NRXN2

NRXN2, or neurexin-2, is a member of the neurexin family of presynaptic cell-adhesion molecules that organize synaptic connectivity in the vertebrate brain. The neurexins (NRXN1-3) form trans-synaptic complexes with postsynaptic ligands such as neuroligins and LRRTMs, helping to specify synapse type, promote synapse maturation, and regulate neurotransmitter release.

NRXN2 gene products arise from alternative promoters and extensive splicing, generating multiple alpha- and beta-neurexin-2 isoforms. Alpha-neurexins contain a long extracellular region with LNS and EGF-like repeats, whereas beta-neurexins are shorter and begin at an alternative promoter. Splicing at specific sites modulates ligand-binding properties, influencing interactions with neuroligins, cerebellins, and GluD receptors, and thereby affecting synaptic specification.

Expression studies show NRXN2 transcripts in various brain regions, with notable presence in cortex and hippocampus and developmental regulation of isoform expression. Functionally, NRXN2 contributes to the assembly and maintenance of presynaptic machinery and to synaptic efficacy, coordinating trans-synaptic adhesion that aligns presynaptic release with postsynaptic receptors.

Clinical and genetic studies have explored NRXN2 in neurodevelopmental and psychiatric disorders. Rare variants and copy-number changes in NRXN2 have been reported in cohorts with autism spectrum disorders and schizophrenia, among others, but associations are less robust and consistent than those for NRXN1. Animal models carrying NRXN2 alterations show synaptic and behavioral phenotypes supporting a role in neural circuitry.