GRIK2 glutamate ionotropic receptor kainate type subunit 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GRIK2provided by HGNC
Official Full Name: glutamate ionotropic receptor kainate type subunit 2provided by HGNC
Primary source: HGNC:HGNC:4580
See related: Ensembl:ENSG00000164418 MIM:138244; AllianceGenome:HGNC:4580
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: EAA4; GLR6; MRT6; GLUK6; GLUR6; GluK2; NEDLAS
Summary: Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to the kainate family of glutamate receptors, which are composed of four subunits and function as ligand-activated ion channels. The subunit encoded by this gene is subject to RNA editing at multiple sites within the first and second transmembrane domains, which is thought to alter the structure and function of the receptor complex. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. Mutations in this gene have been associated with autosomal recessive cognitive disability. [provided by RefSeq, Jul 2008]
Expression: Biased expression in brain (RPKM 2.7), heart (RPKM 0.6) and 5 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6q16.3

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (101393708..102070083)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (102567441..103245122)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (101841584..102517958)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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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?

Epigenetic signature discriminates lymphatic metastasis in BRAF wild-type thyroid carcinoma: methylation role of GRIK2.
Title: Epigenetic signature discriminates lymphatic metastasis in BRAF wild-type thyroid carcinoma: methylation role of GRIK2.
The Deletion of GluK2 Alters Cholinergic Control of Neuronal Excitability.
Title: The Deletion of GluK2 Alters Cholinergic Control of Neuronal Excitability.
Kainate receptor modulation by NETO2.
Title: Kainate receptor modulation by NETO2.
Clustered mutations in the GRIK2 kainate receptor subunit gene underlie diverse neurodevelopmental disorders.
Title: Clustered mutations in the GRIK2 kainate receptor subunit gene underlie diverse neurodevelopmental disorders.
This study suggests that the rs2227283 polymorphism of the GRIK2 gene is related to aggressive behaviors in bipolar manic patients and that the A/A genotype and A allele may increase the risk of the aggressive behavior in bipolar manic patients.
Title: Correlation between GRIK2 rs6922753, rs2227283 polymorphism and aggressive behaviors with Bipolar Mania in the Chinese Han population.
Both the GRIK2 rs4840200-T and rs3213607-A, and the interactions between rs4840200 and rs9390754 are related to the increased risk of epilepsy risk.
Title: Interaction among GRIK2 gene on epilepsy susceptibility in Chinese children.
These results indicate involvement of GRIK2 in senescence and suggests GRIK2 as a potential target for therapeutic intervention of cancer cells.
Title: Isoforms of Ionotropic Glutamate Receptor GRIK2 Induce Senescence of Carcinoma Cells.
Study identifies differentially variable CpG sites in GRIK2 gene displaying increased expression in patients with chronic obstructive pulmonary disease.
Title: Altered DNA methylation is associated with aberrant gene expression in parenchymal but not airway fibroblasts isolated from individuals with COPD.
results suggest that PKC SUMOylation is an important regulator of the 14-3-3 and GluK2a protein complex and may contribute to regulate the decay kinetics of kainate receptor-excitatory postsynaptic currents
Title: PKC SUMOylation inhibits the binding of 14-3-3τ to GluK2.
these findings indicate that GRIK2 has a role in the maintenance of urothelial cancer stem cells and that GRIK2 and ALDH1 can be prognosis prediction markers for urinary tract carcinomas
Title: GRIK2 has a role in the maintenance of urothelial carcinoma stem-like cells, and its expression is associated with poorer prognosis.

Submit: New GeneRIF Correction See all GeneRIFs (57)

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
Intellectual disability, autosomal recessive 6 MedGen: C1970198 OMIM: 611092 GeneReviews: Not available	Compare labs
Neurodevelopmental disorder with impaired language and ataxia and with or without seizures MedGen: C5562006 OMIM: 619580 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association study identifies novel loci associated with concentrations of four plasma phospholipid fatty acids in the de novo lipogenesis pathway: results from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortiu EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of biochemical traits in Korcula Island, Croatia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of obsessive-compulsive disorder. EBI GWAS Catalog EBI GWAS CatalogPubMed
GWAS of Longevity in CHARGE Consortium Confirms APOE and FOXO3 Candidacy. EBI GWAS Catalog EBI GWAS CatalogPubMed
Hypertrophy-associated polymorphisms ascertained in a founder cohort applied to heart failure risk and mortality. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. 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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH46628 (e-PCR)
- UniSTS:79872

SHGC-141507 (e-PCR)
- UniSTS:184327

SHGC-147136 (e-PCR)
- UniSTS:175634

D11S2560 (e-PCR)
- UniSTS:37928

D6S1642 (e-PCR), detects polymorphism
- UniSTS:33836

D6S434 (e-PCR)
- UniSTS:77614

D8S2279 (e-PCR)
- UniSTS:473907

RH123105 (e-PCR)
- UniSTS:135485

D6S283 (e-PCR)
- UniSTS:55872

STS-H15417 (e-PCR)
- UniSTS:65609

G43669 (e-PCR)
- UniSTS:95080

G15813 (e-PCR)
- UniSTS:73067

RH122313 (e-PCR)
- UniSTS:137837

RH119433 (e-PCR)
- UniSTS:132974

D6S449 (e-PCR), detects polymorphism
- UniSTS:63859

D6S1219E (e-PCR)
- UniSTS:43638

D6S1543 (e-PCR), detects polymorphism
- UniSTS:38008

SGC34572 (e-PCR)
- UniSTS:69247

RH92163 (e-PCR)
- UniSTS:92804

GRIK2_3094 (e-PCR)
- UniSTS:462222

D6S449 (e-PCR), detects polymorphism
- UniSTS:8085

D6S434 (e-PCR)
- UniSTS:26775

G65520 (e-PCR)
- UniSTS:166585

D6S1709 (e-PCR), detects polymorphism
- UniSTS:49606

RH123509 (e-PCR)
- UniSTS:135884

D6S283 (e-PCR)
- UniSTS:81103

D6S1028 (e-PCR), detects polymorphism
- UniSTS:35539

D22S958 (e-PCR)
- UniSTS:259319

GDB:373727 (e-PCR)
- UniSTS:156925

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables extracellularly glutamate-gated ion channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables glutamate-gated calcium ion channel activity	IEA Inferred from Electronic Annotation more info
enables glutamate-gated receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables glutamate-gated receptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables kainate selective glutamate receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables kainate selective glutamate 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 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in behavioral fear response	IEA Inferred from Electronic Annotation more info
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 detection of cold stimulus involved in thermoception	ISS Inferred from Sequence or Structural Similarity more info
involved_in excitatory postsynaptic potential	IEA Inferred from Electronic Annotation more info
involved_in glutamate receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in inhibitory postsynaptic potential	IEA Inferred from Electronic Annotation more info
involved_in intracellular calcium ion homeostasis	IEA Inferred from Electronic Annotation more info
involved_in ionotropic glutamate receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in modulation of chemical synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info
involved_in modulation of chemical synaptic transmission	IDA Inferred from Direct Assay more info	PubMed
involved_in monoatomic ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of synaptic transmission, glutamatergic	IEA Inferred from Electronic Annotation more info
involved_in neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in neuronal action potential	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of synaptic transmission	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in presynaptic modulation of chemical synaptic transmission	IEA Inferred from Electronic Annotation more info
involved_in regulation of long-term neuronal synaptic plasticity	IEA Inferred from Electronic Annotation more info
involved_in regulation of presynaptic membrane potential	IEA Inferred from Electronic Annotation more info
involved_in regulation of short-term neuronal synaptic plasticity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in synaptic transmission, glutamatergic	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
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
part_of kainate selective glutamate receptor complex	IBA Inferred from Biological aspect of Ancestor more info
located_in mossy fiber rosette	IEA Inferred from Electronic Annotation more info
located_in neuronal cell body	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	IMP Inferred from Mutant Phenotype more info	PubMed
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
is_active_in presynaptic membrane	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: glutamate receptor ionotropic, kainate 2

Names: GluK2(alt_5'UTR); bA487F5.1; excitatory amino acid receptor 4; gluR-6; glutamate receptor 6; glutamate receptor form A; glutamate receptor form B; glutamate receptor form C; glutamate receptor form D; glutamate receptor form E; putative NMDtranscript(cassette_171nt)

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_009224.3 RefSeqGene

Range

5002..681377

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001166247.1 → NP_001159719.1 glutamate receptor ionotropic, kainate 2 isoform 3 precursor

See identical proteins and their annotated locations for NP_001159719.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an additional exon in the 3' coding region, compared to transcript variant 1. The resulting isoform (3) is shorter and has a distinct C-terminus compared to isoform 1. RNA editing changes Ile567Val, Tyr571Cys and Gln621Arg.

Source sequence(s)

AJ252246, AP002530, BC037954

Consensus CDS

CCDS55045.1

UniProtKB/TrEMBL

A0A804HKP5

Related

ENSP00000358134.1, ENST00000369138.5

Conserved Domains (2) summary

cd06382
Location:37 → 414

PBP1_iGluR_Kainate; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the kainate receptors

cl21456
Location:430 → 800

Periplasmic_Binding_Protein_Type_2; Type 2 periplasmic binding fold superfamily
NM_021956.5 → NP_068775.1 glutamate receptor ionotropic, kainate 2 isoform 1 precursor

See identical proteins and their annotated locations for NP_068775.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1). RNA editing changes Ile567Val, Tyr571Cys and Gln621Arg.

Source sequence(s)

AP002528, AP002529, AP002530

Consensus CDS

CCDS5048.1

UniProtKB/Swiss-Prot

A6NMY9, B5MCV0, D7RWZ3, D7RWZ4, D7RWZ5, D7RWZ6, D7RWZ7, Q13002, Q8WWS1, Q96KS6, Q96KS7, Q96KS8

UniProtKB/TrEMBL

A0A8D9PH75, A8K0H7

Related

ENSP00000358130.6, ENST00000369134.9

Conserved Domains (2) summary

cd06382
Location:37 → 414

PBP1_iGluR_Kainate; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the kainate receptors

cl21456
Location:430 → 800

Periplasmic_Binding_Protein_Type_2; Type 2 periplasmic binding fold superfamily
NM_175768.3 → NP_786944.1 glutamate receptor ionotropic, kainate 2 isoform 2 precursor

See identical proteins and their annotated locations for NP_786944.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an additional exon in the 3' coding region, compared to transcript variant 1. The resulting isoform (2) is shorter and has a distinct C-terminus compared to isoform 1. RNA editing changes Ile567Val, Tyr571Cys and Gln621Arg.

Source sequence(s)

AJ301610, AK289542, AP002530, BC037954

Consensus CDS

CCDS5049.1

UniProtKB/TrEMBL

A0A804HKP5

Related

ENSP00000405596.1, ENST00000413795.5

Conserved Domains (2) summary

cd06382
Location:37 → 414

PBP1_iGluR_Kainate; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the kainate receptors

cl21456
Location:430 → 800

Periplasmic_Binding_Protein_Type_2; Type 2 periplasmic binding fold superfamily

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

101393708..102070083

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047418681.1 → XP_047274637.1 glutamate receptor ionotropic, kainate 2 isoform X1

UniProtKB/Swiss-Prot

A6NMY9, B5MCV0, D7RWZ3, D7RWZ4, D7RWZ5, D7RWZ6, D7RWZ7, Q13002, Q8WWS1, Q96KS6, Q96KS7, Q96KS8

UniProtKB/TrEMBL

A0A8D9PH75
XM_047418682.1 → XP_047274638.1 glutamate receptor ionotropic, kainate 2 isoform X2
XM_017010781.3 → XP_016866270.1 glutamate receptor ionotropic, kainate 2 isoform X4

UniProtKB/TrEMBL

A0A804HI04

Related

ENSP00000506840.1, ENST00000682222.1

Conserved Domains (2) summary

cd06382
Location:37 → 414

PBP1_iGluR_Kainate; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the kainate receptors

cl21456
Location:430 → 702

Periplasmic_Binding_Protein_Type_2; Type 2 periplasmic binding fold superfamily
XM_017010782.3 → XP_016866271.1 glutamate receptor ionotropic, kainate 2 isoform X5

UniProtKB/TrEMBL

A8K7F0

Related

ENSP00000508069.1, ENST00000682115.1
XM_005266946.5 → XP_005267003.1 glutamate receptor ionotropic, kainate 2 isoform X3

See identical proteins and their annotated locations for XP_005267003.1

UniProtKB/TrEMBL

B7Z8P6

Conserved Domains (2) summary

cd06382
Location:1 → 365

PBP1_iGluR_Kainate; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the kainate receptors

cl21456
Location:381 → 751

Periplasmic_Binding_Protein_Type_2; Type 2 periplasmic binding fold superfamily

Alternate T2T-CHM13v2.0

Genomic

NC_060930.1 Alternate T2T-CHM13v2.0

Range

102567441..103245122

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054355243.1 → XP_054211218.1 glutamate receptor ionotropic, kainate 2 isoform X1

UniProtKB/Swiss-Prot

A6NMY9, B5MCV0, D7RWZ3, D7RWZ4, D7RWZ5, D7RWZ6, D7RWZ7, Q13002, Q8WWS1, Q96KS6, Q96KS7, Q96KS8

UniProtKB/TrEMBL

A0A8D9PH75
XM_054355244.1 → XP_054211219.1 glutamate receptor ionotropic, kainate 2 isoform X2
XM_054355246.1 → XP_054211221.1 glutamate receptor ionotropic, kainate 2 isoform X4
XM_054355247.1 → XP_054211222.1 glutamate receptor ionotropic, kainate 2 isoform X5
XM_054355245.1 → XP_054211220.1 glutamate receptor ionotropic, kainate 2 isoform X3