| http://purl.uniprot.org/citations/32790646 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32790646 | http://www.w3.org/2000/01/rdf-schema#comment | "Gain-of-function mutations in with no lysine (K) 1 (WNK1) and WNK4 genes are responsible for familial hyperkalemic hypertension (FHHt), a rare, inherited disorder characterized by arterial hypertension and hyperkalemia with metabolic acidosis. More recently, FHHt-causing mutations in the Kelch-like 3-Cullin 3 (KLHL3-CUL3) E3 ubiquitin ligase complex have shed light on the importance of WNK's cellular degradation on renal ion transport. Using full exome sequencing for a 4-generation family and then targeted sequencing in other suspected cases, we have identified new missense variants in the WNK1 gene clustering in the short conserved acidic motif known to interact with the KLHL3-CUL3 ubiquitin complex. Affected subjects had an early onset of a hyperkalemic hyperchloremic phenotype, but normal blood pressure values"Functional experiments in Xenopus laevis oocytes and HEK293T cells demonstrated that these mutations strongly decrease the ubiquitination of the kidney-specific isoform KS-WNK1 by the KLHL3-CUL3 complex rather than the long ubiquitous catalytically active L-WNK1 isoform. A corresponding CRISPR/Cas9 engineered mouse model recapitulated both the clinical and biological phenotypes. Renal investigations showed increased activation of the Ste20 proline alanine-rich kinase-Na+-Cl-cotransporter (SPAK-NCC) phosphorylation cascade, associated with impaired ROMK apical expression in the distal part of the renal tubule. Together, these new WNK1 genetic variants highlight the importance of the KS-WNK1 isoform abundance on potassium homeostasis."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci94171"xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Grimm R."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Clauser E."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Jeunemaitre X."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Staub O."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Gamba G."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Kouranti I."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Vargas-Poussou R."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Mulatero P."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Coleman R."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Roussey G."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Do Cruzeiro M."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Baron S."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Decramer S."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Welling P.A."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Hadchouel J."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Louis-Dit-Picard H."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Girerd X."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Hureaux M."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Rafael C."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Tack I."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Unwin R."xsd:string |
| http://purl.uniprot.org/citations/32790646 | http://purl.uniprot.org/core/author | "Loisel-Ferreira I."xsd:string |