CGAS
cyclic GMP-AMP synthase
Basic information
Region (hg38): 6:73413515-73452297
Previous symbols: [ "C6orf150", "MB21D1" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (80 variants)
- not_provided (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CGAS gene is commonly pathogenic or not. These statistics are base on transcript: NM_000138441.3. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 77 | 80 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 78 | 3 | 0 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CGAS | protein_coding | protein_coding | ENST00000370315 | 5 | 38762 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 8.69e-9 | 0.295 | 125702 | 0 | 44 | 125746 | 0.000175 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.880 | 226 | 266 | 0.848 | 0.0000128 | 3371 |
| Missense in Polyphen | 50 | 67.088 | 0.74529 | 933 | ||
| Synonymous | -0.863 | 119 | 108 | 1.11 | 0.00000526 | 1011 |
| Loss of Function | 0.657 | 14 | 16.9 | 0.828 | 8.11e-7 | 235 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000475 | 0.000475 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000546 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000177 | 0.000176 |
| Middle Eastern | 0.0000546 | 0.0000544 |
| South Asian | 0.000337 | 0.000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (cGAMP) from ATP and GTP (PubMed:23258413, PubMed:23707061, PubMed:23722159, PubMed:24077100, PubMed:25131990). 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] (PubMed:28363908, PubMed:28214358). 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 (PubMed:28363908). 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 (PubMed:28363908, PubMed:28314590). Has antiviral activity by sensing the presence of dsDNA from DNA viruses in the cytoplasm (PubMed:28363908). 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 (PubMed:23929945). 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 (PubMed:26046437). Also detects the presence of DNA from bacteria, such as M.tuberculosis (PubMed:26048138). 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 (PubMed:24077100). 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 (PubMed:26229115). In addition to antiviral activity, also involved in the response to cellular stresses, such as senescence, DNA damage or genome instability (PubMed:28738408, PubMed:28759889). 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 (PubMed:28738408, PubMed:28759889). 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 (PubMed:28738408, PubMed:28759889). {ECO:0000250|UniProtKB:Q8C6L5, ECO:0000269|PubMed:21478870, ECO:0000269|PubMed:23258413, ECO:0000269|PubMed:23707061, ECO:0000269|PubMed:23707065, ECO:0000269|PubMed:23722159, ECO:0000269|PubMed:23929945, ECO:0000269|PubMed:24077100, ECO:0000269|PubMed:24116191, ECO:0000269|PubMed:24462292, ECO:0000269|PubMed:25131990, ECO:0000269|PubMed:26046437, ECO:0000269|PubMed:26048138, ECO:0000269|PubMed:26229115, ECO:0000269|PubMed:26300263, ECO:0000269|PubMed:28214358, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:28363908, ECO:0000269|PubMed:28738408, ECO:0000269|PubMed:28759889}.;
- Pathway
- Cytosolic DNA-sensing pathway - Homo sapiens (human);STING mediated induction of host immune responses;Innate Immune System;Immune System;Cytosolic sensors of pathogen-associated DNA
(Consensus)
Intolerance Scores
- loftool
- rvis_EVS
- 0.24
- rvis_percentile_EVS
- 69.37
Haploinsufficiency Scores
- pHI
- 0.0494
- hipred
- N
- hipred_score
- 0.153
- ghis
- 0.416
Essentials
- essential_gene_CRISPR
- essential_gene_CRISPR2
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- gene_indispensability_score
Mouse Genome Informatics
- Gene name
- Cgas
- Phenotype
- immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; homeostasis/metabolism phenotype;
Zebrafish Information Network
- Gene name
- cgas
- Affected structure
- whole organism
- Phenotype tag
- abnormal
- Phenotype quality
- decreased pigmentation
Gene ontology
- Biological process
- activation of innate immune response;positive regulation of defense response to virus by host;regulation of immunoglobulin production;cellular response to DNA damage stimulus;determination of adult lifespan;positive regulation of cGMP-mediated signaling;positive regulation of type I interferon production;paracrine signaling;positive regulation of cAMP-mediated signaling;innate immune response;regulation of T cell activation;defense response to virus;cellular response to exogenous dsRNA;positive regulation of cellular senescence
- Cellular component
- cytosol
- Molecular function
- DNA binding;chromatin binding;double-stranded DNA binding;protein binding;ATP binding;GTP binding;metal ion binding;cyclic-GMP-AMP synthase activity