attention deficit disorder/attention deficit hyperactivity disorder, congenital anomalies mainly affecting the heart, eyes, and urogenital system, and subtle facial dysmorphism. Yokotsuka-Ishida et al., 2021 identified a missense variant in the KDM2B gene in a Japanese family with a dominant inheritance of symptoms including Marfan syndrome-like minor physical anomalies, intellectual disability, and schizophrenia. KDM2B has also been proposed to be a contributing gene to phenotypes observed in individuals with 12q24.31 microdeletions (Chouery et al., 2013; Labonne et al., 2016; Krzyzewska et al., 2019).

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.

External Links

Human

Mouse

SFARI Genomic Platforms