GRIN3A
protein-codingglutamate ionotropic receptor NMDA type subunit 3A, the group of Glutamate ionotropic receptor NMDA type subunits
Gene summary
This gene encodes a subunit of the N-methyl-D-aspartate (NMDA) receptors, which belong to the superfamily of glutamate-regulated ion channels, and function in physiological and pathological processes in the central nervous system. This subunit shows greater than 90% identity to the corresponding subunit in rat. Studies in the knockout mouse deficient in this subunit suggest that this gene may be involved in the development of synaptic elements by modulating NMDA receptor activity. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~169.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GRIN3A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_133445.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 145 | 6 | 1 | 152 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 147 | 7 | 1 | 155 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_597702.2 | 9 | MANE Select | |
| Ensembl | ENSP00000355155.3 | 9 | MANE Select | |
| Ensembl | ENSP00000778981.1 | 7 | Standard | |
| RefSeq | XP_011516513.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glutamatergic synapse - Homo sapiens (human)
- Nicotine addiction - Homo sapiens (human)
- cAMP signaling pathway - Homo sapiens (human)
- Amphetamine addiction - Homo sapiens (human)
- Neuroactive ligand-receptor interaction - Homo sapiens (human)
Biological Process
- calcium ion transport
- dendrite development
- ionotropic glutamate receptor signaling pathway
- response to ethanol
- regulation of postsynaptic membrane potential
Molecular Function
- NMDA glutamate receptor activity
- calcium channel activity
- protein binding
- glycine binding
- identical protein binding
Cellular Component
- plasma membrane
- postsynaptic density
- membrane
- integral component of membrane
- NMDA selective glutamate receptor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000361820
- Coding exons
- 9
- Length
- 169228
- Individuals with no LoFs
- 125709
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 39
- Defined
- 125748
- p
- 0.000155
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.743 | 547 | 598 | 0.915 | 0.0000323 | 7298 |
| Missense (PolyPhen) | 179 | 234.01 | 0.76491 | 2973 | ||
| Synonymous | -0.357 | 247 | 240 | 1.03 | 0.0000132 | 2232 |
| Loss of Function | 4.61 | 9 | 40.7 | 0.221 | 0.00000213 | 460 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00025 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00019 | 0.00018 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine. May play a role in the development of dendritic spines. May play a role in PPP2CB-NMDAR mediated signaling mechanism (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.110
Intolerance Scores
- LoFtool
- 0.232
- RVIS EVS
- 0.21
- RVIS percentile EVS
- 67.53
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.673
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |