{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T17:31:26Z","timestamp":1782322286814,"version":"3.54.5"},"reference-count":38,"publisher":"Life Science Alliance, LLC","issue":"10","license":[{"start":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:00:00Z","timestamp":1663804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft, KU","award":["1240\/10-1"],"award-info":[{"award-number":["1240\/10-1"]}]},{"name":"Deutsche Forschungsgemeinschaft, KR","award":["1321\/7-1"],"award-info":[{"award-number":["1321\/7-1"]}]},{"name":"Jordan\u2019s Guardian Angels, Sunderland Foundation and Brotman Baty Institute"}],"content-domain":{"domain":["life-science-alliance.org"],"crossmark-restriction":true},"short-container-title":["Life Sci. Alliance"],"accepted":{"date-parts":[[2022,9,9]]},"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:p>\n                    CASK is a unique membrane-associated guanylate kinase (MAGUK) because of its Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \/calmodulin-dependent kinase (CaMK) domain. We describe four male patients with a severe neurodevelopmental disorder with microcephaly carrying missense variants affecting the CaMK domain. One boy who carried the p.E115K variant and died at an early age showed pontocerebellar hypoplasia (PCH) in addition to microcephaly, thus exhibiting the classical MICPCH phenotype observed in individuals with\n                    <jats:italic>CASK<\/jats:italic>\n                    loss-of-function variants. All four variants selectively weaken the interaction of CASK with Liprin-\u03b12, a component of the presynaptic active zone. Liprin-\u03b1 proteins form spherical phase-separated condensates, which we observe here in Liprin-\u03b12 overexpressing HEK293T cells. Large Liprin-\u03b12 clusters were also observed in transfected primary-cultured neurons. Cluster formation of Liprin-\u03b12 is reversed in the presence of CASK; this is associated with altered phosphorylation of Liprin-\u03b12. The p.E115K variant fails to interfere with condensate formation. As the individual carrying this variant had the severe MICPCH disorder, we suggest that regulation of Liprin-\u03b12\u2013mediated phase condensate formation is a new functional feature of CASK which must be maintained to prevent PCH.\n                  <\/jats:p>","DOI":"10.26508\/lsa.202201512","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T14:30:37Z","timestamp":1663857037000},"page":"e202201512","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Regulation of Liprin-\u03b1 phase separation by CASK is disrupted by a mutation in its CaM kinase domain"],"prefix":"10.26508","volume":"5","author":[{"given":"Debora","family":"Tibbe","sequence":"first","affiliation":[{"name":"Institute for Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, 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