GRIN2C

glutamate ionotropic receptor NMDA type subunit 2C, the group of Glutamate ionotropic receptor NMDA type subunits

Basic information

Region (hg38): 17:74842022-74861504

Previous symbols: [ "NMDAR2C" ]

Links

ENSG00000161509 ∙ NCBI:2905 ∙ OMIM:138254 ∙ HGNC:4587 ∙ Uniprot:Q14957 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GRIN2C gene.

• Inborn genetic diseases (42 variants)
• not provided (14 variants)
• GRIN2C-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRIN2C gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	2	6
missense			43	4	3	50
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	43	8	6

Variants in GRIN2C

This is a list of pathogenic ClinVar variants found in the GRIN2C region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-74842541-CTG-C		GRIN2C-related disorder	Uncertain significance (Jan 22, 2024)
17-74842550-G-A			Benign (Apr 26, 2018)
17-74842556-AGCCCCAGAGTCCTGCCCCTGT-A		GRIN2C-related disorder	Benign (Jun 15, 2020)
17-74842569-T-TGCCCCTGTGCCCCAGAGGCCC		GRIN2C-related disorder	Likely benign (Jun 14, 2022)
17-74842804-G-C		GRIN2C-related disorder	Likely benign (Jul 21, 2022)
17-74842808-C-G		GRIN2C-related disorder	Likely benign (May 23, 2022)
17-74843140-G-A			Likely benign (May 07, 2018)
17-74843226-C-G		not specified	Uncertain significance (Oct 05, 2021)
17-74843247-C-G		not specified	Uncertain significance (Mar 21, 2023)
17-74843252-G-A		not specified	Uncertain significance (Jun 12, 2023)
17-74843279-G-C		not specified	Uncertain significance (Feb 27, 2023)
17-74843279-G-T		not specified	Uncertain significance (Nov 03, 2022)
17-74843322-G-A		not specified	Uncertain significance (Dec 19, 2022)
17-74843478-T-C		not specified	Likely benign (Oct 20, 2023)
17-74843490-C-T		not specified	Uncertain significance (Apr 13, 2022)
17-74843512-G-C		not specified	Uncertain significance (Feb 12, 2024)
17-74843513-C-G		not specified	Uncertain significance (Jan 02, 2024)
17-74844286-G-C		not specified	Uncertain significance (Mar 04, 2024)
17-74844328-C-T		not specified	Uncertain significance (Jan 26, 2022)
17-74844329-G-A		not specified	Uncertain significance (Jan 10, 2022)
17-74844403-A-T		not specified	Uncertain significance (Mar 07, 2024)
17-74844425-T-C		not specified	Uncertain significance (Jul 06, 2021)
17-74846088-C-T			Likely benign (Jan 01, 2023)
17-74846105-G-A		not specified	Uncertain significance (Sep 26, 2022)
17-74846128-A-G		not specified	Uncertain significance (Feb 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRIN2C	protein_coding	protein_coding	ENST00000293190	12	19466

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.31e-7	0.999	125692	0	55	125747	0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.61	519	633	0.820	0.0000395	7799
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000873	0.000826
Ashkenazi Jewish	0.000407	0.000397
East Asian	0.0000544	0.0000544
Finnish	0.000123	0.0000924
European (Non-Finnish)	0.000226	0.000220
Middle Eastern	0.0000544	0.0000544
South Asian	0.000200	0.000196
Other	0.000175	0.000163

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: 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);Circadian entrainment - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Amphetamine addiction - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Alcoholism - Homo sapiens (human);Cocaine addiction - Homo sapiens (human);Alzheimers Disease;NO-cGMP-PKG mediated Neuroprotection;Phosphodiesterases in neuronal function;Signal Transduction;nitric oxide signaling pathway;GPCR Dopamine D1like receptor;Neuronal System;Synaptic adhesion-like molecules;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Neurexins and neuroligins;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Ras activation upon Ca2+ influx through NMDA receptor;CREB phosphorylation through the activation of Ras;Unblocking of NMDA receptor, glutamate binding and activation;CREB phosphorylation through the activation of CaMKII;Post NMDA receptor activation events;Activation of NMDA receptor and postsynaptic events;Protein-protein interactions at synapses (Consensus)

Recessive Scores

• pRec: 0.208

Haploinsufficiency Scores

• pHI: 0.116
• hipred: Y
• hipred_score: 0.753
• ghis: 0.582

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.789

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Grin2c
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal phenotype

Gene ontology

• Biological process: glutamate receptor signaling pathway;brain development;response to wounding;calcium-mediated signaling;directional locomotion;ionotropic glutamate receptor signaling pathway;negative regulation of protein catabolic process;regulation of synaptic plasticity;neuromuscular process controlling balance;excitatory postsynaptic potential;long-term synaptic potentiation;calcium ion transmembrane import into cytosol;excitatory chemical synaptic transmission;protein localization to postsynaptic membrane
• Cellular component: plasma membrane;integral component of plasma membrane;NMDA selective glutamate receptor complex;cell junction;postsynaptic density membrane;glutamatergic synapse
• 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