Two de novo variants in the KDM4B gene (one nonsense, one damaging missense) were identified in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014). KDM4B was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Neuron-specific KDM4B-deficient mice exhibited defective spine maturation, hyperactive behavior, deficits in working memory, and spontaneous epileptic-like seizures (Fujiwara et al., 2016). Duncan et al., 2020 presented a cohort of nine individuals with heterozygous de novo or inherited variants in the KDM4B gene presenting with global developmental delay, with language and motor skills most severely affected, and dysmorphic features; autistic features were observed in one individual from this cohort.
This gene encodes for a histone demethylase that specifically demethylates 'Lys-9' of histone H3 and is involved in chromatin organization and regulation.
Type of Disorder
Synaptic, transcriptional and chromatin genes disrupted in autism.