{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yokoi S"],"funding":["MEXT | Japan Society for the Promotion of Science","Japan Agency for Medical Research and Development"],"pagination":["8881-8896"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9698725"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["42(47)"],"pubmed_abstract":["Fused in sarcoma (FUS) is a pathogenic RNA-binding protein in amyotrophic lateral sclerosis (ALS). We previously reported that FUS stabilizes Synaptic Ras-GTPase activating protein 1 (<i>Syngap1</i>) mRNA at its 3' untranslated region (UTR) and maintains spine maturation. To elucidate the pathologic roles of this mechanism in ALS patients, we identified the <i>SYNGAP1</i> 3'UTR variant rs149438267 in seven (four males and three females) out of 807 ALS patients at the FUS binding site from a multicenter cohort in Japan. Human-induced pluripotent stem cell (hiPSC)-derived motor neurons with the <i>SYNGAP1</i> variant showed aberrant splicing, increased isoform α1 levels, and decreased isoform γ levels, which caused dendritic spine loss. Moreover, the <i>SYNGAP1</i> variant excessively recrui"],"journal":["The Journal of neuroscience : the official journal of the Society for Neuroscience"],"pubmed_title":["The <i>SYNGAP1</i> 3'UTR Variant in ALS Patients Causes Aberrant <i>SYNGAP1</i> Splicing and Dendritic Spine Loss by Recruiting HNRNPK."],"pmcid":["PMC9698725"],"funding_grant_id":["JP21ek0109434","JP20K16489"],"pubmed_authors":["Izumi Y","Kano O","Nakatochi M","Ito T","Okano H","Morita M","Sahashi K","Yokoi S","Oda M","Atsuta N","Okada Y","Ishigaki S","Udagawa T","Sone T","Sobue G","Tohnai G","Nakamura R","Katsuno M","Fujioka Y"],"additional_accession":[]},"is_claimable":false,"name":"The <i>SYNGAP1</i> 3'UTR Variant in ALS Patients Causes Aberrant <i>SYNGAP1</i> Splicing and Dendritic Spine Loss by Recruiting HNRNPK.","description":"Fused in sarcoma (FUS) is a pathogenic RNA-binding protein in amyotrophic lateral sclerosis (ALS). We previously reported that FUS stabilizes Synaptic Ras-GTPase activating protein 1 (<i>Syngap1</i>) mRNA at its 3' untranslated region (UTR) and maintains spine maturation. To elucidate the pathologic roles of this mechanism in ALS patients, we identified the <i>SYNGAP1</i> 3'UTR variant rs149438267 in seven (four males and three females) out of 807 ALS patients at the FUS binding site from a multicenter cohort in Japan. Human-induced pluripotent stem cell (hiPSC)-derived motor neurons with the <i>SYNGAP1</i> variant showed aberrant splicing, increased isoform α1 levels, and decreased isoform γ levels, which caused dendritic spine loss. Moreover, the <i>SYNGAP1</i> variant excessively recrui","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Nov","modification":"2026-06-21T03:14:22.706Z","creation":"2025-04-19T22:46:09.471Z"},"accession":"S-EPMC9698725","cross_references":{"pubmed":["36261283"],"doi":["10.1523/JNEUROSCI.0455-22.2022"]}}