CGAS

cyclic GMP-AMP synthase

Basic information

Region (hg38): 6:73413515-73452297

Previous symbols: [ "C6orf150", "MB21D1" ]

Links

ENSG00000164430 ∙ NCBI:115004 ∙ OMIM:613973 ∙ HGNC:21367 ∙ Uniprot:Q8N884 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CGAS gene.

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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			31	2		33
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			9	2		11
Total	0	0	40	4	0

Variants in CGAS

This is a list of pathogenic ClinVar variants found in the CGAS region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-73413683-T-C		not specified	Uncertain significance (Jan 03, 2024)
6-73413686-T-C		not specified	Uncertain significance (Sep 07, 2022)
6-73413694-A-G		not specified	Uncertain significance (Nov 04, 2023)
6-73413769-G-A		not specified	Uncertain significance (Nov 27, 2023)
6-73414048-T-G		not specified	Uncertain significance (Mar 31, 2023)
6-73414056-A-G		not specified	Likely benign (Feb 28, 2024)
6-73414563-T-A		not specified	Uncertain significance (Mar 01, 2023)
6-73414619-T-A		not specified	Uncertain significance (Apr 26, 2023)
6-73414637-C-T		not specified	Uncertain significance (Jun 09, 2022)
6-73416127-G-T		not specified	Likely benign (Oct 26, 2022)
6-73416149-T-C		not specified	Uncertain significance (Jun 18, 2021)
6-73425261-C-T		not specified	Uncertain significance (Mar 19, 2024)
6-73425331-T-A		not specified	Uncertain significance (Feb 09, 2022)
6-73425340-G-C		not specified	Uncertain significance (Oct 02, 2023)
6-73425426-C-T		not specified	Uncertain significance (Mar 23, 2022)
6-73425427-G-A		not specified	Uncertain significance (Dec 09, 2023)
6-73425441-T-A		not specified	Uncertain significance (Jun 17, 2024)
6-73425486-T-C		not specified	Uncertain significance (Apr 21, 2022)
6-73425497-G-T		not specified	Uncertain significance (Dec 09, 2023)
6-73428748-G-C		not specified	Uncertain significance (Apr 18, 2023)
6-73428779-C-T		not specified	Uncertain significance (Jun 07, 2023)
6-73428799-C-T		not specified	Uncertain significance (Apr 08, 2022)
6-73440233-C-T		not specified	Uncertain significance (Apr 22, 2024)
6-73440307-C-T		not specified	Uncertain significance (Apr 07, 2023)
6-73440308-G-A		not specified	Uncertain significance (Mar 15, 2024)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

• 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_gene_trap: N

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