Relevance to Autism

ZMYM3 was initially identified as a neurodevelopmental disorder candidate gene in a female with intellectual disability who had a balanced translocation affecting the 5'UTR of one isoform of ZMYM3 (van der Maarel et al., 1996) and in three affected brothers with intellectual disability, ADHD, and syndromic features who had a maternally-inherited ZMYM3 missense variant (Philips et al., 2014). Hiatt et al., 2022 utilized the MatchMaker Exchange to assemble a cohort of 27 individuals with rare, protein-altering variation in the ZMYM3 gene; 24 of these individuals were male and presented with overlapping features including developmental delay (23/23 individuals), intellectual disability (17/20 individuals), behavioral abnormalities (including a diagnosis of autism or a report of autistic traits in 15/21 individuals), and a specific facial gestalt, whereas the three affected females in this cohort displayed a more variable phenotype of developmental delay and some facial dysmorphism. Several studies have suggested a link between allelic variation in an exceptionally long short tandem repeat in the 5'UTR of the ZMYM3 gene and schizophrenia, bipolar disorder, and late-onset neurocognitive disorder (Alizadeh et al., 2018; Alizadeh et al., 2019; Afshar et al., 2020).

Molecular Function

This gene is located on the X chromosome and is subject to X inactivation. It is highly conserved in vertebrates and most abundantly expressed in the brain. The encoded protein is a component of histone deacetylase-containing multiprotein complexes that function through modifying chromatin structure to keep genes silent. Plays a role in the regulation of cell morphology and cytoskeletal organization.

External Links

References