{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNeurexin 2 (NRXN2) is emerging as a key presynaptic organizer whose disruption contributes to several neurodevelopmental disorders. Truncating mutations and deletions in NRXN2 have been identified in patients with autism spectrum disorder, intellectual disability, and even schizophrenia, suggesting that loss‐of‐function mutations may disturb the establishment of proper synaptic contacts in critical cognitive circuits. Notably, such mutations may display variable penetrance and, when combined with defects in related neurexin family members, can result in more severe phenotypes such as early infantile epileptic encephalopathy with associated respiratory dysfunction."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDuring early cortical development, NRXN2 exhibits a distinctive expression pattern, with consistently high levels in growing axons and developing neurites. This distribution suggests a role in early synaptogenesis and perhaps in axon guidance, as NRXN2 colocalizes with synaptic markers and proteins involved in growth and cell adhesion. In addition, studies have shown that the complex regulation of NRXN2α translation—mediated by a long 5′‐untranslated region harboring inhibitory elements such as G‑quadruplex structures and upstream AUGs—enables rapid tuning of protein expression to adapt synaptic connectivity. Further, its involvement in the synaptic vesicle machinery has been implicated in migraine susceptibility, underscoring its central role in neurotransmission."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond neurodevelopment, rare NRXN2 variants have been associated with a range of adult-onset conditions. For example, specific rare coding variants in NRXN2 contribute to nicotine dependence, while a distinct NRXN2α mutation has been linked to Parkinson’s disease through mechanisms involving mitochondrial dysfunction and oxidative stress. Intriguingly, reduced NRXN2 expression in thyroid cancer tissues, along with functional evidence showing that its overexpression restricts proliferation, migration, and invasion in vitro, indicates that NRXN2 may also act as a tumor suppressor."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Julie Gauthier, Tabrez J Siddiqui, Peng Huashan, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "A de novo 921 Kb microdeletion at 11q13.1 including neurexin 2 in a boy with developmental delay, deficits in speech and language without autistic behaviors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Med Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejmg.2018.04.002"}], "href": "https://doi.org/10.1016/j.ejmg.2018.04.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29654904"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29654904"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Anne M Rochtus, Sara Trowbridge, Richard D Goldstein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "NRXN1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " and "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "NRXN2"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " in a patient with early-onset epileptic encephalopathy and respiratory depression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cold Spring Harb Mol Case Stud (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/mcs.a003442"}], "href": "https://doi.org/10.1101/mcs.a003442"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30709877"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30709877"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lauren F Harkin, Susan J Lindsay, Yaobo Xu, et al. 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