{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CSMD1 is a large transmembrane protein characterized by multiple CUB and Sushi domains that appears to serve dual roles in normal physiology and disease. Functional studies in rodent models indicate that CSMD1 can regulate the classical complement cascade—acting as an inhibitor of C3b deposition and facilitating factor I–mediated degradation—which, together with its enriched expression in developing neurons (especially in growth cones), suggests that it contributes to immune regulation and neural development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the cancer arena, multiple independent studies have revealed frequent deletions, reduced expression, or aberrant splicing of CSMD1 in several tumor types including oral squamous cell carcinoma, melanoma, and colorectal cancer. In these settings CSMD1 functions as a tumor suppressor whose loss is associated with higher tumor grade, increased cell proliferation, migration, and poorer clinical outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": " Moreover, genetic association and neurocognitive studies have linked variants in CSMD1 with schizophrenia risk and subtle impairments in cognitive function, pointing to a role for CSMD1 in the modulation of brain circuitry and behavior."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Collectively, these findings support a model in which CSMD1 helps maintain tissue homeostasis by regulating complement‐mediated inflammation and cellular interactions in the central nervous system, while its disruption contributes to tumorigenesis and neuropsychiatric vulnerability.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Damian M Kraus, Gary S Elliott, Hilary Chute, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CSMD1 is a novel multiple domain complement-regulatory protein highly expressed in the central nervous system and epithelial tissues."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.176.7.4419"}], "href": "https://doi.org/10.4049/jimmunol.176.7.4419"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16547280"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16547280"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Carmel Toomes, Andrew Jackson, Kristie Maguire, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The presence of multiple regions of homozygous deletion at the CSMD1 locus in oral squamous cell carcinoma question the role of CSMD1 in head and neck carcinogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Chromosomes Cancer (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/gcc.10191"}], "href": "https://doi.org/10.1002/gcc.10191"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12696061"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12696061"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ming-Rui Tang, Yu-Xin Wang, Shu Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CSMD1 exhibits antitumor activity in A375 melanoma cells through activation of the Smad pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Apoptosis (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10495-012-0727-0"}], "href": "https://doi.org/10.1007/s10495-012-0727-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22538441"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22538441"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Rui Zhang, Chun Song "}, {"type": "b", "children": [{"type": "t", "text": "Loss of CSMD1 or 2 may contribute to the poor prognosis of colorectal cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13277-013-1581-6"}], "href": "https://doi.org/10.1007/s13277-013-1581-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24408017"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24408017"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "G Donohoe, J Walters, A Hargreaves, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuropsychological effects of the CSMD1 genome-wide associated schizophrenia risk variant rs10503253."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Brain Behav (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/gbb.12016"}], "href": "https://doi.org/10.1111/gbb.12016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23320435"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23320435"}]}]}]}