CGAS protein expression summary - The Human Protein Atlas

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HUMAN PROTEIN ATLAS SUMMARYⁱ General description of the gene and the encoded protein(s) using information from HGNC and Ensembl, as well as predictions made by the Human Protein Atlas project.
Proteinⁱ Full gene name according to HGNC.	Cyclic GMP-AMP synthase
Gene nameⁱ Official gene symbol, which is typically a short form of the gene name, according to HGNC.	CGAS (C6orf150, cGAS, MB21D1)
Tissue specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed samples based on a combination of data from HPA, GTEX and FANTOM5. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected. Read more	Tissue enhanced (vagina)
Single cell type specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed cell types based on scRNA-seq data from normal tissues. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected. Read more	Cell type enriched (monocytes)
Blood specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed blood cell samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected. Read more	Low immune cell specificity
Brain specificityⁱ The regional specificity category is based on mRNA expression levels in the analyzed brain samples, grouped into 10 main brain regions and calculated for the three different species. The human brain expression profile is based on a combination of data from GTEX and FANTOM5. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category. Read more	Low human brain regional specificity
Cancer prognostic summary	Prognostic marker in renal cancer (unfavorable)
Predicted locationⁱ All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions. Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached. Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s). The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location. Read more	Intracellular
Subcellular summaryⁱ The main location is characterized by presence in all tested cell lines and/or increased intensity compared to other locations. Additional locations are characterized by either a markedly lower staining intensity than the main location, or that it is only observed in a subset of the cell lines.	Located in Centriolar satellite, Cytosol
Protein function (UniProt)ⁱ Useful information about the protein provided by UniProt.	Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (cGAMP) from ATP and GTP and plays a key role in innate immunity 1, 2, 3, 4, 5, 6, 7. Catalysis involves both the formation of a 2',5' phosphodiester linkage at the GpA step and the formation of a 3',5' phosphodiester linkage at the ApG step, producing c[G(2',5')pA(3',5')p] 8, 9. Acts as a key cytosolic DNA sensor, the presence of double-stranded DNA (dsDNA) in the cytoplasm being a danger signal that triggers the immune responses 10. Binds cytosolic DNA directly, leading to activation and synthesis of cGAMP, a second messenger that binds to and activates TMEM173/STING, thereby triggering type-I interferon production 11, 12. Preferentially recognizes and binds curved long DNAs 13. In contrast to other mammals, human CGAS displays species-specific mechanisms of DNA recognition and produces less cyclic GMP-AMP (cGAMP), allowing a more fine-tuned response to pathogens 14. Has antiviral activity by sensing the presence of dsDNA from DNA viruses in the cytoplasm 15. Also acts as an innate immune sensor of infection by retroviruses, such as HIV-1, by detecting the presence of reverse-transcribed DNA in the cytosol 16. Detection of retroviral reverse-transcribed DNA in the cytosol may be indirect and be mediated via interaction with PQBP1, which directly binds reverse-transcribed retroviral DNA 17. Also detects the presence of DNA from bacteria, such as M.tuberculosis 18. cGAMP can be transferred from producing cells to neighboring cells through gap junctions, leading to promote TMEM173/STING activation and convey immune response to connecting cells 19. cGAMP can also be transferred between cells by virtue of packaging within viral particles contributing to IFN-induction in newly infected cells in a cGAS-independent but TMEM173/STING-dependent manner 20. In addition to antiviral activity, also involved in the response to cellular stresses, such as senescence, DNA damage or genome instability 21, 22. Acts as a regulator of cellular senescence by binding to cytosolic chromatin fragments that are present in senescent cells, leading to trigger type-I interferon production via TMEM173/STING and promote cellular senescence (By similarity). Also involved in the inflammatory response to genome instability and double-stranded DNA breaks: acts by localizing to micronuclei arising from genome instability 23, 24. Micronuclei, which as frequently found in cancer cells, consist of chromatin surrounded by its own nuclear membrane: following breakdown of the micronuclear envelope, a process associated with chromothripsis, CGAS binds self-DNA exposed to the cytosol, leading to cGAMP synthesis and subsequent activation of TMEM173/STING and type-I interferon production 25, 26. Acts as a suppressor of DNA repair in response to DNA damage: translocates to the nucleus following dephosphorylation at Tyr-215 and inhibits homologous recombination repair by interacting with PARP1, the CGAS-PARP1 interaction leading to impede the formation of the PARP1-TIMELESS complex 27.... show less
Molecular function (UniProt)ⁱ Keywords assigned by UniProt to proteins due to their particular molecular function.	DNA-binding, Nucleotidyltransferase, Transferase
Biological process (UniProt)ⁱ Keywords assigned by UniProt to proteins because they are involved in a particular biological process.	Antiviral defense, DNA damage, DNA repair, Host-virus interaction, Immunity, Innate immunity
Ligand (UniProt)ⁱ Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.	ATP-binding, GTP-binding, Lipid-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

TISSUE ATLASⁱ Summary of data presented in the Tissue Atlas and representative images of protein expression (left) and mRNA expression (right). The images are clickable and will redirect to more Tissue Atlas data. The Tissue Atlas contains information regarding the expression profiles of protein-coding genes in normal human tissue, both on the mRNA and protein level. The protein expression data is derived from antibody-based protein profiling using immunohistochemistry. Read more

Tissue specificity (RNA)ⁱ The RNA specificity category is based on mRNA expression levels in the analyzed samples based on a combination of data from HPA, GTEX and FANTOM5. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected. Read more	Tissue enhanced (vagina)
Tissue distribution (RNA)ⁱ The RNA distribution category is based on mRNA expression levels in the analyzed samples based on a combination of data from HPA, GTEX and FANTOM5. The categories include: detected in all, detected in many, detected in some, detected in single and not detected. Read more	Detected in all
Protein expressionⁱ A summary of the overall protein expression pattern across the analyzed normal tissues. The summary is based on knowledge-based annotation. "Estimation of protein expression could not be performed. View primary data." is shown for genes analyzed with a knowledge-based approach where available RNA-seq and gene/protein characterization data has been evaluated as not sufficient in combination with immunohistochemistry data to yield a reliable estimation of the protein expression profile. Read more	Cytoplasmic and membranous expression in several tissues.

SINGLE CELL TYPE ATLASⁱ Summary of data presented in the Cell Type Atlas and an interactive image showing mRNA expression in cell type groups e.g. epithelial cells and germ cells. The image is clickable and will redirect to more Cell Type Atlas data. The Cell Type Atlas contains information about single cell type RNA expression based on scRNAseq of human tissues. The data also covers transcriptomics analysis of human blood and cultured cell lines. Read more

Cell type specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed cell types based on scRNA-seq data from normal tissues. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected. Read more	Cell type enriched (monocytes)
Cell line specificityⁱ RNA specificity category based on RNA sequencing data from all cell lines in the Human Protein Atlas. Genes are classified into six different categories (enriched, group enriched, enhanced, low specificity and not detected) according to their RNA expression levels across the panel of cell lines.	Cell line enhanced (Karpas-707, RH-30, RPMI-8226)

PATHOLOGY ATLASⁱ Summary of data presented in the Pathology Atlas , with representative images of protein expression in cancer (left) and correlation between mRNA expression and patient survival (right). Images are clickable and redirect to pages with more Pathology Atlas data. The Pathology Atlas contains mRNA and protein expression data from 17 different forms of human cancer, as well as correlation analysis of mRNA expression and patient survival. The protein expression data is derived from antibody-based protein profiling using immunohistochemistry. Read more
	Renal cancer p<0.001
Prognostic summary	Prognostic marker in renal cancer (unfavorable)
Cancer specificity (RNA)ⁱ Specificity of RNA expression in 17 cancer types is categorized as either cancer enriched, group enriched, cancer enhanced, low cancer specificity and not detected. Read more	Low cancer specificity
Cancer distribution (RNA)ⁱ Distribution of RNA expression in 17 cancer types is categorized as either detected in single, detected in some, detected in many, detected in all, or not detected. Read more	Detected in all

BRAIN ATLASⁱ Summary of data presented in the Brain Atlas and a representative image of mRNA expression in the human brain. The image is clickable and will redirect to more Brain Atlas data. The Brain Atlas explores the protein expression in the mammalian brain by visualization and integration of data from three mammalian species (human, pig and mouse). Transcriptomics data combined with affinity-based protein in situ localization down to single cell level is available in a brain-centric sub atlas of the Human Protein Atlas. Read more

Human regional specificityⁱ The regional specificity category is based on mRNA expression levels in the analyzed brain samples, grouped into 10 main brain regions and calculated for the three different species. The human brain expression profile is based on a combination of data from GTEX and FANTOM5. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category. Read more	Low region specificity
Pig regional specificityⁱ The regional specificity category is based on mRNA expression levels in the analyzed brain samples, grouped into 10 main brain regions and calculated for the three different species. The human brain expression profile is based on a combination of data from GTEX and FANTOM5. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category. Read more	Low region specificity
Mouse regional specificityⁱ The regional specificity category is based on mRNA expression levels in the analyzed brain samples, grouped into 10 main brain regions and calculated for the three different species. The human brain expression profile is based on a combination of data from GTEX and FANTOM5. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category. Read more	Low region specificity

BLOOD ATLASⁱ Summary of data presented in the Blood Atlas and a representative image of mRNA expression in immune cells in the blood. The image is clickable and will redirect to more Blood Atlas data. The Blood Atlas contains single cell type RNA information covering various immune cells in the blood, e.g. B-cells and granulocytes. Analysis of the human secretome (including annotation of the genes predicted to be actively secreted to human blood) and proteins detected in human blood are also presented. Read more

Immune cell specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected. Read more	Low cell type specificity
Detected in blood by immunoassayⁱ The blood-based immunoassay category applies to actively secreted proteins and is based on plasma or serum protein concentrations established with enzyme-linked immunosorbent assays, compiled from a literature search. The categories include: detected and not detected, where detection refers to a concentration found in the literature search. Read more	No (not applicable)
Detected in blood by mass spectrometryⁱ Detection or not of the gene in blood, based on spectral count estimations from a publicly available mass spectrometry-based plasma proteomics data set obtained from the PeptideAtlas.	No

CELL ATLASⁱ Summary of data presented in the Cell Atlas and a representative image of subcellular localization. The Cell Atlas provides RNA expression data derived from RNA sequencing of a large panel of cell lines and protein localization data derived from antibody-based profiling by immunofluorescence confocal microscopy, using a subset of cell lines selected based on RNA expression. Read more

Main locationⁱ Main subcellular location(s) and reliability score(s) for the encoded protein(s) in human cells. The main location(s) may be characterized by presence in all tested cell lines and/or ihigher staining intensity compared to the potential additional location(s). If available, links to overrepresentation analyses in Reactome, a free, open-source, curated and peer reviewed biological pathway database, are provided. An analysis is done for the corresponding gene set of the proteome localizing to the main and additional locations of the protein on this page, respectively. Read more	Localized to the Centriolar satellite
Additional locationⁱ Additonal subcellular location(s) for the encoded protein(s) in human cells. The additional location(s) may not be present i all cell lines and may have lower staining intensity compared to the main location(s). If available, links to overrepresentation analyses in Reactome, a free, open-source, curated and peer reviewed biological pathway database, are provided. An analysis is done for the corresponding gene set of the proteome localizing to the main and additional locations of the protein on this page, respectively. Read more	In addition localized to the Cytosol
Cell cycle dependencyⁱ Cell-cycle dependance of single-cell varations in RNA and/or protein expression as observed in an additional assay for characterizing single-cell varations. "NA" indicates a lack of such data. Read more	NA

GENE INFORMATIONⁱ Gene information from Ensembl and Entrez, as well as links to available gene identifiers are displayed here. Information was retrieved from Ensembl if not indicated otherwise.
Gene name	CGAS (HGNC Symbol)
Synonyms	C6orf150, cGAS, MB21D1
Description	Cyclic GMP-AMP synthase (HGNC Symbol)
Chromosome	6
Cytoband	q13
Chromosome location (bp)	73413515 - 73452276
Number of transcriptsⁱ Number of protein-coding transcripts from the gene as defined by Ensembl.	2
Protein evidence	Evidence at protein level (all genes)
Protein classⁱ Assigned HPA protein class(es) for the encoded protein(s). Read more	Enzymes
Ensembl	ENSG00000164430 (version 92.38)
Entrez gene	115004
UniProt	Q8N884 (UniProt - Evidence at protein level)
neXtProt	NX_Q8N884
Antibodypedia	CGAS antibodies

PROTEIN BROWSERⁱ

CGAS-201

CGAS-202

PROTEIN INFORMATIONⁱ The protein information section displays alternative protein-coding transcripts (splice variants) encoded by this gene according to the Ensembl database. The ENSP identifier links to the Ensembl website protein summary, while the ENST identifier links to the Ensembl website transcript summary for the selected splice variant. The data in the UniProt column can be expanded to show links to all matching UniProt identifiers for this protein. The protein classes assigned to this protein are shown if expanding the data in the protein class column. Parent protein classes are in bold font and subclasses are listed under the parent class. The Gene Ontology terms assigned to this protein are listed if expanding the Gene ontology column. The length of the protein (amino acid residues according to Ensembl), molecular mass (kDalton), predicted signal peptide (according to a majority of the signal peptide predictors SPOCTOPUS, SignalP 4.0, and Phobius) and the number of predicted transmembrane region(s) (according to MDM) are also reported.
Splice variant	UniProt	Protein class	Gene ontology	Length & mass	Signal peptide (predicted)	Transmembrane regions (predicted)
CGAS-201 ENSP00000359339 ENST00000370315	Q8N884 [Direct mapping] Cyclic GMP-AMP synthase Show all	Enzymes ENZYME proteins Transferases Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Peptideatlas) Show all	GO:0000166 [nucleotide binding] GO:0002218 [activation of innate immune response] GO:0002230 [positive regulation of defense response to virus by host] GO:0002376 [immune system process] GO:0003677 [DNA binding] GO:0003682 [chromatin binding] GO:0003690 [double-stranded DNA binding] GO:0005515 [protein binding] GO:0005524 [ATP binding] GO:0005525 [GTP binding] GO:0005737 [cytoplasm] GO:0005829 [cytosol] GO:0006974 [cellular response to DNA damage stimulus] GO:0009190 [cyclic nucleotide biosynthetic process] GO:0016740 [transferase activity] GO:0016779 [nucleotidyltransferase activity] GO:0032481 [positive regulation of type I interferon production] GO:0038001 [paracrine signaling] GO:0045087 [innate immune response] GO:0046872 [metal ion binding] GO:0051607 [defense response to virus] GO:0061501 [cyclic-GMP-AMP synthase activity] GO:0071360 [cellular response to exogenous dsRNA] GO:2000774 [positive regulation of cellular senescence] Show all	522 aa 58.8 kDa	No	0
CGAS-202 ENSP00000359342 ENST00000370318	Q8N884 [Direct mapping] Cyclic GMP-AMP synthase Show all	Enzymes ENZYME proteins Transferases Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Peptideatlas) Show all	GO:0000166 [nucleotide binding] GO:0002218 [activation of innate immune response] GO:0002230 [positive regulation of defense response to virus by host] GO:0002376 [immune system process] GO:0003677 [DNA binding] GO:0003682 [chromatin binding] GO:0003690 [double-stranded DNA binding] GO:0005515 [protein binding] GO:0005524 [ATP binding] GO:0005525 [GTP binding] GO:0005737 [cytoplasm] GO:0005829 [cytosol] GO:0006974 [cellular response to DNA damage stimulus] GO:0009190 [cyclic nucleotide biosynthetic process] GO:0016740 [transferase activity] GO:0016779 [nucleotidyltransferase activity] GO:0032481 [positive regulation of type I interferon production] GO:0038001 [paracrine signaling] GO:0045087 [innate immune response] GO:0046872 [metal ion binding] GO:0051607 [defense response to virus] GO:0061501 [cyclic-GMP-AMP synthase activity] GO:0071360 [cellular response to exogenous dsRNA] GO:2000774 [positive regulation of cellular senescence] Show all	447 aa 49.8 kDa	No	0

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The Human Protein Atlas

The Human Protein Atlas project is funded
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