GNAQ, which encodes the alpha subunit of the heterotrimeric G protein Gq, is crucial in signal transduction through G-protein coupled receptors [3,5]. It activates important signaling pathways like phospholipase C and influences the transcription factor YAP [3]. Mutations in GNAQ are significantly associated with multiple disorders, highlighting its biological importance in normal and diseased states. Genetic models are valuable tools to study its functions.

GNAQ mutations are present in over 90% of uveal melanoma patients, driving the oncogenic process in this malignancy [1,2,3,5]. In zebrafish models, patient-derived GNAQ mutations (GNAQQ209L) combined with a tp53 mutation can drive uveal melanoma development, and MITF deficiency was found to accelerate GNAQ-driven uveal melanoma [8]. Somatic, mosaic GNAQ mutations cause port-wine birthmarks and Sturge-Weber syndrome, characterized by abnormal blood vessel formation in the dermis, eyes, and/or brain [4]. Capillary malformations, the most common vascular malformation, are also caused by a somatic mosaic mutation in GNAQ [6]. Additionally, GNAQ somatic mutations can cause spinal and intracranial extra-axial cavernous hemangiomas, with the GNAQ c.626A>G (p.Gln209Arg) mutation elevating PI3K-AKT-mTOR and angiogenesis-related pathways [7].

In conclusion, GNAQ is essential in signal transduction pathways. Through model-based research, its role in diseases such as uveal melanoma, port-wine birthmark-associated Sturge-Weber syndrome, capillary malformations, and extra-axial cavernous hemangiomas has been revealed. These insights contribute to understanding the pathophysiology of these diseases and potentially developing targeted therapies.