Characterization of the splice variant Gbeta3v of the human G-protein Gbeta3 subunit

A polymorphism (C825T) in the gene of the G-protein Gbeta3 (GNB3) has been the subject of numerous studies which have shown that the 825T-allele is associated with several cardiovascular and metabolic disorders. Furthermore, the T-allele is associated with the occurrence of the splice variant Gbeta3s which has been implicated in the pathogenesis of these disorders. Here, we characterise a novel splice variant of GNB3, termed Gbeta3v, which is generated by alternative splicing of parts from intron 9 as a novel exon 10a. Gbeta proteins belong to the superfamily of propeller proteins composed of seven regular WD-domains. In Gbeta3v, four of these WD-domains are retained but the protein has a novel C terminus. Gbeta3v forms dimers with Ggamma3 and Ggamma12 but these Gbetagamma complexes do not stimulate phospholipase C-beta2. Thus, a physiological role of Gbeta3v remains to be established. Gbeta3v transcripts are detectable in a wide variety of cells and tissues including fibroblasts, B lymphoblasts, retinoblastoma cells, retina, brain, umbilical cord and colon. However, there is no association with an allele of the GNB3 C825T polymorphism, which suggests that Gbeta3v does not contribute to the complex phenotype observed in association with the 825T-allele.