| http://purl.uniprot.org/citations/25701875 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25701875 | http://www.w3.org/2000/01/rdf-schema#comment | "Paget's disease of bone (PDB) is a common disorder with a strong genetic component characterized by increased but disorganized bone remodelling. Previous genome-wide association studies identified a locus on chromosome 14q32 tagged by rs10498635 which was significantly associated with susceptibility to PDB in several European populations. Here we conducted fine-mapping and targeted sequencing of the candidate locus to identify possible functional variants. Imputation in 741 PDB patients and 2699 controls confirmed that the association was confined to a 60 kb region in the RIN3 gene and conditional analysis adjusting for rs10498635 identified no new independent signals. Sequencing of the RIN3 gene identified a common missense variant (p.R279C) that was strongly associated with the disease (OR = 0.64; P = 1.4 × 10(-9)), and was in strong linkage disequilibrium with rs10498635. A further 13 rare missense variants were identified, seven of which were novel and detected only in PDB cases. When combined, these rare variants were over-represented in cases compared with controls (OR = 3.72; P = 8.9 × 10(-10)). Most rare variants were located in a region that encodes a proline-rich, intrinsically disordered domain of the protein and many were predicted to be pathogenic. RIN3 was expressed in bone tissue and its expression level was ∼10-fold higher in osteoclasts compared with osteoblasts. We conclude that susceptibility to PDB at the 14q32 locus is mediated by a combination of common and rare coding variants in RIN3 and suggest that RIN3 may contribute to PDB susceptibility by affecting osteoclast function."xsd:string |
| http://purl.uniprot.org/citations/25701875 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/ddv068"xsd:string |
| http://purl.uniprot.org/citations/25701875 | http://purl.uniprot.org/core/author | "Soares D.C."xsd:string |
| http://purl.uniprot.org/citations/25701875 | http://purl.uniprot.org/core/author | "Warner J."xsd:string |
| http://purl.uniprot.org/citations/25701875 | http://purl.uniprot.org/core/author | "Salter D.M."xsd:string |
| http://purl.uniprot.org/citations/25701875 | http://purl.uniprot.org/core/author | "Ralston S.H."xsd:string |
| http://purl.uniprot.org/citations/25701875 | http://purl.uniprot.org/core/author | "Wani S."xsd:string |
| http://purl.uniprot.org/citations/25701875 | http://purl.uniprot.org/core/author | "Vallet M."xsd:string |
| http://purl.uniprot.org/citations/25701875 | http://purl.uniprot.org/core/author | "Albagha O.M."xsd:string |
| http://purl.uniprot.org/citations/25701875 | http://purl.uniprot.org/core/author | "Sophocleous A."xsd:string |
| http://purl.uniprot.org/citations/25701875 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25701875 | http://purl.uniprot.org/core/name | "Hum Mol Genet"xsd:string |
| http://purl.uniprot.org/citations/25701875 | http://purl.uniprot.org/core/pages | "3286-3295"xsd:string |
| http://purl.uniprot.org/citations/25701875 | http://purl.uniprot.org/core/title | "Targeted sequencing of the Paget's disease associated 14q32 locus identifies several missense coding variants in RIN3 that predispose to Paget's disease of bone."xsd:string |
| http://purl.uniprot.org/citations/25701875 | http://purl.uniprot.org/core/volume | "24"xsd:string |
| http://purl.uniprot.org/citations/25701875 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25701875 |
| http://purl.uniprot.org/citations/25701875 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25701875 |
| http://purl.uniprot.org/uniprot/#_G3V2I7-mappedCitation-25701875 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25701875 |
| http://purl.uniprot.org/uniprot/#_Q86U22-mappedCitation-25701875 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25701875 |
| http://purl.uniprot.org/uniprot/#_Q5CZ74-mappedCitation-25701875 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25701875 |
| http://purl.uniprot.org/uniprot/#_Q6ZRC2-mappedCitation-25701875 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25701875 |
| http://purl.uniprot.org/uniprot/#_Q6NSK7-mappedCitation-25701875 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25701875 |
| http://purl.uniprot.org/uniprot/#_Q8TB24-mappedCitation-25701875 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25701875 |
| http://purl.uniprot.org/uniprot/Q5CZ74 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/25701875 |