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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
SOS1
SOS Ras/Rac guanine nucleotide exchange factor 1
Chromosome 2 Β· 2p22.1
NCBI Gene: 6654Ensembl: ENSG00000115904.15HGNC: HGNC:11187UniProt: G5E9C8
298PubMed Papers
22Diseases
0Drugs
74Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub Gene
RESEARCH IMPACT
TrendingVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
guanyl-nucleotide exchange factor activityT cell activationregulation of cell population proliferationregulation of transcription by RNA polymerase IINoonan syndromehereditary gingival fibromatosisrasopathycancer
✦AI Summary

SOS1 (SOS Ras/Rac guanine nucleotide exchange factor 1) functions as a critical guanine nucleotide exchange factor that activates RAS signaling by promoting the exchange of GDP for GTP on RAS proteins 1. The protein serves as a key component in receptor tyrosine kinase signaling cascades, where it forms complexes with GRB2 to locally concentrate RAS activation 2. SOS1 operates through catalytic domain interactions with KRAS and can function in both membrane-bound and membraneless cytoplasmic protein granule contexts 21. The protein is subject to autoinhibition mechanisms that can be disrupted by pathogenic mutations 3. Clinically, SOS1 mutations cause Noonan syndrome, accounting for a significant portion of cases and typically presenting with distinctive phenotypes including high frequency of ectodermal anomalies, low prevalence of cognitive impairment, and cardiac defects 34. In cancer contexts, SOS1 represents an attractive therapeutic target as it serves as a feedback node in KRAS-driven tumors, with SOS1 inhibitors like BI-3406 showing efficacy when combined with MEK inhibitors 15. The protein's dual role in developmental disorders and cancer highlights its fundamental importance in cellular signaling regulation.

Sources cited
1
SOS1 functions as a guanine nucleotide exchange factor promoting GDP-GTP exchange on KRAS and can be targeted by inhibitors like BI-3406
PMID: 32816843
2
SOS1 forms complexes with GRB2 to activate RAS in both membrane-bound and membraneless cytoplasmic protein granule contexts
PMID: 33848463
3
SOS1 mutations cause Noonan syndrome with specific phenotypic features including ectodermal anomalies and cardiac defects
PMID: 21387466
4
SOS1 is a major contributor to Noonan syndrome cases in both prenatal and postnatal cohorts
PMID: 29907801
5
SOS1 inhibition is a strategy for treating KRAS-driven cancers
PMID: 32711246
Disease Associationsβ“˜22
Noonan syndromeOpen Targets
0.87Strong
hereditary gingival fibromatosisOpen Targets
0.72Strong
rasopathyOpen Targets
0.67Moderate
cancerOpen Targets
0.60Moderate
Noonan syndrome and Noonan-related syndromeOpen Targets
0.56Moderate
Abnormality of the cardiovascular systemOpen Targets
0.54Moderate
bone development diseaseOpen Targets
0.53Moderate
hypertensionOpen Targets
0.42Moderate
Noonan syndrome 3Open Targets
0.41Moderate
endometrial cancerOpen Targets
0.37Weak
Endometrial Endometrioid AdenocarcinomaOpen Targets
0.37Weak
skin basal cell carcinomaOpen Targets
0.37Weak
breast ductal adenocarcinomaOpen Targets
0.37Weak
carcinoma of liver and intrahepatic biliary tractOpen Targets
0.37Weak
gastric carcinomaOpen Targets
0.37Weak
kidney neoplasmOpen Targets
0.37Weak
lymphoid neoplasmOpen Targets
0.37Weak
prostate adenocarcinomaOpen Targets
0.37Weak
skin carcinomaOpen Targets
0.37Weak
skin squamous cell carcinomaOpen Targets
0.37Weak
Fibromatosis, gingival, 1UniProt
Noonan syndrome 4UniProt
Pathogenic Variants74
NM_005633.4(SOS1):c.1656G>C (p.Arg552Ser)Pathogenic
Noonan syndrome 4|Noonan syndrome|not provided|RASopathy|Noonan syndrome 4;Fibromatosis, gingival, 1|Noonan syndrome and Noonan-related syndrome|Noonan syndrome 1
β˜…β˜…β˜…β˜†2025β†’ Residue 552
NM_005633.4(SOS1):c.1656G>T (p.Arg552Ser)Pathogenic
Noonan syndrome|RASopathy|not provided|Noonan syndrome 4;Fibromatosis, gingival, 1|Noonan syndrome and Noonan-related syndrome|Noonan syndrome 4|See cases|Cardiovascular phenotype
β˜…β˜…β˜…β˜†2019β†’ Residue 552
NM_005633.4(SOS1):c.1655G>T (p.Arg552Met)Likely pathogenic
not provided|RASopathy|Noonan syndrome and Noonan-related syndrome|Noonan syndrome
β˜…β˜…β˜…β˜†2019β†’ Residue 552
NM_005633.4(SOS1):c.1655G>C (p.Arg552Thr)Pathogenic
not provided|Noonan syndrome|RASopathy|Abnormal aortic valve morphology|Noonan syndrome 4|Noonan syndrome and Noonan-related syndrome|Cardiovascular phenotype|SOS1-related disorder|Noonan syndrome 1|Fetal anomalies with a likely genetic cause
β˜…β˜…β˜…β˜†2019β†’ Residue 552
NM_005633.4(SOS1):c.1655G>A (p.Arg552Lys)Pathogenic
not provided|Noonan syndrome|Noonan syndrome 3|Noonan syndrome 1|RASopathy|Noonan syndrome 4|Fibromatosis, gingival, 1|Embryonal rhabdomyosarcoma
β˜…β˜…β˜…β˜†2019β†’ Residue 552
NM_005633.4(SOS1):c.1654A>T (p.Arg552Trp)Likely pathogenic
not provided|Noonan syndrome and Noonan-related syndrome|RASopathy
β˜…β˜…β˜…β˜†2019β†’ Residue 552
NM_005633.4(SOS1):c.1867T>A (p.Phe623Ile)Likely pathogenic
Noonan syndrome and Noonan-related syndrome|Noonan syndrome 1|Fibromatosis, gingival, 1|Noonan syndrome 4|not provided
β˜…β˜…β˜…β˜†2019β†’ Residue 623
NM_005633.4(SOS1):c.512T>C (p.Val171Ala)Likely pathogenic
Noonan syndrome|Noonan syndrome and Noonan-related syndrome|not provided
β˜…β˜…β˜…β˜†2019β†’ Residue 171
NM_005633.4(SOS1):c.2536G>A (p.Glu846Lys)Pathogenic
Noonan syndrome|not provided|RASopathy|Noonan syndrome 4;Fibromatosis, gingival, 1|Noonan syndrome and Noonan-related syndrome|Cardiovascular phenotype|SOS1-related disorder|Noonan syndrome 4
β˜…β˜…β˜…β˜†2017β†’ Residue 846
NM_005633.4(SOS1):c.1654A>G (p.Arg552Gly)Pathogenic
Noonan syndrome 4|Noonan syndrome|not provided|RASopathy|Noonan syndrome 4;Fibromatosis, gingival, 1|Cardiovascular phenotype
β˜…β˜…β˜…β˜†2017β†’ Residue 552
NM_005633.4(SOS1):c.322G>A (p.Glu108Lys)Pathogenic
Noonan syndrome|not provided|RASopathy|Noonan syndrome and Noonan-related syndrome|Noonan syndrome 4
β˜…β˜…β˜…β˜†2017β†’ Residue 108
NM_005633.4(SOS1):c.508A>G (p.Lys170Glu)Pathogenic
Noonan syndrome|not provided|RASopathy|not specified|Neonatal hypotonia|Noonan syndrome 4|Cardiovascular phenotype|SOS1-related disorder
β˜…β˜…β˜…β˜†2017β†’ Residue 170
NM_005633.4(SOS1):c.806T>C (p.Met269Thr)Pathogenic
not provided|Noonan syndrome|Noonan syndrome 4|RASopathy|Noonan syndrome and Noonan-related syndrome|Cardiovascular phenotype|Noonan syndrome 1
β˜…β˜…β˜…β˜†2017β†’ Residue 269
NM_005633.4(SOS1):c.1642A>C (p.Ser548Arg)Pathogenic
Noonan syndrome|not provided|RASopathy|Noonan syndrome 4;Fibromatosis, gingival, 1|Noonan syndrome and Noonan-related syndrome|Noonan syndrome 4|Noonan syndrome 1|Cardiovascular phenotype
β˜…β˜…β˜…β˜†2017β†’ Residue 548
NM_005633.4(SOS1):c.2104T>C (p.Tyr702His)Pathogenic
Noonan syndrome|not provided|RASopathy|Noonan syndrome 4;Fibromatosis, gingival, 1|Noonan syndrome 4
β˜…β˜…β˜†β˜†2026β†’ Residue 702
NM_005633.4(SOS1):c.1300G>A (p.Gly434Arg)Pathogenic
Noonan syndrome|Ptosis;Short stature;Pulmonic stenosis;Abnormal sternum morphology|RASopathy|Noonan syndrome 1|not provided|Noonan syndrome 4|Fetal cystic hygroma|Noonan syndrome and Noonan-related syndrome|Noonan syndrome 4;Fibromatosis, gingival, 1|Cardiovascular phenotype
β˜…β˜…β˜†β˜†2025β†’ Residue 434
NM_005633.4(SOS1):c.797C>A (p.Thr266Lys)Pathogenic
Noonan syndrome 4|Noonan syndrome|RASopathy|not provided|Noonan syndrome 4;Fibromatosis, gingival, 1|Noonan syndrome 1|Monogenic short statue
β˜…β˜…β˜†β˜†2025β†’ Residue 266
NM_005633.4(SOS1):c.305C>G (p.Pro102Arg)Pathogenic
RASopathy|not provided|Noonan syndrome 4
β˜…β˜…β˜†β˜†2025β†’ Residue 102
NM_005633.4(SOS1):c.1297G>A (p.Glu433Lys)Pathogenic
Noonan syndrome|not provided|RASopathy|Noonan syndrome and Noonan-related syndrome|Noonan syndrome 4|Noonan syndrome 1
β˜…β˜…β˜†β˜†2025β†’ Residue 433
NM_005633.4(SOS1):c.2207T>G (p.Ile736Arg)Likely pathogenic
Inborn genetic diseases|Fibromatosis, gingival, 1|Noonan syndrome 4
β˜…β˜…β˜†β˜†2025β†’ Residue 736
View on ClinVar β†—
Related Genes
RAPGEF1Protein interaction100%PDPK1Protein interaction100%GRAP2Protein interaction100%VAV1Protein interaction100%VAV2Protein interaction100%SH3KBP1Protein interaction99%
Tissue Expression6 tissues
Ovary
100%
Brain
77%
Heart
68%
Lung
56%
Liver
49%
Bone Marrow
45%
Gene Interaction Network
Click a node to explore
SOS1RAPGEF1PDPK1GRAP2VAV1VAV2SH3KBP1
PROTEIN STRUCTURE
Preparing viewer…
PDB6V9M Β· 1.65 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.29Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.18 [0.12–0.29]
RankingsWhere SOS1 stands among ~20K protein-coding genes
  • #1,181of 20,598
    Most Researched298 Β· top 10%
  • #991of 5,498
    Most Pathogenic Variants74 Β· top quartile
  • #1,042of 17,882
    Most Constrained (LOEUF)0.29 Β· top 10%
Genes detectedSOS1
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Targeting KRAS in pancreatic cancer.
PMID: 38686056
Oncol Res Β· 2024
1.00
2
TargetedΒ protein relocalization via protein transport coupling.
PMID: 39294374
Nature Β· 2024
0.90
3
KRAS: From undruggable to a druggable Cancer Target.
PMID: 32711246
Cancer Treat Rev Β· 2020
0.80
4
Kinase-mediated RAS signaling via membraneless cytoplasmic protein granules.
PMID: 33848463
Cell Β· 2021
0.70
5
Proteomic analyses identify targets, pathways, and cellular consequences of oncogenic KRAS signaling.
PMID: 40729433
Sci Signal Β· 2025
0.68