Relevance to Autism

HDAC9 was identified as an ASD candidate gene in Wilfert et al., 2021 based on the discovery of private likely gene-disruptive (LGD) variants in this highly constrained (pLI 0.99) gene that were exclusively transmitted to three ASD probands in three independent families and its interconnectedness with other ASD candidate genes in protein-protein interaction (PPI) networks in this report. Two de novo missense variants in this gene had previously been identified in ASD probands (Iossifov et al., 2014; Satterstrom et al., 2020). A rare paternally-inherited 40 kb deletion solely affecting the HDAC9 gene had previously been identified in an ASD proband from the Autism Genome Project; no HDAC9 exonic deletions were observed in 4.768 controls (Pinto et al., 2014).

Molecular Function

Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene has sequence homology to members of the histone deacetylase family. This gene is orthologous to the Xenopus and mouse MITR genes. The MITR protein lacks the histone deacetylase catalytic domain. It represses MEF2 activity through recruitment of multicomponent corepressor complexes that include CtBP and HDACs. This encoded protein may play a role in hematopoiesis.

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