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The <jats:italic>btn1<\/jats:italic> gene is the <jats:italic>Schizosaccharomyces pombe<\/jats:italic> orthologue of <jats:italic>CLN3<\/jats:italic>. Here, we have extended the use of synthetic genetic array (SGA) analyses to delineate functional signatures for two different disease-causing mutations in addition to complete deletion of <jats:italic>btn1<\/jats:italic>. We show that genetic-interaction signatures can differ for mutations in the same gene, which helps to dissect their distinct functional effects. The mutation equivalent to the minor transcript arising from the 1-kb deletion (<jats:italic>btn1<\/jats:italic><jats:sup><jats:italic>102\u2013208del<\/jats:italic><\/jats:sup>) shows a distinct interaction pattern. Taken together, our results imply that the minor 1-kb deletion transcript has three consequences for CLN3: to both lose and retain some inherent functions and to acquire abnormal characteristics. This has particular implications for the therapeutic development of juvenile CLN3 disease. In addition, this proof of concept could be applied to conserved genes for other mendelian disorders or any gene of interest, aiding in the dissection of their functional domains, unpacking the global consequences of disease pathogenesis, and clarifying genotype\u2013phenotype correlations. In doing so, this detail will enhance the goals of personalised medicine to improve treatment outcomes and reduce adverse events.<\/jats:p>","DOI":"10.1038\/s41598-021-85471-4","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T16:47:41Z","timestamp":1616086061000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Global network analysis in Schizosaccharomyces pombe reveals three distinct consequences of the common 1-kb deletion causing juvenile CLN3 disease"],"prefix":"10.1038","volume":"11","author":[{"given":"Christopher J.","family":"Minnis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"StJohn","family":"Townsend","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Petschnigg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Tinelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrg","family":"B\u00e4hler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Russell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara E.","family":"Mole","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,18]]},"reference":[{"key":"85471_CR1","doi-asserted-by":"crossref","first-page":"165559","DOI":"10.1016\/j.bbadis.2019.165559","volume":"1866","author":"CJ Minnis","year":"2019","unstructured":"Minnis, C. 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