GRIN1
Chr 9ARADglutamate ionotropic receptor NMDA type subunit 1
Also known as: DEE101, GluN1, MRD8, NDHMSD, NDHMSR, NMD-R1, NMDA1, NMDAR1
The protein is the GluN1 subunit of NMDA receptors, which form heterotetrameric ligand-gated calcium channels essential for synaptic plasticity, learning, and memory formation. Mutations cause developmental and epileptic encephalopathy and neurodevelopmental disorders with or without hyperkinetic movements and seizures through both autosomal dominant and autosomal recessive inheritance patterns. The gene is highly constrained against loss-of-function variants, and mutations can cause disease through multiple mechanisms depending on the specific variant type and location.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Extremely missense-constrained (top ~0.01%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, gain-of-function and dominant-negative). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
400 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 4 | 7 | 39 | 0 | 50 |
Likely Pathogenic | 3 | 15 | 5 | 0 | 23 |
VUS | 5 | 151 | 19 | 5 | 180 |
Likely Benign | 0 | 7 | 64 | 64 | 135 |
Benign | 0 | 0 | 1 | 0 | 1 |
Conflicting | — | 8 | |||
| Total | 12 | 180 | 128 | 69 | 397 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GRIN1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools