{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStudies in muscle biology demonstrate that MYO18B encodes an unconventional myosin that plays a critical structural and regulatory role in striated muscle. Specifically, MYO18B is expressed in cardiac and skeletal myocytes, where it displays a dynamic subcellular localization during myoblast differentiation—including accumulation in a subset of myonuclei—and is implicated in the proper organization of actomyosin bundles and sarcomere assembly. Experimental models have shown that complete loss of MYO18B function disrupts the formation of well‐organized thick and thin filament arrays, leading to a failure in sarcomere biogenesis, while biochemical characterization reveals that MYO18B lacks motor ATPase activity yet contains distinct N‑terminal actin‐binding domains that enable it to crosslink actin and modulate myosin II stack formation and contractile forces."}, {"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 the context of cancer biology, MYO18B appears to function as a tumor suppressor. Its frequent deletion, mutation, and promoter hypermethylation have been documented in lung and ovarian cancers, and re‑expression of MYO18B in malignant cells suppresses anchorage‑independent growth. Similar tumor‐suppressive effects have been observed in hepatocellular carcinoma and malignant pleural mesothelioma models, where restoration of MYO18B expression inhibits cell proliferation and tumor growth by promoting apoptosis. At the molecular level, MYO18B protein levels are at least partly regulated by proteasomal degradation via its interaction with the 19S regulator Sug1."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, genetic studies in humans have associated MYO18B with diverse developmental and neurobehavioral phenotypes. A coding variant in MYO18B (rs133885) was originally linked to mathematical ability and correlated with subtle structural differences in the intraparietal sulcus, though subsequent replication efforts have not confirmed a major effect on cognitive performance. In addition, biallelic loss‐of‑function variants in MYO18B cause Klippel–Feil syndrome type 4, a disorder characterized by congenital vertebral fusions, nemaline myopathy, and distinctive dysmorphic features, underscoring the importance of MYO18B in musculoskeletal development. Finally, while studies in cutaneous squamous‑cell carcinoma underscore ongoing controversy regarding MYO18B’s role in cancer progression, its context‑dependent functions continue to emerge."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Michela Salamon, Caterina Millino, Anna Raffaello, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human MYO18B, a novel unconventional myosin heavy chain expressed in striated muscles moves into the myonuclei upon differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0022-2836(02)01335-9"}], "href": "https://doi.org/10.1016/s0022-2836(02"}, {"type": "t", "text": "01335-9) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12547197"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12547197"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Joachim Berger, Silke Berger, Mei Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Myo18b is essential for sarcomere assembly in fast skeletal muscle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddx025"}], "href": "https://doi.org/10.1093/hmg/ddx025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28104788"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28104788"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yaming Jiu, Reena Kumari, Aidan M Fenix, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Myosin-18B Regulates Higher-Order Organization of the Cardiac Sarcomere through Thin Filament Cross-Linking and Thick Filament Dynamics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2020.108090"}], "href": "https://doi.org/10.1016/j.celrep.2020.108090"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32877672"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32877672"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Michiho Nishioka, Takashi Kohno, Masachika Tani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MYO18B, a candidate tumor suppressor gene at chromosome 22q12.1, deleted, mutated, and methylated in human lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.192445899"}], "href": "https://doi.org/10.1073/pnas.192445899"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12209013"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12209013"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Nozomu Yanaihara, Michiho Nishioka, Takashi Kohno, et al. 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