GNB1-related condition is an autosomal dominant form of neurodevelopmental disability/seizure disorder with complete penetrance but variable expressivity.
The clinical phenotype includes moderate to severe global developmental delay, seizures, infantile hypotonia, abnormalities on brain MRI and abnormal vision. Less common findings include growth delay, dystonia, gastrointestinal issues, genitourinary anomalies in males, hearing loss and mastocytosis.
To date clinical information is available on 46 individuals with a GNB1 gene change, but it is likely more individuals will be diagnosed as genomic testing is more commonly used for undiagnosed intellectual disability.
GNB1 encodes the Gβ1 subunit of trimeric G proteins, which are essential to the signalling function of G protein-coupled receptors (GPCRs). GNB1 is expressed ubiquitously, including in neurons of the central nervous system. GNB1 regulates a number of signalling cascades at the membrane, in the cytoplasm and in the nucleus by interacting with a variety of enzymes, ion channels and other proteins. Some effectors directly regulated by Gβ1 include activation of adenylyl cyclase, interactions with β-adrenergic receptor kinase 1, inhibition of calcium channels, activation of potassium channels, activation of phospholipase C-β2, and activation of phosphoinositide 3-kinase. Gβ1 also regulates major signalling pathways such as MAPK/ERK and PI3K/Akt/mTOR pathways.