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A genetically inherited loss-of-function mutation in Kir7.1 (R162W) has been linked to the rare retinal disease Snowflake Vitreoretinal Degeneration (SVD), for which there are currently no curative treatment options. Here, the cryo-EM structures of wild type Kir7.1 and the R162W disease-related variant are presented, which unveil the molecular basis of SVD: the reorientation of the mutant tryptophan side chains into the pore impedes the flow of potassium ions, which would result in the loss of Kir7.1 transport function. Furthermore, this investigation shows that PIP\n                    <jats:sub>2<\/jats:sub>\n                    binding widens the helix bundle crossing gate diameter, even in the absence of a docked cytoplasmic domain. This observation contrasts with other Kir-PIP\u2082 complexes and suggests that Kir7.1 may adopt an intermediate conformation during channel activation. These findings provide a structural basis for Kir7.1 loss of function in SVD and provide a framework for future therapeutic development.\n                  <\/jats:p>","DOI":"10.1038\/s42003-026-10436-0","type":"journal-article","created":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T06:37:27Z","timestamp":1782023847000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cryo-EM structure of the human Kir7.1 channel reveals the molecular basis of snowflake vitreoretinal degeneration disease"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9669-7532","authenticated-orcid":false,"given":"Niamh","family":"O\u2019Malley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chady","family":"Nasrallah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashton","family":"Churchill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Bertrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda R.","family":"Faust","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9649-5092","authenticated-orcid":false,"given":"B. 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Mutations in KCNJ13 cause autosomal-dominant snowflake vitreoretinal degeneration. Am. J. Hum. Genet. 82, 174\u2013180 (2008).","journal-title":"Am. J. Hum. Genet."},{"key":"10436_CR6","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1002\/humu.22807","volume":"36","author":"BR Pattnaik","year":"2015","unstructured":"Pattnaik, B. R. et al. A novel KCNJ13 nonsense mutation and loss of Kir7.1 channel function causes Leber Congenital Amaurosis (LCA16). Hum. Mutat. 36, 720\u2013727 (2015).","journal-title":"Hum. Mutat."},{"key":"10436_CR7","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1097\/ICB.0000000000000326","volume":"11","author":"S Perez-Roustit","year":"2017","unstructured":"Perez-Roustit, S. et al. Leber Congenital Amaurosis with large retinal pigment clumps caused by compound heterozygous mutations in KCNJ13. Retin. Cases Brief Rep. 11, 221\u2013226 (2017).","journal-title":"Retin. 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