De novo variants in the ZMYND8 gene, including two protein-truncating variants, have been identified in ASD probands from the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genetic Resource Exchange (Iossifov et al., 2014; Yuen et al., 2017; Satterstrom et al., 2020). TADA analysis of de novo variants from the Simons Simplex Collection and the Autism Sequencing Consortium and protein-truncating variants from iPSYCH in Satterstrom et al., 2020 identified ZMYND8 as a candidate gene with a false discovery rate (FDR) between 0.01 and 0.05 (0.01 < FDR 0.05). Dias et al., 2022 reported 11 unrelated individuals with ZMYND8 variants presenting with a neurodevelopmental syndrome characterized by intellectual disability with variable cardiovascular, ophthalmologic and skeletal anomalies; four individuals were diagnosed with autism spectrum disorder, and two others presented with autistic features. Additional functional analysis of ZMYND8 missense variants identified in affected individuals in Dias et al., 2022 demonstrated disrupted protein interactions.
Molecular Function
The protein encoded by this gene is a receptor for activated C-kinase (RACK) protein. The encoded protein has been shown to bind in vitro to activated protein kinase C beta I. In addition, this protein is a cutaneous T-cell lymphoma-associated antigen. Finally, the protein contains a bromodomain and two zinc fingers, and is thought to be a transcriptional regulator.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
The contribution of de novo coding mutations to autism spectrum disorder
