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Here, we report three individuals, from two families, with severe congenital muscular dystrophy (CMD) and biallelic variants in\n                    <jats:italic>BET1<\/jats:italic>\n                    (P1 p.(Asp68His)\/p.(Ala45Valfs*2); P2 and P3 homozygous p.(Ile51Ser)). Due to aberrant splicing and frameshifting, the variants in P1 result in low BET1 protein levels and impaired ER\u2010to\u2010Golgi transport. Since\n                    <jats:italic>in silico<\/jats:italic>\n                    modeling suggested that p.(Ile51Ser) interferes with binding to interaction partners other than SNARE complex subunits, we set off and identified novel BET1 interaction partners with low affinity for p.(Ile51Ser) BET1 protein compared to wild\u2010type, among them ERGIC\u201053. The BET1\/ERGIC\u201053 interaction was validated by endogenous co\u2010immunoprecipitation with both proteins colocalizing to the ERGIC compartment. Mislocalization of ERGIC\u201053 was observed in P1 and P2\u2019s derived fibroblasts; while in the p.(Ile51Ser) P2 fibroblasts specifically, mutant BET1 was also mislocalized along with ERGIC\u201053. Thus, we establish\n                    <jats:italic>BET1<\/jats:italic>\n                    as a novel CMD\/epilepsy gene and confirm the emerging role of ER\/Golgi SNAREs in CMD.\n                  <\/jats:p>","DOI":"10.15252\/emmm.202013787","type":"journal-article","created":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T08:24:17Z","timestamp":1636964657000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["BET1 variants establish impaired vesicular transport as a cause for muscular dystrophy with epilepsy"],"prefix":"10.1038","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6399-1444","authenticated-orcid":false,"given":"Sandra","family":"Donkervoort","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1566-7281","authenticated-orcid":false,"given":"Niklas","family":"Krause","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mykola","family":"Dergai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pomi","family":"Yun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Koliwer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6870-4061","authenticated-orcid":false,"given":"Svetlana","family":"Gorokhova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6249-825X","authenticated-orcid":false,"given":"Janelle","family":"Geist 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