DISEASES

Disease-gene associations mined from literature

Literature associating CGAS and cyclothymic disorder

CGAS [ENSP00000359339]

Cyclic GMP-AMP synthase; Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (cGAMP) from ATP and GTP and plays a key role in innate immunity (PubMed:23258413, PubMed:23707061, PubMed:23722159, PubMed:24077100, PubMed:25131990, PubMed:29976794, PubMed:30799039). 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 . 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 . Preferentially recognizes and binds curved long DNAs . In contrast to other mammals, human CGAS displays species-specific mechanisms of DNA recognition and produces less cyclic GMP-AMP (cGAMP), allowing a more fine-tuned response to pathogens . Has antiviral activity by sensing the presence of dsDNA from DNA viruses in the cytoplasm . 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 . 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 . Also detects the presence of DNA from bacteria, such as M.tuberculosis . 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 . 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 . 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 . 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 . Acts as a suppressor of DNA repair in response to DNA damage: translocates to the nucleus following dephosphorylation at Tyr-215 and inhibits homologous recombination repair by interacting with PARP1, the CGAS-PARP1 interaction leading to impede the formation of the PARP1-TIMELESS complex . 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, ECO:0000269|PubMed:29976794, ECO:0000269|PubMed:30007416,; Belongs to the mab-21 family.

Synonyms:  CGAS,  Q8N884,  Q8N884p,  hQ8N884,  115004 ...

Linkouts:  STRING  Pharos  UniProt