COVID-19 researchGene: GNAQ
Evidence Summary from Illumina curation team: The GNAQ gene encodes the Gq protein alpha subunit and belongs to the Gq/11 subfamily of heterotrimeric G proteins. GNAQ is ubiquitously expressed in mammalian cells and couples a wide variety of receptors to channel proteins, enzymes, and other effector molecules. Wang et al. (2019) found that Gnaq expression was downregulated during viral infection and that Gnaq siRNA transfection of host cells protected against infection from vesicular stomatitis virus (VSV) and HSV type 1 infection. Viral replication was also reduced in Gnaq deficient macrophages in cell culture and Gnaq-deficient mice were more resistant than wildtype mice to VSV infection. Further cell culture experiments showed that Gnaq modulated its antiviral response through the canonical PLC-b/Ca2+ signalling (Wang et al. 2019). PMID: 31324725 Wang et al. (2019) - Wang et al. demonstrated that GNAQ negatively regulates the antiviral innate immune responses in a calcineurin-dependent manner. Viral infection downregulates GNAQ expression in cell culture. mRNA expression levels were measured upon infection with VSV in mouse PEMs, BMMs,the fibroblast line L929 and the macrophage mouse line RAW264.7. Fig1. GNAQ negatively regulates host defence against viruses. Gnaq-specific siRNA knockdown reduced VSV infection in PEMS, overexpression of GNAQ in HEK293 cells increased VSV infection (Fig 2). PEMS and BMMs from myeloid cellspecific Gnaq-deficient mice showed reduced replication of VSV and HSV1 compared to WT. VSV replication and titers in the liver, spleen, and lung of Gnaq-deficient mice were all significantly lower than wt litter mates. Gnaq deficiency increases host resistance to viral infection (Fig 3). IFN-b (both mRNA and protein) was significantly enhanced in Gnaq-knockdown PEMs, Poly I;C (mimicking RNA viral infection), VSV infection and HSV-1 infection enhanced IgnBeta production in Gnaq-knockdown PEMs. In cell lines and in vivo, GNAQ negatively regulates IFN-beta production (Fig 4). GNAQ modulates antiviral innate immune responses through canonical PLC-b/Ca2+ signalling. Chemical inhibitors of the pathway reduced cell resistance to infection (Fig 5).
Created: 28 May 2020, 3:12 p.m. | Last Modified: 28 May 2020, 3:12 p.m.
Panel Version: 0.347
Identified through an OMIM search for potential viral susceptibility genes, and subsequently triaged/reviewed by Illumina curation team.
Created: 28 May 2020, 12:36 p.m. | Last Modified: 28 May 2020, 12:36 p.m.
Panel Version: 0.336
gene: GNAQ was added gene: GNAQ was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber Mode of inheritance for gene: GNAQ was set to Unknown