High Throughput Functional Annotation of Human SCN2A Variants

Project: Research project

Project Details


Dozens of mutations have been identified in genes that code for sodium channel proteins in subjects with autism spectrum disorders, intellectual disability and other disorders of brain development including epilepsy. Sodium channels are proteins that regulate the flow of sodium ions into cells for the purpose of generating bio-electricity needed by nerve cells to function. While the significance of these genetic discoveries is unknown, these are intriguing clues that suggest the existence of shared molecular mechanisms underlying different brain disorders. However, a key barrier to understanding the medical relevance of sodium channels mutation is the lack of simple methods to distinguish mutations that truly contribute to disease from those without functional consequences. Current methods for analyzing the function of sodium channel mutations are time consuming, labor-intensive, expensive and slow. New approaches, possibly using automated methods, are needed. We propose to determine if sodium channel mutations found in subjects with autism spectrum disorders and other neurodevelopmental disorders cause physiological disturbances in the function of these proteins. Because of the large number of mutations, we will employ an automated system to perform experiments that normally require weeks to months for completion. This pilot study will help reveal how mutations might be involved in the susceptibility to autism spectrum disorders, and demonstrate the power of automated electrophysiological analyses to discriminate mutations that contribute to neurodevelopmental disorders from those without functional consequences.
Effective start/end date1/1/1712/31/17


  • Simons Foundation (491201)


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