Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2

GNB2 encodes guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2, a component of heterotrimeric G proteins that functions as a modulator and transducer in transmembrane signaling systems (UniProt: P62879). The beta and gamma subunits are essential for GTPase activity, GDP-GTP exchange, and G protein-effector interactions, making GNB2 a key node in multiple cellular signaling pathways.

GNB2 is broadly expressed across tissues and has been associated with two Mendelian disorders: neurodevelopmental disorder with hypotonia and dysmorphic facies (NEDHYDF; MIM 619503), characterized by developmental delay and variable intellectual impairment, and sick sinus syndrome 4 (SSS4; MIM 619464), an autosomal dominant cardiac conduction disorder (UniProt: P62879).

In Alzheimer's disease, GNB2 protein levels are significantly reduced in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: −0.40; Chaparral AD proteomics). This downregulation was detected via TMT-labeled quantitative proteomics across subcellular fractions. The loss of G protein signaling components may contribute to impaired neurotransmitter-mediated signaling and cellular communication deficits observed in AD pathology.