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Due to the significance of the protein\u2019s functions, mutations often have profound effects on the fitness of the host. This is apparent both from experimental studies, which implicated numerous missense variants in diseases, as well as from evolutionary signals that allow elucidating the physicochemical constraints that intermembrane and aqueous environments bring. In this review, we report on the current state of knowledge acquired on missense variants (referred to as to single amino acid variants) affecting membrane proteins as well as the insights that can be extrapolated from data already available. This includes an overview of the annotations for membrane protein variants that have been collated within databases dedicated to the topic, bioinformatics approaches that leverage evolutionary information in order to shed light on previously uncharacterized membrane protein structures or interaction interfaces, tools for predicting the effects of mutations tailored specifically towards the characteristics of membrane proteins as well as two clinically relevant case studies explaining the implications of mutated membrane proteins in cancer and cardiomyopathy.<\/jats:p>","DOI":"10.1093\/bib\/bbaa132","type":"journal-article","created":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T19:09:56Z","timestamp":1591211396000},"source":"Crossref","is-referenced-by-count":21,"title":["Mutations in transmembrane proteins: diseases, evolutionary insights, prediction and comparison with globular proteins"],"prefix":"10.1093","volume":"22","author":[{"given":"Jan","family":"Zaucha","sequence":"first","affiliation":[{"name":"Department of Bioinformatics of the TUM School of Life Sciences Weihenstephan in Freising, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Heinzinger","sequence":"additional","affiliation":[{"name":"Department of Informatics, Bioinformatics and Computational Biology of the TUM Faculty of Informatics in Garching, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Kulandaisamy","sequence":"additional","affiliation":[{"name":"Department of Biotechnology of the IIT Bhupat and Jyoti Mehta School of BioSciences in Madras, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evans","family":"Kataka","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics of the TUM School of Life Sciences Weihenstephan in Freising, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d3scar Llorian","family":"Salv\u00e1dor","sequence":"additional","affiliation":[{"name":"Department of Informatics, Bioinformatics and Computational Biology of the TUM Faculty of Informatics in Garching, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Popov","sequence":"additional","affiliation":[{"name":"Center for Computational and Data-Intensive Science and Engineering of the Skolkovo Institute of Science and Technology in Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkhard","family":"Rost","sequence":"additional","affiliation":[{"name":"Department of Informatics, Bioinformatics and Computational Biology at the TUM Faculty of Informatics in Garching, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Michael","family":"Gromiha","sequence":"additional","affiliation":[{"name":"Department of Biotechnology of 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