Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	-	522	6q13	CGAS	cyclic GMP-AMP synthase
Mouse	-	507	9 E1	Cgas	cyclic GMP-AMP synthase
Rat	-	358	8q31	Cgas	cyclic GMP-AMP synthase

Database Links
Alphafold	Q8N884 (Hs)
BRENDA	2.7.7.86
ChEMBL Target	CHEMBL4105728 (Hs), CHEMBL4523383 (Mm)
Ensembl Gene	ENSG00000164430 (Hs), ENSMUSG00000032344 (Mm)
Entrez Gene	115004 (Hs), 214763 (Mm), 682147 (Rn)
Human Protein Atlas	ENSG00000164430 (Hs)
KEGG Enzyme	2.7.7.86
KEGG Gene	hsa:115004 (Hs), mmu:214763 (Mm), rno:682147 (Rn)
OMIM	613973 (Hs)
Pharos	Q8N884 (Hs)
RefSeq Nucleotide	NM_138441 (Hs), NM_173386 (Mm)
RefSeq Protein	NP_612450 (Hs), NP_775562 (Mm)
UniProtKB	Q8N884 (Hs), Q8C6L5 (Mm)
Wikipedia	CGAS (Hs)

Enzyme Reaction
EC Number: 2.7.7.86 ATP + GTP <=> 2 diphosphate + cyclic G-P(2'-5')A-P(3'-5')

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Inhibitors
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Reference PF‐06928215 Hs Inhibition 6.7 pKd 1 ⤷ pKd 6.7 (Kd 2x10-7 M) [1] Description: Binding affinity determined by SPR. PF‐06928215 Hs Inhibition 5.3 pIC50 1 ⤷ pIC50 5.3 (IC50 4.9x10-6 M) [1] Description: Enzyme inhibition determined by FP assay.

Immunopharmacology Comments

Cyclic GMP-AMP synthase (cGAS) directly binds to cytosolic DNA, and in response catalyses the synthesis of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). Thus cGAS acts as a sensor of DNA in the cytoplasm, which is an indicator of pathogen invasion [3]. The generated cGAMP then binds to STING (stimulator of interferon genes) which is a key mediator of the innate immune system, whose activation induces production of interferons and inflammatory cytokines (via IRF3‐ and NF-κB‐dependent transcription). The cGAS-STING pathway is also associated with a number of human sterile inflammatory conditions and cancer. Pharmacological modulation of both cGAS [2] and STING is being explored for clinical potential. cGAS‐specific small molecule inhibitor development has primarily identified compounds that occupy the enzyme's active site.