{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRNF213 is a colossal protein that harbors a RING‐finger domain and dual AAA+ ATPase modules, and it forms large, ring‐shaped (toroidal) oligomers whose assembly is dynamically regulated by ATP/ADP binding and hydrolysis. These structural features underpin its dual enzymatic functions, as it acts as an E3 ubiquitin ligase capable not only of catalyzing the formation of K63‐linked polyubiquitin chains but also of targeting unconventional, non–proteinaceous substrates – for example, the lipid A moiety of bacterial lipopolysaccharide – thereby promoting antibacterial autophagy. Such biochemical versatility is thought to contribute to its roles in vascular development and immune defense."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the vascular context, RNF213 has emerged as a critical determinant of cerebrovascular integrity. Genetic variants – most notably the p.R4810K mutation – are strongly associated with moyamoya disease and other intracranial steno‐occlusive disorders. In endothelial cells, pro‐inflammatory mediators such as interferon‑γ and tumor necrosis factor‑α stimulate RNF213 transcription via pathways including AKT and PKR, thereby modulating the expression of cell cycle regulators, angiogenic factors, and matrix metalloproteinases. Functional studies further indicate that pathogenic RNF213 variants impair endothelial migration, tube formation, and proper mitotic progression (often through aberrant interactions with checkpoint proteins like MAD2), promoting genomic instability and disordered vascular remodeling that underlie the clinical phenotypes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_fs", "start_ref": "7", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its vascular functions, RNF213 also contributes to cell‐intrinsic immune defense and metabolic regulation. It is recruited to pathogen‐containing vacuoles – as demonstrated in models of Salmonella and Toxoplasma gondii infection – where its ubiquitin ligase activity facilitates the decoration of vacuoles with ubiquitin and the subsequent activation of autophagic clearance pathways. In parallel, in adipocytes, inflammatory stimuli (such as TNFα acting via the phosphatase PTP1B) and metabolic regulators (for example, the insulin‑sensitizing factor PPARγ) modulate RNF213 expression, suggesting that constitutive RNF213 activity may function as an adipostatic mechanism to limit adipogenesis in obesity. Moreover, numerous genetic studies have linked distinct RNF213 variants not only to moyamoya disease but also to a spectrum of vascular disorders (including intracranial atherosclerosis, pulmonary arterial hypertension, and peripheral arterial stenoses), highlighting the multifaceted role of RNF213 in vascular biology across diverse populations and pathological contexts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "20", "end_ref": "33"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_fs", "start_ref": "34", "end_ref": "36"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Fumiaki Kamada, Yoko Aoki, Ayumi Narisawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genome-wide association study identifies RNF213 as the first Moyamoya disease gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jhg.2010.132"}], "href": "https://doi.org/10.1038/jhg.2010.132"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21048783"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21048783"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Elsje G Otten, Emma Werner, Ana Crespillo-Casado, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitylation of lipopolysaccharide by RNF213 during bacterial infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41586-021-03566-4"}], "href": "https://doi.org/10.1038/s41586-021-03566-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34012115"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34012115"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Munechika Sugihara, Daisuke Morito, Shiori Ainuki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The AAA+ ATPase/ubiquitin ligase mysterin stabilizes cytoplasmic lipid droplets."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201712120"}], "href": "https://doi.org/10.1083/jcb.201712120"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30705059"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30705059"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Daisuke Morito, Kouki Nishikawa, Jun Hoseki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep04442"}], "href": "https://doi.org/10.1038/srep04442"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24658080"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24658080"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Dulcemaria Hernandez, Stephen Walsh, Luz Saavedra Sanchez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interferon-Inducible E3 Ligase RNF213 Facilitates Host-Protective Linear and K63-Linked Ubiquitylation of Toxoplasma gondii Parasitophorous Vacuoles."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "mBio (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/mbio.01888-22"}], "href": "https://doi.org/10.1128/mbio.01888-22"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36154443"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36154443"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Junpeng Ma, Yi Liu, Lu Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNF213 polymorphism and Moyamoya disease: A systematic review and meta-analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurol India (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4103/0028-3886.107927"}], "href": "https://doi.org/10.4103/0028-3886.107927"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23466837"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23466837"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Wanyang Liu, Daisuke Morito, Seiji Takashima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of RNF213 as a susceptibility gene for moyamoya disease and its possible role in vascular development."}]}, {"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.0022542"}], "href": "https://doi.org/10.1371/journal.pone.0022542"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21799892"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21799892"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "S Miyatake, N Miyake, H Touho, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Homozygous c.14576G>A variant of RNF213 predicts early-onset and severe form of moyamoya disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/WNL.0b013e318249f71f"}], "href": "https://doi.org/10.1212/WNL.0b013e318249f71f"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22377813"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22377813"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Alana C Cecchi, Dongchuan Guo, Zhao Ren, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNF213 rare variants in an ethnically diverse population with Moyamoya disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stroke (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/STROKEAHA.114.006244"}], "href": "https://doi.org/10.1161/STROKEAHA.114.006244"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25278557"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25278557"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Satoru Miyawaki, Hideaki Imai, Masahiro Shimizu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variant RNF213 c.14576G>A in various phenotypes of intracranial major artery stenosis/occlusion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stroke (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/STROKEAHA.113.002477"}], "href": "https://doi.org/10.1161/STROKEAHA.113.002477"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23970789"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23970789"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Zhiyuan Wu, Hanqiang Jiang, Lei Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular analysis of RNF213 gene for moyamoya disease in the Chinese Han population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0048179"}], "href": "https://doi.org/10.1371/journal.pone.0048179"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23110205"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23110205"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Satoru Miyawaki, Hideaki Imai, Shunsaku Takayanagi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a genetic variant common to moyamoya disease and intracranial major artery stenosis/occlusion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stroke (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/STROKEAHA.112.663864"}], "href": "https://doi.org/10.1161/STROKEAHA.112.663864"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23010677"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23010677"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Kazuhiro Ohkubo, Yasunari Sakai, Hirosuke Inoue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Moyamoya disease susceptibility gene RNF213 links inflammatory and angiogenic signals in endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep13191"}], "href": "https://doi.org/10.1038/srep13191"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26278786"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26278786"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Stéphanie Guey, Markus Kraemer, Dominique Hervé, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rare RNF213 variants in the C-terminal region encompassing the RING-finger domain are associated with moyamoya angiopathy in Caucasians."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2017.92"}], "href": "https://doi.org/10.1038/ejhg.2017.92"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28635953"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28635953"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Eun-Hee Kim, Mi-Sun Yum, Young-Shin Ra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Importance of RNF213 polymorphism on clinical features and long-term outcome in moyamoya disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosurg (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3171/2015.4.JNS142900"}], "href": "https://doi.org/10.3171/2015.4.JNS142900"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26430847"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26430847"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Midori Takeda, Tohru Tezuka, Minsoo Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Moyamoya disease patient mutations in the RING domain of RNF213 reduce its ubiquitin ligase activity and enhance NFκB activation and apoptosis in an AAA+ domain-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2020.02.024"}], "href": "https://doi.org/10.1016/j.bbrc.2020.02.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32139119"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32139119"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Shinya Sonobe, Miki Fujimura, Kuniyasu Niizuma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased vascular MMP-9 in mice lacking RNF213: moyamoya disease susceptibility gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuroreport (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/WNR.0000000000000289"}], "href": "https://doi.org/10.1097/WNR.0000000000000289"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25383461"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25383461"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Yoshiko Matsuda, Yohei Mineharu, Mitsuru Kimura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNF213 p.R4810K Variant and Intracranial Arterial Stenosis or Occlusion in Relatives of Patients with Moyamoya Disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Stroke Cerebrovasc Dis (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jstrokecerebrovasdis.2017.04.019"}], "href": "https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.04.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28506590"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28506590"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Hatasu Kobayashi, Miroslav Brozman, Kateřina Kyselová, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNF213 Rare Variants in Slovakian and Czech Moyamoya Disease Patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0164759"}], "href": "https://doi.org/10.1371/journal.pone.0164759"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27736983"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27736983"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Jan Cools, Iwona Wlodarska, Riet Somers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Chromosomes Cancer (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/gcc.10033"}], "href": "https://doi.org/10.1002/gcc.10033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12112524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12112524"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Toshiaki Hitomi, Toshiyuki Habu, Hatasu Kobayashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of Securin by the variant RNF213 R4810K (rs112735431, G>A) reduces angiogenic activity of induced pluripotent stem cell-derived vascular endothelial cells from moyamoya patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2013.07.004"}], "href": "https://doi.org/10.1016/j.bbrc.2013.07.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23850618"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23850618"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Robert S Banh, Caterina Iorio, Richard Marcotte, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PTP1B controls non-mitochondrial oxygen consumption by regulating RNF213 to promote tumour survival during hypoxia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb3376"}], "href": "https://doi.org/10.1038/ncb3376"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27323329"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27323329"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Miki Fujimura, Taku Fujimura, Aya Kakizaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased serum production of soluble CD163 and CXCL5 in patients with moyamoya disease: Involvement of intrinsic immune reaction in its pathogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.brainres.2017.11.013"}], "href": "https://doi.org/10.1016/j.brainres.2017.11.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29174692"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29174692"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Oh Young Bang, Jong-Won Chung, Suk Jae Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Caveolin-1, Ring finger protein 213, and endothelial function in Moyamoya disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Stroke (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/1747493016662039"}], "href": "https://doi.org/10.1177/1747493016662039"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27462098"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27462098"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Vincent Roy, Jay P Ross, Rémy Pépin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Moyamoya Disease Susceptibility Gene "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "RNF213"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Regulates Endothelial Barrier Function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stroke (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/STROKEAHA.120.032691"}], "href": "https://doi.org/10.1161/STROKEAHA.120.032691"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34991336"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34991336"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Takaaki Morimoto, Yohei Mineharu, Hatasu Kobayashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Significant Association of the RNF213 p.R4810K Polymorphism with Quasi-Moyamoya Disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Stroke Cerebrovasc Dis (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jstrokecerebrovasdis.2016.07.004"}], "href": "https://doi.org/10.1016/j.jstrokecerebrovasdis.2016.07.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27476341"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27476341"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Takahiro Hiraide, Masaharu Kataoka, Hisato Suzuki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Poor outcomes in carriers of the RNF213 variant (p.Arg4810Lys) with pulmonary arterial hypertension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Heart Lung Transplant (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.healun.2019.08.022"}], "href": "https://doi.org/10.1016/j.healun.2019.08.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31542298"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31542298"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Ming-Jen Lee, Ya-Fang Chen, Pi-Chuan Fan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation genotypes of RNF213 gene from moyamoya patients in Taiwan."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurol Sci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jns.2015.04.019"}], "href": "https://doi.org/10.1016/j.jns.2015.04.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25956231"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25956231"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Soto Romuald Kiando, Cristina Barlassina, Daniele Cusi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exome sequencing in seven families and gene-based association studies indicate genetic heterogeneity and suggest possible candidates for fibromuscular dysplasia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hypertens (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/HJH.0000000000000625"}], "href": "https://doi.org/10.1097/HJH.0000000000000625"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26147384"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26147384"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Satoru Miyawaki, Hideaki Imai, Masahiro Shimizu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic Analysis of RNF213 c.14576G>A Variant in Nonatherosclerotic Quasi-Moyamoya Disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Stroke Cerebrovasc Dis (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jstrokecerebrovasdis.2015.01.005"}], "href": "https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.01.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25817623"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25817623"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Ji Hoon Phi, Jung Won Choi, Moon-Woo Seong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between moyamoya syndrome and the RNF213 c.14576G>A variant in patients with neurofibromatosis Type 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosurg Pediatr (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3171/2015.10.PEDS15537"}], "href": "https://doi.org/10.3171/2015.10.PEDS15537"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26849809"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26849809"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Yue Wang, Michael Mambiya, Qian Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNF213 p.R4810K Polymorphism and the Risk of Moyamoya Disease, Intracranial Major Artery Stenosis/Occlusion, and Quasi-Moyamoya Disease: A Meta-Analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Stroke Cerebrovasc Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jstrokecerebrovasdis.2018.04.013"}], "href": "https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.04.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29752070"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29752070"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Priyanka Sarkar, Kavitha Thirumurugan "}, {"type": "b", "children": [{"type": "t", "text": "New insights into TNFα/PTP1B and PPARγ pathway through RNF213- a link between inflammation, obesity, insulin resistance, and Moyamoya disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2020.145340"}], "href": "https://doi.org/10.1016/j.gene.2020.145340"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33333224"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33333224"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Yuki Shinya, Satoru Miyawaki, Hideaki Imai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic Analysis of Ring Finger Protein 213 (RNF213) c.14576G>A in Intracranial Atherosclerosis of the Anterior and Posterior Circulations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Stroke Cerebrovasc Dis (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jstrokecerebrovasdis.2017.06.043"}], "href": "https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.06.043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28797616"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28797616"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Min-Gyu Park, Jin-Hong Shin, Sang Weon Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNF213 rs112735431 polymorphism in intracranial artery steno-occlusive disease and moyamoya disease in Koreans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurol Sci (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jns.2017.02.033"}], "href": "https://doi.org/10.1016/j.jns.2017.02.033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28320162"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28320162"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Satoko Miyatake, Hajime Touho, Noriko Miyake, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sibling cases of moyamoya disease having homozygous and heterozygous c.14576G>A variant in RNF213 showed varying clinical course and severity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jhg.2012.105"}], "href": "https://doi.org/10.1038/jhg.2012.105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22931863"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22931863"}]}]}]}