GRIN1: Glutamate Ionotropic Receptor NMDA Type Subunit 1
Essential subunit of the NMDA receptor, critical for synaptic plasticity and implicated in neurodevelopmental disorders
Gene Information Card
| Symbol | GRIN1 |
|---|---|
| Full Name | Glutamate Ionotropic Receptor NMDA Type Subunit 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q34.3 |
| NCBI Gene ID | 2902 ncbi.nlm.nih.gov/gene/2902 |
| Ensembl ID | ENSG00000176884 |
| UniProt ID | Q05586 |
| OMIM ID | 138249 |
| HGNC ID | 4584 |
| Aliases | NMDAR1, NR1, GluN1, MRD8, DEE101 |
Description
GRIN1 encodes the GluN1 subunit of the N-methyl-D-aspartate (NMDA) receptor, a ligand-gated ion channel that mediates excitatory neurotransmission. The GluN1 subunit is essential for receptor assembly and function, forming heterotetrameric complexes with GluN2 or GluN3 subunits. GRIN1 is critical for synaptic plasticity, learning, and memory. Pathogenic variants in GRIN1 are associated with neurodevelopmental disorders including intellectual disability, epilepsy, and developmental and epileptic encephalopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Developmental and epileptic encephalopathy 101 (DEE101) | Loss-of-function or gain-of-function variants impair NMDA receptor activity, leading to neuronal hyperexcitability or hypoexcitability | ClinVar, OMIM |
| Intellectual disability, autosomal dominant 8 (MRD8) | Missense variants disrupt receptor function, affecting synaptic transmission and plasticity | OMIM, PubMed |
| Epilepsy, focal, with speech disorder and with or without intellectual disability | GRIN1 variants alter channel gating or ion permeability, contributing to seizure susceptibility | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cerebral cortex | 12.5 | High |
| Hippocampus | 15.2 | High |
| Cerebellum | 8.3 | Medium |
| Spinal cord | 4.1 | Low |
| Testis | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 10.8 | High expression |
| U-87 MG (glioblastoma) | 6.5 | Moderate expression |
| HEK293 (embryonic kidney) | 0.3 | Low/not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1636C>T (p.Arg546Trp) | Missense | Rare | Gain-of-function; increased calcium influx, associated with DEE101 |
| c.1915G>A (p.Val639Met) | Missense | Rare | Loss-of-function; reduced channel activity, linked to intellectual disability |
| c.2440G>A (p.Gly814Arg) | Missense | Rare | Dominant-negative; impairs receptor trafficking, associated with epilepsy |
Mutation functional classification
Loss of Function (LOF)
Variants that reduce NMDA receptor current or surface expression, e.g., p.Val639Met, leading to hypoexcitability and intellectual disability.
Gain of Function (GOF)
Variants that increase channel open probability or calcium permeability, e.g., p.Arg546Trp, causing hyperexcitability and epileptic encephalopathy.
Dominant Negative (DN)
Variants that interfere with wild-type subunit assembly or trafficking, e.g., p.Gly814Arg, resulting in reduced functional receptors.
View complete mutation data：
Gene Ontology (GO)
| • NMDA glutamate receptor activity (GO:0004972) | • extracellular ligand-gated ion channel activity (GO:0005230) |
| • ion transport (GO:0006811) | • chemical synaptic transmission (GO:0007268) |
| • synaptic transmission (GO:0035249) | • synapse (GO:0045202) |
Pathways
• UniProt: hsa04724 – Glutamatergic synapse
• UniProt: hsa05030 – Cocaine addiction
• UniProt: hsa05031 – Amphetamine addiction
• UniProt: hsa05032 – Morphine addiction
• UniProt: hsa05033 – Nicotine addiction
Protein Summary
The GluN1 protein (UniProt Q05586) is a 938-amino acid transmembrane subunit of the NMDA receptor. It contains an extracellular N-terminal domain, a ligand-binding domain for glycine, three transmembrane helices (M1, M3, M4), a re-entrant pore loop (M2), and an intracellular C-terminal domain. GluN1 is essential for receptor assembly and ion channel function. Alternative splicing generates multiple isoforms with distinct C-terminal tails, modulating receptor trafficking and signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GRIN1 Knockout HEK293 Cell Line | EDJ-KQ1219 | Human | 2902 | Details Get a Quote |
| GRIN1 Knockout HCT 116 Cell Line | EDJ-KQ20548 | Human | 2902 | Details Get a Quote |
| GRIN1 Knockout HeLa Cell Line | EDJ-KQ53429 | Human | 2902 | Details Get a Quote |
| GRIN1 Knockout A-549 Cell Line | EDJ-KQ61905 | Human | 2902 | Details Get a Quote |
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