GNAI3

GNAI3 encodes the G protein subunit alpha i3 (Gαi3), also known as GNAI-3. As a member of the Gαi family, it forms heterotrimeric G proteins with βγ subunits, coupling to G protein-coupled receptors (GPCRs) like dopamine D2 and serotonin 5-HT1A receptors. Its core function is to inhibit adenylyl cyclase, reducing intracellular cyclic adenosine monophosphate (cAMP) levels and regulating downstream pathways such as MAPK/ERK and PI3K/Akt.
Aberrant GNAI3 activity links to diseases: overexpression drives colorectal cancer metastasis and breast cancer proliferation, while mutations may contribute to neurodevelopmental disorders like intellectual disability. No direct GNAI3-targeted drugs are approved, but Gαi-coupled GPCR inhibitors (e.g., dopamine antagonists) are used clinically. Preclinical research explores small molecules modulating Gαi signaling for cancer therapy.