GLRA1: Glycine Receptor Alpha 1 Subunit
Key mediator of inhibitory neurotransmission in the central nervous system; mutations cause hyperekplexia and other neurological disorders.
Gene Information Card
| Symbol | GLRA1 |
|---|---|
| Full Name | glycine receptor alpha 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q33.1 |
| NCBI Gene ID | 2741 ncbi.nlm.nih.gov/gene/2741 |
| Ensembl ID | ENSG00000145888 |
| UniProt ID | P23415 |
| OMIM ID | 138491 |
| HGNC ID | 4326 |
| Aliases | STHE, HKPX1, GLR, glycine receptor subunit alpha-1 |
Description
GLRA1 encodes the alpha 1 subunit of the glycine receptor, a ligand-gated chloride channel that mediates inhibitory neurotransmission in the spinal cord and brainstem. The receptor is a pentamer composed of alpha and beta subunits; the alpha subunit contains the glycine-binding site and is essential for channel function. Mutations in GLRA1 cause hereditary hyperekplexia (startle disease) and are associated with other neurological conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hyperekplexia 1 (STHE) | Loss-of-function mutations in GLRA1 reduce glycine-gated chloride conductance, leading to exaggerated startle responses and muscle stiffness. | OMIM #138491; ClinVar |
| Hyperekplexia with epilepsy | Some GLRA1 missense variants impair receptor trafficking or channel gating, co-segregating with seizure phenotypes. | ClinVar; PubMed studies |
| Startle disease (non-syndromic) | Dominant-negative or recessive mutations disrupt pentamer assembly or glycine binding, causing neonatal hypertonia and apnea. | OMIM; HGNC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spinal cord | 12.5 | High |
| Brainstem | 8.3 | Medium |
| Cerebellum | 5.1 | Medium |
| Cerebral cortex | 2.0 | Low |
| Retina | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 3.2 | Moderate expression |
| U-87 MG (glioblastoma) | 1.1 | Low expression |
| HEK293 (embryonic kidney) | 0.5 | Very low; used for recombinant studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg271Gln (R271Q) | Missense | Found in multiple hyperekplexia families | Dominant-negative; reduces single-channel conductance |
| p.Arg271Leu (R271L) | Missense | Rare | Loss of function; impaired glycine binding |
| p.Tyr279Cys (Y279C) | Missense | Reported in sporadic cases | Dominant-negative; defective receptor trafficking |
| p.Ile244Asn (I244N) | Missense | Familial hyperekplexia | Loss of function; reduced chloride current |
Mutation functional classification
Loss of Function (LOF)
Most GLRA1 mutations (e.g., I244N, R271L) reduce or abolish glycine-evoked chloride currents, leading to disinhibition of motor neurons.
Gain of Function (GOF)
Not reported for GLRA1; gain-of-function mutations are rare in glycine receptor subunits.
Dominant Negative (DN)
Mutations such as R271Q and Y279C exert dominant-negative effects by co-assembling with wild-type subunits and impairing overall receptor function.
View complete mutation data：
Gene Ontology (GO)
| • acetylcholine-activated cation-selective channel activity (GO:0004889) | • extracellular ligand-gated ion channel activity (GO:0005230) |
| • glycine-gated chloride channel activity (GO:0016934) | • plasma membrane (GO:0005886) |
| • cell junction (GO:0030054) | • chemical synaptic transmission (GO:0007268) |
| • excitatory postsynaptic potential (GO:0060079) | • inhibitory postsynaptic potential (GO:0060080) |
Pathways
• Glycine receptor signaling (Reactome: R-HSA-975298)
• Neurotransmitter receptor binding and downstream transmission in the postsynaptic cell (KEGG: hsa04727)
Protein Summary
The GLRA1 protein (UniProt P23415) is a 457-amino acid transmembrane glycine receptor subunit. It contains an extracellular N-terminal domain with the glycine-binding site, four transmembrane domains (M1-M4), and a large intracellular loop. The mature protein forms homopentameric or heteropentameric chloride channels. Post-translational modifications include N-glycosylation and disulfide bond formation. The channel opens upon glycine binding, allowing Cl- influx and neuronal hyperpolarization.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GLRA1 Knockout HEK293 Cell Line | EDJ-KQ4720 | Human | 2741 | Details Get a Quote |
| GLRA1 Knockout HeLa Cell Line | EDJ-KQ53357 | Human | 2741 | Details Get a Quote |
| GLRA1 Knockout A-549 Cell Line | EDJ-KQ61835 | Human | 2741 | Details Get a Quote |
| GLRA1 Knockout HCT 116 Cell Line | EDJ-KQ70319 | Human | 2741 | Details Get a Quote |
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