| http://purl.uniprot.org/citations/28684635 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28684635 | http://www.w3.org/2000/01/rdf-schema#comment | "Molecular mechanisms remain unknown for most type 2 diabetes genome-wide association study identified loci. Variants associated with type 2 diabetes and fasting glucose levels reside in introns of ADCY5, a gene that encodes adenylate cyclase 5. Adenylate cyclase 5 catalyzes the production of cyclic AMP, which is a second messenger molecule involved in cell signaling and pancreatic β-cell insulin secretion. We demonstrated that type 2 diabetes risk alleles are associated with decreased ADCY5 expression in human islets and examined candidate variants for regulatory function. rs11708067 overlaps a predicted enhancer region in pancreatic islets. The type 2 diabetes risk rs11708067-A allele showed fewer H3K27ac ChIP-seq reads in human islets, lower transcriptional activity in reporter assays in rodent β-cells (rat 832/13 and mouse MIN6), and increased nuclear protein binding compared with the rs11708067-G allele. Homozygous deletion of the orthologous enhancer region in 832/13 cells resulted in a 64% reduction in expression level of Adcy5, but not adjacent gene Sec22a, and a 39% reduction in insulin secretion. Together, these data suggest that rs11708067-A risk allele contributes to type 2 diabetes by disrupting an islet enhancer, which results in reduced ADCY5 expression and impaired insulin secretion."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.org/dc/terms/identifier | "doi:10.2337/db17-0464"xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Collins F.S."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Parker S.C.J."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Wu Y."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Boehnke M."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Laakso M."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Jackson A.U."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Mohlke K.L."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Erdos M.R."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Stitzel M.L."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Scott L.J."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Varshney A."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Kuusisto J."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Vadlamudi S."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Cannon M.E."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Morken M.A."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Kursawe R."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Welch R.P."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Buchkovich M.L."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Roman T.S."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Kwon G.J."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/author | "Wolford B.N."xsd:string |
| http://purl.uniprot.org/citations/28684635 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |