Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

GNB1 encodes guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, a core component of heterotrimeric G proteins that modulate transmembrane signaling. The beta subunit, along with gamma chains, is essential for GTPase activity, GDP-GTP exchange, and G protein–effector interactions (UniProt: P62873).

GNB1 functions broadly across G protein signaling pathways that regulate diverse cellular processes. A pathogenic variant in GNB1 is associated with intellectual developmental disorder, autosomal dominant 42 (MRD42, MIM 616973), characterized by global developmental delay, hypotonia, seizures, and growth impairment (UniProt: P62873).

In Alzheimer's disease, GNB1 is downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.30 across 2 of 4 subcellular fractions (P2, P3, S2, S3) in TMT-labeled proteomics analysis (Chaparral AD proteomics). This reduction may reflect altered G protein signaling capacity in AD pathology.