{"id":586,"date":"2026-05-13T07:43:27","date_gmt":"2026-05-12T22:43:27","guid":{"rendered":"https:\/\/neuroclub.jikei-neuroscience.com\/?p=586"},"modified":"2026-05-13T07:43:27","modified_gmt":"2026-05-12T22:43:27","slug":"2026-5-13-%e6%8b%85%e5%bd%93-%e4%b8%ad%e6%9d%91%e8%a1%8c%e5%ae%8f","status":"publish","type":"post","link":"https:\/\/neuroclub.jikei-neuroscience.com\/?p=586","title":{"rendered":"2026-5-13 \u62c5\u5f53 \u4e2d\u6751\u884c\u5b8f"},"content":{"rendered":"

5\u670813\u65e5\u62c5\u5f53\u306eNeuroclub\u3067\u306f\u4ee5\u4e0b\u306e\u8ad6\u6587\u3092\u7d39\u4ecb\u3044\u305f\u3057\u307e\u3059\u3002<\/p>\n

Asadollahi et al.
\nNature Genetics 57, 2691\u20132704 (2025)
\nhttps:\/\/doi.org\/10.1038\/s41588-025-02361-5<\/a><\/p>\n

Pathogenic UNC13A variants cause a neurodevelopmental syndrome by
\nimpairing synaptic function<\/p>\n

Abstract
\nThe UNC13A gene encodes a presynaptic protein that is crucial for
\nsetting the strength and dynamics of information transfer between
\nneurons. Here we describe a neurodevelopmental syndrome caused by
\ngermline coding or splice-site variants in UNC13A. The syndrome presents
\nwith variable degrees of developmental delay and intellectual
\ndisability, seizures of different types, tremor and dyskinetic movements
\nand, in some cases, death in early childhood. Using assays with
\nexpression of UNC13A variants in mouse hippocampal neurons and in
\nCaenorhabditis elegans, we identify three mechanisms of pathogenicity,
\nincluding reduction in synaptic strength caused by reduced UNC13A
\nprotein expression, increased neurotransmission caused by UNC13A
\ngain-of-function and impaired regulation of neurotransmission by second
\nmessenger signalling. Based on a strong genotype\u2013phenotype-functional
\ncorrelation, we classify three UNC13A syndrome subtypes (types A\u2013C). We
\nconclude that the precise regulation of neurotransmitter release by
\nUNC13A is critical for human nervous system function.<\/p>\n

\u3088\u308d\u3057\u304f\u304a\u9858\u3044\u3044\u305f\u3057\u307e\u3059\u3002<\/p>\n","protected":false},"excerpt":{"rendered":"

5\u670813\u65e5\u62c5\u5f53\u306eNeuroclub\u3067\u306f\u4ee5\u4e0b\u306e\u8ad6\u6587\u3092\u7d39\u4ecb\u3044\u305f\u3057\u307e\u3059\u3002 Asadollahi et al. Nature Genetics 57, 2691\u20132704 (2025) https:\/\/doi.org\/10.10…<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[3],"tags":[],"class_list":["post-586","post","type-post","status-publish","format-standard","hentry","category-journal-club"],"jetpack_sharing_enabled":true,"jetpack_featured_media_url":"","_links":{"self":[{"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/posts\/586","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=586"}],"version-history":[{"count":0,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/posts\/586\/revisions"}],"wp:attachment":[{"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=586"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=586"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=586"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}