STAT2 Gene

HGNC Family	SH2 domain containing
Name	signal transducer and activator of transcription 2, 113kDa
Description	The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. In response to interferon (IFN), this protein forms a complex with STAT1 and IFN regulatory factor family protein p48 (ISGF3G), in which this protein acts as a transactivator, but lacks the ability to bind DNA directly. The protein mediates innate antiviral activity. Mutations in this gene result in Immunodeficiency 44. [provided by RefSeq, Aug 2020]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSTAT2 is a pivotal transcription factor in type I interferon (IFN) signaling, serving as an essential component of the ISGF3 complex that, upon IFN stimulation, translocates to the nucleus and activates hundreds of antiviral genes. In resting cells, STAT2 exists largely in the cytoplasm but shuttles dynamically between the cytosol and nucleus—this trafficking is mediated by its constitutive association with IRF9 and the recognition of its nuclear‐localization signals by importin α5, thereby coupling its function to the regulation of basal and IFN-induced gene expression. Moreover, structural studies of STAT2 and its interaction with IRF9 have provided critical insights into the formation of transcriptionally active ISGF3 and noncanonical STAT2‐containing complexes, while post-translational modifications—notably palmitoylation of the IFN receptor and phosphorylation events including an inhibitory T387 modification—finely tune STAT2’s activity and recruitment of negative regulators such as USP18."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA wide range of viruses have evolved sophisticated strategies to disable host antiviral defenses by targeting STAT2. Several flaviviruses such as dengue virus use their NS5 protein to bind STAT2 and promote its ubiquitination and proteasomal degradation, thereby impairing IFN-α signaling and facilitating viral replication. Similarly, other pathogens—including West Nile virus, Nipah virus, measles virus, Sendai virus, rabies virus, and porcine deltacoronavirus—either sequester STAT2 in high-molecular-weight complexes, induce its cleavage or degradation, or block its tyrosine phosphorylation and nuclear translocation. Such viral antagonism is further underscored by species-specific differences observed in the interaction between viral proteins and STAT2, highlighting its central role as a target in immune evasion mechanisms."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in mediating IFN responses, emerging studies have revealed noncanonical and context‐dependent functions of STAT2 in human health and disease. Genetic defects in STAT2 have been linked to severe viral infections in children, underscoring its nonredundant role in antiviral immunity, while evolutionary analyses show evidence of archaic introgression of STAT2 variants in Eurasian populations. In addition, STAT2 contributes to IFN-induced apoptosis and participates in alternative, STAT1-independent transcriptional programs, such as those driven by unphosphorylated ISGF3 that regulate basal antiviral gene expression. Aberrant regulation of STAT2 stability—for example, via ubiquitination by the cellular E3 ligase FBXW7 or through inhibitory phosphorylation events—has been implicated in tumor cell survival and immune evasion in cancers. Collectively, these findings highlight the multifaceted role of STAT2 as an essential positive effector in antiviral defense and as a critical node subject to both viral subversion and host regulatory mechanisms."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "22", "end_ref": "28"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jean-Patrick Parisien, Joe F Lau, Jason J Rodriguez, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Arginine/lysine-rich nuclear localization signals mediate interactions between dimeric STATs and importin alpha 5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M202943200"}], "href": "https://doi.org/10.1074/jbc.M202943200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12048190"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12048190"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jean-Patrick Parisien, Joe F Lau, Curt M Horvath "}, {"type": "b", "children": [{"type": "t", "text": "STAT2 acts as a host range determinant for species-specific paramyxovirus interferon antagonism and simian virus 5 replication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/jvi.76.13.6435-6441.2002"}], "href": "https://doi.org/10.1128/jvi.76.13.6435-6441.2002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12050355"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12050355"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Gregg Banninger, Nancy C Reich "}, {"type": "b", "children": [{"type": "t", "text": "STAT2 nuclear trafficking."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M400815200"}], "href": "https://doi.org/10.1074/jbc.M400815200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15175343"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15175343"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Melissa M Brierley, Eleanor N Fish "}, {"type": "b", "children": [{"type": "t", "text": "Functional relevance of the conserved DNA-binding domain of STAT2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M500426200"}], "href": "https://doi.org/10.1074/jbc.M500426200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15668228"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15668228"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Julie Claudinon, Pauline Gonnord, Emilie Beslard, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Deletion of Kaposi's sarcoma-associated herpesvirus FLICE inhibitory protein, vFLIP, from the viral genome compromises the activation of STAT1-responsive cellular genes and spindle cell formation in endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.00226-11"}], "href": "https://doi.org/10.1128/JVI.00226-11"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21795355"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21795355"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Kei-Ichiro Arimoto, Sara Löchte, Samuel A Stoner, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Dengue virus co-opts UBR4 to degrade STAT2 and antagonize type I interferon signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Pathog (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.ppat.1003265"}], "href": "https://doi.org/10.1371/journal.ppat.1003265"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23555265"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23555265"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Shota Yamauchi, Kenji Takeuchi, Kazuyasu Chihara, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Porcine Deltacoronavirus nsp5 Antagonizes Type I Interferon Signaling by Cleaving STAT2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.00003-17"}], "href": "https://doi.org/10.1128/JVI.00003-17"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28250121"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28250121"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Ana L Romero-Weaver, Hsiang-Wen Wang, Håkan C Steen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Resistance to IFN-alpha-induced apoptosis is linked to a loss of STAT2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-08-0344"}], "href": "https://doi.org/10.1158/1541-7786.MCR-08-0344"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20068068"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20068068"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Fernando L Mendez, Joseph C Watkins, Michael F Hammer "}, {"type": "b", "children": [{"type": "t", "text": "A haplotype at STAT2 Introgressed from neanderthals and serves as a candidate of positive selection in Papua New Guinea."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2012.06.015"}], "href": "https://doi.org/10.1016/j.ajhg.2012.06.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22883142"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22883142"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Sophie Hambleton, Stephen Goodbourn, Dan F Young, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The Chemopreventive Phytochemical Moringin Isolated from Moringa oleifera Seeds Inhibits JAK/STAT Signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0157430"}], "href": "https://doi.org/10.1371/journal.pone.0157430"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27304884"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27304884"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Yuxin Wang, Jing Nan, Belinda Willard, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "FBXW7-mediated stability regulation of signal transducer and activator of transcription 2 in melanoma formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1909879116"}], "href": "https://doi.org/10.1073/pnas.1909879116"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31843895"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31843895"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Jun-Bao Fan, Sayuri Miyauchi, Hui-Zhong Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Type I Interferon Regulates a Coordinated Gene Network to Enhance Cytotoxic T Cell-Mediated Tumor Killing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Discov (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/2159-8290.CD-19-0608"}], "href": "https://doi.org/10.1158/2159-8290.CD-19-0608"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31974171"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31974171"}]}]}]}
Synonyms	P113, STAT113, IMD44
Proteins	STAT2_HUMAN
NCBI Gene ID	6773
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

STAT2 has 11,204 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 139 datasets.

Click the + buttons to view associations for STAT2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

STAT2 Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of STAT2 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 STAT2 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 STAT2 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 STAT2 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 STAT2 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 STAT2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving STAT2 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of STAT2 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 STAT2 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 STAT2 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 STAT2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of STAT2 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 STAT2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with STAT2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with STAT2 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 STAT2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of STAT2 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 STAT2 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 STAT2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing STAT2 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 STAT2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing STAT2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing STAT2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing STAT2 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 STAT2 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 STAT2 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 STAT2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing STAT2 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of STAT2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with STAT2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with STAT2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with STAT2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with STAT2 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 STAT2 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 STAT2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with STAT2 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 STAT2 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 STAT2 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 STAT2 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 STAT2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.