GRID2 (Glutamate Ionotropic Receptor Delta Type Subunit 2)
Key regulator of cerebellar synaptic plasticity and motor coordination; implicated in spinocerebellar ataxia and neurodevelopmental disorders.
Gene Information Card
| Symbol | GRID2 |
|---|---|
| Full Name | Glutamate Ionotropic Receptor Delta Type Subunit 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q22.1 |
| NCBI Gene ID | 2895 ncbi.nlm.nih.gov/gene/2895 |
| Ensembl ID | ENSG00000152207 |
| UniProt ID | O43424 |
| OMIM ID | 602368 |
| HGNC ID | 4576 |
| Aliases | GluD2, delta 2 glutamate receptor |
Description
GRID2 encodes the glutamate ionotropic receptor delta type subunit 2 (GluD2), a member of the ionotropic glutamate receptor family. Unlike AMPA, kainate, and NMDA receptors, GluD2 does not function as a ligand-gated ion channel but instead mediates trans-synaptic signaling and cerebellar long-term depression (LTD). It is predominantly expressed in cerebellar Purkinje cells and is essential for motor coordination, synaptic plasticity, and climbing fiber synapse formation. Mutations in GRID2 are associated with spinocerebellar ataxia type 18 (SCA18) and other neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spinocerebellar ataxia type 18 (SCA18) | Loss-of-function mutations impair cerebellar LTD and Purkinje cell signaling, leading to progressive ataxia and motor incoordination. | ClinVar, OMIM |
| Autosomal recessive spinocerebellar ataxia 18 (SCAR18) | Biallelic loss-of-function variants disrupt GluD2-mediated synapse formation and plasticity. | ClinVar, OMIM |
| Neurodevelopmental disorder with cerebellar ataxia and intellectual disability | Missense and truncating mutations affect GluD2 protein folding and synaptic localization. | ClinVar, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cerebellum | 45.2 | High |
| Cerebral cortex | 1.8 | Low |
| Testis | 0.5 | Not detected |
| Heart | 0.1 | Not detected |
| Liver | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Purkinje cells (primary) | 45.2 | Highest expression; essential for function |
| SH-SY5Y (neuroblastoma) | 0.3 | Low expression; not physiologically relevant |
| HEK293 (embryonic kidney) | 0.0 | No endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1970G>A (p.Arg657His) | Missense | Rare | Impaired GluD2 trafficking and reduced surface expression; associated with SCA18 |
| c.2446C>T (p.Arg816*) | Nonsense | Very rare | Premature truncation; loss of C-terminal domain; causes SCAR18 |
| c.1321_1323del (p.Phe441del) | In-frame deletion | Rare | Disrupts ligand-binding domain; dominant-negative effect |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations (e.g., nonsense, frameshift, missense affecting trafficking) lead to reduced or absent GluD2 function, impairing cerebellar LTD and motor coordination.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported for GRID2.
Dominant Negative (DN)
Some missense mutations (e.g., p.Phe441del) may exert dominant-negative effects by interfering with wild-type GluD2 assembly or signaling.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cerebellar long-term depression (LTD)
• Glutamatergic synapse
• Neuroactive ligand-receptor interaction
Protein Summary
GluD2 is a 1,007-amino acid transmembrane protein with an extracellular N-terminal domain (NTD), a ligand-binding domain (LBD), three transmembrane helices, and an intracellular C-terminal domain. It forms homotetramers and interacts with presynaptic neurexins and postsynaptic scaffold proteins (e.g., PSD-95). GluD2 does not bind glutamate but is activated by D-serine and glycine, modulating synaptic plasticity. Its C-terminal domain is critical for interaction with signaling molecules and synaptic localization.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GRID2 Knockout HEK293 Cell Line | EDJ-KQ4789 | Human | 2895 | Details Get a Quote |
| GRID2IP Knockout HEK293 Cell Line | EDJ-KQ13685 | Human | 392862 | Details Get a Quote |
| GRID2 Knockout HeLa Cell Line | EDJ-KQ53424 | Human | 2895 | Details Get a Quote |
| GRID2IP Knockout HeLa Cell Line | EDJ-KQ60239 | Human | 392862 | Details Get a Quote |
| GRID2 Knockout A-549 Cell Line | EDJ-KQ61900 | Human | 2895 | Details Get a Quote |
| GRID2IP Knockout A-549 Cell Line | EDJ-KQ68700 | Human | 392862 | Details Get a Quote |
| GRID2 Knockout HCT 116 Cell Line | EDJ-KQ70380 | Human | 2895 | Details Get a Quote |
| GRID2IP Knockout HCT 116 Cell Line | EDJ-KQ77067 | Human | 392862 | Details Get a Quote |
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