{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T16:25:38Z","timestamp":1774542338610,"version":"3.50.1"},"reference-count":79,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Potishman Foundation","award":["02"],"award-info":[{"award-number":["02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Arterial aneurysms are vascular conditions associated with life-threatening consequences in patients, such as dissection and rupture. Understanding their genetic basis is an evolving field, driven by the robust reporting of genetic variants associated with aneurysms in patients. In this study, we present clinical and genetic data from nine unrelated subjects with arterial aneurysms who were identified to harbor rare variants in the TNXB gene, mainly affecting fibronectin type III (FNIII) domains. The cohort included three female and six male subjects with a mean age of 53.5 years (SD = 14.4). The most frequently affected vascular territory was the thoracic ascending aorta (n = 7). A range of pathogenic impacts was predicted via multiple in silico tools that analyze evolutionary conservation and biochemical properties. Computational protein structure modeling with AlphaFold 3 predicted domain-specific alterations across multiple FNIII regions for four unique missense variants and one in-frame deletion, and premature protein truncation resulting from two frameshift variants. To our knowledge, this study is one of the first and largest to associate TNXB variants with arterial aneurysmal disease. Our findings demonstrate the potential of computational genomics and structural modeling to advance the understanding of extracellular matrix gene alterations in aneurysm pathogenesis.<\/jats:p>","DOI":"10.3390\/ijms26136535","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T08:58:23Z","timestamp":1751878703000},"page":"6535","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic Variants in the Extracellular Matrix Gene TNXB Predicted to Alter Fibronectin III Domains in Arterial Aneurysmal and Dissection Diseases"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9294-7192","authenticated-orcid":false,"given":"Charlene","family":"Norgan Radler","sequence":"first","affiliation":[{"name":"Sathyamoorthy Laboratory, Department of Medicine, Anne Burnett Marion School of Medicine at TCU, Fort Worth, TX 76104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianci","family":"Wang","sequence":"additional","affiliation":[{"name":"Sathyamoorthy Laboratory, Department of Medicine, Anne Burnett Marion School of Medicine at TCU, Fort Worth, TX 76104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaden","family":"LeGate","sequence":"additional","affiliation":[{"name":"Sathyamoorthy Laboratory, Department of Medicine, Anne Burnett Marion School of Medicine at TCU, Fort Worth, TX 76104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lily","family":"Crone","sequence":"additional","affiliation":[{"name":"Sathyamoorthy Laboratory, Department of Medicine, Anne Burnett Marion School of Medicine at TCU, Fort Worth, TX 76104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5613-9646","authenticated-orcid":false,"given":"Parminder","family":"Deo","sequence":"additional","affiliation":[{"name":"Sathyamoorthy Laboratory, Department of Medicine, Anne Burnett Marion School of Medicine at TCU, Fort Worth, TX 76104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Wortley","sequence":"additional","affiliation":[{"name":"Sathyamoorthy Laboratory, Department of Medicine, Anne Burnett Marion School of Medicine at TCU, Fort Worth, TX 76104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6542-0746","authenticated-orcid":false,"given":"Peyton","family":"Moore","sequence":"additional","affiliation":[{"name":"Sathyamoorthy Laboratory, Department of Medicine, Anne Burnett Marion School of Medicine at TCU, Fort Worth, TX 76104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Griffin","family":"Bryant","sequence":"additional","affiliation":[{"name":"Sathyamoorthy Laboratory, Department of Medicine, Anne Burnett Marion School of Medicine at TCU, Fort Worth, TX 76104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Smitherman","sequence":"additional","affiliation":[{"name":"Sathyamoorthy Laboratory, Department of Medicine, Anne Burnett Marion School of Medicine at TCU, Fort Worth, TX 76104, USA"},{"name":"College of Arts and Sciences, Cornell University, Ithaca, NY 14850, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1686-9264","authenticated-orcid":false,"given":"Mohanakrishnan","family":"Sathyamoorthy","sequence":"additional","affiliation":[{"name":"Sathyamoorthy Laboratory, Department of Medicine, Anne Burnett Marion School of Medicine at TCU, Fort Worth, TX 76104, USA"},{"name":"Consultants in Cardiovascular Medicine and Science, Fort Worth, TX 76104, USA"},{"name":"Fort Worth Institute for Molecular Medicine and Genomics Research, Fort Worth, TX 76104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.amjcard.2024.12.009","article-title":"Gender- and Age-Based Differences in Nonsyndromic Arteriopathies in Younger Adults","volume":"239","author":"Bcharah","year":"2025","journal-title":"Am. J. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41572-018-0030-7","article-title":"Abdominal aortic aneurysms","volume":"4","author":"Sakalihasan","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e223","DOI":"10.1016\/j.jacc.2022.08.004","article-title":"2022 ACC\/AHA Guideline for the Diagnosis and Management of Aortic Disease","volume":"80","author":"Isselbacher","year":"2022","journal-title":"JACC"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/s41569-020-00472-6","article-title":"Epidemiology and management of aortic disease: Aortic aneurysms and acute aortic syndromes","volume":"18","author":"Bossone","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.jvs.2017.12.023","article-title":"Testing patterns for genetically triggered aortic and arterial aneurysms and dissections at an academic center","volume":"68","author":"Hicks","year":"2018","journal-title":"J. Vasc. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2516","DOI":"10.1161\/CIRCULATIONAHA.116.009762","article-title":"Hereditary Influence in Thoracic Aortic Aneurysm and Dissection","volume":"133","author":"Isselbacher","year":"2016","journal-title":"Circulation"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ostberg, N.P., Zafar, M.A., Ziganshin, B.A., and Elefteriades, J.A. (2020). The Genetics of Thoracic Aortic Aneurysms and Dissection: A Clinical Perspective. Biomolecules, 10.","DOI":"10.3390\/biom10020182"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Rega, S., Farina, F., Bouhuis, S., de Donato, S., Chiesa, M., Poggio, P., Cavallotti, L., Bonalumi, G., Giambuzzi, I., and Pompilio, G. (2023). Multi-omics in thoracic aortic aneurysm: The complex road to the simplification. Cell Biosci., 13.","DOI":"10.1186\/s13578-023-01080-w"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/nrcardio.2009.191","article-title":"Cellular and molecular mechanisms of thoracic aortic aneurysms","volume":"6","author":"Yacoub","year":"2009","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1161\/CIRCRESAHA.118.312436","article-title":"Genetics of Thoracic and Abdominal Aortic Diseases","volume":"124","author":"Pinard","year":"2019","journal-title":"Circ. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"154","DOI":"10.4161\/19336918.2014.994893","article-title":"Tenascin-X: Beyond the architectural function","volume":"9","author":"Valcourt","year":"2015","journal-title":"Cell Adhes. Migr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1111\/j.1365-2133.2010.09949.x","article-title":"Tenascin-X deficiency and Ehlers\u2013Danlos syndrome: A case report and review of the literature","volume":"163","author":"Burrows","year":"2010","journal-title":"Br. J. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3400\/avd.ra.17-00118","article-title":"Multiple Roles of Tenascins in Homeostasis and Pathophysiology of Aorta","volume":"11","author":"Matsumoto","year":"2018","journal-title":"Ann. Vasc. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1086\/376564","article-title":"Haploinsufficiency of TNXB Is Associated with Hypermobility Type of Ehlers-Danlos Syndrome","volume":"73","author":"Zweers","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"ref_15","unstructured":"Wortley, J. (2025, May 27). Created in BioRender. Available online: https:\/\/BioRender.com\/03tl3gs."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"W420","DOI":"10.1093\/nar\/gkac373","article-title":"IBS 2.0: An upgraded illustrator for the visualization of biological sequences","volume":"50","author":"Xie","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"ref_19","unstructured":"National Center for Biotechnology Information (2025, May 01). VCV001797774.2-ClinVar-NCBI, Available online: https:\/\/www.ncbi.nlm.nih.gov\/clinvar\/variation\/1797774\/."},{"key":"ref_20","unstructured":"National Center for Biotechnology Information (2025, May 15). VCV001763690.2-ClinVar-NCBI, Available online: https:\/\/www.ncbi.nlm.nih.gov\/clinvar\/variation\/1763690\/."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"D368","DOI":"10.1093\/nar\/gkad1011","article-title":"AlphaFold Protein Structure Database in 2024: Providing structure coverage for over 214 million protein sequences","volume":"52","author":"Varadi","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"D439","DOI":"10.1093\/nar\/gkab1061","article-title":"AlphaFold Protein Structure Database: Massively expanding the structural coverage of protein-sequence space with high-accuracy models","volume":"50","author":"Varadi","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"D980","DOI":"10.1093\/nar\/gkt1113","article-title":"ClinVar: Public archive of relationships among sequence variation and human phenotype","volume":"42","author":"Landrum","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_25","first-page":"E128","article-title":"Children with vesicoureteric reflux have joint hypermobility and occasional tenascin XB sequence variants","volume":"14","author":"Tokhmafshan","year":"2020","journal-title":"Can. Urol. Assoc. J."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Davydov, E.V., Goode, D.L., Sirota, M., Cooper, G.M., Sidow, A., and Batzoglou, S. (2010). Identifying a High Fraction of the Human Genome to be under Selective Constraint Using GERP++. PLoS Comput. Biol., 6.","DOI":"10.1371\/journal.pcbi.1001025"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1101\/gr.097857.109","article-title":"Detection of nonneutral substitution rates on mammalian phylogenies","volume":"20","author":"Pollard","year":"2010","journal-title":"Genome Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1136\/jmg.2005.033878","article-title":"Comprehensive statistical study of 452 BRCA1 missense substitutions with classification of eight recurrent substitutions as neutral","volume":"43","author":"Tavtigian","year":"2006","journal-title":"J. Med. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1093\/nar\/gkj518","article-title":"Computational approaches for predicting the biological effect of p53 missense mutations: A comparison of three sequence analysis based methods","volume":"34","author":"Mathe","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"W452","DOI":"10.1093\/nar\/gks539","article-title":"SIFT web server: Predicting effects of amino acid substitutions on proteins","volume":"40","author":"Sim","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/humu.22225","article-title":"Predicting the Functional, Molecular, and Phenotypic Consequences of Amino Acid Substitutions using Hidden Markov Models","volume":"34","author":"Shihab","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1038\/s41588-018-0167-z","article-title":"Predicting the clinical impact of human mutation with deep neural networks","volume":"50","author":"Sundaram","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1002\/humu.23158","article-title":"PERCH: A Unified Framework for Disease Gene Prioritization","volume":"38","author":"Feng","year":"2017","journal-title":"Hum. Mutat."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"D1143","DOI":"10.1093\/nar\/gkad989","article-title":"CADD v1.7: Using protein language models, regulatory CNNs and other nucleotide-level scores to improve genome-wide variant predictions","volume":"52","author":"Schubach","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Carter, H., Douville, C., Stenson, P.D., Cooper, D.N., and Karchin, R. (2013). Identifying Mendelian disease genes with the Variant Effect Scoring Tool. BMC Genom., 14.","DOI":"10.1186\/1471-2164-14-S3-S3"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.ajhg.2016.08.016","article-title":"REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants","volume":"99","author":"Ioannidis","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5918","DOI":"10.1038\/s41467-020-19669-x","article-title":"Inferring the molecular and phenotypic impact of amino acid variants with MutPred2","volume":"11","author":"Pejaver","year":"2020","journal-title":"Nat Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. Methods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.hjc.2022.09.009","article-title":"The genetic basis of thoracic aortic disease: The future of aneurysm classification?","volume":"69","author":"Salmasi","year":"2023","journal-title":"Hell. J. Cardiol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Miller, W.L. (2021). Tenascin-X\u2014Discovery and Early Research. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.612497"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6281","DOI":"10.1016\/j.febslet.2006.10.037","article-title":"A model of tenascin-X integration within the collagenous network","volume":"580","author":"Lethias","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1161\/CIRCRESAHA.121.320694","article-title":"Tenascin-X Mediates Flow-Induced Suppression of EndMT and Atherosclerosis","volume":"130","author":"Liang","year":"2022","journal-title":"Circ. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1083\/jcb.201308031","article-title":"Tenascin-X promotes epithelial-to-mesenchymal transition by activating latent TGF-\u03b2","volume":"205","author":"Alcaraz","year":"2014","journal-title":"J. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/aja.1002030411","article-title":"Embryonic expression of tenascin-X suggests a role in limb, muscle, and heart development","volume":"203","author":"Burch","year":"1995","journal-title":"Dev. Dyn."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1046\/j.1432-0436.2003.7104506.x","article-title":"The dynamic expression of tenascin-C and tenascin-X during early heart development in the mouse","volume":"71","author":"Matsumoto","year":"2003","journal-title":"Differentiation"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Matsumoto, K., and Aoki, H. (2020). The Roles of Tenascins in Cardiovascular, Inflammatory, and Heritable Connective Tissue Diseases. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.609752"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1159\/000481911","article-title":"Tenascin-X, Congenital Adrenal Hyperplasia, and the CAH-X Syndrome","volume":"89","author":"Miller","year":"2018","journal-title":"Horm. Res. Paediatr."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Neogi, A., Towne, M., Dykas, D., Parsa, N., Attar, A., Fathzadeh, M., Bale, A., and Mani, A. (2022). Abstract 554: The Association of Multiple Variants In the TNXB Gene With Vascular Aneurysms and Dissections. Arterioscler. Thromb. Vasc. Biol., 42.","DOI":"10.1161\/atvb.42.suppl_1.554"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.pcad.2020.06.005","article-title":"Genetics in bicuspid aortic valve disease: Where are we?","volume":"63","author":"Prakash","year":"2020","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1016\/j.ajhg.2024.08.001","article-title":"Whole-exome sequencing uncovers the genetic complexity of bicuspid aortic valve in families with early-onset complications","volume":"111","author":"Mansoorshahi","year":"2024","journal-title":"Am. J. Hum. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1007\/s00423-024-03488-5","article-title":"Genetic variants in patients with multiple arterial aneurysms","volume":"409","author":"Peters","year":"2024","journal-title":"Langenbecks Arch. Surg."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1248\/bpb.33.1898","article-title":"Increased expression of tenascin-x in thoracic and abdominal aortic aneurysm tissues","volume":"33","author":"Satoh","year":"2010","journal-title":"Biol. Pharm. Bull."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1161\/CIRCULATIONAHA.104.513820","article-title":"Abdominal Aortic Aneurysm Is Associated With High Serum Levels of Tenascin-X and Decreased Aneurysmal Tissue Tenascin-X","volume":"113","author":"Zweers","year":"2006","journal-title":"Circulation"},{"key":"ref_54","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (2022). TNXB-Related Classical-Like Ehlers-Danlos Syndrome. GeneReviews(\u00ae), University of Washington."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/ng0997-104","article-title":"Tenascin-X deficiency is associated with Ehlers-Danlos syndrome","volume":"17","author":"Burch","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1056\/NEJMoa002939","article-title":"A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency","volume":"345","author":"Schalkwijk","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"E379","DOI":"10.1210\/jc.2012-3148","article-title":"Tenascin-X Haploinsufficiency Associated with Ehlers-Danlos Syndrome in Patients with Congenital Adrenal Hyperplasia","volume":"98","author":"Merke","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1038\/s12276-023-01130-w","article-title":"Aortic aneurysms: Current pathogenesis and therapeutic targets","volume":"55","author":"Cho","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.yexcr.2004.04.030","article-title":"Modulation of collagen fibrillogenesis by tenascin-X and type VI collagen","volume":"298","author":"Minamitani","year":"2004","journal-title":"Exp. Cell Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/ng850","article-title":"Tenascin-X deficiency mimics Ehlers-Danlos syndrome in mice through alteration of collagen deposition","volume":"30","author":"Mao","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.bpc.2009.12.011","article-title":"Tenascin-X increases the stiffness of collagen gels without affecting fibrillogenesis","volume":"147","author":"Margaron","year":"2010","journal-title":"Biophys. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1161\/ATVBAHA.123.321067","article-title":"Loss of Smooth Muscle Tenascin-X Inhibits Vascular Remodeling Through Increased TGF-\u03b2 Signaling","volume":"44","author":"Liang","year":"2024","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1006\/jmbi.1997.1147","article-title":"Folding and stability of a fibronectin type III domain of human tenascin","volume":"270","author":"Clarke","year":"1997","journal-title":"J. Mol. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e63458","DOI":"10.1002\/ajmg.a.63458","article-title":"Aortic dissection in a young male with persistent ductus arteriosus and a novel variant in MYLK","volume":"194","author":"Boelman","year":"2024","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1161\/CIRCRESAHA.124.323051","article-title":"Discovery of Titin and Its Role in Heart Function and Disease","volume":"136","author":"Granzier","year":"2025","journal-title":"Circ. Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Rees, M., Nikoopour, R., Alexandrovich, A., Pfuhl, M., Lopes, L.R., Akhtar, M.M., Syrris, P., Elliott, P., Carr-White, G., and Gautel, M. (2023). Structure determination and analysis of titin A-band fibronectin type III domains provides insights for disease-linked variants and protein oligomerisation. J. Struct. Biol., 215.","DOI":"10.1016\/j.jsb.2023.108009"},{"key":"ref_67","unstructured":"Ambry Genetics (2025, May 15). TAADNext: Analyses of 35 Genes Associated with Thoracic Aortic Aneurysms and Dissections. Available online: https:\/\/www.ambrygen.com\/providers\/genetic-testing\/12\/cardiology\/taadnext."},{"key":"ref_68","unstructured":"UniProt Consortium (2025). UniProt: The Universal Protein Knowledgebase in 2025. Nucleic Acids Res., 53, D609\u2013D617."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Garcia, F.A.d.O., Andrade, E.S.d., and Palmero, E.I. (2022). Insights on variant analysis in silico tools for pathogenicity prediction. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.1010327"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"D1243","DOI":"10.1093\/nar\/gkae974","article-title":"The UCSC Genome Browser database: 2025 update","volume":"53","author":"Perez","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1016\/j.ajhg.2022.10.013","article-title":"Calibration of computational tools for missense variant pathogenicity classification and ClinGen recommendations for PP3\/BP4 criteria","volume":"109","author":"Pejaver","year":"2022","journal-title":"Am. J. Hum. Genet."},{"key":"ref_72","unstructured":"Nucleotide (2024, December 27). Homo Sapiens Tenascin XB (TNXB), Transcript Variant XB, mRNA, Available online: https:\/\/www.ncbi.nlm.nih.gov\/nuccore\/NM_019105.8."},{"key":"ref_73","unstructured":"Nucleotide (2025, May 01). Homo sapiens tenascin XB (TNXB), Transcript Variant 3, mRNA, Available online: https:\/\/www.ncbi.nlm.nih.gov\/nuccore\/NM_001365276.2."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e4792","DOI":"10.1002\/pro.4792","article-title":"UCSF ChimeraX: Tools for structure building and analysis","volume":"32","author":"Meng","year":"2023","journal-title":"Protein Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Pak, M.A., Markhieva, K.A., Novikova, M.S., Petrov, D.S., Vorobyev, I.S., Maksimova, E.S., Kondrashov, F.A., and Ivankov, D.N. (2023). Using AlphaFold to predict the impact of single mutations on protein stability and function. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0282689"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"eadg7492","DOI":"10.1126\/science.adg7492","article-title":"Accurate proteome-wide missense variant effect prediction with AlphaMissense","volume":"381","author":"Cheng","year":"2023","journal-title":"Science"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1038\/s41588-023-01465-0","article-title":"Genome-wide prediction of disease variant effects with a deep protein language model","volume":"55","author":"Brandes","year":"2023","journal-title":"Nat. Genet."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1002\/prot.26764","article-title":"Protein-Variant-Phenotype Study of NBAS Using AlphaFold in the Aspect of SOPH Syndrome","volume":"93","author":"Zhozhikov","year":"2025","journal-title":"Proteins"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/13\/6535\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:05:57Z","timestamp":1760033157000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/13\/6535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,7]]},"references-count":79,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ijms26136535"],"URL":"https:\/\/doi.org\/10.3390\/ijms26136535","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,7]]}}}