Neurexins and neuropsychiatric disorders

Neurexins are a family of presynaptic single-pass transmembrane proteins that act as synaptic organizers in mammals. The neurexins consist of three genes (NRXN1, NRXN2, and NRXN3), each of which produces a longer α- and shorter β-form. Genomic alterations in NRXN genes have been identified in a wide variety of neuropsychiatric disorders, including autism spectrum disorders (ASD), schizophrenia, intellectual disability (ID), and addiction. Remarkably, a bi-allelic deficiency of NRXN1 was recently linked to Pitt-Hopkins syndrome. The fact that some mono-allelic functional variants of NRXNs are also found in healthy controls indicates that other genetic or environmental factors affect the penetrance of NRXN deficiency. In this review, we summarize the common research methods and representative results of human genetic studies that have implicated NRXN variants in various neuropsychiatric disorders. We also summarize studies of rodent models with NRXN deficiencies that complement our knowledge of human genetics.