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    CGAS cyclic GMP-AMP synthase [ Homo sapiens (human) ]

    Gene ID: 115004, updated on 16-Apr-2024

    Summary

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    Official Symbol
    CGASprovided by HGNC
    Official Full Name
    cyclic GMP-AMP synthaseprovided by HGNC
    Primary source
    HGNC:HGNC:21367
    See related
    Ensembl:ENSG00000164430 MIM:613973; AllianceGenome:HGNC:21367
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    D4; MB21D1; h-cGAS; C6orf150
    Summary
    Enables several functions, including 2',3'-cyclic GMP-AMP synthase activity; chromatin binding activity; and phosphatidylinositol-4,5-bisphosphate binding activity. Involved in several processes, including cellular response to exogenous dsRNA; positive regulation of intracellular signal transduction; and regulation of defense response. Located in several cellular components, including cytosol; nucleus; and site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Broad expression in bone marrow (RPKM 4.9), lymph node (RPKM 3.8) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    6q13
    Exon count:
    5
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (73423711..73452297, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (74600410..74628713, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (74133434..74162020, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene small nucleolar RNA U13 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:74104168-74104668 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:74108069-74108726 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:74113715-74113899 Neighboring gene oocyte expressed protein Neighboring gene DEAD-box helicase 43 Neighboring gene Sharpr-MPRA regulatory region 12175 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17333 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24743 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17334 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:74171453-74172298 Neighboring gene RNA, U6 small nuclear 975, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24747 Neighboring gene mitochondrial tRNA translation optimization 1 Neighboring gene RNA, 7SL, cytoplasmic 827, pseudogene

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Methionine restriction promotes cGAS activation and chromatin untethering through demethylation to enhance antitumor immunity. Fang L, et al. Cancer Cell, 2023 Jun 12. PMID 37267951
    2. The expression of cyclic GMP-AMP synthase in human apical periodontitis: A laboratory investigation. Yang F, et al. Int Endod J, 2023 Jun. PMID 36806027
    3. Human papillomaviruses sensitize cells to DNA damage induced apoptosis by targeting the innate immune sensor cGAS. Gusho E, et al. PLoS Pathog, 2022 Jul. PMID 35877778, Free PMC Article
    4. Varicella-Zoster virus ORF9 is an antagonist of the DNA sensor cGAS. Hertzog J, et al. EMBO J, 2022 Jul 18. PMID 35670106, Free PMC Article
    5. Nuclear soluble cGAS senses double-stranded DNA virus infection. Wu Y, et al. Commun Biol, 2022 May 10. PMID 35538147, Free PMC Article

    See all (236) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The CRL5-SPSB3 ubiquitin ligase targets nuclear cGAS for degradation.
      Title: The CRL5-SPSB3 ubiquitin ligase targets nuclear cGAS for degradation.
    2. Arginine methylation-dependent cGAS stability promotes non-small cell lung cancer cell proliferation.
      Title: Arginine methylation-dependent cGAS stability promotes non-small cell lung cancer cell proliferation.
    3. The cytosolic DNA-sensing cGAS-STING pathway in neurodegenerative diseases.
      Title: The cytosolic DNA-sensing cGAS-STING pathway in neurodegenerative diseases.
    4. Severe COVID-19 and long COVID are associated with high expression of STING, cGAS and IFN-alpha.
      Title: Severe COVID-19 and long COVID are associated with high expression of STING, cGAS and IFN-α.
    5. IUPHAR ECR review: The cGAS-STING pathway: Novel functions beyond innate immune and emerging therapeutic opportunities.
      Title: IUPHAR ECR review: The cGAS-STING pathway: Novel functions beyond innate immune and emerging therapeutic opportunities.
    6. Hypoxic glioblastoma-cell-derived extracellular vesicles impair cGAS-STING activity in macrophages.
      Title: Hypoxic glioblastoma-cell-derived extracellular vesicles impair cGAS-STING activity in macrophages.
    7. FBXO38 deficiency promotes lysosome-dependent STING degradation and inhibits cGAS-STING pathway activation.
      Title: FBXO38 deficiency promotes lysosome-dependent STING degradation and inhibits cGAS-STING pathway activation.
    8. Molecular map of cGAS-STING pathway-related genes in bladder cancer: the perspective toward immune microenvironment and prognosis.
      Title: Molecular map of cGAS-STING pathway-related genes in bladder cancer: the perspective toward immune microenvironment and prognosis.
    9. MRE11 liberates cGAS from nucleosome sequestration during tumorigenesis.
      Title: MRE11 liberates cGAS from nucleosome sequestration during tumorigenesis.
    10. Cardiovascular diseases crossroads: cGAS-STING signaling and disease progression.
      Title: Cardiovascular diseases crossroads: cGAS-STING signaling and disease progression.
    Submit: New GeneRIF Correction See all GeneRIFs (225)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    capsid gag HIV-1 CA is a determinant of innate sensing of the viral cDNA by MB21D1 (cGAS) in dendritic cells (DCs). DCs sense capsid-mutated HIV-1 and enhance stimulation of T cells in the absence of productive infection PubMed
    reverse transcriptase gag-pol HIV-1 infection induces the production of endogenous cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) in a manner that depends on cGAMP synthase (cGAS) and the reserve transcription of viral RNA to cDNA by RT PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC131892, MGC142166, MGC142168

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 2',3'-cyclic GMP-AMP synthase activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables 2',3'-cyclic GMP-AMP synthase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 2',3'-cyclic GMP-AMP synthase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables 2',3'-cyclic GMP-AMP synthase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables GTP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables chromatin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables chromatin binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables double-stranded DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables double-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables double-stranded DNA binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables molecular condensate scaffold activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables nucleosome binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables phosphatidylinositol-4,5-bisphosphate binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables poly-ADP-D-ribose modification-dependent protein binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA damage response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in DNA damage response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in DNA repair IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in activation of innate immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in activation of innate immune response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in activation of innate immune response IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cAMP-mediated signaling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cGAS/STING signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cGAS/STING signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in cGMP-mediated signaling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to exogenous dsRNA IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cytoplasmic pattern recognition receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in defense response to virus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in determination of adult lifespan IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in innate immune response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in innate immune response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in negative regulation of cGAS/STING signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of double-strand break repair via homologous recombination IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of double-strand break repair via homologous recombination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in paracrine signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in paracrine signaling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in pattern recognition receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of cellular senescence ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of defense response to virus by host IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of defense response to virus by host IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of defense response to virus by host IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of type I interferon production IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of type I interferon production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of type I interferon production TAS
    Traceable Author Statement
    more info
    		  
    involved_in regulation of T cell activation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of immunoglobulin production IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytosol TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nuclear body IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in site of double-strand break IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in site of double-strand break IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    cyclic GMP-AMP synthase
    Names
    2'3'-cGAMP synthase
    DANGER family member 4
    Mab-21 domain containing 1
    cGAMP synthase
    mab-21 domain-containing protein 1
    protein MB21D1
    NP_001397840.1
    NP_612450.2

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001410911.1 → NP_001397840.1  cyclic GMP-AMP synthase isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC019205, AL603910
      Consensus CDS
      CCDS93943.1
      UniProtKB/TrEMBL
      A0A7P0TBQ3
      Related
      ENSP00000506638.1, ENST00000680833.1

    2. NM_138441.3 → NP_612450.2  cyclic GMP-AMP synthase isoform 1

      See identical proteins and their annotated locations for NP_612450.2

      Status: VALIDATED

      Source sequence(s)
      AC019205, AK097148, BC108714, DA375117
      Consensus CDS
      CCDS4978.1
      UniProtKB/Swiss-Prot
      L0L2J9, Q14CV6, Q32NC9, Q5SWL0, Q5SWL1, Q8N884, Q96E45
      Related
      ENSP00000359339.3, ENST00000370315.4
      Conserved Domains (2) summary
      pfam03281
      Location:214 → 510
      Mab-21; Mab-21 protein
      cl00936
      Location:15 → 117
      RecX; RecX family

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      73423711..73452297 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      74600410..74628713 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8N884.2 GenPept UniProtKB/Swiss-Prot:Q8N884

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Molecular Biology Databases
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