{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNELL1 has emerged as a critical molecule in defining unique pathological and diagnostic subtypes of membranous nephropathy. In PLA2R‐negative patients, NELL1 accumulates along the glomerular basement membrane and co‐localizes with IgG, serving as an antigenic target that distinguishes a distinct form of primary membranous nephropathy. Furthermore, NELL1‐associated membranous nephropathy often exhibits unusual histopathologic features and a greater correlation with concurrent malignancy, highlighting its potential as both a biomarker and a prognostic indicator in kidney disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the skeletal system, NELL1 is a potent osteoinductive factor that plays a dual role in directing bone formation and craniofacial development. Overexpression in animal models leads to premature cranial suture closure and marked calvarial overgrowth, indicating its contribution to craniosynostosis. At the cellular level, NELL1 promotes osteoblast differentiation by activating non‐Smad signal cascades—including MAPK pathways and integrin–Wnt signaling—and by enhancing the function of key osteogenic transcription factors such as Runx2. Its synergistic activity with other morphogens like BMP2 and Sonic Hedgehog further accentuates its specificity for osteochondral lineages while simultaneously inhibiting adipogenesis. In addition, lentiviral‐mediated gene transfer of NELL1 significantly improves osteogenic differentiation in various stem cell populations including pericytes, adipose-derived, gingiva‐derived, and periodontal ligament stem cells, thereby advancing strategies for bone regeneration and distraction osteogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in normal bone development and repair, NELL1 is implicated in the pathogenesis of several cancers through epigenetic and expression-level alterations. Hypermethylation of the NELL1 promoter has been observed in esophageal adenocarcinoma and gastric cancer, correlating with reduced mRNA expression, whereas loss of NELL1 protein expression is noted in renal cell carcinoma. In bone tumors, benign lesions exhibit strong and diffuse NELL1 expression that is diminished in malignant osteosarcomas, with additional data implicating factors such as ANO5 in the degradation of NELL1 protein and promotion of tumor aggressiveness. Moreover, specific germline variants in NELL1 have been identified as risk modifiers in tobacco-related oral squamous cell carcinoma, underscoring its putative tumor suppressor functions in distinct tissue contexts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent investigations have further revealed that NELL1 engages in complex interactions with receptors and signaling molecules beyond osteogenesis. Notably, NELL1 (and its homolog NELL2) can bind to the first fibronectin type III domain of Robo2 under acidic conditions—a process influenced by conformational changes in the Robo2 ectodomain—which may have implications in neural development and the regulation of cell migration. Complementing these mechanistic insights, genome-wide association studies have uncovered NELL1 variants associated with inflammatory bowel disease and metabolic side effects, while reviews of GWAS data emphasize its multifaceted roles across bone biology, metabolic regulation, neuropsychiatric conditions, and cancer."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "27", "end_ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sanjeev Sethi, Hanna Debiec, Benjamin Madden, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neural epidermal growth factor-like 1 protein (NELL-1) associated membranous nephropathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Kidney Int (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.kint.2019.09.014"}], "href": "https://doi.org/10.1016/j.kint.2019.09.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31901340"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31901340"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tiffany N Caza, Samar I Hassen, Zeljko Dvanajscak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NELL1 is a target antigen in malignancy-associated membranous nephropathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Kidney Int (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.kint.2020.07.039"}], "href": "https://doi.org/10.1016/j.kint.2020.07.039"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32828756"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32828756"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xuan-Li Tang, Yuan-Yuan DU, Jin Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Clinical Significance of Thrombospondin Type 1 Domain-Containing 7A and Neural Epidermal Growth Factor-Like 1 Protein in M-Type Phospholipase A2 Receptor-Negative Membranous Nephropathy]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhongguo Yi Xue Ke Xue Yuan Xue Bao (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3881/j.issn.1000-503X.15212"}], "href": "https://doi.org/10.3881/j.issn.1000-503X.15212"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37157070"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37157070"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xinli Zhang, Shun'ichi Kuroda, Dale Carpenter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Craniosynostosis in transgenic mice overexpressing Nell-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI15375"}], "href": "https://doi.org/10.1172/JCI15375"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12235118"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12235118"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "X Zhang, J Zara, R K Siu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of NELL-1, a growth factor associated with craniosynostosis, in promoting bone regeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Dent Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/0022034510376401"}], "href": "https://doi.org/10.1177/0022034510376401"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20647499"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20647499"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Aaron W James, Jia Shen, Xinli Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NELL-1 in the treatment of osteoporotic bone loss."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms8362"}], "href": "https://doi.org/10.1038/ncomms8362"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26082355"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26082355"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Aaron W James, Shen Pang, Asal Askarinam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Additive effects of sonic hedgehog and Nell-1 signaling in osteogenic versus adipogenic differentiation of human adipose-derived stromal cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cells Dev (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/scd.2011.0461"}], "href": "https://doi.org/10.1089/scd.2011.0461"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22264144"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22264144"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Nobuyuki Bokui, Takayuki Otani, Koichi Igarashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of MAPK signaling molecules and Runx2 in the NELL1-induced osteoblastic differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2007.12.006"}], "href": "https://doi.org/10.1016/j.febslet.2007.12.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18082140"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18082140"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Thien Truong, Xinli Zhang, Dharmini Pathmanathan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Craniosynostosis-associated gene nell-1 is regulated by runx2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Bone Miner Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1359/jbmr.061012"}], "href": "https://doi.org/10.1359/jbmr.061012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17042739"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17042739"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Jia Shen, Aaron W James, Xinli Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel Wnt Regulator NEL-Like Molecule-1 Antagonizes Adipogenesis and Augments Osteogenesis Induced by Bone Morphogenetic Protein 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajpath.2015.10.011"}], "href": "https://doi.org/10.1016/j.ajpath.2015.10.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26772960"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26772960"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Xinli Zhang, Bruno Péault, Weiwei Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Nell-1 growth factor stimulates bone formation by purified human perivascular cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tissue Eng Part A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/ten.TEA.2010.0705"}], "href": "https://doi.org/10.1089/ten.TEA.2010.0705"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21615216"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21615216"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Jing Xue, Jiang Peng, Mei Yuan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NELL1 promotes high-quality bone regeneration in rat femoral distraction osteogenesis model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bone (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bone.2010.10.166"}], "href": "https://doi.org/10.1016/j.bone.2010.10.166"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20959151"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20959151"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Chen-Shuang Li, Xinli Zhang, Bruno Péault, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Accelerated Chondrogenic Differentiation of Human Perivascular Stem Cells with NELL-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tissue Eng Part A (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/ten.TEA.2015.0250"}], "href": "https://doi.org/10.1089/ten.TEA.2015.0250"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26700847"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26700847"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Catherine M Cowan, Xinli Zhang, Aaron W James, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NELL-1 increases pre-osteoblast mineralization using both phosphate transporter Pit1 and Pit2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2012.04.077"}], "href": "https://doi.org/10.1016/j.bbrc.2012.04.077"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22580275"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22580275"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Xuan Zou, Jia Shen, Feng Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NELL-1 binds to APR3 affecting human osteoblast proliferation and differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2011.06.024"}], "href": "https://doi.org/10.1016/j.febslet.2011.06.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21723284"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21723284"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Xiufen Tian, Qiang Wang, Jiameng Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of Nel-like molecule 1 with apoptosis related protein 3 with its influence on human dental pulp cells proliferation and differentiation into odontoblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2019.08.042"}], "href": "https://doi.org/10.1016/j.bbrc.2019.08.042"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31416616"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31416616"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Yajing Liu, Caiyun Chen, Huixia He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lentiviral-mediated gene transfer into human adipose-derived stem cells: role of NELL1 versus BMP2 in osteogenesis and adipogenesis in vitro."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Biochim Biophys Sin (Shanghai) (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/abbs/gms070"}], "href": "https://doi.org/10.1093/abbs/gms070"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23017834"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23017834"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Runsang Pan, Qiaoying Lu, Chong Ren, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Anoctamin 5 promotes osteosarcoma development by increasing degradation of Nel-like proteins 1 and 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.203212"}], "href": "https://doi.org/10.18632/aging.203212"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34238763"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34238763"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Cai-Yun Chen, Ya-Jing Liu, Sheng-Gen Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Osteogenic differentiation of human periodontal ligament stem cells expressing lentiviral NEL-like protein 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Med (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijmm.2012.1053"}], "href": "https://doi.org/10.3892/ijmm.2012.1053"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22767336"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22767336"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Jong-Ho Lee, Young-Min Song, Sae-Kyung Min, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NELL-1 Increased the Osteogenic Differentiation and mRNA Expression of Spheroids Composed of Stem Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Medicina (Kaunas) (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/medicina57060586"}], "href": "https://doi.org/10.3390/medicina57060586"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34201046"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34201046"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Z Jin, Y Mori, J Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypermethylation of the nel-like 1 gene is a common and early event and is associated with poor prognosis in early-stage esophageal adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1210461"}], "href": "https://doi.org/10.1038/sj.onc.1210461"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17452981"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17452981"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Ritsuko Nakamura, Takeru Oyama, Ryosuke Tajiri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and regulatory effects on cancer cell behavior of NELL1 and NELL2 in human renal cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Sci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cas.12649"}], "href": "https://doi.org/10.1111/cas.12649"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25726761"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25726761"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Jia Shen, Greg LaChaud, Kevork Khadarian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NELL-1 expression in benign and malignant bone tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2015.03.040"}], "href": "https://doi.org/10.1016/j.bbrc.2015.03.040"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25791475"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25791475"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Kaneyoshi Takahashi, Arisa Imai, Masumi Iijima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mapping the heparin-binding site of the osteoinductive protein NELL1 by site-directed mutagenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2015.11.032"}], "href": "https://doi.org/10.1016/j.febslet.2015.11.032"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26627376"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26627376"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Changlu Gao, Qian Zhang, Deyang Kong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MALDI-TOF Mass Array Analysis of Nell-1 Promoter Methylation Patterns in Human Gastric Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res Int (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2015/136941"}], "href": "https://doi.org/10.1155/2015/136941"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26090379"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26090379"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Sharbadeb Kundu, Vijayalakshmi Ramshankar, Akalesh Kumar Verma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of DFNA5, SYK, and NELL1 variants along with HPV infection in oral cancer among the prolonged tobacco-chewers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/1010428318793023"}], "href": "https://doi.org/10.1177/1010428318793023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30091681"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30091681"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Andre Franke, Jochen Hampe, Philip Rosenstiel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Systematic association mapping identifies NELL1 as a novel IBD disease gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0000691"}], "href": "https://doi.org/10.1371/journal.pone.0000691"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17684544"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17684544"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "J L Del-Aguila, A L Beitelshees, R M Cooper-Dehoff, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharmacogenomics J (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/tpj.2013.3"}], "href": "https://doi.org/10.1038/tpj.2013.3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23400010"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23400010"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Naoka Yamamoto, Manabu Kashiwagi, Manami Ishihara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Robo2 contains a cryptic binding site for neural EGFL-like (NELL) protein 1/2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA118.005819"}], "href": "https://doi.org/10.1074/jbc.RA118.005819"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30700556"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30700556"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Masaki Miyaguchi, Yoichi Nakanishi, Andrés D Maturana, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Conformational Change of the Hairpin-like-structured Robo2 Ectodomain Allows NELL1/2 Binding."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2022.167777"}], "href": "https://doi.org/10.1016/j.jmb.2022.167777"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35940226"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35940226"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Feng Chen, Ben Walder, Aaron W James, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NELL-1-dependent mineralisation of Saos-2 human osteosarcoma cells is mediated via c-Jun N-terminal kinase pathway activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int Orthop (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00264-012-1590-x"}], "href": "https://doi.org/10.1007/s00264-012-1590-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22797704"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22797704"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Xu Cheng, Jiayu Shi, Zhonglin Jia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NELL-1 in Genome-Wide Association Studies across Human Diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajpath.2021.11.006"}], "href": "https://doi.org/10.1016/j.ajpath.2021.11.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34890556"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34890556"}]}]}]}