Gnb2, or Guanine-nucleotide binding protein 2, encodes for the β2 subunit (Gβ2) of the G-protein complex. G-proteins mediate signalling pathways involved in diverse cellular functions [2,3,5,9]. The G-protein complex, consisting of Gα and Gβγ units, is integral in integrating signals between receptors and effector proteins [3,9].

Mutations in Gnb2 have been associated with several diseases. In Sturge-Weber syndrome (SWS), a rare neurovascular disorder, a somatic mutation in Gnb2 was found in one patient negative for the common GNAQ mutation. This mutation in Gnb2, like the GNAQ mutation, may lead to failure of G-protein complex reassembly, dysregulated MAPK signalling, and reduced synthesis of Yes-associated protein (YAP), suggesting a role of the Hippo signalling pathway in SWS vascular pathogenesis [1,8]. In addition, de novo missense variants in Gnb2 can cause syndromic intellectual disability with variable dysmorphism and extraneurologic features [3,5,9]. A heterozygous mutation in Gnb2 clinically leads to sinus bradycardia and sinus node dysfunction [6].

In cancer, Gnb2 is notably up-regulated in twenty-three cancer types relative to controls, and its elevated expression is associated with reduced overall survival in Liver Hepatocellular Carcinoma and Rectum Adenocarcinoma, suggesting it plays a role in the tumorigenesis of these cancers [2]. Also, in breast cancer, miR-142-3p can improve paclitaxel sensitivity by targeting Gnb2 and inhibiting autophagy through the GNB2-AKT-mTOR pathway [7]. In colorectal cancer, lncRNA CCAT2 promotes cancer cell proliferation and metastasis by regulating GNB2 expression and activating the ERK and Wnt signalling pathways [10]. Lidocaine-induced apoptosis in rat pheochromocytoma PC12 cells is mediated by Gnb2 [4].

In conclusion, Gnb2 is crucial for the normal function of G-protein-mediated signalling pathways. Its mutations and dysregulation are associated with various diseases including SWS, neurodevelopmental disorders, sinus node dysfunction, and multiple cancers. Understanding Gnb2's role through these disease associations helps in elucidating disease mechanisms and may potentially guide future therapeutic strategies.