{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CSMD2 is a member of the CSMD gene family that encodes a large transmembrane protein featuring multiple CUB and Sushi domains. These domains are thought to mediate protein–protein and protein–ligand interactions, suggesting that CSMD2 may function as a receptor or adhesion molecule. In the nervous system, CSMD2 is expressed in both fetal and adult brains and has been implicated in brain morphogenesis. Its variants have been associated via genome‐wide studies with differences in brain structure and with neuropsychiatric disorders such as schizophrenia—findings that point to roles in neural development, synaptic regulation, and complement‐mediated immune processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its functions in the brain, CSMD2 has emerged in several studies as being altered in various human cancers. Reduced expression, somatic mutations, and epigenetic modifications (including promoter hypermethylation) of CSMD2 have been reported in colorectal, pancreatic, stomach, lung, thyroid, and melanoma tumors, where such alterations are associated with adverse clinicopathological features and poorer outcome."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "9"}]}, {"type": "t", "text": " Additionally, viral integration events affecting the CSMD2 region have been observed in hepatocellular carcinomas"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", and aberrant circular RNA species originating from CSMD2 have been linked to acute myeloid leukemia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, in a genome‐wide analysis of sudden cardiac arrest, CSMD2 was prioritized as one of several loci of interest, indicating that its role may extend into cardiovascular pathology although this association awaits further clarification."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Taken together, the current body of evidence supports a multifunctional role for CSMD2 in modulating neural development and immune-related signaling—as well as in maintaining cellular adhesion—with important implications for neuropsychiatric disorders and oncogenesis. Further mechanistic studies will be essential to elucidate its precise pathways and to assess its potential as a diagnostic biomarker or therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jason L Stein, Xue Hua, Suh Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Voxelwise genome-wide association study (vGWAS)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuroimage (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuroimage.2010.02.032"}], "href": "https://doi.org/10.1016/j.neuroimage.2010.02.032"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20171287"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20171287"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Bjarte Håvik, Stephanie Le Hellard, Marcella Rietschel, et al. 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