Gene: SOS1
Alternate names for this Gene: GF1|GGF1|GINGF|HGF|NS4|SOS-1
Gene Summary: This gene encodes a protein that is a guanine nucleotide exchange factor for RAS proteins, membrane proteins that bind guanine nucleotides and participate in signal transduction pathways. GTP binding activates and GTP hydrolysis inactivates RAS proteins. The product of this gene may regulate RAS proteins by facilitating the exchange of GTP for GDP. Mutations in this gene are associated with gingival fibromatosis 1 and Noonan syndrome type 4.
Gene is located in Chromosome: 2
Location in Chromosome : 2p22.1
Description of this Gene: SOS Ras/Rac guanine nucleotide exchange factor 1
Type of Gene: protein-coding
rs1057519963 in
SOS1 gene and
Adenocarcinoma of lung (disorder)
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs137852813 in
SOS1 gene and
Blepharoptosis
PMID 17586837 2007 SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome.
PMID 19953625 2010 Tumor spectrum in children with Noonan syndrome and SOS1 or RAF1 mutations.
PMID 19020799 2008 PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype correlation in Korean patients with Noonan syndrome.
PMID 21387466 2011 SOS1 mutations in Noonan syndrome: molecular spectrum, structural insights on pathogenic effects, and genotype-phenotype correlations.
PMID 20683980 2010 Noonan syndrome associated with both a new Jnk-activating familial SOS1 and a de novo RAF1 mutations.
rs137852813 in
SOS1 gene and
Coarse features
PMID 17586837 2007 SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome.
PMID 19020799 2008 PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype correlation in Korean patients with Noonan syndrome.
PMID 19953625 2010 Tumor spectrum in children with Noonan syndrome and SOS1 or RAF1 mutations.
PMID 21387466 2011 SOS1 mutations in Noonan syndrome: molecular spectrum, structural insights on pathogenic effects, and genotype-phenotype correlations.
PMID 20683980 2010 Noonan syndrome associated with both a new Jnk-activating familial SOS1 and a de novo RAF1 mutations.
rs963731 in
SOS1 gene and
Corticobasal degeneration
PMID 26077951 2015 Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy.
rs137852813 in
SOS1 gene and
Dysmorphic features
PMID 26708403 2016 SOS1 frameshift mutations cause pure mucosal neuroma syndrome, a clinical phenotype distinct from multiple endocrine neoplasia type 2B.
PMID 25180280 2014 Cardio-facio-cutaneous syndrome: clinical features, diagnosis, and management guidelines.
PMID 22551697 2012 Decreased bone mineralization in children with Noonan syndrome: another consequence of dysregulated RAS MAPKinase pathway?
PMID 19438935 2009 SOS1: a new player in the Noonan-like/multiple giant cell lesion syndrome.
PMID 22604720 2012 Evolution and functional impact of rare coding variation from deep sequencing of human exomes.
PMID 17586837 2007 SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome.
PMID 21387466 2011 SOS1 mutations in Noonan syndrome: molecular spectrum, structural insights on pathogenic effects, and genotype-phenotype correlations.
PMID 21784453 2011 Spectrum of mutations in Noonan syndrome and their correlation with phenotypes.
PMID 21396583 2011 Noonan syndrome and clinically related disorders.
PMID 23165751 2012 Medical complications, clinical findings, and educational outcomes in adults with Noonan syndrome.
PMID 19077116 2009 Genotype differences in cognitive functioning in Noonan syndrome.
PMID 25073238 2014 Unilateral giant cell lesion of the jaw in Noonan syndrome.
PMID 19467855 2009 The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation.
PMID 11868160 2002 A mutation in the SOS1 gene causes hereditary gingival fibromatosis type 1.
PMID 26249544 2015 Craniosynostosis and Noonan syndrome with KRAS mutations: Expanding the phenotype with a case report and review of the literature.
PMID 17143282 2007 Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome.
PMID 19020799 2008 PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype correlation in Korean patients with Noonan syndrome.
PMID 18651097 2008 Clinical manifestations in patients with SOS1 mutations range from Noonan syndrome to CFC syndrome.
PMID 16773572 2006 Germline missense mutations affecting KRAS Isoform B are associated with a severe Noonan syndrome phenotype.
PMID 17143285 2007 Germline gain-of-function mutations in SOS1 cause Noonan syndrome.
PMID 17510059 2007 Germ line gain of function with SOS1 mutation in hereditary gingival fibromatosis.
rs397517159 in
SOS1 gene and
Feeding difficulties
PMID 17143282 2007 Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome.
PMID 17586837 2007 SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome.
PMID 17143285 2007 Germline gain-of-function mutations in SOS1 cause Noonan syndrome.
rs137852813 in
SOS1 gene and
Foramen Ovale, Patent
PMID 21387466 2011 SOS1 mutations in Noonan syndrome: molecular spectrum, structural insights on pathogenic effects, and genotype-phenotype correlations.
PMID 19953625 2010 Tumor spectrum in children with Noonan syndrome and SOS1 or RAF1 mutations.
PMID 20683980 2010 Noonan syndrome associated with both a new Jnk-activating familial SOS1 and a de novo RAF1 mutations.
PMID 19020799 2008 PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype correlation in Korean patients with Noonan syndrome.
PMID 17586837 2007 SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome.
rs1057519963 in
SOS1 gene and
Malignant Uterine Corpus Neoplasm
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs137852813 in
SOS1 gene and
Multiple congenital anomalies
PMID 26249544 2015 Craniosynostosis and Noonan syndrome with KRAS mutations: Expanding the phenotype with a case report and review of the literature.
PMID 23165751 2012 Medical complications, clinical findings, and educational outcomes in adults with Noonan syndrome.
PMID 22551697 2012 Decreased bone mineralization in children with Noonan syndrome: another consequence of dysregulated RAS MAPKinase pathway?
PMID 25073238 2014 Unilateral giant cell lesion of the jaw in Noonan syndrome.
PMID 26708403 2016 SOS1 frameshift mutations cause pure mucosal neuroma syndrome, a clinical phenotype distinct from multiple endocrine neoplasia type 2B.
PMID 22604720 2012 Evolution and functional impact of rare coding variation from deep sequencing of human exomes.
PMID 21396583 2011 Noonan syndrome and clinically related disorders.
PMID 25180280 2014 Cardio-facio-cutaneous syndrome: clinical features, diagnosis, and management guidelines.
PMID 21784453 2011 Spectrum of mutations in Noonan syndrome and their correlation with phenotypes.
PMID 21387466 2011 SOS1 mutations in Noonan syndrome: molecular spectrum, structural insights on pathogenic effects, and genotype-phenotype correlations.
PMID 18651097 2008 Clinical manifestations in patients with SOS1 mutations range from Noonan syndrome to CFC syndrome.
PMID 17143285 2007 Germline gain-of-function mutations in SOS1 cause Noonan syndrome.
PMID 17510059 2007 Germ line gain of function with SOS1 mutation in hereditary gingival fibromatosis.
PMID 17143282 2007 Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome.
PMID 11868160 2002 A mutation in the SOS1 gene causes hereditary gingival fibromatosis type 1.
PMID 16773572 2006 Germline missense mutations affecting KRAS Isoform B are associated with a severe Noonan syndrome phenotype.
PMID 19467855 2009 The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation.
PMID 17586837 2007 SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome.
PMID 19020799 2008 PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype correlation in Korean patients with Noonan syndrome.
PMID 19077116 2009 Genotype differences in cognitive functioning in Noonan syndrome.
PMID 19438935 2009 SOS1: a new player in the Noonan-like/multiple giant cell lesion syndrome.
rs397517154 in
SOS1 gene and
NOONAN SYNDROME 3
PMID 17143282 2007 Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome.
PMID 21784453 2011 Spectrum of mutations in Noonan syndrome and their correlation with phenotypes.
PMID 17586837 2007 SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome.
PMID 21387466 2011 SOS1 mutations in Noonan syndrome: molecular spectrum, structural insights on pathogenic effects, and genotype-phenotype correlations.
PMID 20186801 2010 Effects of germline mutations in the Ras/MAPK signaling pathway on adaptive behavior: cardiofaciocutaneous syndrome and Noonan syndrome.
PMID 23487764 2013 NMR-based functional profiling of RASopathies and oncogenic RAS mutations.
rs137852813 in
SOS1 gene and
Narrow forehead
PMID 21387466 2011 SOS1 mutations in Noonan syndrome: molecular spectrum, structural insights on pathogenic effects, and genotype-phenotype correlations.
PMID 19953625 2010 Tumor spectrum in children with Noonan syndrome and SOS1 or RAF1 mutations.
PMID 20683980 2010 Noonan syndrome associated with both a new Jnk-activating familial SOS1 and a de novo RAF1 mutations.
PMID 17586837 2007 SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome.
PMID 19020799 2008 PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype correlation in Korean patients with Noonan syndrome.
rs137852812 in
SOS1 gene and
Noonan Syndrome
PMID 19020799 2008 PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype correlation in Korean patients with Noonan syndrome.
PMID 19077116 2009 Genotype differences in cognitive functioning in Noonan syndrome.
PMID 19953625 2010 Tumor spectrum in children with Noonan syndrome and SOS1 or RAF1 mutations.
PMID 17143285 2007 Germline gain-of-function mutations in SOS1 cause Noonan syndrome.
PMID 18678287 2009 Clinical and molecular characterization of 40 patients with Noonan syndrome.
PMID 17586837 2007 SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome.
PMID 17143282 2007 Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome.
PMID 21387466 2011 SOS1 mutations in Noonan syndrome: molecular spectrum, structural insights on pathogenic effects, and genotype-phenotype correlations.
PMID 20683980 2010 Noonan syndrome associated with both a new Jnk-activating familial SOS1 and a de novo RAF1 mutations.
PMID 21340158 2010 Co-occurring PTPN11 and SOS1 gene mutations in Noonan syndrome: does this predict a more severe phenotype?
PMID 24522193 2014 Intriguingly, CIIA failed to inhibit the Ras-specific GEF activity of Noonan-syndrome-associated SOS1 mutants (M269R, R552G, W729L and E846K).
PMID 23487764 2013 NMR-based functional profiling of RASopathies and oncogenic RAS mutations.
PMID 18854871 2009 Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome.
PMID 19352411 2009 SOS1 and PTPN11 mutations in five cases of Noonan syndrome with multiple giant cell lesions.
PMID 20305546 2010 Noonan-like/multiple giant cell lesion syndrome in two adult patients with SOS1 gene mutations.
PMID 19438935 2009 SOS1: a new player in the Noonan-like/multiple giant cell lesion syndrome.
PMID 20133692 2010 Role of the histone domain in the autoinhibition and activation of the Ras activator Son of Sevenless.
PMID 18772396 2008 An integrated genomic analysis of human glioblastoma multiforme.
PMID 18456719 2008 The SOS1 E433K mutation, identified in a patient diagnosed with CFC, has previously been reported in patients with NS.
PMID 29493581 2018 ClinGen's RASopathy Expert Panel consensus methods for variant interpretation.
PMID 29037749 2018 Psychopathological features in Noonan syndrome.
PMID 26214590 2015 Exome sequencing identifies recurrent mutations in NF1 and RASopathy genes in sun-exposed melanomas.
PMID 30266093 2018 Clinical exome sequencing for fetuses with ultrasound abnormalities and a suspected Mendelian disorder.
PMID 28378436 2017 Visual perception skills: a comparison between patients with Noonan syndrome and 22q11.2 deletion syndrome.
PMID 27236105 2016 RASopathy Gene Mutations in Melanoma.
PMID 26918529 2016 Retrospective study of prenatal ultrasound findings in newborns with a Noonan spectrum disorder.
PMID 25337068 2014 Clinical and Molecular Findings of Tunisian Patients with RASopathies.
PMID 22190897 2011 RASopathies: Clinical Diagnosis in the First Year of Life.
PMID 26686981 2016 Coronary artery ectasia in Noonan syndrome: Report of an individual with SOS1 mutation and literature review.
PMID 21274610 2011 Long term memory profile of disorders associated with dysregulation of the RAS-MAPK signaling cascade.
PMID 21784453 2011 Spectrum of mutations in Noonan syndrome and their correlation with phenotypes.
PMID 22465605 2012 Alterations in RAS-MAPK genes in 200 Spanish patients with Noonan and other neuro-cardio-facio-cutaneous syndromes. Genotype and cardiopathy.
PMID 20461756 2010 Noonan syndrome, the SOS1 gene and embryonal rhabdomyosarcoma.
PMID 21041952 2010 Activation of multiple signaling pathways causes developmental defects in mice with a Noonan syndrome–associated Sos1 mutation.
PMID 23673306 2013 Ulerythema ophryogenes, a rarely reported cutaneous manifestation of noonan syndrome: case report and review of the literature.
PMID 24270602 2014 A quantitative liposome microarray to systematically characterize protein-lipid interactions.
PMID 23452850 2013 Interaction domains of Sos1/Grb2 are finely tuned for cooperative control of embryonic stem cell fate.
PMID 20133694 2010 Allosteric gating of Son of sevenless activity by the histone domain.
PMID 1758637 1991 [Observations on cancer metastasis from an unknown primary location].
PMID 18651097 2008 Clinical manifestations in patients with SOS1 mutations range from Noonan syndrome to CFC syndrome.
PMID 20673819 2011 Two cases of Noonan syndrome with severe respiratory and gastroenteral involvement and the SOS1 mutation F623I.
PMID 11333268 2001 Structure-based mutagenesis reveals distinct functions for Ras switch 1 and switch 2 in Sos-catalyzed guanine nucleotide exchange.
PMID 24803665 2014 Structure-energy-based predictions and network modelling of RASopathy and cancer missense mutations.
rs1367714753 in
SOS1 gene and
Noonan Syndrome 4
PMID 19020799 2008 PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype correlation in Korean patients with Noonan syndrome.
PMID 21387466 2011 SOS1 mutations in Noonan syndrome: molecular spectrum, structural insights on pathogenic effects, and genotype-phenotype correlations.
PMID 17143285 2007 Germline gain-of-function mutations in SOS1 cause Noonan syndrome.
PMID 19438935 2009 SOS1: a new player in the Noonan-like/multiple giant cell lesion syndrome.
PMID 20683980 2010 Noonan syndrome associated with both a new Jnk-activating familial SOS1 and a de novo RAF1 mutations.
PMID 20673819 2011 Two cases of Noonan syndrome with severe respiratory and gastroenteral involvement and the SOS1 mutation F623I.
PMID 17143282 2007 Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome.
PMID 19953625 2010 Tumor spectrum in children with Noonan syndrome and SOS1 or RAF1 mutations.
PMID 20876176 2010 Noonan syndrome: clinical features, diagnosis, and management guidelines.
rs137852813 in
SOS1 gene and
Ventricular Septal Defects
PMID 19953625 2010 Tumor spectrum in children with Noonan syndrome and SOS1 or RAF1 mutations.
PMID 19020799 2008 PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype correlation in Korean patients with Noonan syndrome.
PMID 17586837 2007 SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome.
PMID 21387466 2011 SOS1 mutations in Noonan syndrome: molecular spectrum, structural insights on pathogenic effects, and genotype-phenotype correlations.
PMID 20683980 2010 Noonan syndrome associated with both a new Jnk-activating familial SOS1 and a de novo RAF1 mutations.