Gna11, encoding the alpha subunit of the heterotrimeric G protein G11, is involved in multiple signaling pathways, most notably the activation of phospholipase C upon mutation, which in turn impacts the activity of the transcription factor YAP [2]. These signaling cascades are crucial for normal cellular functions and their dysregulation can lead to various biological consequences. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, would be valuable in further elucidating its function.

Mutations in Gna11 are associated with several diseases. In uveal melanoma, Gna11 mutations, occurring in nearly 80-90% of cases in a mutually exclusive pattern with Gnaq mutations, act as driver genes in oncogenesis [2,3,6,7]. In Sturge-Weber syndrome, Gna11 somatic mutations have been reported, and patients with Gna11-SWS show distinct neurological and dermatological features compared to classic Gnaq-SWS, including disseminated capillary malformation, extremity hyper-or hypotrophy, and a milder neurological picture [1,4]. Additionally, Gna11 germline variants are related to disorders of calcium metabolism, with loss-and gain-of-function mutations causing familial hypocalciuric hypercalcemia type 2 (FHH2) and autosomal dominant hypocalcemia type 2 (ADH2) respectively [5].

In conclusion, Gna11 plays a significant role in multiple biological processes through its involvement in signaling pathways. Its mutations are linked to diseases like uveal melanoma, Sturge-Weber syndrome, and calcium metabolism disorders. The study of Gna11 using KO/CKO mouse models could potentially provide more in-depth insights into these disease mechanisms, contributing to the development of targeted therapies for these conditions.