GRIN3A

Chr 9

glutamate ionotropic receptor NMDA type subunit 3A

Also known as: GluN3A, NMDAR-L, NMDAR3A, NR3A

This gene encodes the GluN3A subunit of NMDA glutamate receptors, which are ion channels that regulate synaptic transmission and development in the central nervous system. Mutations cause neurodevelopmental disorders with intellectual disability, autism spectrum disorder, and seizures, inherited in an autosomal dominant pattern. The pathogenic mechanism involves haploinsufficiency, as the protein is intolerant to loss-of-function variants based on constraint metrics.

Summary from RefSeq, UniProt
0
Active trials
12
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.39
LOEUF
GOF
Mechanism· predicted
Clinical SummaryGRIN3A
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.39LOEUF
pLI 0.453
Z-score 4.61
OE 0.22 (0.130.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.74Z-score
OE missense 0.91 (0.850.98)
547 obs / 598.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.22 (0.130.39)
00.351.4
Missense OE0.91 (0.850.98)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 9 / 40.7Missense obs/exp: 547 / 598.1Syn Z: -0.36
DN
0.6259th %ile
GOF
0.6541th %ile
LOF
0.4234th %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

GRIN3A · protein map & ClinVar variants

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

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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