A de novo missense variant in the YWHAG gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014. Heterozygous variants in YWHAG are also responsible for a form of early infantile epileptic encephalopathy (EIEE56; OMIM 617665); in addition to early-onset seizures, intellectual disability and behavioral abnormalities including autism spectrum disorder have been observed in affected individuals (Guella et al., 2017; Kanani et al., 2020). YWHAG is located within the 7q11.23 chromosomal region associated with Williams-Beuren syndrome; Fusco et al., 2014 suggested that, based on genotype-phenotype correlation of deletions within this region, YWHAG haploinsufficiency may cause the severe neurological and neuropsychological deficits including epilepsy and autistic behavior observed in individuals with this syndrome.
Molecular Function
This gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. It has been shown to interact with RAF1 and protein kinase C, proteins involved in various signal transduction pathways. Both ablation and overexpression of YWHAG have been demonstrated to result in neuronal migration delay in the developing cerebral cortex (Wachi et al., 2016; Cornell et al., 2016).
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Synaptic, transcriptional and chromatin genes disrupted in autism.
