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To comprehensively characterize the functional landscape of\n                    <jats:italic toggle=\"yes\">SPOP<\/jats:italic>\n                    alteration, we performed a deep mutational screening (DMS), elucidating the functionality of 7,933 out of 8,228 possible single amino acid changes (96.4% coverage). Leveraging the observation that overexpression of human\n                    <jats:italic toggle=\"yes\">SPOP<\/jats:italic>\n                    leads to yeast growth arrest, we assessed the functionality of each variant using a yeast proliferation assay. In addition, our approach combined long-read and short-read sequencing. Finally, our DMS model enables a clear distinction of likely-loss-of-function variants that are enriched in prostate cancers and reveals their differential characteristics in both protein structure and genetic assessments. These results demonstrate the utility of our approach in high-resolution mapping and amino acid\u2013level interpretation of protein function.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2523210123","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T16:20:47Z","timestamp":1778084447000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Functional dissection of\n                    <i>SPOP<\/i>\n                    at the amino acid level reveals a comprehensive functional landscape of variants during tumorigenesis"],"prefix":"10.1073","volume":"123","author":[{"given":"Seong Kyun","family":"Park","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01mh5ph17","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University","place":["Chuncheon, Republic of 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