This Notice of Funding Opportunity announcement (NOFO) supports systematic and scalable approaches to profile the biological function of genes with an excess of damaging mutations in patients with neurodevelopmental and psychiatric disorders. Current understanding of the relationship between genetic and phenotypic variation is limited and one of the main bottlenecks in translating disease-associated genes to biology lies in the lack of scalable experimental platforms that can extend the unbiased nature of gene discovery to the discovery of biological mechanisms. This concept will attempt to fill that gap while also providing a bridge between existing NIMH efforts such as PsychENCODE and Convergent Neuroscience. New technologies and approaches are now making it possible to systematically implement high-throughput assays to determine how disease-linked genetic variation impacts neural function across biological levels of organization. This initiative proposes a series of NOFOs to support the large-scale implementation of high-throughput assays to interrogate the molecular, cellular and physiological function of hundreds of disease-associated genes in parallel. A combination of full-scale and pilot projects will form a consortium for broad characterization of risk genes across an array of endpoints relevant to CNS function using a variety of experimental platforms (e.g., cellular, organismal). A consortium coordination center (CCC) will serve as a central hub providing administrative coordination across projects, including data and tools harmonization, development of an open-source portal to create a unified dataset and creating a standardized set of biological resources for use by the research community.