GRIN3B

Chr 19

glutamate ionotropic receptor NMDA type subunit 3B

Also known as: GluN3B, NR3B

NCBI Gene: 116444 ENSG00000116032 UniProt: O60391 OMIM: 606651

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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a subunit of an N-methyl-D-aspartate (NMDA) receptor. The encoded protein is found primarily in motor neurons, where it forms a heterotetramer with GRIN1 to create an excitatory glycine receptor. Variations in this gene have been proposed to be linked to schizophrenia. [provided by RefSeq, Nov 2015]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.98

Clinical Summary— GRIN3B

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

248 VUS of 273 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.98LOEUF

pLI 0.000

Z-score 1.64

OE 0.63 (0.41–0.98)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-1.03Z-score

OE missense 1.12 (1.05–1.20)

632 obs / 563.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.63 (0.41–0.98)

0≤0.351.4

Missense OE?1.12 (1.05–1.20)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 14 / 22.4Missense obs/exp: 632 / 563.0Syn Z: -1.69

This gene — mechanism propensity

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

273 submitted variants in ClinVar

ClinVar

Classification Summary

VUS248

Likely Benign10

Benign7

Conflicting1

248

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	248	0	0	248
Likely Benign	0	6	0	4	10
Benign	0	4	1	2	7
Conflicting	—				1
Total	0	258	1	6	266

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

32 pathogenic / likely-pathogenic (of 43) ClinVar copy-number / structural variants overlap GRIN3B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →