GABRA4
Gamma-Aminobutyric Acid Type A Receptor Subunit Alpha4
Gene Information Card
| Symbol | GABRA4 |
|---|---|
| Full Name | Gamma-aminobutyric acid type A receptor subunit alpha4 |
| Gene Type | protein-coding |
| Chromosomal Location | 4p12 |
| NCBI Gene ID | 2557 ncbi.nlm.nih.gov/gene/2557 |
| Ensembl ID | ENSG00000109158 |
| UniProt ID | P48169 |
| OMIM ID | 137141 |
| HGNC ID | 4080 |
| Aliases | GABRA4, GABA(A) receptor subunit alpha-4 |
Description
GABRA4 encodes the alpha4 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 alpha4 subunit is predominantly expressed in the hippocampus, thalamus, and cortex, and is involved in tonic inhibition, synaptic plasticity, and modulation of neuronal excitability. Variants in GABRA4 have been associated with epilepsy, autism spectrum disorder, and anxiety disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epilepsy, idiopathic generalized | Altered GABA-A receptor function leading to neuronal hyperexcitability | ClinVar, OMIM |
| Autism spectrum disorder | Disrupted inhibitory neurotransmission affecting synaptic balance | ClinVar, NCBI |
| Anxiety disorders | Modulation of tonic inhibition in limbic circuits | OMIM, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 32.5 | High |
| Cerebral cortex | 45.2 | High |
| Hippocampus | 38.7 | High |
| Thalamus | 28.1 | Medium |
| Cerebellum | 12.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 15.4 | Neuroblastoma cell line |
| U-87 MG | 8.2 | Glioblastoma cell line |
| HEK293 | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.874G>A (p.Gly292Arg) | Missense | Rare | Reduced receptor surface expression and function |
| c.1123C>T (p.Arg375Trp) | Missense | Rare | Altered channel gating and decreased chloride conductance |
| c.1465G>A (p.Gly489Ser) | Missense | Rare | Impaired subunit assembly and trafficking |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., p.Gly292Arg, p.Arg375Trp) reduce receptor expression or channel function, leading to decreased inhibitory neurotransmission.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in GABRA4.
Dominant Negative (DN)
Some missense variants may exert dominant-negative effects by disrupting pentamer assembly.
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) | • 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)
• Ion channel transport (Reactome: R-HSA-1296071)
Protein Summary
The GABRA4 protein is a 554-amino acid subunit of the GABA-A receptor. It contains an extracellular N-terminal domain, four transmembrane domains (M1-M4), and a large intracellular loop. The alpha4 subunit confers unique pharmacological properties, including insensitivity to benzodiazepines and high affinity for GABA. It assembles predominantly with beta and delta subunits to form extrasynaptic receptors mediating tonic inhibition.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GABRA4 Knockout HEK293 Cell Line | EDJ-KQ4661 | Human | 2557 | Details Get a Quote |
| GABRA4 Knockout HeLa Cell Line | EDJ-KQ53288 | Human | 2557 | Details Get a Quote |
| GABRA4 Knockout A-549 Cell Line | EDJ-KQ61771 | Human | 2557 | Details Get a Quote |
| GABRA4 Knockout HCT 116 Cell Line | EDJ-KQ70253 | Human | 2557 | Details Get a Quote |
