| http://purl.uniprot.org/citations/36333503 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/36333503 | http://www.w3.org/2000/01/rdf-schema#comment | "Gene expression is tightly regulated, with many genes exhibiting cell-specific silencing when their protein product would disrupt normal cellular function1. This silencing is largely controlled by non-coding elements, and their disruption might cause human disease2. We performed gene-agnostic screening of the non-coding regions to discover new molecular causes of congenital hyperinsulinism. This identified 14 non-coding de novo variants affecting a 42-bp conserved region encompassed by a regulatory element in intron 2 of the hexokinase 1 gene (HK1). HK1 is widely expressed across all tissues except in the liver and pancreatic beta cells and is thus termed a 'disallowed gene' in these specific tissues. We demonstrated that the variants result in a loss of repression of HK1 in pancreatic beta cells, thereby causing insulin secretion and congenital hyperinsulinism. Using epigenomic data accessed from public repositories, we demonstrated that these variants reside within a regulatory region that we determine to be critical for cell-specific silencing. Importantly, this has revealed a disease mechanism for non-coding variants that cause inappropriate expression of a disallowed gene."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41588-022-01204-x"xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "Ellard S."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "Dunne M.J."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "Flanagan S.E."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "Hattersley A.T."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "de Vries L."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "De Franco E."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "Baric I."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "Johnson M.B."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "Wakeling M.N."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "Hassan S.S."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "Banerjee I."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "Richardson S.J."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "Weedon M.N."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "Morgan N.G."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "Wiltshire E."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "Cheesman E."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "Mericq V."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "Laver T.W."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "Owens N.D.L."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "Flaxman C.S."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "Patel K.A."xsd:string |
| http://purl.uniprot.org/citations/36333503 | http://purl.uniprot.org/core/author | "Limbert C."xsd:string |