SOS2 Gene

HGNC Family	Pleckstrin homology domain containing (PLEKH), Rho guanine nucleotide exchange factors (ARHGEF)
Name	son of sevenless homolog 2 (Drosophila)
Description	This gene encodes a regulatory protein that is involved in the positive regulation of ras proteins. Mutations in this gene are associated with Noonan Syndrome-9. [provided by RefSeq, Jul 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStudies in patients with Noonan syndrome have revealed that SOS2—a RAS guanine nucleotide exchange factor—is a causative gene in a modest subset of cases. Pathogenic missense mutations in SOS2 affect evolutionarily conserved residues within its Dbl homology (DH) domain, disrupting its autoinhibited conformation and thereby enhancing RAS-to-ERK signaling. Clinically, individuals harboring these variants exhibit a phenotype overlapping with SOS1‐associated Noonan syndrome, including distinctive ectodermal features and a particularly high prevalence of lymphatic complications."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the realm of oncogenesis and neurological disease, SOS2 also plays a critical role. In non‐small‐cell lung cancer, its expression is directly downregulated by the tumor‐suppressive microRNA miR-148a-3p, thereby curtailing Ras activation and subsequent cell proliferation and epithelial-mesenchymal transition. Moreover, genetic analyses have identified polymorphisms in the SOS2 locus that are associated with increased risk for Alzheimer’s disease and poorer overall survival in HBV-related hepatocellular carcinoma, underscoring its potential as a prognostic biomarker in these settings."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond developmental and oncogenic contexts, SOS2 is integral to immune signaling pathways. In response to intracellular infection by Francisella tularensis, SOS2 is recruited into a quaternary complex with GrB2 and protein kinase C isoforms (PKCα and PKCβI), leading to rapid, transient activation of Ras. This event is critical for supporting intracellular bacterial proliferation by promoting cell survival and delaying caspase-3 activation. Complementary findings demonstrate that knockdown of MADD—a modulator that facilitates the recruitment of GrB2 along with SOS1/2 to the TNF receptor complex—significantly reduces MAPK signaling without impacting other related cascades, thereby emphasizing the specificity of SOS2’s function in TNFα-triggered Ras activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Viviana Cordeddu, Jiani C Yin, Cecilia Gunnarsson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activating Mutations Affecting the Dbl Homology Domain of SOS2 Cause Noonan Syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.22834"}], "href": "https://doi.org/10.1002/humu.22834"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26173643"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26173643"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Christina Lissewski, Valérie Chune, Francesca Pantaleoni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variants of SOS2 are a rare cause of Noonan syndrome with particular predisposition for lymphatic complications."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41431-020-00708-6"}], "href": "https://doi.org/10.1038/s41431-020-00708-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32788663"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32788663"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mattia Gentile, Tiziana Fanelli, Francesca Romana Lepri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "First prenatal case of Noonan syndrome with SOS2 mutation: Implications of early diagnosis for genetic counseling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.62180"}], "href": "https://doi.org/10.1002/ajmg.a.62180"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33750022"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33750022"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Qiong Xie, Zipu Yu, Yuan Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "microRNA-148a-3p inhibited the proliferation and epithelial-mesenchymal transition progression of non-small-cell lung cancer via modulating Ras/MAPK/Erk signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.27899"}], "href": "https://doi.org/10.1002/jcp.27899"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30536836"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30536836"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Qiuling Lin, Moqin Qiu, Xueyan Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variants of SOS2, MAP2K1 and RASGRF2 in the RAS pathway genes predict survival of HBV-related hepatocellular carcinoma patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Toxicol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00204-023-03469-5"}], "href": "https://doi.org/10.1007/s00204-023-03469-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37029817"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37029817"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Gillian Hamilton, Petra Proitsi, Luke Jehu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Candidate gene association study of insulin signaling genes and Alzheimer's disease: evidence for SOS2, PCK1, and PPARgamma as susceptibility loci."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet B Neuropsychiatr Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.b.30503"}], "href": "https://doi.org/10.1002/ajmg.b.30503"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17440948"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17440948"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Souhaila Al-Khodor, Yousef Abu Kwaik "}, {"type": "b", "children": [{"type": "t", "text": "Triggering Ras signalling by intracellular Francisella tularensis through recruitment of PKCα and βI to the SOS2/GrB2 complex is essential for bacterial proliferation in the cytosol."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Microbiol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1462-5822.2010.01494.x"}], "href": "https://doi.org/10.1111/j.1462-5822.2010.01494.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20618341"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20618341"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Bapi Raju V V S N Kurada, Liang Cheng Li, Nirupama Mulherkar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MADD, a splice variant of IG20, is indispensable for MAPK activation and protection against apoptosis upon tumor necrosis factor-alpha treatment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M808554200"}], "href": "https://doi.org/10.1074/jbc.M808554200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19289468"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19289468"}]}]}]}
Synonyms	NS9, SOS-2
Proteins	SOS2_HUMAN
NCBI Gene ID	6655
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SOS2 has 7,304 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 127 datasets.

Click the + buttons to view associations for SOS2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SOS2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by SOS2 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SOS2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of SOS2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of SOS2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of SOS2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of SOS2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SOS2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of SOS2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SOS2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SOS2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of SOS2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SOS2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of SOS2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SOS2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SOS2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SOS2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of SOS2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with SOS2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing SOS2 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SOS2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SOS2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing SOS2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing SOS2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SOS2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with SOS2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of SOS2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SOS2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with SOS2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with SOS2 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of SOS2 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by SOS2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving SOS2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with SOS2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SOS2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SOS2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with SOS2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with SOS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SOS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at SOS2 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SOS2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.