G-alpha-q （GNAQ） is the alpha subunit of the heterotrimeric GTP-binding proteins that mediates the regulators of several downstream signaling through coupling cell surface receptors. Recently, lesions within port-wine stains are found harbor mutations in GNAQ p.Arg183 and may at least associate with ERK （extracellular signal-regulated kinase） signaling pathways. In this paper, the mutations of GNAQ within port-wine stains and the multiple activated signaling targets downstream of mutant GNAQ, including MAPK, RGS5, PKC and YAP pathways were reviewed.