{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTMEM176A is a member of the MS4A family that is broadly expressed in human tissues and has been shown to physically interact with its homolog TMEM176B. Together, these proteins function as intracellular cation channels that predominantly localize around the trans-Golgi network. Notably, TMEM176A is highly expressed in immune cells, including RORγt(+) cells associated with type 17 immunity, suggesting a role in modulating intracellular ion flow that may influence immune cell function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in immune cells, TMEM176A appears to regulate immune responsiveness under pathological conditions. Elevated levels of TMEM176A, along with TMEM176B, have been linked to the inhibition of dendritic cell maturation and antigen presentation. This upregulation is observed, for instance, in chronic spinal cord injury, where increased TMEM176A expression may contribute to impaired dendritic cell function and a compromised protective immune response in the central nervous system."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTMEM176A also plays significant, though context-dependent, roles in oncogenesis and tumor suppression. In colorectal and lung cancers, aberrant promoter methylation of TMEM176A is associated with reduced expression, which in turn facilitates cell survival by diminishing apoptosis and enhancing cell migration and invasion; in these contexts, TMEM176A acts as a tumor suppressor and its methylation status serves as a prognostic marker. In contrast, some studies report elevated protein levels of TMEM176A in lymphomas and lung carcinoma, suggesting that altered expression levels may serve as potential markers for specific cancer subtypes. Moreover, investigations into hepatocellular and pancreatic cancers have identified aberrant TMEM176A expression, although its exact role in these tumor types remains to be fully elucidated. Finally, genetic studies have implicated variants in TMEM176A with increased schizophrenia risk, indicating that its function may extend beyond oncogenesis into neuropsychiatric disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Math P Cuajungco, William Podevin, Vinod K Valluri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Abnormal accumulation of human transmembrane (TMEM)-176A and 176B proteins is associated with cancer pathology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Histochem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.acthis.2011.12.006"}], "href": "https://doi.org/10.1016/j.acthis.2011.12.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22244448"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22244448"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lucile Drujont, Aurélie Lemoine, Aurélie Moreau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RORγt+ cells selectively express redundant cation channels linked to the Golgi apparatus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep23682"}], "href": "https://doi.org/10.1038/srep23682"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27009467"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27009467"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Gabriela Picotto, Leslie R Morse, Nguyen Nguyen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM176A and TMEM176B Are Candidate Regulators of Inhibition of Dendritic Cell Maturation and Function after Chronic Spinal Cord Injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurotrauma (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/neu.2019.6498"}], "href": "https://doi.org/10.1089/neu.2019.6498"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31354034"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31354034"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Dan Gao, Yingjie Han, Yang Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Methylation of TMEM176A is an independent prognostic marker and is involved in human colorectal cancer development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epigenetics (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15592294.2017.1341027"}], "href": "https://doi.org/10.1080/15592294.2017.1341027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28678648"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28678648"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hongxia Li, Meiying Zhang, Enqiang Linghu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epigenetic silencing of TMEM176A activates ERK signaling in human hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Epigenetics (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13148-018-0570-4"}], "href": "https://doi.org/10.1186/s13148-018-0570-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30400968"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30400968"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yulin Guo, Feng Cao, Shun Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM176A acts as a tumor suppressor gene in pancreatic cancer by inhibiting ERK signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Discov Med (2020)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33593482"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33593482"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hongxia Li, Weili Yang, Meiying Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Methylation of "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "TMEM176A"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": ", a key ERK signaling regulator, is a novel synthetic lethality marker of ATM inhibitors in human lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epigenomics (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2217/epi-2021-0217"}], "href": "https://doi.org/10.2217/epi-2021-0217"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34558311"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34558311"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Mark Z Kos, Melanie A Carless, Juan Peralta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exome sequences of multiplex, multigenerational families reveal schizophrenia risk loci with potential implications for neurocognitive performance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet B Neuropsychiatr Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.b.32597"}], "href": "https://doi.org/10.1002/ajmg.b.32597"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28902459"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28902459"}]}]}]}