GABRA5
Gamma-aminobutyric acid type A receptor subunit alpha5
Gene Information Card
| Symbol | GABRA5 |
|---|---|
| Full Name | gamma-aminobutyric acid type A receptor subunit alpha5 |
| Gene Type | protein-coding |
| Chromosomal Location | 15q12 |
| NCBI Gene ID | 2558 ncbi.nlm.nih.gov/gene/2558 |
| Ensembl ID | ENSG00000166206 |
| UniProt ID | P31644 |
| OMIM ID | 137142 |
| HGNC ID | 4085 |
| Aliases | GABA(A) receptor, alpha 5 |
Description
GABRA5 encodes the alpha5 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 alpha5 subunit is predominantly expressed in the hippocampus and is involved in cognitive processes such as learning and memory. Mutations in GABRA5 are associated with neurodevelopmental disorders including intellectual disability, epilepsy, and autism spectrum disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability, autosomal dominant 46 (MRD46) | Loss-of-function mutations reduce GABA-A receptor-mediated inhibition, leading to neuronal hyperexcitability and cognitive impairment. | ClinVar, OMIM #617832 |
| Epilepsy, early infantile epileptic encephalopathy 50 (EIEE50) | De novo missense mutations impair receptor function, contributing to seizure susceptibility. | ClinVar, OMIM #617832 |
| Autism spectrum disorder (ASD) | Rare variants in GABRA5 are implicated in ASD pathogenesis through altered inhibitory signaling. | ClinVar, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 17.2 | High |
| Hippocampus | 28.5 | Very High |
| Cerebral cortex | 15.8 | High |
| Cerebellum | 8.3 | Medium |
| Spinal cord | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 12.5 | Moderate expression |
| U-87 MG (glioblastoma) | 6.8 | Low expression |
| HEK293 (embryonic kidney) | 0.2 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.880G>A (p.Gly294Arg) | Missense | Rare | Loss of function; reduced GABA-evoked currents |
| c.1003C>T (p.Arg335Trp) | Missense | De novo | Dominant negative; impaired receptor trafficking |
| c.1129G>A (p.Gly377Ser) | Missense | De novo | Gain of function; increased channel desensitization |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., p.Gly294Arg) reduce chloride conductance and synaptic inhibition.
Gain of Function (GOF)
p.Gly377Ser increases desensitization, reducing net inhibitory current.
Dominant Negative (DN)
p.Arg335Trp disrupts subunit assembly and surface expression of the receptor.
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) | • ionotropic glutamate receptor binding (GO:0035255) |
| • plasma membrane (GO:0005886) | • synapse (GO:0045202) |
| • GABAergic synapse (GO:0098982) | • chemical synaptic transmission (GO:0007268) |
Pathways
• GABAergic synapse (KEGG: hsa04727)
• Neuroactive ligand-receptor interaction (KEGG: hsa04080)
• Nicotine addiction (KEGG: hsa05033)
Protein Summary
The GABRA5 protein (UniProt P31644) is a 462-amino acid subunit of the GABA-A receptor. It contains an extracellular N-terminal domain with a signal peptide, four transmembrane domains (M1-M4), and a large intracellular loop between M3 and M4 that mediates receptor clustering and trafficking. The alpha5 subunit confers high affinity for GABA and benzodiazepine binding, and its expression is enriched in hippocampal pyramidal neurons, where it modulates tonic inhibition and cognitive function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GABRA5 Knockout HEK293 Cell Line | EDJ-KQ4654 | Human | 2558 | Details Get a Quote |
| GABRA5 Knockout A-549 Cell Line | EDJ-KQ27345 | Human | 2558 | Details Get a Quote |
| GABRA5 Knockout HeLa Cell Line | EDJ-KQ53289 | Human | 2558 | Details Get a Quote |
| GABRA5 Knockout HCT 116 Cell Line | EDJ-KQ70254 | Human | 2558 | Details Get a Quote |
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