Gna12, encoding the G-protein α subunit, is involved in multiple signaling pathways. It is associated with inflammatory bowel disease (IBD) according to genome-wide association studies (GWAS), and also plays roles in ovarian cancer, acute liver injury, preeclampsia, and other conditions. It participates in pathways like C5a-induced migration-related C5aR1-PLCβ2-PI3K-AKT-ERK1/2 signaling, and is part of the LPA-mediated signaling pathway in ovarian cancer [1,2].

In macrophages, Gna12 deficiency leads to enhanced C5a-induced migration, as Gna12 suppresses this migration by downregulating the C5aR1-PLCβ2-PI3K-AKT-ERK1/2 signaling, suggesting it is an anti-inflammatory factor [1]. In hepatocytes, Gα12 overexpression by ER stress exacerbates acute liver injury through ROCK1-mediated dysregulation of ALOX12 and miR-15a [3]. In preeclampsia, decreased methylation of the GNA12 promoter is associated with its overexpression [4].

In conclusion, Gna12 has diverse functions in different biological processes and disease conditions. Its role in inflammation regulation and disease-related signaling pathways is crucial. Studies on Gna12 knockout or overexpression models, such as in macrophages and hepatocytes, have provided insights into its functions in IBD, acute liver injury, and preeclampsia, helping to understand the underlying molecular mechanisms and potentially guiding new therapeutic strategies.