GNB2 gene

The GNB2 gene (GNB2 stands for: G Protein Subunit Beta 2) is a protein-coding gene located on chromosome 7q22.1. An important paralog of this gene is GNB4.

Heterotrimeric guanine nucleotide-binding proteins (G proteins) mediate signals between receptors and effector proteins. They consist of an alpha, a beta and a gamma subunit. These subunits are encoded by families of related genes.

The GNB2 gene codes for a beta subunit. The beta subunits are important regulators of the alpha subunits as well as certain receptors and effectors for signal transmission. The GNB2 gene contains a trinucleotide (CCG) repeat length polymorphism in its 5'-UTR. Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The beta and gamma chains are required for GTPase activity, for the replacement of GDP by GTP and for G-protein effector interaction.

Diseases associated with GNB2 include:

• Familial Sick Sinus Syndrome 4 (Stallmeyer B et al. 2017)
• Neurodevelopmental Disorder With Hypotonia And Dysmorphic Facies (Lansdon LA et al. 2021): NEDHYDF is an autosomal dominant disorder characterized by global developmental delay, hypotonia, and variably impaired intellectual development. Speech delay and delayed walking are common, while seizures are usually absent. Dysmorphic facial features are conspicuous in most patients. Other features may include congenital heart defects, non-specific renal anomalies, joint contractures or hyperextensibility, dry skin and cryptorchidism. There is considerable variability in both the neurological and extraneurological manifestations).
• Sturge-Weber syndrome (mutation: NM_005273.3:c.232A>G, p.Lys78Glu) (Fjær R et al. 2021): Ectopic expression of the mutant proteins in endothelial cells showed that expression of both mutants decreased cell proliferation but differentially regulated MAPK signaling, suggesting that dysregulated MAPK signaling cannot fully explain the SWS phenotype. Instead, both mutants decreased the synthesis of Yes-associated protein (YAP), a transcriptional co-activator of the Hippo signaling pathway, suggesting a key role of this pathway in the vascular pathogenesis of SWS. The discovery of the GNB2 mutation suggests that future research for treatment targets should focus on the YAP signaling pathway rather than the MAPK signaling pathway (Fjær R et al. 2021).