GABRD: Gamma-Aminobutyric Acid Type A Receptor Subunit Delta
A key inhibitory neurotransmitter receptor subunit implicated in epilepsy, neurodevelopmental disorders, and psychiatric conditions.
Gene Information Card
| Symbol | GABRD |
|---|---|
| Full Name | Gamma-aminobutyric acid type A receptor subunit delta |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.33 |
| NCBI Gene ID | 2563 ncbi.nlm.nih.gov/gene/2563 |
| Ensembl ID | ENSG00000187730 |
| UniProt ID | P14770 |
| OMIM ID | 137163 |
| HGNC ID | 4084 |
| Aliases | GABA(A) receptor subunit delta, GABRD1 |
Description
GABRD encodes the delta (δ) 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 δ subunit is predominantly extrasynaptic and contributes to tonic inhibition, modulating neuronal excitability. Mutations in GABRD are associated with epilepsy, neurodevelopmental disorders, and psychiatric conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epilepsy, generalized, with febrile seizures plus, type 5 (GEFS+5) | Loss-of-function variants reduce GABA-A receptor-mediated tonic inhibition, increasing neuronal excitability and seizure susceptibility. | OMIM #137163; ClinVar |
| Epileptic encephalopathy, early infantile, 59 | De novo missense mutations impair receptor trafficking and channel function, leading to severe developmental and epileptic phenotypes. | OMIM #617904; ClinVar |
| Autism spectrum disorder (ASD) | Rare variants in GABRD may alter GABAergic signaling, contributing to excitatory/inhibitory imbalance in ASD. | PubMed; ClinVar |
| Schizophrenia | Genetic association studies implicate GABRD variants in altered inhibitory neurotransmission and cognitive dysfunction. | OMIM; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Brain (cerebellum) | 8.3 | Low |
| Brain (hippocampus) | 15.1 | Medium |
| Brain (thalamus) | 10.2 | Medium |
| Spinal cord | 6.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 9.8 | Neuronal model |
| U-87 MG (glioblastoma) | 4.2 | Glial expression |
| HEK293 (embryonic kidney) | 0.5 | Low/background |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.662C>T (p.Pro221Leu) | Missense | Rare | Reduced surface expression and channel function; associated with GEFS+5. |
| c.874G>A (p.Gly292Ser) | Missense | Rare | Impaired GABA sensitivity; linked to epileptic encephalopathy. |
| c.1013T>C (p.Ile338Thr) | Missense | Rare | Dominant-negative effect on receptor assembly; associated with ASD. |
| c.1291C>T (p.Arg431*) | Nonsense | Very rare | Premature truncation; loss of function; reported in epilepsy cohort. |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic missense and nonsense variants reduce channel conductance, surface expression, or GABA sensitivity, leading to decreased tonic inhibition.
Gain of Function (GOF)
Not well documented; no clear gain-of-function variants reported in GABRD.
Dominant Negative (DN)
Some missense variants (e.g., p.Ile338Thr) interfere with wild-type subunit assembly, reducing overall functional receptor number.
View complete mutation data：
Gene Ontology (GO)
| • GABA-A receptor activity (GO:0004890) | • extracellular ligand-gated ion channel activity (GO:0005230) |
| • chloride channel activity (GO:0005254) | • ion transport (GO:0006811) |
| • chemical synaptic transmission (GO:0007268) | • ion transmembrane transport (GO:0034220) |
| • synapse (GO:0045202) | • GABA-ergic synapse (GO:0098982) |
Pathways
• Neuroactive ligand-receptor interaction (KEGG: hsa04080)
• GABAergic synapse (KEGG: hsa04727)
• Ion channel transport (Reactome: R-HSA-983712)
Protein Summary
The GABRD protein (UniProt P14770) is a 452-amino acid transmembrane subunit that assembles with alpha and beta subunits to form extrasynaptic GABA-A receptors. These receptors mediate tonic inhibition via slow, persistent chloride currents. The δ subunit confers high GABA affinity and sensitivity to neurosteroids, playing a critical role in regulating neuronal network excitability. Structural features include a large extracellular N-terminal domain, four transmembrane helices (M1-M4), and a cytoplasmic loop involved in trafficking and modulation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GABRD Knockout HEK293 Cell Line | EDJ-KQ2098 | Human | 2563 | Details Get a Quote |
| GABRD Knockout HCT 116 Cell Line | EDJ-KQ22203 | Human | 2563 | Details Get a Quote |
| GABRD Knockout HeLa Cell Line | EDJ-KQ53294 | Human | 2563 | Details Get a Quote |
| GABRD Knockout A-549 Cell Line | EDJ-KQ61775 | Human | 2563 | Details Get a Quote |
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