GRIN2B
Chr 12ADglutamate ionotropic receptor NMDA type subunit 2B
Also known as: DEE27, EIEE27, GluN2B, MRD6, NMDAR2B, NR2B, NR3, hNR3
The protein functions as the GluN2B subunit of NMDA receptors, forming heterotetrameric calcium-permeable ion channels that bind glutamate and mediate excitatory synaptic transmission critical for synaptic plasticity, learning, and memory. Autosomal dominant mutations cause developmental and epileptic encephalopathy 27 and intellectual developmental disorder with or without seizures, predominantly through loss-of-function mechanisms. The gene shows extreme intolerance to loss-of-function variants, consistent with haploinsufficiency as a primary disease mechanism.
Definitive — sufficient evidence for diagnostic panels
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Extremely missense-constrained (top ~0.01%)
NMDA receptor GluN2B subunit. GOF variants in TM/linker regions cause severe DEE. LOF variants cause ID without epilepsy. G2P lists as undetermined/LOF but GOF is well-established for DEE variants.
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
200 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 | 17 | 1 | 5 | 0 | 23 |
Likely Pathogenic | 0 | 4 | 0 | 0 | 4 |
VUS | 3 | 87 | 3 | 1 | 94 |
Likely Benign | 0 | 6 | 19 | 52 | 77 |
Benign | 0 | 2 | 0 | 0 | 2 |
| Total | 20 | 100 | 27 | 53 | 200 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GRIN2B · 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
Efficacy of a Prediction Model-based Algorithm to PREVENT Drug-induced Impulse Control Disorders in Parkinson's Disease
NOT YET RECRUITINGOnline Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight
RECRUITINGExternal Resources
Links to major genomics databases and tools