GABBR2

Chr 9AD

gamma-aminobutyric acid type B receptor subunit 2

Also known as: DEE59, EIEE59, GABABR2, GPR51, GPRC3B, HG20, HRIHFB2099, NDPLHS

NCBI Gene: 9568 ENSG00000136928 UniProt: O75899 OMIM: 607340

GABBR2 encodes a subunit of the heterodimeric GABA-B receptor that inhibits neuronal activity by modulating neurotransmitter release and ion channel activity, with the GABBR2 subunit specifically mediating G-protein coupling. Mutations cause autosomal dominant developmental and epileptic encephalopathy and neurodevelopmental disorder with poor language and loss of hand skills. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.167), reflecting its critical role in inhibitory synaptic transmission.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The multi-pass membrane protein encoded by this gene belongs to the G-protein coupled receptor 3 family and GABA-B receptor subfamily. The GABA-B receptors inhibit neuronal activity through G protein-coupled second-messenger systems, which regulate the release of neurotransmitters, and the activity of ion channels and adenylyl cyclase. This receptor subunit forms an active heterodimeric complex with GABA-B receptor subunit 1, neither of which is effective on its own. Allelic variants of this gene have been associated with nicotine dependence.[provided by RefSeq, Jan 2010]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Nicotine dependence, protection against}MIM #188890

{Nicotine dependence, susceptibility to}MIM #188890

Developmental and epileptic encephalopathy 59MIM #617904

Neurodevelopmental disorder with poor language and loss of hand skillsMIM #617903

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADModerateconsider for supplementary testing

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.17

LOEUF· LoF intol.

Multiple*

Mechanism· predicted