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Here, we describe the first example of NAFLD caused by genetic disruption of a mammalian potassium channel subunit. Mice with germline deletion of the KCNE2 potassium channel \u03b2 subunit exhibited NAFLD as early as postnatal day 7. Using mouse genetics, histology, liver damage assays and transcriptomics we discovered that iron deficiency arising from KCNE2-dependent achlorhydria is a major factor in early-onset NAFLD in <jats:italic>Kcne2<\/jats:italic><jats:sup>\u2500\/\u2500<\/jats:sup> mice, while two other KCNE2-dependent defects did not initiate NAFLD. The findings uncover a novel genetic basis for NAFLD and an unexpected potential factor in human KCNE2-associated cardiovascular pathologies, including atherosclerosis.<\/jats:p>","DOI":"10.1038\/srep23118","type":"journal-article","created":{"date-parts":[[2016,3,17]],"date-time":"2016-03-17T10:25:41Z","timestamp":1458210341000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Kcne2 deletion causes early-onset nonalcoholic fatty liver disease via iron deficiency anemia"],"prefix":"10.1038","volume":"6","author":[{"given":"Soo Min","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dara","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Anand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ritu","family":"Kant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clemens","family":"K\u00f6hncke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"Lisewski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Torsten K.","family":"Roepke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoyang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey W.","family":"Abbott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,3,17]]},"reference":[{"key":"BFsrep23118_CR1","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/nrgastro.2013.182","volume":"10","author":"QM Anstee","year":"2013","unstructured":"Anstee, Q. 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