| http://purl.uniprot.org/citations/26280581 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26280581 | http://www.w3.org/2000/01/rdf-schema#comment | "Heterozygous mutations in the syntaxin-binding protein 1 (STXBP1) gene, which encodes Munc18-1, a core component of the presynaptic membrane-fusion machinery, cause infantile early epileptic encephalopathy (Ohtahara syndrome), but it is unclear how a partial loss of Munc18-1 produces this severe clinical presentation. Here, we generated human ES cells designed to conditionally express heterozygous and homozygous STXBP1 loss-of-function mutations and studied isogenic WT and STXBP1-mutant human neurons derived from these conditionally mutant ES cells. We demonstrated that heterozygous STXBP1 mutations lower the levels of Munc18-1 protein and its binding partner, the t-SNARE-protein Syntaxin-1, by approximately 30% and decrease spontaneous and evoked neurotransmitter release by nearly 50%. Thus, our results confirm that using engineered human embryonic stem (ES) cells is a viable approach to studying disease-associated mutations in human neurons on a controlled genetic background, demonstrate that partial STXBP1 loss of function robustly impairs neurotransmitter release in human neurons, and suggest that heterozygous STXBP1 mutations cause early epileptic encephalopathy specifically through a presynaptic impairment."xsd:string |
| http://purl.uniprot.org/citations/26280581 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci78612"xsd:string |
| http://purl.uniprot.org/citations/26280581 | http://purl.uniprot.org/core/author | "Han Y."xsd:string |
| http://purl.uniprot.org/citations/26280581 | http://purl.uniprot.org/core/author | "Sudhof T.C."xsd:string |
| http://purl.uniprot.org/citations/26280581 | http://purl.uniprot.org/core/author | "Maxeiner S."xsd:string |
| http://purl.uniprot.org/citations/26280581 | http://purl.uniprot.org/core/author | "Wernig M."xsd:string |
| http://purl.uniprot.org/citations/26280581 | http://purl.uniprot.org/core/author | "Yi F."xsd:string |
| http://purl.uniprot.org/citations/26280581 | http://purl.uniprot.org/core/author | "Patzke C."xsd:string |
| http://purl.uniprot.org/citations/26280581 | http://purl.uniprot.org/core/author | "Covy J."xsd:string |
| http://purl.uniprot.org/citations/26280581 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26280581 | http://purl.uniprot.org/core/name | "J Clin Invest"xsd:string |
| http://purl.uniprot.org/citations/26280581 | http://purl.uniprot.org/core/pages | "3560-3571"xsd:string |
| http://purl.uniprot.org/citations/26280581 | http://purl.uniprot.org/core/title | "Analysis of conditional heterozygous STXBP1 mutations in human neurons."xsd:string |
| http://purl.uniprot.org/citations/26280581 | http://purl.uniprot.org/core/volume | "125"xsd:string |
| http://purl.uniprot.org/citations/26280581 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26280581 |
| http://purl.uniprot.org/citations/26280581 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/26280581 |
| http://purl.uniprot.org/uniprot/#_P61764-mappedCitation-26280581 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26280581 |
| http://purl.uniprot.org/uniprot/#_B7Z1V5-mappedCitation-26280581 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26280581 |
| http://purl.uniprot.org/uniprot/#_B7Z2V7-mappedCitation-26280581 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26280581 |
| http://purl.uniprot.org/uniprot/#_B7Z3F4-mappedCitation-26280581 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26280581 |
| http://purl.uniprot.org/uniprot/#_Q59GC9-mappedCitation-26280581 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26280581 |
| http://purl.uniprot.org/uniprot/B7Z1V5 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/26280581 |
| http://purl.uniprot.org/uniprot/P61764 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/26280581 |
| http://purl.uniprot.org/uniprot/Q59GC9 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/26280581 |