{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T20:56:55Z","timestamp":1777928215527,"version":"3.51.4"},"reference-count":49,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["OMICS: A Journal of Integrative Biology"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:p>\n                    Rare diseases and conditions have thus far received relatively less attention in the field of precision\/personalized medicine than common chronic diseases. There is a dire need for orphan drug discovery and therapeutics in ways that are informed by the precision\/personalized medicine scholarship. Moreover, people with rare conditions, when considered collectively across diseases worldwide, impact many communities. In this overarching context, Activin A Receptor Type 1 (ACVR1) is a transmembrane kinase from the transforming growth factor-\u03b2 superfamily and plays a critical role in modulating the bone morphogenetic protein signaling. Missense variants of the\n                    <jats:italic toggle=\"yes\">ACVR1<\/jats:italic>\n                    gene result in modifications in structure and function and, by extension, abnormalities and have been predominantly linked with two rare conditions: fibrodysplasia ossificans progressiva and diffuse intrinsic pontine glioma. We report here an extensive bioinformatic analyses assessing the pool of 50,951 variants and forecast seven highly destabilizing mutations (R206H, G356D, R258S, G328W, G328E, R375P, and R202I) that can significantly alter the structure and function of the native protein. Protein\u2013protein interaction and ConSurf analyses revealed the crucial interactions and localization of highly deleterious mutations in highly conserved domains that may impact the binding and functioning of the protein. cBioPortal, CanSAR Black, and existing literature affirmed the association of these destabilizing mutations with posterior fossa ependymoma, uterine corpus carcinoma, and pediatric brain cancer. The current findings suggest these deleterious nonsynonymous single nucleotide polymorphisms as potential candidates for future functional annotations and validations associated with rare conditions, further aiding the development of precision medicine in rare diseases.\n                  <\/jats:p>","DOI":"10.1089\/omi.2024.0140","type":"journal-article","created":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T12:42:26Z","timestamp":1726576946000},"page":"526-536","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Unlocking the Door for Precision Medicine in Rare Conditions: Structural and Functional Consequences of Missense\n                    <i>ACVR1<\/i>\n                    Variants"],"prefix":"10.1177","volume":"28","author":[{"given":"Garima","family":"Nagar","sequence":"first","affiliation":[{"name":"Molecular Biology Research Lab, Department of Zoology, &amp; DBC-I4 Center Deshbandhu College, University of Delhi, New Delhi, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shradheya R.R.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Molecular Biology Research Lab, Department of Zoology, &amp; DBC-I4 Center Deshbandhu College, University of Delhi, New Delhi, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanshika","family":"Rustagi","sequence":"additional","affiliation":[{"name":"Molecular Biology Research Lab, Department of Zoology, &amp; DBC-I4 Center Deshbandhu College, University of Delhi, New Delhi, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravindran Kumar","family":"Pramod","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research, National Animal Resource Facility for Biomedical Research, Hyderabad, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3916-7513","authenticated-orcid":false,"given":"Archana","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Plant Molecular Biology, University of Delhi South Campus, New Delhi, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Pahuja","sequence":"additional","affiliation":[{"name":"Discovery Research Division, Extramural Wing, Indian Council of Medical Research, New Delhi, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3211-8471","authenticated-orcid":false,"given":"Indrakant Kumar","family":"Singh","sequence":"additional","affiliation":[{"name":"Molecular Biology Research Lab, Department of Zoology, &amp; DBC-I4 Center Deshbandhu College, University of Delhi, New Delhi, India."},{"name":"Delhi School of Public Health, Institute of Eminence, University of Delhi, New Delhi, India."},{"name":"Division of Medical Oncology, USC Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,10,10]]},"reference":[{"key":"e_1_3_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.softx.2015.06.001"},{"issue":"1","key":"e_1_3_7_3_1","article-title":"Predicting functional effect of human missense mutations using PolyPhen\u20102","author":"Adzhubei I","year":"2013","unstructured":"Adzhubei I, , Jordan DM, , Sunyaev SR. 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