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Here, we present the first computational analysis of 13 somatic missense PTEN mutations associated with these phenotypes. We found that a majority of the mutations are associated in conserved positions within the active site and are clustered within the signature motif, which contain residues that play a crucial role in loop conformation and are essential for catalysis. In silico analyses were utilized to identify the putative effects of these mutations. In addition, coarse\u2010grained models of both wild\u2010type (WT) PTEN and mutants were constructed using elastic network models to explore the interplay of the structural and global dynamic effects that the mutations have on the relationship between genotype and phenotype. The effects of the mutations reveal that the local structure and interactions affect polarity, protein structure stability, electrostatic surface potential, and global dynamics of the protein. Our results offer new insight into the role in which PTEN missense mutations contribute to the molecular mechanism and genotypic\u2010phenotypic correlation of endometriosis, endometrial cancer, and ovarian cancer. Proteins 2016; 84:1625\u20131643. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/prot.25105","type":"journal-article","created":{"date-parts":[[2016,8,3]],"date-time":"2016-08-03T13:14:02Z","timestamp":1470230042000},"page":"1625-1643","source":"Crossref","is-referenced-by-count":49,"title":["Structural mutation analysis of PTEN and its genotype\u2010phenotype correlations in endometriosis and cancer"],"prefix":"10.1002","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5560-8871","authenticated-orcid":false,"given":"Iris N.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Biology and Biochemistry University of Houston Houston Texas 77204\u20105001"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James M.","family":"Briggs","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry University of Houston Houston Texas 77204\u20105001"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,8,13]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"4736","article-title":"PTEN\/MMAC1 mutations in endometrial cancers","volume":"57","author":"Risinger JI","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_8_3_1","first-page":"2124","article-title":"TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta","volume":"57","author":"Li DM","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5308.1943"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0497-356"},{"key":"e_1_2_8_6_1","doi-asserted-by":"crossref","DOI":"10.1016\/B978-012289631-6\/50027-2","volume-title":". 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