GABRG2
Gamma-aminobutyric acid type A receptor subunit gamma2
Gene Information Card
| Symbol | GABRG2 |
|---|---|
| Full Name | Gamma-aminobutyric acid type A receptor subunit gamma2 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q34 |
| NCBI Gene ID | 2566 ncbi.nlm.nih.gov/gene/2566 |
| Ensembl ID | ENSG00000113327 |
| UniProt ID | P18507 |
| OMIM ID | 137164 |
| HGNC ID | 4087 |
| Aliases | GABA(A) receptor subunit gamma-2, GABRG2 |
Description
GABRG2 encodes the gamma2 subunit of the gamma-aminobutyric acid type A (GABA-A) receptor, a pentameric ligand-gated chloride channel that mediates fast inhibitory neurotransmission in the central nervous system. The gamma2 subunit is essential for receptor clustering, synaptic localization, and benzodiazepine sensitivity. Mutations in GABRG2 are associated with a spectrum of epilepsy syndromes, including genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Genetic epilepsy with febrile seizures plus (GEFS+) | Missense mutations reduce GABA-evoked currents or impair receptor trafficking, leading to decreased inhibitory neurotransmission. | OMIM #604233; multiple families with GABRG2 mutations |
| Dravet syndrome (severe myoclonic epilepsy of infancy) | Loss-of-function mutations (e.g., nonsense, frameshift) cause haploinsufficiency or dominant-negative effects, resulting in severe epilepsy with developmental delay. | ClinVar; case reports |
| Childhood absence epilepsy | Missense variants (e.g., R43Q) alter channel gating or surface expression, contributing to absence seizures. | Functional studies in heterologous systems |
| Febrile seizures | Mutations in GABRG2 increase susceptibility to fever-induced seizures by reducing receptor function. | Family-based association studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Cerebral cortex | 15.2 | High |
| Hippocampus | 14.8 | High |
| Cerebellum | 10.3 | Medium |
| Spinal cord | 6.7 | Medium |
| Heart | 0.5 | Not detected |
| Liver | 0.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.9 | Moderate expression |
| U-87 MG (glioblastoma) | 6.3 | Low expression |
| HEK293 (embryonic kidney) | 0.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R43Q | Missense | Rare (found in families) | Reduces GABA-evoked current amplitude and alters benzodiazepine sensitivity; associated with childhood absence epilepsy and febrile seizures. |
| R177G | Missense | Rare | Impairs receptor trafficking to the cell surface; linked to GEFS+. |
| Q351X | Nonsense | Rare | Premature truncation leads to nonsense-mediated decay and haploinsufficiency; causes Dravet syndrome. |
| IVS6+2T>G | Splice site | Rare | Disrupts splicing, leading to loss of functional protein; associated with severe epilepsy. |
Mutation functional classification
Loss of Function (LOF)
Many GABRG2 mutations (e.g., Q351X, IVS6+2T>G) reduce or eliminate receptor function by impairing subunit expression, trafficking, or channel activity.
Gain of Function (GOF)
No well-established gain-of-function mutations reported for GABRG2.
Dominant Negative (DN)
Some missense variants (e.g., R43Q, R177G) exert dominant-negative effects by co-assembling with wild-type subunits and reducing overall receptor function.
View complete mutation data：
Gene Ontology (GO)
| • GABA-A receptor activity (GO:0004890) | • chloride channel activity (GO:0005254) |
| • extracellular ligand-gated ion channel activity (GO:0005230) | • benzodiazepine receptor activity (GO:0008503) |
| • GABAergic (GO:0051932) | • ion transmembrane transport (GO:0034220) |
| • plasma membrane (GO:0005886) | • GABA-A receptor complex (GO:1902711) |
Pathways
• Neuroactive ligand-receptor interaction (KEGG: hsa04080)
• GABAergic synapse (KEGG: hsa04727)
• Nicotine addiction (KEGG: hsa05033)
Protein Summary
The gamma-aminobutyric acid type A receptor subunit gamma2 (GABRG2) is a 467-amino-acid protein that forms part of the pentameric GABA-A receptor. It contains an extracellular N-terminal domain, four transmembrane domains (M1-M4), and a large intracellular loop between M3 and M4. The gamma2 subunit is critical for receptor clustering at synapses via interaction with gephyrin and for high-affinity benzodiazepine binding. Alternative splicing generates two isoforms: gamma2L (long) and gamma2S (short), which differ in the intracellular loop and modulate receptor function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GABRG2 Knockout HEK293 Cell Line | EDJ-KQ3192 | Human | 2566 | Details Get a Quote |
| GABRG2 Knockout HCT 116 Cell Line | EDJ-KQ25997 | Human | 2566 | Details Get a Quote |
| GABRG2 Knockout HeLa Cell Line | EDJ-KQ25998 | Human | 2566 | Details Get a Quote |
| GABRG2 Knockout A-549 Cell Line | EDJ-KQ61778 | Human | 2566 | Details Get a Quote |
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