GRIN2D glutamate ionotropic receptor NMDA type subunit 2D [Homo sapiens (human)] - Gene

Summary

Official Symbol: GRIN2Dprovided by HGNC
Official Full Name: glutamate ionotropic receptor NMDA type subunit 2Dprovided by HGNC
Primary source: HGNC:HGNC:4588
See related: Ensembl:ENSG00000105464 MIM:602717; AllianceGenome:HGNC:4588
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: EB11; NR2D; DEE46; EIEE46; GluN2D; NMDAR2D
Summary: N-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate receptors. NMDA channel has been shown to be involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. NMDA receptor channels are heteromers composed of the key receptor subunit NMDAR1 (GRIN1) and 1 or more of the 4 NMDAR2 subunits: NMDAR2A (GRIN2A), NMDAR2B (GRIN2B), NMDAR2C (GRIN2C), and NMDAR2D (GRIN2D). [provided by RefSeq, Mar 2010]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 19q13.33

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (48393668..48444931)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (51387832..51439100)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (48896925..48948188)

Chromosome 19 - NC_000019.10 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?

Multivariate GWAS of Alzheimer's disease CSF biomarker profiles implies GRIN2D in synaptic functioning.
Title: Multivariate GWAS of Alzheimer's disease CSF biomarker profiles implies GRIN2D in synaptic functioning.
Potential Roles for the GluN2D NMDA Receptor Subunit in Schizophrenia.
Title: Potential Roles for the GluN2D NMDA Receptor Subunit in Schizophrenia.
GRIN2D knockdown suppresses the progression of lung adenocarcinoma by regulating the E2F signalling pathway.
Title: GRIN2D knockdown suppresses the progression of lung adenocarcinoma by regulating the E2F signalling pathway.
Structural insights into assembly and function of GluN1-2C, GluN1-2A-2C, and GluN1-2D NMDARs.
Title: Structural insights into assembly and function of GluN1-2C, GluN1-2A-2C, and GluN1-2D NMDARs.
MicroRNA-129-1-3p Represses the Progression of Triple-Negative Breast Cancer by Targeting the GRIN2D Gene.
Title: MicroRNA-129-1-3p Represses the Progression of Triple-Negative Breast Cancer by Targeting the GRIN2D Gene.
GluN2D-mediated excitatory drive onto medial prefrontal cortical PV+ fast-spiking inhibitory interneurons.
Title: GluN2D-mediated excitatory drive onto medial prefrontal cortical PV+ fast-spiking inhibitory interneurons.
we identified three patients with novel GRIN2D variants, providing the solid evidence that GRIN2D variants cause epileptic encephalopathy.
Title: GRIN2D variants in three cases of developmental and epileptic encephalopathy.
ultra-rare variants with loss of function (frameshift, nonsense or splice site) in NMDARs genes like GRIN2C and GRIN2D may contribute to possible risk of schizophrenia
Title: Rare loss of function mutations in N-methyl-D-aspartate glutamate receptors and their contributions to schizophrenia susceptibility.
This study found that NMDAR activation, NR2D in particular, is involved in human fetal lung fibroblast proliferation and collagen production through a potential ERK1/2-mediated mechanism.
Title: The excitotoxity of NMDA receptor NR2D subtype mediates human fetal lung fibroblasts proliferation and collagen production.
High GRIN2D expression is associated with colorectal cancer.
Title: Glutamate dependent NMDA receptor 2D is a novel angiogenic tumour endothelial marker in colorectal cancer.

Submit: New GeneRIF Correction See all GeneRIFs (19)

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, 46 MedGen: C4310687 OMIM: 617162 GeneReviews: GRIN2D-Related Developmental and Epileptic Encephalopathy	Compare labs

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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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	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 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 activates NMDA receptor directly and phosphorylates JNK through a gp120-mediated apoptotic pathway in human neuroblastoma cells	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 GRIN2D 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 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

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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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 glutamate binding	IEA Inferred from Electronic Annotation more info
enables glutamate-gated calcium ion channel activity	IDA Inferred from Direct Assay more info	PubMed
enables glutamate-gated receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential	IEA Inferred from Electronic Annotation more info
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 voltage-gated monoatomic cation channel activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in adult locomotory behavior	IEA Inferred from Electronic Annotation more info
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-mediated signaling	IEA Inferred from Electronic Annotation more info
involved_in cellular response to L-glutamate	IEA Inferred from Electronic Annotation more info
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 ionotropic glutamate receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in long-term synaptic potentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in monoatomic cation transmembrane transport	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of excitatory postsynaptic potential	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of synaptic transmission, glutamatergic	ISO Inferred from Sequence Orthology more info
involved_in regulation of monoatomic cation transmembrane transport	ISO Inferred from Sequence Orthology 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 sensory perception of pain	IEA Inferred from Electronic Annotation more info
involved_in regulation of synaptic plasticity	NAS Non-traceable Author Statement more info	PubMed
involved_in startle response	IEA Inferred from Electronic Annotation more info
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	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 endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in hippocampal mossy fiber to CA3 synapse	IEA Inferred from Electronic Annotation 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	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement 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 presynaptic active zone membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: glutamate receptor ionotropic, NMDA 2D

Names: N-methyl D-aspartate receptor subtype 2D; N-methyl-d-aspartate receptor subunit 2D; estrogen receptor binding CpG island; glutamate [NMDA] receptor subunit epsilon-4; glutamate receptor, ionotropic, N-methyl D-aspartate 2D

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_052829.1 RefSeqGene

Range

3794..55057

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000836.4 → NP_000827.2 glutamate receptor ionotropic, NMDA 2D precursor

See identical proteins and their annotated locations for NP_000827.2

Status: REVIEWED

Source sequence(s)

AB209292, AC011527, AW139866, U77783

Consensus CDS

CCDS12719.1

UniProtKB/Swiss-Prot

O15399

Related

ENSP00000263269.2, ENST00000263269.4

Conserved Domains (2) summary

cd13718
Location:430 → 830

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:49 → 413

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

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_000019.10 Reference GRCh38.p14 Primary Assembly

Range

48393668..48444931

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011526872.2 → XP_011525174.1 glutamate receptor ionotropic, NMDA 2D isoform X1

See identical proteins and their annotated locations for XP_011525174.1

UniProtKB/Swiss-Prot

O15399

Conserved Domains (2) summary

cd13718
Location:430 → 830

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:49 → 413

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