{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTCN1 encodes transcobalamin I, an important high‐affinity carrier protein for vitamin B12 that protects and transports this vital micronutrient to various tissues. Several studies have demonstrated that common polymorphisms—such as the C776→G substitution—may alter the binding capacity and cellular delivery of vitamin B12. These genetic variations have been linked to disturbances in one‐carbon metabolism, influencing plasma homocysteine levels and, in turn, modulating the risk for neurodegenerative conditions such as Alzheimer’s disease, as well as other metabolic derangements."}, {"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": "\nIn addition to its central role in vitamin B12 transport, TCN1 is critical for understanding clinical presentations of altered cobalamin status. Molecular investigations have identified mutations in TCN1 that result in transcobalamin I deficiency—with compound heterozygous mutations producing markedly low protein levels and heterozygous states leading to a milder phenotype. Beyond inherited deficiency syndromes, aberrant TCN1 expression has emerged as a promising biomarker in several malignancies. Elevated TCN1 immunoreactivity has been associated with aggressive tumor behavior in breast phyllodes tumors, colorectal cancer, and gastric cancer, where high expression correlates with poorer overall survival and may aid in tumor grading and prognostication."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence also suggests that TCN1 may have utility beyond nutritional and oncologic pathways. For instance, increased expression of TCN1 in sputum has been correlated with markers of airway inflammation and impaired lung function, highlighting its potential as a biomarker in chronic respiratory diseases such as asthma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Andrew McCaddon, Kaj Blennow, Peter Hudson, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Transcobalamin 776C->G polymorphism negatively affects vitamin B-12 metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Clin Nutr (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/ajcn/81.6.1436"}], "href": "https://doi.org/10.1093/ajcn/81.6.1436"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15941899"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15941899"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "M G Garrod, L H Allen, M N Haan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcobalamin C776G genotype modifies the association between vitamin B12 and homocysteine in older Hispanics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Clin Nutr (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejcn.2010.20"}], "href": "https://doi.org/10.1038/ejcn.2010.20"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20216556"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20216556"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ralph Carmel, James Parker, Zvi Kelman "}, {"type": "b", "children": [{"type": "t", "text": "Genomic mutations associated with mild and severe deficiencies of transcobalamin I (haptocorrin) that cause mildly and severely low serum cobalamin levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Haematol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2141.2009.07855.x"}], "href": "https://doi.org/10.1111/j.1365-2141.2009.07855.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19686235"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19686235"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Luke Yong-Zheng Chong, Poh Yian Cheok, Wai-Jin Tan, et al. 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