{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ARMS2 (also known as LOC387715) is one of the major susceptibility genes for age‐related macular degeneration (AMD) identified in multiple genome‐wide studies (e.g."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " This gene harbors a common nonsynonymous variant, rs10490924, which causes an A69S substitution and is tightly linked to other risk alleles at the 10q26 locus. Early functional studies demonstrated that ARMS2 messenger RNA is expressed in the human retina and that the predicted 12‐kDa protein localizes to the mitochondrial outer membrane in retinal cells, suggesting a role in mitochondrial function and in maintaining photoreceptor health."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, a deletion–insertion variant in ARMS2 that disrupts its polyadenylation signal leads to absent expression, further implicating ARMS2 deficiency and dysfunction in AMD pathogenesis via mitochondria‐related pathways. However, subsequent investigations employing immunofluorescence and immunoblot techniques observed that ARMS2 is predominantly cytosolic and may associate with the cytoskeleton, hinting at alternative mechanisms of action."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In addition, ARMS2 risk alleles appear to confer differential risks for AMD subtypes—with stronger associations noted for retinal angiomatous proliferation—and may intersect with inflammatory and complement‐mediated pathways, potentially in concert with neighboring HTRA1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Although the precise cellular function of ARMS2 remains to be fully elucidated, the cumulative genetic and functional evidence supports its involvement in key cellular processes such as mitochondrial/energy homeostasis, cytoskeletal interactions, and regulation of local inflammatory responses that together contribute to the complex pathogenesis of AMD.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wei Chen, Dwight Stambolian, Albert O Edwards, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0912702107"}], "href": "https://doi.org/10.1073/pnas.0912702107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20385819"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20385819"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Atsuhiro Kanda, Wei Chen, Mohammad Othman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A variant of mitochondrial protein LOC387715/ARMS2, not HTRA1, is strongly associated with age-related macular degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0703933104"}], "href": "https://doi.org/10.1073/pnas.0703933104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17884985"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17884985"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lars G Fritsche, Thomas Loenhardt, Andreas Janssen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.170"}], "href": "https://doi.org/10.1038/ng.170"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18511946"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18511946"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Gaofeng Wang, Kylee L Spencer, Brenda L Court, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Localization of age-related macular degeneration-associated ARMS2 in cytosol, not mitochondria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Invest Ophthalmol Vis Sci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1167/iovs.08-3240"}], "href": "https://doi.org/10.1167/iovs.08-3240"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19255159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19255159"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hisako Hayashi, Kenji Yamashiro, Norimoto Gotoh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CFH and ARMS2 variations in age-related macular degeneration, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Invest Ophthalmol Vis Sci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1167/iovs.10-5554"}], "href": "https://doi.org/10.1167/iovs.10-5554"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20574013"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20574013"}]}]}]}