CGAS Gene

Name cyclic GMP-AMP synthase
Description Enables several functions, including 2',3'-cyclic GMP-AMP synthase activity; molecular condensate scaffold activity; and phosphatidylinositol-4,5-bisphosphate binding activity. Involved in several processes, including defense response to symbiont; intracellular signal transduction; and regulation of defense response. Located in nuclear body; plasma membrane; and site of double-strand break. Is active in cytosol and nucleus. [provided by Alliance of Genome Resources, Mar 2025]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cyclic GMP‐AMP synthase (cGAS) is a pivotal cytosolic sensor of double‐stranded DNA that initiates innate immune responses. Upon binding DNA originating from pathogens or from self (due to cellular damage, genomic instability, or mitochondrial stress), cGAS catalyzes the formation of the second messenger cGAMP. cGAMP in turn binds to and activates the adaptor STING, triggering a signaling cascade (via kinases such as TBK1 and transcription factors including IRF3) that culminates in the production of type I interferons and inflammatory cytokines."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its essential role in antiviral and antibacterial defenses, cGAS-mediated signaling contributes to tumor immunosurveillance and cellular senescence. Activation of this pathway has been shown to enhance the efficacy of radiotherapy and immune checkpoint blockade, while also restraining aberrant cell proliferation by promoting a senescence-associated secretory phenotype."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, cGAS detects pathogen-associated DNA during infections by diverse bacteria and viruses, thereby orchestrating host defenses that limit microbial replication."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n However, when self-DNA is aberrantly present in the cytosol, sustained cGAS activation can drive chronic inflammation and autoimmunity. Dysregulation of this pathway has been implicated in the pathogenesis of various inflammatory and autoimmune disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Structural studies have revealed that cGAS harbors a unique zinc ribbon domain appended to a nucleotidyltransferase core. Conformational changes upon DNA binding prestructure the catalytic site to enable the synthesis of cGAMP—a process that is central to linking DNA detection with downstream signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "16"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the central role of cGAS as a molecular bridge between cytosolic DNA detection and the activation of innate and adaptive immune responses in contexts ranging from pathogen defense and tumorigenesis to autoimmunity and cellular senescence.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lijun Sun, Jiaxi Wu, Fenghe Du, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1244040"}], "href": "https://doi.org/10.1126/science.1244040"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23989956"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23989956"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Daxing Gao, Jiaxi Wu, You-Tong Wu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature12862"}], "href": "https://doi.org/10.1038/nature12862"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24284630"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24284630"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hui Yang, Hanze Wang, Junyao Ren, et al. "}, {"type": "b", "children": [{"type": "t", "text": "cGAS is essential for cellular senescence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1705499114"}], "href": "https://doi.org/10.1073/pnas.1705499114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28533362"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28533362"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Selene Glück, Baptiste Guey, Muhammet Fatih Gulen, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The Cytosolic Sensor cGAS Detects Mycobacterium tuberculosis DNA to Induce Type I Interferons and Activate Autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Host Microbe (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.chom.2015.05.004"}], "href": "https://doi.org/10.1016/j.chom.2015.05.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26048136"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26048136"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Filiz Civril, Tobias Deimling, Carina C de Oliveira Mann, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2013.05.009"}], "href": "https://doi.org/10.1016/j.celrep.2013.05.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23707065"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23707065"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Daxing Gao, Tuo Li, Xiao-Dong Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of cyclic GMP-AMP synthase by self-DNA causes autoimmune diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1516465112"}], "href": "https://doi.org/10.1073/pnas.1516465112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26371324"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26371324"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Chien-Hsiung Yu, Sophia Davidson, Cassandra R Harapas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2020.09.020"}], "href": "https://doi.org/10.1016/j.cell.2020.09.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33031745"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33031745"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Hiroshi Maekawa, Tsuyoshi Inoue, Haruki Ouchi, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Structure of human cGAS reveals a conserved family of second-messenger enzymes in innate immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2013.05.008"}], "href": "https://doi.org/10.1016/j.celrep.2013.05.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23707061"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23707061"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Xu Zhang, Jiaxi Wu, Fenghe Du, et al. 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NCBI Gene ID 115004
API
Download Associations
Predicted Functions View CGAS's ARCHS4 Predicted Functions.
Co-expressed Genes View CGAS's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View CGAS's ARCHS4 Predicted Functions.

Functional Associations

CGAS has 4,218 functional associations with biological entities spanning 6 categories (functional term, phrase or reference, chemical, disease, phenotype or trait, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 37 datasets.

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

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles tissue samples with high or low expression of CGAS gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
CCLE Cell Line Proteomics Cell lines associated with CGAS protein from the CCLE Cell Line Proteomics dataset.
ChEA Transcription Factor Targets 2022 transcription factors binding the promoter of CGAS gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
CM4AI KOLF21J CRISPRi Gene Perturbation Atlas gene perturbations changing expression of CGAS gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
CM4AI U2OS Cell Map Protein Localization Assemblies assemblies containing CGAS protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 cellular components containing CGAS protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 cellular components containing CGAS 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 2025 cellular components co-occuring with CGAS protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
DepMap CRISPR Gene Dependency cell lines with fitness changed by CGAS gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
DGIdb Drug Targets 2026 interacting drugs for CGAS protein from the DGIdb Drug Targets 2026 dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with CGAS 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 CGAS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
DisGeNET Gene-Phenotype Associations phenotypes associated with CGAS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
GO Biological Process Annotations 2023 biological processes involving CGAS gene from the curated GO Biological Process Annotations 2023 dataset.
GO Biological Process Annotations 2025 biological processes involving CGAS gene from the curated GO Biological Process Annotations2025 dataset.
GO Cellular Component Annotations 2023 cellular components containing CGAS protein from the curated GO Cellular Component Annotations 2023 dataset.
GO Cellular Component Annotations 2025 cellular components containing CGAS protein from the curated GO Cellular Component Annotations 2025 dataset.
GO Molecular Function Annotations 2023 molecular functions performed by CGAS gene from the curated GO Molecular Function Annotations 2023 dataset.
GO Molecular Function Annotations 2025 molecular functions performed by CGAS gene from the curated GO Molecular Function Annotations 2025 dataset.
GTEx eQTL 2025 SNPs regulating expression of CGAS gene from the GTEx eQTL 2025 dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of CGAS gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
JASPAR Predicted Human Transcription Factor Targets 2025 transcription factors regulating expression of CGAS gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset.
JASPAR Predicted Mouse Transcription Factor Targets 2025 transcription factors regulating expression of CGAS gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset.
KEGG Pathways 2026 pathways involving CGAS protein from the KEGG Pathways 2026 dataset.
MGI Mouse Phenotype Associations 2023 phenotypes of transgenic mice caused by CGAS gene mutations from the MGI Mouse Phenotype Associations 2023 dataset.
NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles drug perturbations changing expression of CGAS gene from the NIBR DRUG-seq U2OS MoA Box dataset.
PFOCR Pathway Figure Associations 2023 pathways involving CGAS protein from the PFOCR Pathway Figure Associations 2023 dataset.
PFOCR Pathway Figure Associations 2024 pathways involving CGAS protein from the Wikipathways PFOCR 2024 dataset.
Reactome Pathways 2024 pathways involving CGAS protein from the Reactome Pathways 2024 dataset.
Rummagene Transcription Factor Associations 2026 transcription factors regulating expression of CGAS gene from the Rummagene Transcription Factor Associations 2026 dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of CGAS gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of CGAS gene from the RummaGEO Gene Perturbation Signatures dataset.
Sci-Plex Drug Perturbation Signatures drug perturbations changing expression of CGAS gene from the Sci-Plex Drug Perturbation Signatures dataset.
Tahoe Therapeutics Tahoe 100M Perturbation Atlas drug perturbations changing expression of CGAS gene from the Tahoe Therapeutics Tahoe 100M Perturbation Atlas dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of CGAS protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with CGAS protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.
WikiPathways Pathways 2024 pathways involving CGAS protein from the WikiPathways Pathways 2024 dataset.