GRIN2B glutamate ionotropic receptor NMDA type subunit 2B [Homo sapiens (human)] - Gene

Summary

Official Symbol: GRIN2Bprovided by HGNC
Official Full Name: glutamate ionotropic receptor NMDA type subunit 2Bprovided by HGNC
Primary source: HGNC:HGNC:4586
See related: Ensembl:ENSG00000273079 MIM:138252; AllianceGenome:HGNC:4586
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NR3; MRD6; NR2B; hNR3; DEE27; EIEE27; GluN2B; NMDAR2B
Summary: This gene encodes a member of the N-methyl-D-aspartate (NMDA) receptor family within the ionotropic glutamate receptor superfamily. The encoded protein is a subunit of the NMDA receptor ion channel which acts as an agonist binding site for glutamate. The NMDA receptors mediate a slow calcium-permeable component of excitatory synaptic transmission in the central nervous system. The NMDA receptors are heterotetramers of seven genetically encoded, differentially expressed subunits including NR1 (GRIN1), NR2 (GRIN2A, GRIN2B, GRIN2C, or GRIN2D) and NR3 (GRIN3A or GRIN3B). The early expression of this gene in development suggests a role in brain development, circuit formation, synaptic plasticity, and cellular migration and differentiation. Naturally occurring mutations within this gene are associated with neurodevelopmental disorders including autism spectrum disorder, attention deficit hyperactivity disorder, epilepsy, and schizophrenia. [provided by RefSeq, Aug 2017]
Expression: Biased expression in brain (RPKM 5.9) and testis (RPKM 0.2) See more
Orthologs: mouse all
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Genomic context

Location:: 12p13.1

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (13537337..13982134, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (13411758..13856548, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (13690271..14134536, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Disease-associated nonsense and frame-shift variants resulting in the truncation of the GluN2A or GluN2B C-terminal domain decrease NMDAR surface expression and reduce potentiating effects of neurosteroids.
Title: Disease-associated nonsense and frame-shift variants resulting in the truncation of the GluN2A or GluN2B C-terminal domain decrease NMDAR surface expression and reduce potentiating effects of neurosteroids.
Single-locus and Haplotype Associations of GRIN2B Gene with Autism Spectrum Disorders and the Demographic and Clinical Characteristics of Patients in Guilan, Iran.
Title: Single-locus and Haplotype Associations of GRIN2B Gene with Autism Spectrum Disorders and the Demographic and Clinical Characteristics of Patients in Guilan, Iran.
Gene Interaction of Dopaminergic Synaptic Pathway Genes in Attention-Deficit Hyperactivity Disorder: a Case-Control Study in Chinese Children.
Title: Gene Interaction of Dopaminergic Synaptic Pathway Genes in Attention-Deficit Hyperactivity Disorder: a Case-Control Study in Chinese Children.
The GluN2B-Containing NMDA Receptor Alleviates Neuronal Apoptosis in Neonatal Hypoxic-Ischemic Encephalopathy by Activating PI3K-Akt-CREB Signaling Pathwa.
Title: The GluN2B-Containing NMDA Receptor Alleviates Neuronal Apoptosis in Neonatal Hypoxic-Ischemic Encephalopathy by Activating PI3K-Akt-CREB Signaling Pathwa.
Classification of missense variants in the N-methyl-d-aspartate receptor GRIN gene family as gain- or loss-of-function.
Title: Classification of missense variants in the N-methyl-d-aspartate receptor GRIN gene family as gain- or loss-of-function.
Functional effects of disease-associated variants reveal that the S1-M1 linker of the NMDA receptor critically controls channel opening.
Title: Functional effects of disease-associated variants reveal that the S1-M1 linker of the NMDA receptor critically controls channel opening.
Correlations between GRIN2B and GRIN3A gene polymorphisms and postpartum depressive symptoms in Chinese parturients undergoing cesarean section: A prospective cohort study.
Title: Correlations between GRIN2B and GRIN3A gene polymorphisms and postpartum depressive symptoms in Chinese parturients undergoing cesarean section: A prospective cohort study.
GRIN2B gene expression is increased in the anterior cingulate cortex in major depression.
Title: GRIN2B gene expression is increased in the anterior cingulate cortex in major depression.
Overlapping cortical malformations in patients with pathogenic variants in GRIN1 and GRIN2B.
Title: Overlapping cortical malformations in patients with pathogenic variants in GRIN1 and GRIN2B.
NMDA Receptor GluN2B Subunit Is Involved in Excitotoxicity Mediated by Death-Associated Protein Kinase 1 in Alzheimer's Disease.
Title: NMDA Receptor GluN2B Subunit Is Involved in Excitotoxicity Mediated by Death-Associated Protein Kinase 1 in Alzheimer's Disease.

Submit: New GeneRIF Correction See all GeneRIFs (208)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Developmental and epileptic encephalopathy, 27 MedGen: C4015316 OMIM: 616139 GeneReviews: GRIN2B-Related Neurodevelopmental Disorder	Compare labs
Intellectual disability, autosomal dominant 6 MedGen: C3151411 OMIM: 613970 GeneReviews: GRIN2B-Related Neurodevelopmental Disorder	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2019-09-25) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2019-09-25) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
A genome-wide association study of aging. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic variants and environmental factors associated with hormonal markers of ovarian reserve in Caucasian and African American women. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide analysis reveals novel genes influencing temporal lobe structure with relevance to neurodegeneration in Alzheimer's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of glutamate receptor, ionotropic, N-methyl D-aspartate 2B (GRIN2B) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 induced-neurotoxicity involves upregulation of NR2B and downregulation of PSD-95 expressions in neuron cells	PubMed
	env	HIV-1 gp120-induced dephosphorylation of KV2.1 is dependent on NMDA receptor-mediated activation of protein phosphatase 2B or calcineurin	PubMed
	env	HIV-1 gp120 activates forward trafficking and surface clustering of NMDA receptors in membrane microdomains by a PKA-dependent phosphorylation of the NR1 C-terminal Ser897, followed by a PKC-dependent phosphorylation of Ser896	PubMed
	env	HIV-1 gp120-induced synapse loss requires sequential activation of CXCR4, IL-1beta receptor, and NMDA receptor	PubMed
	env	HIV-1 gp120 activates NMDA receptor directly and phosphorylates JNK through a gp120-mediated apoptotic pathway in human neuroblastoma cells	PubMed
	env	HIV-1 clade B gp120 significantly downregulates NMDA receptor gene and protein expression and levels of glutamine compared to clade C gp120	PubMed
	env	HIV-1 gp120-mediated human cell death involves the NMDA receptor complex; antagonists of the NMDA receptor reverse the gp120-mediated effects	PubMed
	env	HIV-1 gp120 causes an activation of phospholipase A2, resulting in the increased release of arachidonic acid, which may sensitize the NMDA receptor	PubMed
	env	HIV-1 gp120 binds to cells expressing epsilon1/zeta1 or epsilon2/zeta1 combined NMDA receptor subunits, but not to cells expressing a single epsilon1, epsilon2, or zeta1 NMDA receptor subunit	PubMed
Tat	tat	The gene expression of GRIN2B is significantly upregulated in both clade B and clade C Tat treated SK-N-MC neuroblastoma cells	PubMed
	tat	Ca(2+) influx through the NMDA receptor is necessary for HIV-1 Tat-induced synapse loss	PubMed
	tat	HIV-1 Tat upregulates the expression of NMDARs for the apoptosis of retinal pigmen epithelium (RPE) cells. Silencing of NMDARs by siRNA abolishes Tat-induced RPE apoptosis	PubMed
	tat	HIV-1 Tat-induced activation of spermine oxidase (SMO) activity involves NMDAR stimulation in human neuroblastoma	PubMed
	tat	HIV-1 Tat-induced loss of presynaptic terminals is recovered by ifenprodil, an NR2B subunit-selective NMDA receptor antagonist	PubMed
	tat	HIV-1 Tat and methamphetamine inhibit the normal conjunction of signaling between D1 and NMDA receptors, resulting in neural dysfunction and death	PubMed
	tat	HIV-1 Tat interacts with NMDA receptors in primary neuronal-glial cultures and in hippocampal slice cultures	PubMed
	tat	Tat treatment causes activation of neuronal nitric oxide synthase (nNOS) through association with NMDA receptors	PubMed
	tat	HIV-1 Tat treatment induces the formation of complexes involving the low-density lipoprotein receptor-related protein (LRP), postsynaptic density protein-95 (PSD-95), and N-methyl-d-aspartic acid (NMDA) receptors at the neuron surface	PubMed
	tat	HIV-1 Tat-induced NMDA receptor activation is clade dependent. The Cys 30-Cys 31 motif in Tat is critical for the NMDA receptor activation	PubMed
	tat	HIV-1 Tat induces apoptosis of neurons and neurotoxicity through the activation of both NMDA and non-NMDA receptors	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G62303 (e-PCR)
- UniSTS:139270

D12S1274 (e-PCR)
- UniSTS:151828

D12S364 (e-PCR), detects polymorphism
- UniSTS:30766

GRIN2B_968 (e-PCR)
- UniSTS:277297

GRIN2B_V248 (e-PCR)
- UniSTS:277297

G41299 (e-PCR)
- UniSTS:12850

SHGC-78950 (e-PCR)
- UniSTS:95830

D12S847 (e-PCR)
- UniSTS:45945

RH121528 (e-PCR)
- UniSTS:134269

D12S2089 (e-PCR)
- UniSTS:29848

D12S1946 (e-PCR)
- UniSTS:52167

G41304 (e-PCR)
- UniSTS:23496

WI-18930 (e-PCR)
- UniSTS:58072

SHGC-145043 (e-PCR)
- UniSTS:172512

G60183 (e-PCR)
- UniSTS:137442

G11784 (e-PCR)
- UniSTS:7908

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables NMDA glutamate receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables NMDA glutamate receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables NMDA glutamate receptor activity	ISS Inferred from Sequence or Structural Similarity more info
enables NMDA glutamate receptor activity	TAS Traceable Author Statement more info	PubMed
enables amyloid-beta binding	NAS Non-traceable Author Statement more info	PubMed
enables glutamate binding	ISS Inferred from Sequence or Structural Similarity more info
enables glutamate-gated calcium ion channel activity	IDA Inferred from Direct Assay more info	PubMed
enables glutamate-gated calcium ion channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables glycine binding	IDA Inferred from Direct Assay more info	PubMed
enables ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential	IDA Inferred from Direct Assay more info	PubMed
enables ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential	IMP Inferred from Mutant Phenotype more info	PubMed
enables ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential	NAS Non-traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	IBA Inferred from Biological aspect of Ancestor more info
enables zinc ion binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in brain development	NAS Non-traceable Author Statement more info	PubMed
involved_in calcium ion transmembrane import into cytosol	IDA Inferred from Direct Assay more info	PubMed
involved_in calcium ion transmembrane import into cytosol	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in calcium-mediated signaling	IEA Inferred from Electronic Annotation more info
involved_in chemical synaptic transmission	TAS Traceable Author Statement more info	PubMed
involved_in excitatory chemical synaptic transmission	NAS Non-traceable Author Statement more info	PubMed
involved_in excitatory postsynaptic potential	IBA Inferred from Biological aspect of Ancestor more info
involved_in glutamate receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in ionotropic glutamate receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in ionotropic glutamate receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in learning or memory	ISS Inferred from Sequence or Structural Similarity more info
involved_in long-term synaptic potentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in monoatomic cation transmembrane transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of dendritic spine maintenance	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cysteine-type endopeptidase activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of excitatory postsynaptic potential	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of excitatory postsynaptic potential	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of synaptic transmission, glutamatergic	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of synaptic transmission, glutamatergic	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein heterotetramerization	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of monoatomic cation transmembrane transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of neuronal synaptic plasticity	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of presynaptic membrane potential	IEA Inferred from Electronic Annotation more info
involved_in regulation of synaptic plasticity	NAS Non-traceable Author Statement more info	PubMed
involved_in response to ethanol	IDA Inferred from Direct Assay more info	PubMed
involved_in synaptic transmission, glutamatergic	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
part_of NMDA selective glutamate receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of NMDA selective glutamate receptor complex	IDA Inferred from Direct Assay more info	PubMed
part_of NMDA selective glutamate receptor complex	ISO Inferred from Sequence Orthology more info
part_of NMDA selective glutamate receptor complex	ISS Inferred from Sequence or Structural Similarity more info
part_of NMDA selective glutamate receptor complex	TAS Traceable Author Statement more info	PubMed
located_in cell surface	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in cytoskeleton	IEA Inferred from Electronic Annotation more info
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in late endosome	ISS Inferred from Sequence or Structural Similarity more info
located_in lysosome	ISS Inferred from Sequence or Structural Similarity more info
located_in neuron projection	ISS Inferred from Sequence or Structural Similarity more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynaptic density	ISS Inferred from Sequence or Structural Similarity more info
is_active_in postsynaptic density membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in postsynaptic membrane	NAS Non-traceable Author Statement more info	PubMed
located_in postsynaptic membrane	TAS Traceable Author Statement more info	PubMed
located_in synaptic membrane	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: glutamate receptor ionotropic, NMDA 2B

Names: GluN2B(alt_5'UTR); N-methyl D-aspartate receptor subtype 2B; N-methyl-D-aspartate receptor subunit 3; glutamate [NMDA] receptor subunit epsilon-2; glutamate receptor subunit epsilon-2; glutamate receptor, ionotropic, N-methyl D-aspartate 2B

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_031854.2 RefSeqGene

Range

5411..449676

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000834.5 → NP_000825.2 glutamate receptor ionotropic, NMDA 2B isoform a precursor

See identical proteins and their annotated locations for NP_000825.2

Status: REVIEWED

Source sequence(s)

AC007527, AC007535, AC007916, U88963, U90278

Consensus CDS

CCDS8662.1

UniProtKB/Swiss-Prot

Q12919, Q13220, Q13224, Q13225, Q14CU4, Q9UM56

UniProtKB/TrEMBL

A0A8D9PHB2

Related

ENSP00000477455.1, ENST00000609686.4

Conserved Domains (3) summary

cd13718
Location:403 → 803

PBP2_iGluR_NMDA_Nr2; The ligand-binding domain of the NR2 subunit of ionotropic NMDA (N-methyl-D-aspartate) glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily

cd06378
Location:33 → 388

PBP1_iGluR_NMDA_NR2; N-terminal leucine-isoleucine-valine-binding protein (LIVBP)-like domain of the NR2 subunit of NMDA receptor family

pfam10565
Location:840 → 1484

NMDAR2_C; N-methyl D-aspartate receptor 2B3 C-terminus
NM_001413992.1 → NP_001400921.1 glutamate receptor ionotropic, NMDA 2B isoform a precursor

Status: REVIEWED

Source sequence(s)

AC007397, AC007527, AC007535, AC007784, AC007916

UniProtKB/Swiss-Prot

Q12919, Q13220, Q13224, Q13225, Q14CU4, Q9UM56

UniProtKB/TrEMBL

A0A8D9PHB2
NM_001413993.1 → NP_001400922.1 glutamate receptor ionotropic, NMDA 2B isoform b precursor

Status: REVIEWED

Source sequence(s)

AC007397, AC007784, AC007916
NM_001413994.1 → NP_001400923.1 glutamate receptor ionotropic, NMDA 2B isoform b precursor

Status: REVIEWED

Source sequence(s)

AC007397, AC007784, AC007916
NM_001413995.1 → NP_001400924.1 glutamate receptor ionotropic, NMDA 2B isoform b precursor

Status: REVIEWED

Source sequence(s)

AC007397, AC007784, AC007916

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

13537337..13982134 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005253351.3 → XP_005253408.1 glutamate receptor ionotropic, NMDA 2B isoform X1

Conserved Domains (2) summary

pfam10565
Location:102 → 746

NMDAR2_C; N-methyl D-aspartate receptor 2B3 C-terminus

cl21456
Location:1 → 65

Periplasmic_Binding_Protein_Type_2; Type 2 periplasmic binding fold superfamily

Alternate T2T-CHM13v2.0

Genomic

NC_060936.1 Alternate T2T-CHM13v2.0

Range

13411758..13856548 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054371855.1 → XP_054227830.1 glutamate receptor ionotropic, NMDA 2B isoform X2

UniProtKB/Swiss-Prot

Q12919, Q13220, Q13224, Q13225, Q14CU4, Q9UM56

UniProtKB/TrEMBL

A0A8D9PHB2
XM_054371854.1 → XP_054227829.1 glutamate receptor ionotropic, NMDA 2B isoform X2

UniProtKB/Swiss-Prot

Q12919, Q13220, Q13224, Q13225, Q14CU4, Q9UM56

UniProtKB/TrEMBL

A0A8D9PHB2
XM_054371856.1 → XP_054227831.1 glutamate receptor ionotropic, NMDA 2B isoform X1