CGAS Gene - Cyclic GMP-AMP Synthase
Key cytosolic DNA sensor and innate immune activator
Gene Information Card
| Symbol | CGAS |
|---|---|
| Full Name | Cyclic GMP-AMP Synthase |
| Gene Type | Protein coding |
| Chromosomal Location | 6q13 |
| NCBI Gene ID | 115004 ncbi.nlm.nih.gov/gene/115004 |
| Ensembl ID | ENSG00000172915 |
| UniProt ID | Q8N884 |
| OMIM ID | 613973 |
| HGNC ID | 21367 |
| Aliases | cGAS, C6orf150, h-cGAS, MB21D1 |
Description
The CGAS gene encodes cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor that binds double-stranded DNA (dsDNA) from pathogens or damaged host cells. Upon DNA binding, cGAS catalyzes the synthesis of the second messenger cyclic GMP-AMP (cGAMP), which activates the STING (TMEM173) adaptor protein, leading to type I interferon production and pro-inflammatory cytokine expression. cGAS is a critical component of the innate immune system, involved in antiviral defense, cellular senescence, and autoimmune regulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Aicardi-Goutières syndrome (AGS) | Gain-of-function mutations in CGAS lead to constitutive cGAMP production and chronic type I interferon signaling, causing neuroinflammation and autoimmunity. | OMIM #613973; PMID: 32371413 |
| Systemic lupus erythematosus (SLE) | CGAS variants and overexpression contribute to aberrant interferon activation via the cGAS-STING pathway, promoting autoantibody production. | PMID: 28813417 |
| Cancer (various) | CGAS loss-of-function or epigenetic silencing reduces tumor immune surveillance; cGAS activation can promote antitumor immunity or, in some contexts, metastasis via STING-dependent inflammation. | PMID: 31570896; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 10.2 | Medium |
| Spleen | 8.5 | Medium |
| Whole blood | 6.1 | Medium |
| Liver | 4.8 | Low |
| Brain | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 12.3 | High expression; used in cGAS functional studies |
| HeLa (cervical) | 7.8 | Medium expression |
| HEK293 (embryonic kidney) | 5.4 | Low expression |
| Jurkat (T-cell) | 3.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.490G>A (p.Gly164Arg) | Missense | <0.01% | Gain-of-function; associated with Aicardi-Goutières syndrome |
| c.715C>T (p.Arg239Trp) | Missense | <0.01% | Gain-of-function; increased cGAMP production |
| c.1000C>T (p.Arg334Trp) | Missense | <0.01% | Loss-of-function; reduced DNA binding |
| c.1240G>A (p.Glu414Lys) | Missense | <0.01% | Loss-of-function; impaired catalytic activity |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce cGAS DNA binding or catalytic activity (e.g., p.Arg334Trp, p.Glu414Lys) impair cGAMP synthesis and downstream STING activation, potentially compromising antiviral immunity.
Gain of Function (GOF)
Mutations that enhance cGAS activity (e.g., p.Gly164Arg, p.Arg239Trp) lead to constitutive cGAMP production, chronic interferon signaling, and autoimmune phenotypes such as Aicardi-Goutières syndrome.
Dominant Negative (DN)
No well-characterized dominant-negative mutations have been reported for CGAS; most pathogenic variants are gain- or loss-of-function.
View complete mutation data：
Gene Ontology (GO)
| • cytosolic DNA sensing pathway | • cGAMP synthase activity |
| • double-stranded DNA binding | • innate immune response |
| • nucleotidyltransferase activity | • STING binding |
| • type I interferon production |
Pathways
• cGAS-STING signaling pathway
• Cytosolic DNA-sensing pathway
• Innate immune system
• Interferon signaling
Protein Summary
Cyclic GMP-AMP synthase (cGAS) is a 522-amino-acid protein containing a nucleotidyltransferase domain and a DNA-binding domain. It exists as a monomer in the cytosol and, upon binding dsDNA, undergoes conformational changes that activate its catalytic activity. cGAS synthesizes 2'3'-cGAMP from ATP and GTP, which acts as a second messenger to activate STING. The protein is post-translationally modified by phosphorylation, ubiquitination, and glutamylation, which regulate its stability and activity. cGAS is essential for antiviral responses against DNA viruses and for sensing cytosolic self-DNA in autoimmune and inflammatory diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CGAS Knockout HEK293 Cell Line | EDJ-KQ3916 | Human | 115004 | Details Get a Quote |
| CGAS Knockout HeLa Cell Line | EDC90494 | Human | 115004 | Details Get a Quote |
| CGAS Knockout A-549 Cell Line | EDJ-KQ26140 | Human | 115004 | Details Get a Quote |
| Cgas Knockout 4T1 Cell Line | EDJ-KZ155 | Mouse | 214763 | Details Get a Quote |
| CGAS Knockout HCT 116 Cell Line | EDJ-KQ74860 | Human | 115004 | Details Get a Quote |
| CGAS Knockout THP-1 Cell Line | EDJ-KQ78073 | Human | 21367 | Details Get a Quote |
| Cgas Knock-in BV-2-cas9 Stable Cell Line | EDC06024 | Mouse | 115004 | Details Get a Quote |
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