GRIN2C
protein-codingglutamate ionotropic receptor NMDA type subunit 2C, the group of Glutamate ionotropic receptor NMDA type subunits
Gene summary
This gene encodes a subunit of the N-methyl-D-aspartate (NMDA) receptor, which is a subtype of ionotropic glutamate receptor. NMDA receptors are found in the central nervous system, are permeable to cations and have an important role in physiological processes such as learning, memory, and synaptic development. The receptor is a tetramer of different subunits (typically heterodimer of subunit 1 with one or more of subunits 2A-D), forming a channel that is permeable to calcium, potassium, and sodium, and whose properties are determined by subunit composition. Alterations in the subunit composition of the receptor are associated with pathophysiological conditions such as Parkinson's disease, Alzheimer's disease, depression, and schizophrenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]
- NMDAR2C
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0004975
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GRIN2C variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000835.6. 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 | 2 | 8 | 1 | 11 | ||
| missense | 155 | 11 | 2 | 168 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 159 | 19 | 3 | 181 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000826.2 | 12 | MANE Select | |
| Ensembl | ENSP00000293190.5 | 12 | MANE Select | |
| RefSeq | NP_001265482.1 | 11 | Standard | |
| Ensembl | ENSP00000338645.4 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Long-term potentiation - Homo sapiens (human)
- Glutamatergic synapse - Homo sapiens (human)
- Alzheimer,s disease - Homo sapiens (human)
- Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human)
- Nicotine addiction - Homo sapiens (human)
Biological Process
- glutamate receptor signaling pathway
- brain development
- response to wounding
- calcium-mediated signaling
- directional locomotion
Molecular Function
- NMDA glutamate receptor activity
- protein binding
- glutamate-gated calcium ion channel activity
- transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential
Cellular Component
- plasma membrane
- integral component of plasma membrane
- NMDA selective glutamate receptor complex
- cell junction
- postsynaptic density membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000293190
- Coding exons
- 12
- Length
- 19466
- Individuals with no LoFs
- 125692
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 55
- Defined
- 125747
- p
- 0.000219
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.61 | 519 | 633 | 0.820 | 0.0000395 | 7799 |
| Missense (PolyPhen) | 230 | 295.17 | 0.77922 | 3179 | ||
| Synonymous | 0.686 | 268 | 283 | 0.948 | 0.0000196 | 2645 |
| Loss of Function | 2.89 | 17 | 35.6 | 0.477 | 0.00000162 | 423 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00072 | 0.00068 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0.00041 | 0.00040 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00012 | 0.000092 | rare |
| European (Non-Finnish) | 0.00023 | 0.00022 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00018 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:26875626). Sensitivity to glutamate and channel kinetics depend on the subunit composition (Probable). Plays a role in regulating the balance between excitatory and inhibitory activity of pyramidal neurons in the prefrontal cortex. Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (By similarity). {ECO:0000250|UniProtKB:Q01098, ECO:0000269|PubMed:26875626, ECO:0000269|PubMed:28095420, ECO:0000305}.;
Recessive Scores
- pRec
- 0.208
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.789
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |