{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LRP12, a member of the low‐density lipoprotein receptor (LDLR) superfamily, has emerged as a multifaceted protein involved in neuromuscular, oncologic, and neurodevelopmental processes. In the neuromuscular realm, noncoding CGG repeat expansions within the 5′ untranslated region of LRP12 have been identified as causative for oculopharyngodistal myopathy (OPDM), a condition characterized by ptosis, ophthalmoplegia, dysphagia, and distal muscle weakness, thereby expanding the spectrum of repeat‐expansion disorders affecting muscle function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": " In oncology, aberrant regulation of LRP12 is evidenced by promoter hypermethylation—which has been correlated with increased resistance to platinum‐based chemotherapy in non–small cell lung cancer—and by genomic amplification leading to its overexpression in oral tumors, suggesting that LRP12 may also function in tumor development and progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " At the molecular level, LRP12 was initially identified as ST7, a putative tumor suppressor that, through its cytoplasmic motifs, participates in endocytosis and signal transduction events."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Furthermore, LRP12 is subject to posttranscriptional regulation; for instance, in osteoarthritis, chondroprotective extracellular vesicles deliver miR‑130b‑3p, which targets LRP12 to modulate the AKT/β‑catenin pathway and thereby promote chondrocyte survival and reduce extracellular matrix degradation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In the developing brain, studies have demonstrated that reduced LRP12 expression disrupts neuronal arborization and cortical lamination while predisposing to seizure activity, and in model organisms its interaction with cytoskeletal regulators facilitates neuroblast migration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "12"}]}, {"type": "t", "text": " Additional genetic studies have implicated structural variations in the LRP12 genomic region with ocular phenotypes, and emerging evidence suggests a role in modulating lipid and cholesterol homeostasis in neuronal cells, which may be relevant to neurodegenerative processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hiroyuki Ishiura, Shota Shibata, Jun Yoshimura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Noncoding CGG repeat expansions in neuronal intranuclear inclusion disease, oculopharyngodistal myopathy and an overlapping disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41588-019-0458-z"}], "href": "https://doi.org/10.1038/s41588-019-0458-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31332380"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31332380"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Masashi Ogasawara, Aritoshi Iida, Theerawat Kumutpongpanich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CGG expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy with neurological manifestations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s40478-020-01084-4"}], "href": "https://doi.org/10.1186/s40478-020-01084-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33239111"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33239111"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Theerawat Kumutpongpanich, Masashi Ogasawara, Ayami Ozaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinicopathologic Features of Oculopharyngodistal Myopathy With LRP12 CGG Repeat Expansions Compared With Other Oculopharyngodistal Myopathy Subtypes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JAMA Neurol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/jamaneurol.2021.1509"}], "href": "https://doi.org/10.1001/jamaneurol.2021.1509"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34047774"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34047774"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Masashi Ogasawara, Nobuyuki Eura, Utako Nagaoka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Intranuclear inclusions in skin biopsies are not limited to neuronal intranuclear inclusion disease but can also be seen in oculopharyngodistal myopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropathol Appl Neurobiol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/nan.12787"}], "href": "https://doi.org/10.1111/nan.12787"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34927285"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34927285"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jianying Xi, Xilu Wang, Dongyue Yue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "5' UTR CGG repeat expansion in GIPC1 is associated with oculopharyngodistal myopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/brain/awaa426"}], "href": "https://doi.org/10.1093/brain/awaa426"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33374016"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33374016"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sabrina Grasse, Matthias Lienhard, Steffen Frese, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epigenomic profiling of non-small cell lung cancer xenografts uncover LRP12 DNA methylation as predictive biomarker for carboplatin resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genome Med (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13073-018-0562-1"}], "href": "https://doi.org/10.1186/s13073-018-0562-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30029672"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30029672"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Cathie Garnis, Bradley P Coe, Lewei Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of LRP12, a gene contained within an 8q22 amplicon identified by high-resolution array CGH analysis of oral squamous cell carcinomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1207367"}], "href": "https://doi.org/10.1038/sj.onc.1207367"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14676824"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14676824"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Michele A Battle, Veronica M Maher, J Justin McCormick "}, {"type": "b", "children": [{"type": "t", "text": "ST7 is a novel low-density lipoprotein receptor-related protein (LRP) with a cytoplasmic tail that interacts with proteins related to signal transduction pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi034081y"}], "href": "https://doi.org/10.1021/bi034081y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12809483"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12809483"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Zhenhua Zeng, Yi Dai, Shuo Deng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Synovial mesenchymal stem cell-derived extracellular vesicles alleviate chondrocyte damage during osteoarthritis through microRNA-130b-3p-mediated inhibition of the LRP12/AKT/β-catenin axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunopharmacol Immunotoxicol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/08923973.2022.2038192"}], "href": "https://doi.org/10.1080/08923973.2022.2038192"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35174753"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35174753"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Alexander Grote, Barbara K Robens, Ingmar Blümcke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LRP12 silencing during brain development results in cortical dyslamination and seizure sensitization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Dis (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.nbd.2015.11.021"}], "href": "https://doi.org/10.1016/j.nbd.2015.11.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26639854"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26639854"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Barbara K Robens, Eva Gembé, Jana Fassunke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Abundance of LRP12 C-rs9694676 allelic promoter variant in epilepsy-associated gangliogliomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Life Sci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.lfs.2016.01.049"}], "href": "https://doi.org/10.1016/j.lfs.2016.01.049"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27142828"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27142828"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Zhiwen Zhu, Yongping Chai, Yuxiang Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional Coordination of WAVE and WASP in C. elegans Neuroblast Migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2016.09.029"}], "href": "https://doi.org/10.1016/j.devcel.2016.09.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27780040"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27780040"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Chien-Hua Peng, Chun-Ta Liao, Shih-Chi Peng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel molecular signature identified by systems genetics approach predicts prognosis in oral squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0023452"}], "href": "https://doi.org/10.1371/journal.pone.0023452"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21853135"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21853135"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Taha Mohseni Ahooyi, Masoud Shekarabi, Bahareh Torkzaban, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dysregulation of Neuronal Cholesterol Homeostasis upon Exposure to HIV-1 Tat and Cocaine Revealed by RNA-Sequencing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-34539-9"}], "href": "https://doi.org/10.1038/s41598-018-34539-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30390000"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30390000"}]}]}]}