| http://purl.uniprot.org/citations/17143282 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17143282 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17143282 | http://www.w3.org/2000/01/rdf-schema#comment | "Noonan syndrome is a developmental disorder characterized by short stature, facial dysmorphia, congenital heart defects and skeletal anomalies. Increased RAS-mitogen-activated protein kinase (MAPK) signaling due to PTPN11 and KRAS mutations causes 50% of cases of Noonan syndrome. Here, we report that 22 of 129 individuals with Noonan syndrome without PTPN11 or KRAS mutation have missense mutations in SOS1, which encodes a RAS-specific guanine nucleotide exchange factor. SOS1 mutations cluster at codons encoding residues implicated in the maintenance of SOS1 in its autoinhibited form. In addition, ectopic expression of two Noonan syndrome-associated mutants induces enhanced RAS and ERK activation. The phenotype associated with SOS1 defects lies within the Noonan syndrome spectrum but is distinctive, with a high prevalence of ectodermal abnormalities but generally normal development and linear growth. Our findings implicate gain-of-function mutations in a RAS guanine nucleotide exchange factor in disease for the first time and define a new mechanism by which upregulation of the RAS pathway can profoundly change human development."xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.org/dc/terms/identifier | "doi:10.1038/ng1939"xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.org/dc/terms/identifier | "doi:10.1038/ng1939"xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.uniprot.org/core/author | "Bristow J."xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.uniprot.org/core/author | "Bristow J."xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.uniprot.org/core/author | "Martin J."xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.uniprot.org/core/author | "Martin J."xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.uniprot.org/core/author | "Oishi K."xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.uniprot.org/core/author | "Oishi K."xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.uniprot.org/core/author | "Pennacchio L.A."xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.uniprot.org/core/author | "Pennacchio L.A."xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.uniprot.org/core/author | "Ustaszewska A."xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.uniprot.org/core/author | "Ustaszewska A."xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.uniprot.org/core/author | "Zhao C."xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.uniprot.org/core/author | "Zhao C."xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.uniprot.org/core/author | "Schackwitz W."xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.uniprot.org/core/author | "Schackwitz W."xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.uniprot.org/core/author | "Tartaglia M."xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.uniprot.org/core/author | "Tartaglia M."xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.uniprot.org/core/author | "Bar-Sagi D."xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.uniprot.org/core/author | "Bar-Sagi D."xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.uniprot.org/core/author | "Pandit B."xsd:string |
| http://purl.uniprot.org/citations/17143282 | http://purl.uniprot.org/core/author | "Pandit B."xsd:string |