CGAS

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0002218 activation of innate immune response	IBA GO_REF:0000033	ACCEPT	Summary: cGAS detection of cytosolic DNA activates the innate immune response via cGAMP/STING/IRF3. Reason: Core innate-immune function of cGAS, supported by knockdown/reconstitution and many downstream studies. Retain.
GO:0002218 activation of innate immune response	IDA PMID:23929945 Cyclic GMP-AMP synthase is an innate immune sensor of HIV an...	ACCEPT	Summary: cGAS detection of cytosolic DNA activates the innate immune response via cGAMP/STING/IRF3. Reason: Core innate-immune function of cGAS, supported by knockdown/reconstitution and many downstream studies. Retain.
GO:0002218 activation of innate immune response	IDA PMID:24077100 Cell intrinsic immunity spreads to bystander cells via the i...	ACCEPT	Summary: cGAS detection of cytosolic DNA activates the innate immune response via cGAMP/STING/IRF3. Reason: Core innate-immune function of cGAS, supported by knockdown/reconstitution and many downstream studies. Retain.
GO:0002218 activation of innate immune response	IDA PMID:26046437 PQBP1 Is a Proximal Sensor of the cGAS-Dependent Innate Resp...	ACCEPT	Summary: cGAS detection of cytosolic DNA activates the innate immune response via cGAMP/STING/IRF3. Reason: Core innate-immune function of cGAS, supported by knockdown/reconstitution and many downstream studies. Retain.
GO:0002218 activation of innate immune response	IDA PMID:28363908 Nonspecific DNA Binding of cGAS N Terminus Promotes cGAS Act...	ACCEPT	Summary: cGAS detection of cytosolic DNA activates the innate immune response via cGAMP/STING/IRF3. Reason: Core innate-immune function of cGAS, supported by knockdown/reconstitution and many downstream studies. Retain.
GO:0002218 activation of innate immune response	IDA PMID:29426904 TRIM56-mediated monoubiquitination of cGAS for cytosolic DNA...	ACCEPT	Summary: cGAS detection of cytosolic DNA activates the innate immune response via cGAMP/STING/IRF3. Reason: Core innate-immune function of cGAS, supported by knockdown/reconstitution and many downstream studies. Retain.
GO:0002218 activation of innate immune response	IDA PMID:30007416 Structure of the Human cGAS-DNA Complex Reveals Enhanced Con...	ACCEPT	Summary: cGAS detection of cytosolic DNA activates the innate immune response via cGAMP/STING/IRF3. Reason: Core innate-immune function of cGAS, supported by knockdown/reconstitution and many downstream studies. Retain.
GO:0002218 activation of innate immune response	IDA PMID:32817552 KAT5 acetylates cGAS to promote innate immune response to DN...	ACCEPT	Summary: cGAS detection of cytosolic DNA activates the innate immune response via cGAMP/STING/IRF3. Reason: Core innate-immune function of cGAS, supported by knockdown/reconstitution and many downstream studies. Retain.
GO:0002218 activation of innate immune response	IDA PMID:32911482 Structural mechanism of cGAS inhibition by the nucleosome.	ACCEPT	Summary: cGAS detection of cytosolic DNA activates the innate immune response via cGAMP/STING/IRF3. Reason: Core innate-immune function of cGAS, supported by knockdown/reconstitution and many downstream studies. Retain.
GO:0002218 activation of innate immune response	IDA PMID:32912999 Structural basis for the inhibition of cGAS by nucleosomes.	ACCEPT	Summary: cGAS detection of cytosolic DNA activates the innate immune response via cGAMP/STING/IRF3. Reason: Core innate-immune function of cGAS, supported by knockdown/reconstitution and many downstream studies. Retain.
GO:0002218 activation of innate immune response	IDA PMID:33542149 Phosphorylation and chromatin tethering prevent cGAS activat...	ACCEPT	Summary: cGAS detection of cytosolic DNA activates the innate immune response via cGAMP/STING/IRF3. Reason: Core innate-immune function of cGAS, supported by knockdown/reconstitution and many downstream studies. Retain.
GO:0002218 activation of innate immune response	IDA PMID:35438208 ZDHHC18 negatively regulates cGAS-mediated innate immunity t...	ACCEPT	Summary: cGAS detection of cytosolic DNA activates the innate immune response via cGAMP/STING/IRF3. Reason: Core innate-immune function of cGAS, supported by knockdown/reconstitution and many downstream studies. Retain.
GO:0002218 activation of innate immune response	IEA GO_REF:0000107	ACCEPT	Summary: cGAS detection of cytosolic DNA activates the innate immune response via cGAMP/STING/IRF3. Reason: Core innate-immune function of cGAS, supported by knockdown/reconstitution and many downstream studies. Retain.
GO:0002218 activation of innate immune response	IMP PMID:23258413 Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activ...	ACCEPT	Summary: cGAS detection of cytosolic DNA activates the innate immune response via cGAMP/STING/IRF3. Reason: Core innate-immune function of cGAS, supported by knockdown/reconstitution and many downstream studies. Retain.
GO:0002221 pattern recognition receptor signaling pathway	IDA PMID:23258413 Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activ...	ACCEPT	Summary: cGAS functions as a cytosolic pattern-recognition receptor for DNA, initiating PRR signaling. Reason: cGAS is a bona fide cytosolic DNA PRR; supported by its discovery paper. Retain.
GO:0002230 positive regulation of defense response to virus by host	IBA GO_REF:0000033	ACCEPT	Summary: cGAS positively regulates host defense against viruses by sensing viral DNA and inducing interferon. Reason: Supported by experimental studies of DNA-virus and retrovirus sensing. Retain.
GO:0002230 positive regulation of defense response to virus by host	IDA PMID:23929945 Cyclic GMP-AMP synthase is an innate immune sensor of HIV an...	ACCEPT	Summary: cGAS positively regulates host defense against viruses by sensing viral DNA and inducing interferon. Reason: Supported by experimental studies of DNA-virus and retrovirus sensing. Retain.
GO:0002230 positive regulation of defense response to virus by host	IDA PMID:24077100 Cell intrinsic immunity spreads to bystander cells via the i...	ACCEPT	Summary: cGAS positively regulates host defense against viruses by sensing viral DNA and inducing interferon. Reason: Supported by experimental studies of DNA-virus and retrovirus sensing. Retain.
GO:0002230 positive regulation of defense response to virus by host	IDA PMID:26046437 PQBP1 Is a Proximal Sensor of the cGAS-Dependent Innate Resp...	ACCEPT	Summary: cGAS positively regulates host defense against viruses by sensing viral DNA and inducing interferon. Reason: Supported by experimental studies of DNA-virus and retrovirus sensing. Retain.
GO:0002230 positive regulation of defense response to virus by host	IEA GO_REF:0000120	ACCEPT	Summary: cGAS positively regulates host defense against viruses by sensing viral DNA and inducing interferon. Reason: Supported by experimental studies of DNA-virus and retrovirus sensing. Retain.
GO:0002230 positive regulation of defense response to virus by host	IMP PMID:23258413 Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activ...	ACCEPT	Summary: cGAS positively regulates host defense against viruses by sensing viral DNA and inducing interferon. Reason: Supported by experimental studies of DNA-virus and retrovirus sensing. Retain.
GO:0002753 cytoplasmic pattern recognition receptor signaling pathway	IDA PMID:23258413 Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activ...	ACCEPT	Summary: cGAS mediates cytoplasmic pattern-recognition receptor signaling in response to cytosolic DNA. Reason: A specific and accurate description of cGAS PRR signaling, experimentally supported. Retain.
GO:0003677 DNA binding	IDA PMID:23258413 Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activ...	MODIFY	Summary: cGAS binds DNA, but the experimentally supported and biologically informative activity is specifically double-stranded DNA binding. Reason: 'DNA binding' is more general than warranted; cGAS specifically binds dsDNA (and does not bind RNA). Replace with the more specific double-stranded DNA binding term, which is already annotated with strong experimental support. Proposed replacements: double-stranded DNA binding Supporting Evidence: PMID:23258413 cGAS may contain two separate DNA binding domains at the N-terminus
GO:0003677 DNA binding	IEA GO_REF:0000107	MODIFY	Summary: cGAS binds DNA, but the experimentally supported and biologically informative activity is specifically double-stranded DNA binding. Reason: 'DNA binding' is more general than warranted; cGAS specifically binds dsDNA (and does not bind RNA). Replace with the more specific double-stranded DNA binding term, which is already annotated with strong experimental support. Proposed replacements: double-stranded DNA binding
GO:0003682 chromatin binding	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Nuclear cGAS associates with chromatin; this reflects its steady-state nuclear tethering and nucleosome-mediated sequestration rather than its core cytosolic sensing function. Reason: Chromatin binding is experimentally supported and biologically real, but it describes the inhibitory nuclear pool of cGAS (and its enzyme-independent nuclear roles), not the core DNA-sensing/synthase function. The more informative molecular descriptor is nucleosome binding (GO:0031491). Keep as non-core.
GO:0003682 chromatin binding	IDA PMID:28738408 cGAS surveillance of micronuclei links genome instability to...	KEEP AS NON CORE	Summary: Nuclear cGAS associates with chromatin; this reflects its steady-state nuclear tethering and nucleosome-mediated sequestration rather than its core cytosolic sensing function. Reason: Chromatin binding is experimentally supported and biologically real, but it describes the inhibitory nuclear pool of cGAS (and its enzyme-independent nuclear roles), not the core DNA-sensing/synthase function. The more informative molecular descriptor is nucleosome binding (GO:0031491). Keep as non-core.
GO:0003682 chromatin binding	IDA PMID:32817552 KAT5 acetylates cGAS to promote innate immune response to DN...	KEEP AS NON CORE	Summary: Nuclear cGAS associates with chromatin; this reflects its steady-state nuclear tethering and nucleosome-mediated sequestration rather than its core cytosolic sensing function. Reason: Chromatin binding is experimentally supported and biologically real, but it describes the inhibitory nuclear pool of cGAS (and its enzyme-independent nuclear roles), not the core DNA-sensing/synthase function. The more informative molecular descriptor is nucleosome binding (GO:0031491). Keep as non-core.
GO:0003682 chromatin binding	IDA PMID:32911482 Structural mechanism of cGAS inhibition by the nucleosome.	KEEP AS NON CORE	Summary: Nuclear cGAS associates with chromatin; this reflects its steady-state nuclear tethering and nucleosome-mediated sequestration rather than its core cytosolic sensing function. Reason: Chromatin binding is experimentally supported and biologically real, but it describes the inhibitory nuclear pool of cGAS (and its enzyme-independent nuclear roles), not the core DNA-sensing/synthase function. The more informative molecular descriptor is nucleosome binding (GO:0031491). Keep as non-core.
GO:0003682 chromatin binding	IDA PMID:32912999 Structural basis for the inhibition of cGAS by nucleosomes.	KEEP AS NON CORE	Summary: Nuclear cGAS associates with chromatin; this reflects its steady-state nuclear tethering and nucleosome-mediated sequestration rather than its core cytosolic sensing function. Reason: Chromatin binding is experimentally supported and biologically real, but it describes the inhibitory nuclear pool of cGAS (and its enzyme-independent nuclear roles), not the core DNA-sensing/synthase function. The more informative molecular descriptor is nucleosome binding (GO:0031491). Keep as non-core.
GO:0003682 chromatin binding	IDA PMID:33051594 Structural basis for nucleosome-mediated inhibition of cGAS ...	KEEP AS NON CORE	Summary: Nuclear cGAS associates with chromatin; this reflects its steady-state nuclear tethering and nucleosome-mediated sequestration rather than its core cytosolic sensing function. Reason: Chromatin binding is experimentally supported and biologically real, but it describes the inhibitory nuclear pool of cGAS (and its enzyme-independent nuclear roles), not the core DNA-sensing/synthase function. The more informative molecular descriptor is nucleosome binding (GO:0031491). Keep as non-core.
GO:0003682 chromatin binding	IDA PMID:33542149 Phosphorylation and chromatin tethering prevent cGAS activat...	KEEP AS NON CORE	Summary: Nuclear cGAS associates with chromatin; this reflects its steady-state nuclear tethering and nucleosome-mediated sequestration rather than its core cytosolic sensing function. Reason: Chromatin binding is experimentally supported and biologically real, but it describes the inhibitory nuclear pool of cGAS (and its enzyme-independent nuclear roles), not the core DNA-sensing/synthase function. The more informative molecular descriptor is nucleosome binding (GO:0031491). Keep as non-core.
GO:0003682 chromatin binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Nuclear cGAS associates with chromatin; this reflects its steady-state nuclear tethering and nucleosome-mediated sequestration rather than its core cytosolic sensing function. Reason: Chromatin binding is experimentally supported and biologically real, but it describes the inhibitory nuclear pool of cGAS (and its enzyme-independent nuclear roles), not the core DNA-sensing/synthase function. The more informative molecular descriptor is nucleosome binding (GO:0031491). Keep as non-core.
GO:0003690 double-stranded DNA binding	IBA GO_REF:0000033	ACCEPT	Summary: cGAS directly binds double-stranded DNA in a sequence-independent, length-dependent manner; dsDNA binding is the sensing/input activity that triggers catalysis. Reason: Direct dsDNA binding is a well-established core function shown by many experimental studies and is required for cGAS activation. Retain as core.
GO:0003690 double-stranded DNA binding	IDA PMID:24077100 Cell intrinsic immunity spreads to bystander cells via the i...	ACCEPT	Summary: cGAS directly binds double-stranded DNA in a sequence-independent, length-dependent manner; dsDNA binding is the sensing/input activity that triggers catalysis. Reason: Direct dsDNA binding is a well-established core function shown by many experimental studies and is required for cGAS activation. Retain as core.
GO:0003690 double-stranded DNA binding	IDA PMID:28363908 Nonspecific DNA Binding of cGAS N Terminus Promotes cGAS Act...	ACCEPT	Summary: cGAS directly binds double-stranded DNA in a sequence-independent, length-dependent manner; dsDNA binding is the sensing/input activity that triggers catalysis. Reason: Direct dsDNA binding is a well-established core function shown by many experimental studies and is required for cGAS activation. Retain as core.
GO:0003690 double-stranded DNA binding	IDA PMID:29937271 Human Cytomegalovirus Protein UL31 Inhibits DNA Sensing of c...	ACCEPT	Summary: cGAS directly binds double-stranded DNA in a sequence-independent, length-dependent manner; dsDNA binding is the sensing/input activity that triggers catalysis. Reason: Direct dsDNA binding is a well-established core function shown by many experimental studies and is required for cGAS activation. Retain as core.
GO:0003690 double-stranded DNA binding	IDA PMID:30007416 Structure of the Human cGAS-DNA Complex Reveals Enhanced Con...	ACCEPT	Summary: cGAS directly binds double-stranded DNA in a sequence-independent, length-dependent manner; dsDNA binding is the sensing/input activity that triggers catalysis. Reason: Direct dsDNA binding is a well-established core function shown by many experimental studies and is required for cGAS activation. Retain as core.
GO:0003690 double-stranded DNA binding	IDA PMID:32792394 BAF restricts cGAS on nuclear DNA to prevent innate immune a...	ACCEPT	Summary: cGAS directly binds double-stranded DNA in a sequence-independent, length-dependent manner; dsDNA binding is the sensing/input activity that triggers catalysis. Reason: Direct dsDNA binding is a well-established core function shown by many experimental studies and is required for cGAS activation. Retain as core.
GO:0003690 double-stranded DNA binding	IDA PMID:32817552 KAT5 acetylates cGAS to promote innate immune response to DN...	ACCEPT	Summary: cGAS directly binds double-stranded DNA in a sequence-independent, length-dependent manner; dsDNA binding is the sensing/input activity that triggers catalysis. Reason: Direct dsDNA binding is a well-established core function shown by many experimental studies and is required for cGAS activation. Retain as core.
GO:0003690 double-stranded DNA binding	IDA PMID:32911482 Structural mechanism of cGAS inhibition by the nucleosome.	ACCEPT	Summary: cGAS directly binds double-stranded DNA in a sequence-independent, length-dependent manner; dsDNA binding is the sensing/input activity that triggers catalysis. Reason: Direct dsDNA binding is a well-established core function shown by many experimental studies and is required for cGAS activation. Retain as core.
GO:0003690 double-stranded DNA binding	IDA PMID:32912999 Structural basis for the inhibition of cGAS by nucleosomes.	ACCEPT	Summary: cGAS directly binds double-stranded DNA in a sequence-independent, length-dependent manner; dsDNA binding is the sensing/input activity that triggers catalysis. Reason: Direct dsDNA binding is a well-established core function shown by many experimental studies and is required for cGAS activation. Retain as core.
GO:0003690 double-stranded DNA binding	IDA PMID:33051594 Structural basis for nucleosome-mediated inhibition of cGAS ...	ACCEPT	Summary: cGAS directly binds double-stranded DNA in a sequence-independent, length-dependent manner; dsDNA binding is the sensing/input activity that triggers catalysis. Reason: Direct dsDNA binding is a well-established core function shown by many experimental studies and is required for cGAS activation. Retain as core.
GO:0003690 double-stranded DNA binding	IDA PMID:33542149 Phosphorylation and chromatin tethering prevent cGAS activat...	ACCEPT	Summary: cGAS directly binds double-stranded DNA in a sequence-independent, length-dependent manner; dsDNA binding is the sensing/input activity that triggers catalysis. Reason: Direct dsDNA binding is a well-established core function shown by many experimental studies and is required for cGAS activation. Retain as core.
GO:0003690 double-stranded DNA binding	IDA PMID:33762328 Arginine methyltransferase PRMT5 negatively regulates cGAS-m...	ACCEPT	Summary: cGAS directly binds double-stranded DNA in a sequence-independent, length-dependent manner; dsDNA binding is the sensing/input activity that triggers catalysis. Reason: Direct dsDNA binding is a well-established core function shown by many experimental studies and is required for cGAS activation. Retain as core.
GO:0003690 double-stranded DNA binding	IDA PMID:35438208 ZDHHC18 negatively regulates cGAS-mediated innate immunity t...	ACCEPT	Summary: cGAS directly binds double-stranded DNA in a sequence-independent, length-dependent manner; dsDNA binding is the sensing/input activity that triggers catalysis. Reason: Direct dsDNA binding is a well-established core function shown by many experimental studies and is required for cGAS activation. Retain as core.
GO:0003690 double-stranded DNA binding	IDA PMID:35460603 Cytoplasmic PARP1 links the genome instability to the inhibi...	ACCEPT	Summary: cGAS directly binds double-stranded DNA in a sequence-independent, length-dependent manner; dsDNA binding is the sensing/input activity that triggers catalysis. Reason: Direct dsDNA binding is a well-established core function shown by many experimental studies and is required for cGAS activation. Retain as core.
GO:0003690 double-stranded DNA binding	IEA GO_REF:0000107	ACCEPT	Summary: cGAS directly binds double-stranded DNA in a sequence-independent, length-dependent manner; dsDNA binding is the sensing/input activity that triggers catalysis. Reason: Direct dsDNA binding is a well-established core function shown by many experimental studies and is required for cGAS activation. Retain as core.
GO:0003690 double-stranded DNA binding	TAS PMID:37403426 MicroRNA-4691-3p inhibits the inflammatory response by targe...	ACCEPT	Summary: cGAS directly binds double-stranded DNA in a sequence-independent, length-dependent manner; dsDNA binding is the sensing/input activity that triggers catalysis. Reason: Direct dsDNA binding is a well-established core function shown by many experimental studies and is required for cGAS activation. Retain as core.
GO:0005515 protein binding	IPI PMID:26046437 PQBP1 Is a Proximal Sensor of the cGAS-Dependent Innate Resp...	REMOVE	Summary: Generic 'protein binding' is uninformative about cGAS molecular function; the specific interaction is captured elsewhere or does not define a distinct cGAS activity. Reason: Per curation guidelines, GO:0005515 conveys no functional information. Removal does not imply the reported interaction is false; the biologically relevant consequences of specific interactors are captured by process/regulatory terms and by more informative MF terms where warranted.
GO:0005515 protein binding	IPI PMID:30135424 ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innat...	REMOVE	Summary: Generic 'protein binding' is uninformative about cGAS molecular function; the specific interaction is captured elsewhere or does not define a distinct cGAS activity. Reason: Per curation guidelines, GO:0005515 conveys no functional information. Removal does not imply the reported interaction is false; the biologically relevant consequences of specific interactors are captured by process/regulatory terms and by more informative MF terms where warranted.
GO:0005515 protein binding	IPI PMID:30356214 Nuclear cGAS suppresses DNA repair and promotes tumorigenesi...	REMOVE	Summary: Generic 'protein binding' is uninformative about cGAS molecular function; the specific interaction is captured elsewhere or does not define a distinct cGAS activity. Reason: Per curation guidelines, GO:0005515 conveys no functional information. Removal does not imply the reported interaction is false; the biologically relevant consequences of specific interactors are captured by process/regulatory terms and by more informative MF terms where warranted.
GO:0005515 protein binding	IPI PMID:30356214 Nuclear cGAS suppresses DNA repair and promotes tumorigenesi...	REMOVE	Summary: Generic 'protein binding' is uninformative about cGAS molecular function; the specific interaction is captured elsewhere or does not define a distinct cGAS activity. Reason: Per curation guidelines, GO:0005515 conveys no functional information. Removal does not imply the reported interaction is false; the biologically relevant consequences of specific interactors are captured by process/regulatory terms and by more informative MF terms where warranted.
GO:0005515 protein binding	IPI PMID:30510222 G3BP1 promotes DNA binding and activation of cGAS.	REMOVE	Summary: Generic 'protein binding' is uninformative about cGAS molecular function; the specific interaction is captured elsewhere or does not define a distinct cGAS activity. Reason: Per curation guidelines, GO:0005515 conveys no functional information. Removal does not imply the reported interaction is false; the biologically relevant consequences of specific interactors are captured by process/regulatory terms and by more informative MF terms where warranted.
GO:0005515 protein binding	IPI PMID:35322803 PCBP2 maintains antiviral signaling homeostasis by regulatin...	REMOVE	Summary: Generic 'protein binding' is uninformative about cGAS molecular function; the specific interaction is captured elsewhere or does not define a distinct cGAS activity. Reason: Per curation guidelines, GO:0005515 conveys no functional information. Removal does not imply the reported interaction is false; the biologically relevant consequences of specific interactors are captured by process/regulatory terms and by more informative MF terms where warranted.
GO:0005546 phosphatidylinositol-4,5-bisphosphate binding	IDA PMID:30827685 Phosphoinositide Interactions Position cGAS at the Plasma Me...	KEEP AS NON CORE	Summary: cGAS binds phosphatidylinositol-4,5-bisphosphate, which positions a pool of cGAS at the plasma membrane to help distinguish self from viral DNA. Reason: PI(4,5)P2 binding is experimentally shown and biologically meaningful for membrane targeting, but it is an accessory localization mechanism rather than the core sensing/catalytic function. Keep as non-core.
GO:0005634 nucleus	EXP PMID:29263269 Human Cytomegalovirus Tegument Protein pp65 (pUL83) Dampens ...	ACCEPT	Summary: cGAS is predominantly nuclear at steady state, tightly tethered to chromatin; the nucleus is a major site of localization and of its enzyme-independent functions. Reason: Nuclear localization is supported by many independent experimental studies. Retain.
GO:0005634 nucleus	EXP PMID:30270045 NONO Detects the Nuclear HIV Capsid to Promote cGAS-Mediated...	ACCEPT	Summary: cGAS is predominantly nuclear at steady state, tightly tethered to chromatin; the nucleus is a major site of localization and of its enzyme-independent functions. Reason: Nuclear localization is supported by many independent experimental studies. Retain.
GO:0005634 nucleus	EXP PMID:30811988 The N-Terminal Domain of cGAS Determines Preferential Associ...	ACCEPT	Summary: cGAS is predominantly nuclear at steady state, tightly tethered to chromatin; the nucleus is a major site of localization and of its enzyme-independent functions. Reason: Nuclear localization is supported by many independent experimental studies. Retain.
GO:0005634 nucleus	EXP PMID:31299200 The Cytoplasmic DNA Sensor cGAS Promotes Mitotic Cell Death.	ACCEPT	Summary: cGAS is predominantly nuclear at steady state, tightly tethered to chromatin; the nucleus is a major site of localization and of its enzyme-independent functions. Reason: Nuclear localization is supported by many independent experimental studies. Retain.
GO:0005634 nucleus	EXP PMID:31808743 Tight nuclear tethering of cGAS is essential for preventing ...	ACCEPT	Summary: cGAS is predominantly nuclear at steady state, tightly tethered to chromatin; the nucleus is a major site of localization and of its enzyme-independent functions. Reason: Nuclear localization is supported by many independent experimental studies. Retain.
GO:0005634 nucleus	EXP PMID:33476576 ER-directed TREX1 limits cGAS activation at micronuclei.	ACCEPT	Summary: cGAS is predominantly nuclear at steady state, tightly tethered to chromatin; the nucleus is a major site of localization and of its enzyme-independent functions. Reason: Nuclear localization is supported by many independent experimental studies. Retain.
GO:0005634 nucleus	EXP PMID:34111399 Translation stress and collided ribosomes are co-activators ...	ACCEPT	Summary: cGAS is predominantly nuclear at steady state, tightly tethered to chromatin; the nucleus is a major site of localization and of its enzyme-independent functions. Reason: Nuclear localization is supported by many independent experimental studies. Retain.
GO:0005634 nucleus	EXP PMID:35438208 ZDHHC18 negatively regulates cGAS-mediated innate immunity t...	ACCEPT	Summary: cGAS is predominantly nuclear at steady state, tightly tethered to chromatin; the nucleus is a major site of localization and of its enzyme-independent functions. Reason: Nuclear localization is supported by many independent experimental studies. Retain.
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: cGAS is predominantly nuclear at steady state, tightly tethered to chromatin; the nucleus is a major site of localization and of its enzyme-independent functions. Reason: Nuclear localization is supported by many independent experimental studies. Retain.
GO:0005634 nucleus	IDA PMID:29937271 Human Cytomegalovirus Protein UL31 Inhibits DNA Sensing of c...	ACCEPT	Summary: cGAS is predominantly nuclear at steady state, tightly tethered to chromatin; the nucleus is a major site of localization and of its enzyme-independent functions. Reason: Nuclear localization is supported by many independent experimental studies. Retain.
GO:0005634 nucleus	IDA PMID:30356214 Nuclear cGAS suppresses DNA repair and promotes tumorigenesi...	ACCEPT	Summary: cGAS is predominantly nuclear at steady state, tightly tethered to chromatin; the nucleus is a major site of localization and of its enzyme-independent functions. Reason: Nuclear localization is supported by many independent experimental studies. Retain.
GO:0005634 nucleus	IDA PMID:31544964 Chromatin-bound cGAS is an inhibitor of DNA repair and hence...	ACCEPT	Summary: cGAS is predominantly nuclear at steady state, tightly tethered to chromatin; the nucleus is a major site of localization and of its enzyme-independent functions. Reason: Nuclear localization is supported by many independent experimental studies. Retain.
GO:0005634 nucleus	IDA PMID:32792394 BAF restricts cGAS on nuclear DNA to prevent innate immune a...	ACCEPT	Summary: cGAS is predominantly nuclear at steady state, tightly tethered to chromatin; the nucleus is a major site of localization and of its enzyme-independent functions. Reason: Nuclear localization is supported by many independent experimental studies. Retain.
GO:0005634 nucleus	IDA PMID:33230297 cGAS-mediated induction of type I interferon due to inborn e...	ACCEPT	Summary: cGAS is predominantly nuclear at steady state, tightly tethered to chromatin; the nucleus is a major site of localization and of its enzyme-independent functions. Reason: Nuclear localization is supported by many independent experimental studies. Retain.
GO:0005634 nucleus	IDA PMID:33406424 A Nuclear Export Signal Is Required for cGAS to Sense Cytoso...	ACCEPT	Summary: cGAS is predominantly nuclear at steady state, tightly tethered to chromatin; the nucleus is a major site of localization and of its enzyme-independent functions. Reason: Nuclear localization is supported by many independent experimental studies. Retain.
GO:0005634 nucleus	IDA PMID:38418882 The CRL5-SPSB3 ubiquitin ligase targets nuclear cGAS for deg...	ACCEPT	Summary: cGAS is predominantly nuclear at steady state, tightly tethered to chromatin; the nucleus is a major site of localization and of its enzyme-independent functions. Reason: Nuclear localization is supported by many independent experimental studies. Retain.
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: cGAS is predominantly nuclear at steady state, tightly tethered to chromatin; the nucleus is a major site of localization and of its enzyme-independent functions. Reason: Nuclear localization is supported by many independent experimental studies. Retain.
GO:0005654 nucleoplasm	IDA GO_REF:0000052	ACCEPT	Summary: cGAS localizes to the nucleoplasm (immunofluorescence, HPA). Reason: Consistent with the well-established nuclear localization of cGAS. Retain.
GO:0005694 chromosome	EXP PMID:30811988 The N-Terminal Domain of cGAS Determines Preferential Associ...	ACCEPT	Summary: Nuclear cGAS associates with chromosomes, including centromeric DNA and mitotic chromatin. Reason: Chromosome association is supported by multiple experimental studies and underlies chromatin tethering and nuclear functions. Retain.
GO:0005694 chromosome	EXP PMID:31299200 The Cytoplasmic DNA Sensor cGAS Promotes Mitotic Cell Death.	ACCEPT	Summary: Nuclear cGAS associates with chromosomes, including centromeric DNA and mitotic chromatin. Reason: Chromosome association is supported by multiple experimental studies and underlies chromatin tethering and nuclear functions. Retain.
GO:0005694 chromosome	EXP PMID:31544964 Chromatin-bound cGAS is an inhibitor of DNA repair and hence...	ACCEPT	Summary: Nuclear cGAS associates with chromosomes, including centromeric DNA and mitotic chromatin. Reason: Chromosome association is supported by multiple experimental studies and underlies chromatin tethering and nuclear functions. Retain.
GO:0005694 chromosome	EXP PMID:32351706 Phosphorylation of cGAS by CDK1 impairs self-DNA sensing in ...	ACCEPT	Summary: Nuclear cGAS associates with chromosomes, including centromeric DNA and mitotic chromatin. Reason: Chromosome association is supported by multiple experimental studies and underlies chromatin tethering and nuclear functions. Retain.
GO:0005694 chromosome	EXP PMID:32912999 Structural basis for the inhibition of cGAS by nucleosomes.	ACCEPT	Summary: Nuclear cGAS associates with chromosomes, including centromeric DNA and mitotic chromatin. Reason: Chromosome association is supported by multiple experimental studies and underlies chromatin tethering and nuclear functions. Retain.
GO:0005694 chromosome	EXP PMID:33051594 Structural basis for nucleosome-mediated inhibition of cGAS ...	ACCEPT	Summary: Nuclear cGAS associates with chromosomes, including centromeric DNA and mitotic chromatin. Reason: Chromosome association is supported by multiple experimental studies and underlies chromatin tethering and nuclear functions. Retain.
GO:0005694 chromosome	IEA GO_REF:0000044	ACCEPT	Summary: Nuclear cGAS associates with chromosomes, including centromeric DNA and mitotic chromatin. Reason: Chromosome association is supported by multiple experimental studies and underlies chromatin tethering and nuclear functions. Retain.
GO:0005737 cytoplasm	IDA PMID:23258413 Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activ...	ACCEPT	Summary: cGAS acts in the cytoplasm; the more specific compartment for its active pool is the cytosol. Reason: Cytoplasm is accurate and consistent with the specific cytosol annotations. Retain.
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: The cytosol is where cGAS carries out active detection of aberrant/foreign dsDNA and synthesizes cGAMP. Reason: Cytosolic localization of the DNA-sensing, catalytically active pool of cGAS is well established. Retain.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: The cytosol is where cGAS carries out active detection of aberrant/foreign dsDNA and synthesizes cGAMP. Reason: Cytosolic localization of the DNA-sensing, catalytically active pool of cGAS is well established. Retain.
GO:0005829 cytosol	IDA PMID:23258413 Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activ...	ACCEPT	Summary: The cytosol is where cGAS carries out active detection of aberrant/foreign dsDNA and synthesizes cGAMP. Reason: Cytosolic localization of the DNA-sensing, catalytically active pool of cGAS is well established. Retain.
GO:0005829 cytosol	IDA PMID:29937271 Human Cytomegalovirus Protein UL31 Inhibits DNA Sensing of c...	ACCEPT	Summary: The cytosol is where cGAS carries out active detection of aberrant/foreign dsDNA and synthesizes cGAMP. Reason: Cytosolic localization of the DNA-sensing, catalytically active pool of cGAS is well established. Retain.
GO:0005829 cytosol	IDA PMID:30356214 Nuclear cGAS suppresses DNA repair and promotes tumorigenesi...	ACCEPT	Summary: The cytosol is where cGAS carries out active detection of aberrant/foreign dsDNA and synthesizes cGAMP. Reason: Cytosolic localization of the DNA-sensing, catalytically active pool of cGAS is well established. Retain.
GO:0005829 cytosol	IDA PMID:30827685 Phosphoinositide Interactions Position cGAS at the Plasma Me...	ACCEPT	Summary: The cytosol is where cGAS carries out active detection of aberrant/foreign dsDNA and synthesizes cGAMP. Reason: Cytosolic localization of the DNA-sensing, catalytically active pool of cGAS is well established. Retain.
GO:0005829 cytosol	IDA PMID:31544964 Chromatin-bound cGAS is an inhibitor of DNA repair and hence...	ACCEPT	Summary: The cytosol is where cGAS carries out active detection of aberrant/foreign dsDNA and synthesizes cGAMP. Reason: Cytosolic localization of the DNA-sensing, catalytically active pool of cGAS is well established. Retain.
GO:0005829 cytosol	IDA PMID:32792394 BAF restricts cGAS on nuclear DNA to prevent innate immune a...	ACCEPT	Summary: The cytosol is where cGAS carries out active detection of aberrant/foreign dsDNA and synthesizes cGAMP. Reason: Cytosolic localization of the DNA-sensing, catalytically active pool of cGAS is well established. Retain.
GO:0005829 cytosol	IDA PMID:32912999 Structural basis for the inhibition of cGAS by nucleosomes.	ACCEPT	Summary: The cytosol is where cGAS carries out active detection of aberrant/foreign dsDNA and synthesizes cGAMP. Reason: Cytosolic localization of the DNA-sensing, catalytically active pool of cGAS is well established. Retain.
GO:0005829 cytosol	IDA PMID:33406424 A Nuclear Export Signal Is Required for cGAS to Sense Cytoso...	ACCEPT	Summary: The cytosol is where cGAS carries out active detection of aberrant/foreign dsDNA and synthesizes cGAMP. Reason: Cytosolic localization of the DNA-sensing, catalytically active pool of cGAS is well established. Retain.
GO:0005829 cytosol	IDA PMID:35438208 ZDHHC18 negatively regulates cGAS-mediated innate immunity t...	ACCEPT	Summary: The cytosol is where cGAS carries out active detection of aberrant/foreign dsDNA and synthesizes cGAMP. Reason: Cytosolic localization of the DNA-sensing, catalytically active pool of cGAS is well established. Retain.
GO:0005829 cytosol	IDA PMID:38421872 HERC5-catalyzed ISGylation potentiates cGAS-mediated innate ...	ACCEPT	Summary: The cytosol is where cGAS carries out active detection of aberrant/foreign dsDNA and synthesizes cGAMP. Reason: Cytosolic localization of the DNA-sensing, catalytically active pool of cGAS is well established. Retain.
GO:0005829 cytosol	IEA GO_REF:0000120	ACCEPT	Summary: The cytosol is where cGAS carries out active detection of aberrant/foreign dsDNA and synthesizes cGAMP. Reason: Cytosolic localization of the DNA-sensing, catalytically active pool of cGAS is well established. Retain.
GO:0005829 cytosol	TAS PMID:37403426 MicroRNA-4691-3p inhibits the inflammatory response by targe...	ACCEPT	Summary: The cytosol is where cGAS carries out active detection of aberrant/foreign dsDNA and synthesizes cGAMP. Reason: Cytosolic localization of the DNA-sensing, catalytically active pool of cGAS is well established. Retain.
GO:0005829 cytosol	TAS Reactome:R-HSA-3244614	ACCEPT	Summary: The cytosol is where cGAS carries out active detection of aberrant/foreign dsDNA and synthesizes cGAMP. Reason: Cytosolic localization of the DNA-sensing, catalytically active pool of cGAS is well established. Retain.
GO:0005829 cytosol	TAS Reactome:R-HSA-3244647	ACCEPT	Summary: The cytosol is where cGAS carries out active detection of aberrant/foreign dsDNA and synthesizes cGAMP. Reason: Cytosolic localization of the DNA-sensing, catalytically active pool of cGAS is well established. Retain.
GO:0005829 cytosol	TAS Reactome:R-HSA-9920882	ACCEPT	Summary: The cytosol is where cGAS carries out active detection of aberrant/foreign dsDNA and synthesizes cGAMP. Reason: Cytosolic localization of the DNA-sensing, catalytically active pool of cGAS is well established. Retain.
GO:0005886 plasma membrane	EXP PMID:32351706 Phosphorylation of cGAS by CDK1 impairs self-DNA sensing in ...	KEEP AS NON CORE	Summary: A pool of cGAS is a peripheral plasma-membrane protein, positioned there via PI(4,5)P2 and MYO1F. Reason: Plasma-membrane localization is experimentally supported and functionally relevant to self/non-self discrimination, but is an accessory location rather than the core compartment. Keep as non-core.
GO:0005886 plasma membrane	IDA PMID:30827685 Phosphoinositide Interactions Position cGAS at the Plasma Me...	KEEP AS NON CORE	Summary: A pool of cGAS is a peripheral plasma-membrane protein, positioned there via PI(4,5)P2 and MYO1F. Reason: Plasma-membrane localization is experimentally supported and functionally relevant to self/non-self discrimination, but is an accessory location rather than the core compartment. Keep as non-core.
GO:0005886 plasma membrane	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: A pool of cGAS is a peripheral plasma-membrane protein, positioned there via PI(4,5)P2 and MYO1F. Reason: Plasma-membrane localization is experimentally supported and functionally relevant to self/non-self discrimination, but is an accessory location rather than the core compartment. Keep as non-core.
GO:0006974 DNA damage response	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: cGAS surveils micronuclei and self-DNA arising from genome instability/DNA damage, linking DNA damage to innate immunity. Reason: cGAS senses the DNA products of damage/genome instability rather than executing canonical DNA-damage repair; this connects to but is not the core sensing/synthase function. Keep as non-core.
GO:0006974 DNA damage response	IDA PMID:28738408 cGAS surveillance of micronuclei links genome instability to...	KEEP AS NON CORE	Summary: cGAS surveils micronuclei and self-DNA arising from genome instability/DNA damage, linking DNA damage to innate immunity. Reason: cGAS senses the DNA products of damage/genome instability rather than executing canonical DNA-damage repair; this connects to but is not the core sensing/synthase function. Keep as non-core. Supporting Evidence: PMID:28738408 cGAS localises to micronuclei upon nuclear envelope rupture
GO:0009898 cytoplasmic side of plasma membrane	IDA PMID:39694035 MYO1F positions cGAS on the plasma membrane to ensure full a...	KEEP AS NON CORE	Summary: MYO1F positions cGAS on the cytoplasmic (inner) side of the plasma membrane for full signaling. Reason: A specific, experimentally supported membrane localization for a cGAS pool; accessory to the core function. Keep as non-core.
GO:0016604 nuclear body	IDA GO_REF:0000052	ACCEPT	Summary: Immunofluorescence localizes a fraction of cGAS to nuclear bodies (HPA). Reason: Supported by curated immunofluorescence evidence and consistent with nuclear cGAS pools. Retain.
GO:0031491 nucleosome binding	IDA PMID:32911482 Structural mechanism of cGAS inhibition by the nucleosome.	KEEP AS NON CORE	Summary: cGAS binds the nucleosome via the histone H2A-H2B acidic patch, which competitively blocks DNA binding and keeps nuclear cGAS inactive. Reason: Nucleosome binding is a specific, structurally-defined molecular interaction that is the mechanistic basis of cGAS auto-inhibition in the nucleus. It is accurate and informative but regulatory/inhibitory rather than the core activating function; keep as non-core.
GO:0031491 nucleosome binding	IDA PMID:32912999 Structural basis for the inhibition of cGAS by nucleosomes.	KEEP AS NON CORE	Summary: cGAS binds the nucleosome via the histone H2A-H2B acidic patch, which competitively blocks DNA binding and keeps nuclear cGAS inactive. Reason: Nucleosome binding is a specific, structurally-defined molecular interaction that is the mechanistic basis of cGAS auto-inhibition in the nucleus. It is accurate and informative but regulatory/inhibitory rather than the core activating function; keep as non-core. Supporting Evidence: PMID:32912999 cGAS monomer binds to the proximal NCP at the acidic patch on the H2A-H2B dimer surface
GO:0031491 nucleosome binding	IDA PMID:33051594 Structural basis for nucleosome-mediated inhibition of cGAS ...	KEEP AS NON CORE	Summary: cGAS binds the nucleosome via the histone H2A-H2B acidic patch, which competitively blocks DNA binding and keeps nuclear cGAS inactive. Reason: Nucleosome binding is a specific, structurally-defined molecular interaction that is the mechanistic basis of cGAS auto-inhibition in the nucleus. It is accurate and informative but regulatory/inhibitory rather than the core activating function; keep as non-core.
GO:0031491 nucleosome binding	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: cGAS binds the nucleosome via the histone H2A-H2B acidic patch, which competitively blocks DNA binding and keeps nuclear cGAS inactive. Reason: Nucleosome binding is a specific, structurally-defined molecular interaction that is the mechanistic basis of cGAS auto-inhibition in the nucleus. It is accurate and informative but regulatory/inhibitory rather than the core activating function; keep as non-core.
GO:0032481 positive regulation of type I interferon production	IBA GO_REF:0000033	ACCEPT	Summary: cGAS-generated cGAMP activates STING1, positively regulating type I interferon (IFN-beta) production. Reason: A direct and central downstream output of cGAS signaling, well supported experimentally. Retain as core.
GO:0032481 positive regulation of type I interferon production	IDA PMID:24077100 Cell intrinsic immunity spreads to bystander cells via the i...	ACCEPT	Summary: cGAS-generated cGAMP activates STING1, positively regulating type I interferon (IFN-beta) production. Reason: A direct and central downstream output of cGAS signaling, well supported experimentally. Retain as core.
GO:0032481 positive regulation of type I interferon production	IDA PMID:26046437 PQBP1 Is a Proximal Sensor of the cGAS-Dependent Innate Resp...	ACCEPT	Summary: cGAS-generated cGAMP activates STING1, positively regulating type I interferon (IFN-beta) production. Reason: A direct and central downstream output of cGAS signaling, well supported experimentally. Retain as core.
GO:0032481 positive regulation of type I interferon production	IDA PMID:28363908 Nonspecific DNA Binding of cGAS N Terminus Promotes cGAS Act...	ACCEPT	Summary: cGAS-generated cGAMP activates STING1, positively regulating type I interferon (IFN-beta) production. Reason: A direct and central downstream output of cGAS signaling, well supported experimentally. Retain as core.
GO:0032481 positive regulation of type I interferon production	IDA PMID:28738408 cGAS surveillance of micronuclei links genome instability to...	ACCEPT	Summary: cGAS-generated cGAMP activates STING1, positively regulating type I interferon (IFN-beta) production. Reason: A direct and central downstream output of cGAS signaling, well supported experimentally. Retain as core.
GO:0032481 positive regulation of type I interferon production	IDA PMID:32792394 BAF restricts cGAS on nuclear DNA to prevent innate immune a...	ACCEPT	Summary: cGAS-generated cGAMP activates STING1, positively regulating type I interferon (IFN-beta) production. Reason: A direct and central downstream output of cGAS signaling, well supported experimentally. Retain as core.
GO:0032481 positive regulation of type I interferon production	IDA PMID:33230297 cGAS-mediated induction of type I interferon due to inborn e...	ACCEPT	Summary: cGAS-generated cGAMP activates STING1, positively regulating type I interferon (IFN-beta) production. Reason: A direct and central downstream output of cGAS signaling, well supported experimentally. Retain as core.
GO:0032481 positive regulation of type I interferon production	IDA PMID:33406424 A Nuclear Export Signal Is Required for cGAS to Sense Cytoso...	ACCEPT	Summary: cGAS-generated cGAMP activates STING1, positively regulating type I interferon (IFN-beta) production. Reason: A direct and central downstream output of cGAS signaling, well supported experimentally. Retain as core.
GO:0032481 positive regulation of type I interferon production	IEA GO_REF:0000107	ACCEPT	Summary: cGAS-generated cGAMP activates STING1, positively regulating type I interferon (IFN-beta) production. Reason: A direct and central downstream output of cGAS signaling, well supported experimentally. Retain as core.
GO:0032481 positive regulation of type I interferon production	TAS Reactome:R-HSA-1834941	ACCEPT	Summary: cGAS-generated cGAMP activates STING1, positively regulating type I interferon (IFN-beta) production. Reason: A direct and central downstream output of cGAS signaling, well supported experimentally. Retain as core.
GO:0035861 site of double-strand break	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: cGAS can localize to sites of DNA double-strand breaks, relating to its nuclear role in suppressing homologous recombination. Reason: Supported experimentally and consistent with the enzyme-independent DNA-repair-suppressing function, but peripheral to the core sensing/synthase activity. Keep as non-core.
GO:0035861 site of double-strand break	IDA PMID:30356214 Nuclear cGAS suppresses DNA repair and promotes tumorigenesi...	KEEP AS NON CORE	Summary: cGAS can localize to sites of DNA double-strand breaks, relating to its nuclear role in suppressing homologous recombination. Reason: Supported experimentally and consistent with the enzyme-independent DNA-repair-suppressing function, but peripheral to the core sensing/synthase activity. Keep as non-core.
GO:0038001 paracrine signaling	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: cGAMP produced by cGAS is transferred to neighboring cells through gap junctions, spreading STING activation (paracrine/bystander immunity). Reason: Experimentally supported but represents a downstream, intercellular consequence of cGAMP rather than the core cell-intrinsic function of cGAS. Keep as non-core.
GO:0038001 paracrine signaling	IDA PMID:24077100 Cell intrinsic immunity spreads to bystander cells via the i...	KEEP AS NON CORE	Summary: cGAMP produced by cGAS is transferred to neighboring cells through gap junctions, spreading STING activation (paracrine/bystander immunity). Reason: Experimentally supported but represents a downstream, intercellular consequence of cGAMP rather than the core cell-intrinsic function of cGAS. Keep as non-core. Supporting Evidence: PMID:24077100 transferred from producing cells to neighbouring cells through gap junctions
GO:0038001 paracrine signaling	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: cGAMP produced by cGAS is transferred to neighboring cells through gap junctions, spreading STING activation (paracrine/bystander immunity). Reason: Experimentally supported but represents a downstream, intercellular consequence of cGAMP rather than the core cell-intrinsic function of cGAS. Keep as non-core.
GO:0042802 identical protein binding	IEA GO_REF:0000107	MODIFY	Summary: cGAS self-association is more precisely captured as protein homodimerization activity, the DNA-induced 2:2 dimer required for activation. Reason: 'Identical protein binding' is redundant with, and less informative than, the experimentally supported protein homodimerization activity that is already annotated. Replace with the more specific term. Proposed replacements: protein homodimerization activity
GO:0042803 protein homodimerization activity	IDA PMID:29426904 TRIM56-mediated monoubiquitination of cGAS for cytosolic DNA...	ACCEPT	Summary: DNA binding drives cGAS to form a 2:2 homodimer with dsDNA, an oligomerization step required for enzymatic activation. Reason: Protein homodimerization activity is experimentally and structurally supported and is mechanistically integral to cGAS activation. Retain.
GO:0042803 protein homodimerization activity	IDA PMID:32911482 Structural mechanism of cGAS inhibition by the nucleosome.	ACCEPT	Summary: DNA binding drives cGAS to form a 2:2 homodimer with dsDNA, an oligomerization step required for enzymatic activation. Reason: Protein homodimerization activity is experimentally and structurally supported and is mechanistically integral to cGAS activation. Retain.
GO:0042803 protein homodimerization activity	IDA PMID:32912999 Structural basis for the inhibition of cGAS by nucleosomes.	ACCEPT	Summary: DNA binding drives cGAS to form a 2:2 homodimer with dsDNA, an oligomerization step required for enzymatic activation. Reason: Protein homodimerization activity is experimentally and structurally supported and is mechanistically integral to cGAS activation. Retain.
GO:0042803 protein homodimerization activity	IDA PMID:33051594 Structural basis for nucleosome-mediated inhibition of cGAS ...	ACCEPT	Summary: DNA binding drives cGAS to form a 2:2 homodimer with dsDNA, an oligomerization step required for enzymatic activation. Reason: Protein homodimerization activity is experimentally and structurally supported and is mechanistically integral to cGAS activation. Retain.
GO:0042803 protein homodimerization activity	IDA PMID:33542149 Phosphorylation and chromatin tethering prevent cGAS activat...	ACCEPT	Summary: DNA binding drives cGAS to form a 2:2 homodimer with dsDNA, an oligomerization step required for enzymatic activation. Reason: Protein homodimerization activity is experimentally and structurally supported and is mechanistically integral to cGAS activation. Retain.
GO:0042803 protein homodimerization activity	IDA PMID:35438208 ZDHHC18 negatively regulates cGAS-mediated innate immunity t...	ACCEPT	Summary: DNA binding drives cGAS to form a 2:2 homodimer with dsDNA, an oligomerization step required for enzymatic activation. Reason: Protein homodimerization activity is experimentally and structurally supported and is mechanistically integral to cGAS activation. Retain.
GO:0042803 protein homodimerization activity	IEA GO_REF:0000120	ACCEPT	Summary: DNA binding drives cGAS to form a 2:2 homodimer with dsDNA, an oligomerization step required for enzymatic activation. Reason: Protein homodimerization activity is experimentally and structurally supported and is mechanistically integral to cGAS activation. Retain.
GO:0045738 negative regulation of DNA repair	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: cGAS negatively regulates DNA repair (mouse-based electronic annotation), consistent with its documented suppression of homologous recombination. Reason: This broader term is consistent with the more specific, experimentally supported negative regulation of HR-mediated DSB repair; an IEA being more general is acceptable. Keep as a non-core regulatory role, matching the KEEP_AS_NON_CORE treatment of the specific child term GO:2000042, so the broad IEA does not outrank the specific experimental term in the core set.
GO:0051607 defense response to virus	IDA PMID:21478870 A diverse range of gene products are effectors of the type I...	ACCEPT	Summary: cGAS mediates defense against DNA viruses (e.g., HSV-1, vaccinia) and retroviruses through the cGAMP/STING/IFN axis. Reason: Antiviral defense is a core physiological role of cGAS supported by multiple experimental studies. Retain.
GO:0051607 defense response to virus	IDA PMID:23929945 Cyclic GMP-AMP synthase is an innate immune sensor of HIV an...	ACCEPT	Summary: cGAS mediates defense against DNA viruses (e.g., HSV-1, vaccinia) and retroviruses through the cGAMP/STING/IFN axis. Reason: Antiviral defense is a core physiological role of cGAS supported by multiple experimental studies. Retain.
GO:0051607 defense response to virus	IDA PMID:24077100 Cell intrinsic immunity spreads to bystander cells via the i...	ACCEPT	Summary: cGAS mediates defense against DNA viruses (e.g., HSV-1, vaccinia) and retroviruses through the cGAMP/STING/IFN axis. Reason: Antiviral defense is a core physiological role of cGAS supported by multiple experimental studies. Retain.
GO:0051607 defense response to virus	IDA PMID:26046437 PQBP1 Is a Proximal Sensor of the cGAS-Dependent Innate Resp...	ACCEPT	Summary: cGAS mediates defense against DNA viruses (e.g., HSV-1, vaccinia) and retroviruses through the cGAMP/STING/IFN axis. Reason: Antiviral defense is a core physiological role of cGAS supported by multiple experimental studies. Retain.
GO:0051607 defense response to virus	IEA GO_REF:0000107	ACCEPT	Summary: cGAS mediates defense against DNA viruses (e.g., HSV-1, vaccinia) and retroviruses through the cGAMP/STING/IFN axis. Reason: Antiviral defense is a core physiological role of cGAS supported by multiple experimental studies. Retain.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	EXP PMID:23258412 Cyclic GMP-AMP is an endogenous second messenger in innate i...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	EXP PMID:23707061 Structure of human cGAS reveals a conserved family of second...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	EXP PMID:23722159 Structural mechanism of cytosolic DNA sensing by cGAS.	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	EXP PMID:25131990 Structure-guided reprogramming of human cGAS dinucleotide li...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	EXP PMID:29976794 DNA-induced liquid phase condensation of cGAS activates inna...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	EXP PMID:30799039 Acetylation Blocks cGAS Activity and Inhibits Self-DNA-Induc...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	EXP PMID:31142647 Human cGAS catalytic domain has an additional DNA-binding in...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	EXP PMID:32814054 Mn(2+) Directly Activates cGAS and Structural Analysis Sugge...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	EXP PMID:37802025 Targeting LYPLAL1-mediated cGAS depalmitoylation enhances th...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	IBA GO_REF:0000033	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	IDA PMID:23258413 Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activ...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core. Supporting Evidence: PMID:23258413 purified cGAS catalyzes the synthesis of cGAMP from ATP and GTP
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	IDA PMID:24077100 Cell intrinsic immunity spreads to bystander cells via the i...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	IDA PMID:26300263 Ancient Origin of cGAS-STING Reveals Mechanism of Universal ...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	IDA PMID:28214358 The N terminus of cGAS de-oligomerizes the cGAS:DNA complex ...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	IDA PMID:28363908 Nonspecific DNA Binding of cGAS N Terminus Promotes cGAS Act...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	IDA PMID:28738408 cGAS surveillance of micronuclei links genome instability to...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	IDA PMID:28934246 Discovery of PF-06928215 as a high affinity inhibitor of cGA...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	IDA PMID:29426904 TRIM56-mediated monoubiquitination of cGAS for cytosolic DNA...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	IDA PMID:29937271 Human Cytomegalovirus Protein UL31 Inhibits DNA Sensing of c...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	IDA PMID:30007416 Structure of the Human cGAS-DNA Complex Reveals Enhanced Con...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	IDA PMID:32792394 BAF restricts cGAS on nuclear DNA to prevent innate immune a...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	IDA PMID:32911482 Structural mechanism of cGAS inhibition by the nucleosome.	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	IDA PMID:32912999 Structural basis for the inhibition of cGAS by nucleosomes.	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	IDA PMID:33542149 Phosphorylation and chromatin tethering prevent cGAS activat...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	IDA PMID:38740774 The structural basis for 2'-5'/3'-5'-cGAMP synthesis by cGAS...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	IEA GO_REF:0000120	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0061501 2',3'-cyclic GMP-AMP synthase activity	TAS PMID:37403426 MicroRNA-4691-3p inhibits the inflammatory response by targe...	ACCEPT	Summary: cGAS is the DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP; this is its defining catalytic activity (EC 2.7.7.86). Reason: This is the core molecular function of cGAS, established biochemically at its discovery and confirmed by numerous structural and enzymatic studies. Retain as core.
GO:0071360 cellular response to exogenous dsRNA	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Human cGAS is a DNA sensor and does not bind or respond to RNA; a 'response to exogenous dsRNA' role is not supported for human cGAS. Reason: cGAS specifically binds dsDNA and not RNA, and RNA does not stimulate its activity. The dsRNA term is a stimulus term-selection error in the donor annotation rather than a family-level RNA-sensing signal - the PTN002579681 IBD for GO:0071360 is seeded solely by mouse Cgas (interpro/panther/PTHR10656/PTHR10656-paint.tsv), not by any RNA-sensing invertebrate cGLR, and the mouse donor evidence assays cytosolic/exogenous DNA rather than exogenous dsRNA. Marking as over-annotated rather than removing, since the donor biology is genuine cGAS nucleic-acid sensing carrying the wrong stimulus term. Propagation Review Root cause: SOURCE BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN002579681 · cGAS node (PTHR10656) SOURCE BAD This IBD node inherits the mouse dsRNA stimulus term-selection error; PTHR10656-paint.tsv shows the GO:0071360 IBD is seeded only by MGI:MGI:2442261, so the node carries no independent RNA-sensing cGLR evidence. MGI:MGI:2442261 · mouse Cgas SOURCE BAD Mouse cGAS is likewise a DNA sensor; the dsRNA-response term is not a demonstrated cGAS function, so the source annotation is itself wrong rather than merely untransferable. Supporting Evidence: PMID:23258413 biotinylated RNA did not bind cGAS
GO:0071360 cellular response to exogenous dsRNA	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Human cGAS is a DNA sensor and does not bind or respond to RNA; a 'response to exogenous dsRNA' role is not supported for human cGAS. Reason: cGAS specifically binds dsDNA and not RNA, and RNA does not stimulate its activity. The dsRNA term is a stimulus term-selection error in the donor annotation rather than a family-level RNA-sensing signal - the PTN002579681 IBD for GO:0071360 is seeded solely by mouse Cgas (interpro/panther/PTHR10656/PTHR10656-paint.tsv), not by any RNA-sensing invertebrate cGLR, and the mouse donor evidence assays cytosolic/exogenous DNA rather than exogenous dsRNA. Marking as over-annotated rather than removing, since the donor biology is genuine cGAS nucleic-acid sensing carrying the wrong stimulus term. Supporting Evidence: PMID:23258413 biotinylated RNA did not bind cGAS
GO:0140374 antiviral innate immune response	IDA PMID:38421872 HERC5-catalyzed ISGylation potentiates cGAS-mediated innate ...	ACCEPT	Summary: cGAS contributes to the antiviral innate immune response. Reason: Supported by experimental evidence for cGAS-driven antiviral immunity. Retain.
GO:0140693 molecular condensate scaffold activity	IDA PMID:32911482 Structural mechanism of cGAS inhibition by the nucleosome.	ACCEPT	Summary: cGAS acts as the scaffold of DNA-induced biomolecular condensates (liquid-like droplets) that concentrate enzyme and substrates and are the sites of its activation. Reason: DNA-driven liquid-liquid phase separation into cGAS-DNA condensates is experimentally and structurally supported and is integral to how cGAS becomes catalytically active. Retain as core. Supporting Evidence: PMID:29976794 DNA binding to cGAS induces a robust phase transition to liquid-like droplets, which function as micro reactors in which the enzyme and reactants are concentrated to greatly enhance the production of cGAMP.
GO:0140693 molecular condensate scaffold activity	IDA PMID:32912999 Structural basis for the inhibition of cGAS by nucleosomes.	ACCEPT	Summary: cGAS acts as the scaffold of DNA-induced biomolecular condensates (liquid-like droplets) that concentrate enzyme and substrates and are the sites of its activation. Reason: DNA-driven liquid-liquid phase separation into cGAS-DNA condensates is experimentally and structurally supported and is integral to how cGAS becomes catalytically active. Retain as core. Supporting Evidence: PMID:29976794 DNA binding to cGAS induces a robust phase transition to liquid-like droplets, which function as micro reactors in which the enzyme and reactants are concentrated to greatly enhance the production of cGAMP.
GO:0140693 molecular condensate scaffold activity	IDA PMID:35322803 PCBP2 maintains antiviral signaling homeostasis by regulatin...	ACCEPT	Summary: cGAS acts as the scaffold of DNA-induced biomolecular condensates (liquid-like droplets) that concentrate enzyme and substrates and are the sites of its activation. Reason: DNA-driven liquid-liquid phase separation into cGAS-DNA condensates is experimentally and structurally supported and is integral to how cGAS becomes catalytically active. Retain as core. Supporting Evidence: PMID:29976794 DNA binding to cGAS induces a robust phase transition to liquid-like droplets, which function as micro reactors in which the enzyme and reactants are concentrated to greatly enhance the production of cGAMP.
GO:0140693 molecular condensate scaffold activity	IDA PMID:38421872 HERC5-catalyzed ISGylation potentiates cGAS-mediated innate ...	ACCEPT	Summary: cGAS acts as the scaffold of DNA-induced biomolecular condensates (liquid-like droplets) that concentrate enzyme and substrates and are the sites of its activation. Reason: DNA-driven liquid-liquid phase separation into cGAS-DNA condensates is experimentally and structurally supported and is integral to how cGAS becomes catalytically active. Retain as core. Supporting Evidence: PMID:29976794 DNA binding to cGAS induces a robust phase transition to liquid-like droplets, which function as micro reactors in which the enzyme and reactants are concentrated to greatly enhance the production of cGAMP.
GO:0140693 molecular condensate scaffold activity	IDA PMID:38740774 The structural basis for 2'-5'/3'-5'-cGAMP synthesis by cGAS...	ACCEPT	Summary: cGAS acts as the scaffold of DNA-induced biomolecular condensates (liquid-like droplets) that concentrate enzyme and substrates and are the sites of its activation. Reason: DNA-driven liquid-liquid phase separation into cGAS-DNA condensates is experimentally and structurally supported and is integral to how cGAS becomes catalytically active. Retain as core. Supporting Evidence: PMID:29976794 DNA binding to cGAS induces a robust phase transition to liquid-like droplets, which function as micro reactors in which the enzyme and reactants are concentrated to greatly enhance the production of cGAMP.
GO:0140693 molecular condensate scaffold activity	IDA PMID:39322678 AARS1 and AARS2 sense L-lactate to regulate cGAS as global l...	ACCEPT	Summary: cGAS acts as the scaffold of DNA-induced biomolecular condensates (liquid-like droplets) that concentrate enzyme and substrates and are the sites of its activation. Reason: DNA-driven liquid-liquid phase separation into cGAS-DNA condensates is experimentally and structurally supported and is integral to how cGAS becomes catalytically active. Retain as core. Supporting Evidence: PMID:29976794 DNA binding to cGAS induces a robust phase transition to liquid-like droplets, which function as micro reactors in which the enzyme and reactants are concentrated to greatly enhance the production of cGAMP.
GO:0140693 molecular condensate scaffold activity	IEA GO_REF:0000120	ACCEPT	Summary: cGAS acts as the scaffold of DNA-induced biomolecular condensates (liquid-like droplets) that concentrate enzyme and substrates and are the sites of its activation. Reason: DNA-driven liquid-liquid phase separation into cGAS-DNA condensates is experimentally and structurally supported and is integral to how cGAS becomes catalytically active. Retain as core. Supporting Evidence: PMID:29976794 DNA binding to cGAS induces a robust phase transition to liquid-like droplets, which function as micro reactors in which the enzyme and reactants are concentrated to greatly enhance the production of cGAMP.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:23258413 Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activ...	ACCEPT	Summary: cGAS is the initiating sensor of the cGAS/STING signaling pathway: DNA-triggered cGAMP synthesis activates STING1 and downstream type I interferon signaling. Reason: This is the defining biological process for cGAS and is supported by extensive experimental evidence. Retain as core. Supporting Evidence: PMID:23258413 cGAS functions upstream of STING and is required for IFNβ induction by cytosolic DNA
GO:0140896 cGAS/STING signaling pathway	IDA PMID:24077100 Cell intrinsic immunity spreads to bystander cells via the i...	ACCEPT	Summary: cGAS is the initiating sensor of the cGAS/STING signaling pathway: DNA-triggered cGAMP synthesis activates STING1 and downstream type I interferon signaling. Reason: This is the defining biological process for cGAS and is supported by extensive experimental evidence. Retain as core.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:32911482 Structural mechanism of cGAS inhibition by the nucleosome.	ACCEPT	Summary: cGAS is the initiating sensor of the cGAS/STING signaling pathway: DNA-triggered cGAMP synthesis activates STING1 and downstream type I interferon signaling. Reason: This is the defining biological process for cGAS and is supported by extensive experimental evidence. Retain as core.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:32912999 Structural basis for the inhibition of cGAS by nucleosomes.	ACCEPT	Summary: cGAS is the initiating sensor of the cGAS/STING signaling pathway: DNA-triggered cGAMP synthesis activates STING1 and downstream type I interferon signaling. Reason: This is the defining biological process for cGAS and is supported by extensive experimental evidence. Retain as core.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:33542149 Phosphorylation and chromatin tethering prevent cGAS activat...	ACCEPT	Summary: cGAS is the initiating sensor of the cGAS/STING signaling pathway: DNA-triggered cGAMP synthesis activates STING1 and downstream type I interferon signaling. Reason: This is the defining biological process for cGAS and is supported by extensive experimental evidence. Retain as core.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:33762328 Arginine methyltransferase PRMT5 negatively regulates cGAS-m...	ACCEPT	Summary: cGAS is the initiating sensor of the cGAS/STING signaling pathway: DNA-triggered cGAMP synthesis activates STING1 and downstream type I interferon signaling. Reason: This is the defining biological process for cGAS and is supported by extensive experimental evidence. Retain as core.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:35322803 PCBP2 maintains antiviral signaling homeostasis by regulatin...	ACCEPT	Summary: cGAS is the initiating sensor of the cGAS/STING signaling pathway: DNA-triggered cGAMP synthesis activates STING1 and downstream type I interferon signaling. Reason: This is the defining biological process for cGAS and is supported by extensive experimental evidence. Retain as core.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:35438208 ZDHHC18 negatively regulates cGAS-mediated innate immunity t...	ACCEPT	Summary: cGAS is the initiating sensor of the cGAS/STING signaling pathway: DNA-triggered cGAMP synthesis activates STING1 and downstream type I interferon signaling. Reason: This is the defining biological process for cGAS and is supported by extensive experimental evidence. Retain as core.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:35460603 Cytoplasmic PARP1 links the genome instability to the inhibi...	ACCEPT	Summary: cGAS is the initiating sensor of the cGAS/STING signaling pathway: DNA-triggered cGAMP synthesis activates STING1 and downstream type I interferon signaling. Reason: This is the defining biological process for cGAS and is supported by extensive experimental evidence. Retain as core.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:38421872 HERC5-catalyzed ISGylation potentiates cGAS-mediated innate ...	ACCEPT	Summary: cGAS is the initiating sensor of the cGAS/STING signaling pathway: DNA-triggered cGAMP synthesis activates STING1 and downstream type I interferon signaling. Reason: This is the defining biological process for cGAS and is supported by extensive experimental evidence. Retain as core.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:38740774 The structural basis for 2'-5'/3'-5'-cGAMP synthesis by cGAS...	ACCEPT	Summary: cGAS is the initiating sensor of the cGAS/STING signaling pathway: DNA-triggered cGAMP synthesis activates STING1 and downstream type I interferon signaling. Reason: This is the defining biological process for cGAS and is supported by extensive experimental evidence. Retain as core.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:39322678 AARS1 and AARS2 sense L-lactate to regulate cGAS as global l...	ACCEPT	Summary: cGAS is the initiating sensor of the cGAS/STING signaling pathway: DNA-triggered cGAMP synthesis activates STING1 and downstream type I interferon signaling. Reason: This is the defining biological process for cGAS and is supported by extensive experimental evidence. Retain as core.
GO:0140896 cGAS/STING signaling pathway	IDA PMID:39694035 MYO1F positions cGAS on the plasma membrane to ensure full a...	ACCEPT	Summary: cGAS is the initiating sensor of the cGAS/STING signaling pathway: DNA-triggered cGAMP synthesis activates STING1 and downstream type I interferon signaling. Reason: This is the defining biological process for cGAS and is supported by extensive experimental evidence. Retain as core.
GO:0140896 cGAS/STING signaling pathway	IEA GO_REF:0000120	ACCEPT	Summary: cGAS is the initiating sensor of the cGAS/STING signaling pathway: DNA-triggered cGAMP synthesis activates STING1 and downstream type I interferon signaling. Reason: This is the defining biological process for cGAS and is supported by extensive experimental evidence. Retain as core.
GO:0140896 cGAS/STING signaling pathway	TAS PMID:37403426 MicroRNA-4691-3p inhibits the inflammatory response by targe...	ACCEPT	Summary: cGAS is the initiating sensor of the cGAS/STING signaling pathway: DNA-triggered cGAMP synthesis activates STING1 and downstream type I interferon signaling. Reason: This is the defining biological process for cGAS and is supported by extensive experimental evidence. Retain as core.
GO:0160004 poly-ADP-D-ribose modification-dependent protein binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: cGAS interaction with poly-ADP-ribosylated PARP1 (ISS/IEA from mouse) relates to its nuclear, enzyme-independent regulation of DNA repair. Reason: This modification-dependent binding is tied to the nuclear PARP1 interaction underlying suppression of homologous recombination, a non-core moonlighting activity. Keep as non-core.
GO:0160004 poly-ADP-D-ribose modification-dependent protein binding	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: cGAS interaction with poly-ADP-ribosylated PARP1 (ISS/IEA from mouse) relates to its nuclear, enzyme-independent regulation of DNA repair. Reason: This modification-dependent binding is tied to the nuclear PARP1 interaction underlying suppression of homologous recombination, a non-core moonlighting activity. Keep as non-core.
GO:2000042 negative regulation of double-strand break repair via homologous recombination	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Nuclear cGAS suppresses homologous-recombination-mediated repair of DNA double-strand breaks, an enzyme-independent function involving interaction with PARP1. Reason: This moonlighting activity is experimentally supported in mouse and human models and is independent of catalytic activity and STING; it is a genuine but non-core function distinct from DNA sensing. Keep as non-core.
GO:2000042 negative regulation of double-strand break repair via homologous recombination	IDA PMID:30356214 Nuclear cGAS suppresses DNA repair and promotes tumorigenesi...	KEEP AS NON CORE	Summary: Nuclear cGAS suppresses homologous-recombination-mediated repair of DNA double-strand breaks, an enzyme-independent function involving interaction with PARP1. Reason: This moonlighting activity is experimentally supported in mouse and human models and is independent of catalytic activity and STING; it is a genuine but non-core function distinct from DNA sensing. Keep as non-core.
GO:2000042 negative regulation of double-strand break repair via homologous recombination	IDA PMID:31544964 Chromatin-bound cGAS is an inhibitor of DNA repair and hence...	KEEP AS NON CORE	Summary: Nuclear cGAS suppresses homologous-recombination-mediated repair of DNA double-strand breaks, an enzyme-independent function involving interaction with PARP1. Reason: This moonlighting activity is experimentally supported in mouse and human models and is independent of catalytic activity and STING; it is a genuine but non-core function distinct from DNA sensing. Keep as non-core. Supporting Evidence: PMID:31544964 cGAS also promotes DNA damage by inhibiting DSB repair independently of STING.
GO:2000042 negative regulation of double-strand break repair via homologous recombination	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Nuclear cGAS suppresses homologous-recombination-mediated repair of DNA double-strand breaks, an enzyme-independent function involving interaction with PARP1. Reason: This moonlighting activity is experimentally supported in mouse and human models and is independent of catalytic activity and STING; it is a genuine but non-core function distinct from DNA sensing. Keep as non-core.
GO:2000774 positive regulation of cellular senescence	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: cGAS promotes cellular senescence by sensing cytoplasmic chromatin fragments and driving STING-dependent interferon/SASP responses (mouse-based ISS/IEA). Reason: A physiologically important downstream role, but a specialized/context-dependent process rather than the core function. Keep as non-core.
GO:2000774 positive regulation of cellular senescence	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: cGAS promotes cellular senescence by sensing cytoplasmic chromatin fragments and driving STING-dependent interferon/SASP responses (mouse-based ISS/IEA). Reason: A physiologically important downstream role, but a specialized/context-dependent process rather than the core function. Keep as non-core.

Gene Description

Existing Annotations Review

Core Functions

Cytosolic double-stranded DNA sensor: directly binds aberrant/foreign dsDNA as the input for innate immune activation.

DNA-activated nucleotidyltransferase that synthesizes the second messenger 2',3'-cGAMP from ATP and GTP (EC 2.7.7.86), initiating cGAS/STING signaling and type I interferon production.

Forms DNA-induced biomolecular condensates (liquid-like droplets) in which cGAS is concentrated with substrates and becomes catalytically active; cGAS is the scaffold of these condensates.

References

📚 Additional Documentation

Notes

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