GLRA2: Glycine Receptor Alpha 2 Subunit
A key inhibitory neurotransmitter receptor subunit involved in neurodevelopmental disorders and synaptic plasticity
Gene Information Card
| Symbol | GLRA2 |
|---|---|
| Full Name | Glycine Receptor Alpha 2 |
| Gene Type | Protein coding |
| Chromosomal Location | Xp22.2 |
| NCBI Gene ID | 2743 ncbi.nlm.nih.gov/gene/2743 |
| Ensembl ID | ENSG00000101958 |
| UniProt ID | P23416 |
| OMIM ID | 305990 |
| HGNC ID | 4327 |
| Aliases | GLRA2_HUMAN, glycine receptor, alpha 2, GLR, GLR2 |
Description
GLRA2 encodes the alpha 2 subunit of the glycine receptor, a ligand-gated chloride channel that mediates inhibitory neurotransmission in the central nervous system. The receptor is a pentamer composed of alpha and beta subunits; GLRA2 forms functional homomeric or heteromeric channels. It plays critical roles in spinal cord and brainstem reflexes, retinal processing, and synaptic plasticity. Mutations in GLRA2 are associated with hyperekplexia (startle disease) and autism spectrum disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hyperekplexia 4 (startle disease) | Loss-of-function mutations in GLRA2 reduce glycine-gated chloride currents, leading to exaggerated startle responses and hypertonia in infancy. | ClinVar, OMIM #305990 |
| Autism spectrum disorder (ASD) | Missense variants (e.g., p.Arg252Cys) impair receptor trafficking and synaptic clustering, disrupting inhibitory/excitatory balance. | ClinVar, PubMed studies |
| Intellectual disability | Deleterious GLRA2 variants identified in X-linked intellectual disability cohorts, likely due to disrupted glycinergic signaling. | OMIM, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spinal cord | 12.5 | High |
| Brain (cerebellum) | 8.3 | Medium |
| Brain (cortex) | 6.1 | Medium |
| Retina | 5.4 | Medium |
| Testis | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 3.8 | Neuronal model |
| U-87 MG (glioblastoma) | 2.1 | Glial expression |
| HEK293 (embryonic kidney) | 0.5 | Low endogenous |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.754C>T (p.Arg252Cys) | Missense | Rare | Impaired surface expression and reduced chloride conductance; associated with ASD |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of protein; linked to hyperekplexia |
| c.1072G>A (p.Gly358Arg) | Missense | Rare | Altered channel gating; reported in intellectual disability |
| c.1267_1269del (p.Phe423del) | In-frame deletion | Unique | Disrupts transmembrane domain; dominant-negative effect |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and start-loss mutations that abolish GLRA2 protein expression or channel function, leading to hyperekplexia.
Gain of Function (GOF)
Not reported for GLRA2; gain-of-function is rare in glycine receptor subunits.
Dominant Negative (DN)
Missense variants (e.g., p.Phe423del) that co-assemble with wild-type subunits and impair overall receptor function in heterozygous females.
View complete mutation data：
Gene Ontology (GO)
| • extracellular ligand-gated ion channel activity (GO:0005230) | • acetylcholine-activated cation-selective channel activity (GO:0004889) |
| • glycine-gated chloride channel activity (GO:0016934) | • plasma membrane (GO:0005886) |
| • dendrite membrane (GO:0032590) | • inhibitory synapse (GO:0060077) |
| • ion transport (GO:0006811) | • chemical synaptic transmission (GO:0007268) |
Pathways
• Glycine receptor signaling (Reactome: R-HSA-975298)
• Neurotransmitter receptor binding and downstream transmission in the postsynaptic cell (KEGG: hsa04727)
• Inhibitory neurotransmission (GO:0060077)
Protein Summary
The GLRA2 protein (UniProt P23416) is a 452-amino acid transmembrane glycine receptor subunit with four transmembrane domains (M1-M4), a large extracellular N-terminal domain containing the glycine-binding site, and an intracellular loop between M3 and M4 that mediates trafficking and clustering via gephyrin. It forms homopentameric or heteropentameric chloride channels. The protein is predominantly expressed in the spinal cord, brainstem, and retina. Post-translational modifications include N-glycosylation and palmitoylation, which regulate surface expression and synaptic localization.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GLRA2 Knockout HEK293 Cell Line | EDJ-KQ4723 | Human | 2742 | Details Get a Quote |
| GLRA2 Knockout HeLa Cell Line | EDJ-KQ53358 | Human | 2742 | Details Get a Quote |
| GLRA2 Knockout A-549 Cell Line | EDJ-KQ61836 | Human | 2742 | Details Get a Quote |
| GLRA2 Knockout HCT 116 Cell Line | EDJ-KQ70320 | Human | 2742 | Details Get a Quote |
