GABBR2 (Gamma-Aminobutyric Acid Type B Receptor Subunit 2) encodes the GABA-B2 subunit of the metabotropic GABA receptor. While [GABBR1](/genes/gabbr1) provides the ligand-binding domain, GABBR2 is essential for receptor trafficking to the cell surface and for coupling to intracellular G-protein signaling cascades. The obligate heterodimer formed by GABBR1 and GABBR2 constitutes the functional GABA-B receptor that mediates slow inhibitory neurotransmission throughout the brain.
De novo gain-of-function mutations in GABBR2 have been identified in patients with epileptic encephalopathy and Rett-like phenotypes, establishing this gene as a critical node in inhibitory neurotransmission with relevance to multiple neurological disorders.
The protein encoded by GABBR2 is [GABA-B Receptor Subunit 2](/proteins/gabbr2-protein). See the protein page for detailed structural and functional information.
Function
Normal Gene Function
GABBR2 encodes an 941-amino acid seven-transmembrane domain protein with the following functional roles:
G-protein coupling: The heptahelical domain of GABBR2 activates Gi/o heterotrimeric G-proteins upon receptor activation
Surface trafficking: Masks the ER retention signal (RSRR motif) on [GABBR1](/genes/gabbr1), enabling the heterodimer to exit the ER
Allosteric modulation: The venus flytrap domain of GABBR2 does not bind GABA but allosterically enhances agonist affinity at GABBR1
Scaffolding: The C-terminal domain interacts with KCTD proteins (KCTD8, KCTD12, KCTD16) that modulate receptor kinetics and desensitization
Downstream Signaling
Through Gi/o activation, GABBR2-containing receptors regulate:
[Bettler et al., Molecular structure and physiological functions of GABA-B receptors (2004) (2004)](https://doi.org/10.1152/physrev.00036.2003)
[Yoo et al., GABBR2 mutations determine phenotype in Rett syndrome and epileptic encephalopathy (2017) (2017)](https://doi.org/10.1002/ana.24830)
[Schwenk et al., Native GABA-B receptors are heteromultimers with a family of auxiliary subunits (2010) (2010)](https://doi.org/10.1038/nature09321)
[Unknown, Gassmann & Bettler, Regulation of neuronal GABA-B receptor functions by subunit composition (2012) (2012)](https://doi.org/10.1038/nrn3351)
[Jo et al., GABA from reactive astrocytes impairs memory in mouse models of Alzheimer's disease (2014) (2014)](https://doi.org/10.1038/nm.3639)
[Fatemi et al., Altered levels of the synaptosomal associated protein SNAP-25 in hippocampus of subjects with mood disorders and schizophrenia (2001) (2001)](https://doi.org/10.1097/00001756-200109170-00014)