GRIN3A
Chr 9glutamate 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.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
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.
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
228 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 | 0 | 0 | 32 | 0 | 32 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 175 | 4 | 0 | 179 |
Likely Benign | 0 | 7 | 0 | 1 | 8 |
Benign | 0 | 1 | 0 | 0 | 1 |
| Total | 0 | 183 | 38 | 1 | 222 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View 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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools