GRIN3B

Chr 19

glutamate ionotropic receptor NMDA type subunit 3B

Also known as: GluN3B, NR3B

GRIN3B encodes the GluN3B subunit of NMDA receptors, which forms excitatory glycine receptor complexes with GluN1 and modulates glutamatergic signaling with low calcium permeability and reduced magnesium block. The gene shows minimal constraint against loss-of-function variants (pLI near 0, LOEUF 0.98), and while genetic variations have been proposed to associate with schizophrenia, definitive Mendelian disease associations and inheritance patterns have not been established. The protein is primarily expressed in motor neurons where it contributes to excitatory neurotransmission through both glycinergic and glutamatergic pathways.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.98
Clinical SummaryGRIN3B
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.98LOEUF
pLI 0.000
Z-score 1.64
OE 0.63 (0.410.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-1.03Z-score
OE missense 1.12 (1.051.20)
632 obs / 563.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.63 (0.410.98)
00.351.4
Missense OE1.12 (1.051.20)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 14 / 22.4Missense obs/exp: 632 / 563.0Syn Z: -1.69
DN
0.74top 25%
GOF
0.81top 10%
LOF
0.2679th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

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.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GRIN3B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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