GRIK4 glutamate ionotropic receptor kainate type subunit 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GRIK4provided by HGNC
Official Full Name: glutamate ionotropic receptor kainate type subunit 4provided by HGNC
Primary source: HGNC:HGNC:4582
See related: Ensembl:ENSG00000149403 MIM:600282; AllianceGenome:HGNC:4582
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: KA1; EAA1; GRIK; GluK4; GluK4-2
Summary: This gene encodes a protein that belongs to the glutamate-gated ionic channel family. Glutamate functions as the major excitatory neurotransmitter in the central nervous system through activation of ligand-gated ion channels and G protein-coupled membrane receptors. The protein encoded by this gene forms functional heteromeric kainate-preferring ionic channels with the subunits encoded by related gene family members. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]
Expression: Biased expression in brain (RPKM 2.8), ovary (RPKM 0.9) and 4 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q23.3

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (120511748..120988906)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (120535497..121012594)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (120382457..120859615)

Chromosome 11 - NC_000011.10 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Impact of GRIK4 gene polymorphisms on cognitive dysfunction in patients with major depression.
Title: Impact of GRIK4 gene polymorphisms on cognitive dysfunction in patients with major depression.
In addition, while GRIK4 was not associated with sertraline tolerability and response, both HTR2A and SLC6A4 could influence tolerability and accelerate treatment response in pediatric patients.
Title: Pharmacogenetics of Sertraline Tolerability and Response in Pediatric Anxiety and Depressive Disorders.
GluK4 deletion carriers who had a mental health problem (predominately depression) showed better performance in visuo-spatial ability and mental processing speed compared to individuals with mental health problems homozygous for the insertion.
Title: A kainate receptor GluK4 deletion, protective against bipolar disorder, is associated with enhanced cognitive performance across diagnoses in the TwinsUK cohort.
the GRIK4 polymorphisms genotypes were distributed as follows: rs79526501: CC696: 16, CG302: 274, GG31: 35; rs11218016: CC455: 483, CT473: 436, TT101: 108; and rs6589847: AA32: 29, AG307: 314, GG690: 686. However, there was no significant difference in allelic or genotypic frequency distributions between patients and controls. We did not find any significant association between GRIK4 polymorphisms and schizophrenia.
Title: No association of GRIK4 polymorphisms with schizophrenia in the Chinese Han population.
Results firstly indicated that rs56275759 of GRIK4 gene might be associated with major depressive disorder in Chinese Han population.
Title: Common variants in GRIK4 and major depressive disorder: An association study in the Chinese Han population.
This study showed the lower GluK4 mRNA levels in pregnant women.
Title: AMPA, NMDA and kainate glutamate receptor subunits are expressed in human peripheral blood mononuclear cells (PBMCs) where the expression of GluK4 is altered by pregnancy and GluN2D by depression in pregnant women.
Data suggest the involvement of glutamate receptor, ionotropic, kainate 4 protein (GRIK4) in treatment-resistant depression (TRD) and in the risk of developing psychotic symptoms during depressive episodes.
Title: The role of GRIK4 gene in treatment-resistant depression.
Subjects possessing the C allele or CC genotype of the GRIK4 polymorphism rs1954787 are more likely to respond to antidepressant treatment.
Title: GRIK4 polymorphism and its association with antidepressant response in depressed patients: a meta-analysis.
The deletion allele affords protection against bipolar disorder through increased KA1 protein abundance in neuronal cells.
Title: GRIK4/KA1 protein expression in human brain and correlation with bipolar disorder risk variant status.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.

Submit: New GeneRIF Correction See all GeneRIFs (20)

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

EBI GWAS Catalog

Description
Common genetic variation and performance on standardized cognitive tests. EBI GWAS Catalog EBI GWAS CatalogPubMed
Polygenic transmission and complex neuro developmental network for attention deficit hyperactivity disorder: genome-wide association study of both common and rare variants. 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

D11S925 (e-PCR)
- UniSTS:82447

D11S4460 (e-PCR)
- UniSTS:29199

WI-9274 (e-PCR)
- UniSTS:44565

D11S925 (e-PCR)
- UniSTS:11289

contig_77245 (e-PCR)
- UniSTS:517402

D11S2999 (e-PCR)
- UniSTS:152107

SHGC-112055 (e-PCR)
- UniSTS:182366

RH27748 (e-PCR)
- UniSTS:90742

D11S1263 (e-PCR)
- UniSTS:148356

RH27747 (e-PCR)
- UniSTS:91268

D11S1265 (e-PCR)
- UniSTS:148359

D11S3484 (e-PCR)
- UniSTS:152725

D11S1774 (e-PCR), detects polymorphism
- UniSTS:21934

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables kainate selective glutamate receptor activity	IBA Inferred from Biological aspect of Ancestor more info
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 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 chemical synaptic transmission	TAS Traceable Author Statement more info	PubMed
involved_in glutamate receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
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 monoatomic ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of postsynaptic membrane potential	IEA Inferred from Electronic Annotation more info
involved_in regulation of presynaptic membrane potential	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
located_in cell projection	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
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor 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
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 4

Names: GluK4(alt_5'UTR); excitatory amino acid receptor 1; glutamate receptor KA1; glutamate receptor, ionotropic, kainate 4; putative NMDtranscript(altAcc_e11)

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_042194.1 RefSeqGene

Range

5001..482060

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1012

mRNA and Protein(s)

NM_001282470.3 → NP_001269399.1 glutamate receptor ionotropic, kainate 4 isoform 1 precursor

See identical proteins and their annotated locations for NP_001269399.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript. Both this variant and variant 2 encode the same isoform (1).

Source sequence(s)

AK292726, AK314284, AP001929, AP002348, AW016926

Consensus CDS

CCDS8433.1

UniProtKB/Swiss-Prot

A8K9L1, Q16099

UniProtKB/TrEMBL

A0A8D9PH79, B2RAP6

Related

ENSP00000404063.2, ENST00000438375.2

Conserved Domains (2) summary

cd13724
Location:415 → 785

PBP2_iGluR_kainate_KA1; The ligand-binding domain of the kainate subtype KA1 of ionotropic glutamate receptors, a member of the type 2 periplasmic-binding fold protein superfamily

cd06394
Location:24 → 402

PBP1_iGluR_Kainate_KA1_2; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the KA1 and KA2 subunits of Kainate receptor
NM_001282473.3 → NP_001269402.1 glutamate receptor ionotropic, kainate 4 isoform 2 precursor

See identical proteins and their annotated locations for NP_001269402.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) has an additional exon in the 5' UTR but lacks several 3' terminal exons, compared to variant 1. Its transcription extends past a splice site that is used in variant 1, resulting in a novel 3' coding region and 3' UTR. The resulting isoform (2) is shorter and has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AK314284, AP001929, AP002348, BC146652

UniProtKB/TrEMBL

A6H8K8

Related

ENST00000533291.5

Conserved Domains (4) summary

cd06394
Location:26 → 400

PBP1_iGluR_Kainate_KA1_2; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the KA1 and KA2 subunits of Kainate receptor

pfam00060
Location:547 → 756

Lig_chan; Ligand-gated ion channel

pfam01094
Location:43 → 382

ANF_receptor; Receptor family ligand binding region

cl21456
Location:415 → 763

Periplasmic_Binding_Protein_Type_2; Type 2 periplasmic binding fold superfamily
NM_014619.5 → NP_055434.2 glutamate receptor ionotropic, kainate 4 isoform 1 precursor

See identical proteins and their annotated locations for NP_055434.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and encodes the same isoform (1), compared to variant 1.

Source sequence(s)

AK292726, AP001929, AW016926, DA246271, DB306924

Consensus CDS

CCDS8433.1

UniProtKB/Swiss-Prot

A8K9L1, Q16099

UniProtKB/TrEMBL

A0A8D9PH79, B2RAP6

Related

ENSP00000435648.2, ENST00000527524.8

Conserved Domains (2) summary

cd13724
Location:415 → 785

PBP2_iGluR_kainate_KA1; The ligand-binding domain of the kainate subtype KA1 of ionotropic glutamate receptors, a member of the type 2 periplasmic-binding fold protein superfamily

cd06394
Location:24 → 402

PBP1_iGluR_Kainate_KA1_2; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the KA1 and KA2 subunits of Kainate receptor

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_000011.10 Reference GRCh38.p14 Primary Assembly

Range

120511748..120988906

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017017621.3 → XP_016873110.1 glutamate receptor ionotropic, kainate 4 isoform X2

UniProtKB/TrEMBL

B2RAP6
XM_017017622.3 → XP_016873111.1 glutamate receptor ionotropic, kainate 4 isoform X3

UniProtKB/TrEMBL

B2RAP6
XM_011542784.3 → XP_011541086.1 glutamate receptor ionotropic, kainate 4 isoform X1

UniProtKB/TrEMBL

A0A8D9UJ88, B2RAP6

Conserved Domains (2) summary

cd13724
Location:361 → 731

PBP2_iGluR_kainate_KA1; The ligand-binding domain of the kainate subtype KA1 of ionotropic glutamate receptors, a member of the type 2 periplasmic-binding fold protein superfamily

cl10011
Location:24 → 348

Periplasmic_Binding_Protein_type1; Type 1 periplasmic binding fold superfamily
XM_047426840.1 → XP_047282796.1 glutamate receptor ionotropic, kainate 4 isoform X4
XM_011542786.3 → XP_011541088.1 glutamate receptor ionotropic, kainate 4 isoform X5

Conserved Domains (3) summary

cd13724
Location:173 → 543

PBP2_iGluR_kainate_KA1; The ligand-binding domain of the kainate subtype KA1 of ionotropic glutamate receptors, a member of the type 2 periplasmic-binding fold protein superfamily

pfam00060
Location:305 → 574

Lig_chan; Ligand-gated ion channel

cl10011
Location:7 → 158

Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily
XM_011542787.3 → XP_011541089.1 glutamate receptor ionotropic, kainate 4 isoform X6

See identical proteins and their annotated locations for XP_011541089.1

Conserved Domains (3) summary

cd13724
Location:161 → 531

PBP2_iGluR_kainate_KA1; The ligand-binding domain of the kainate subtype KA1 of ionotropic glutamate receptors, a member of the type 2 periplasmic-binding fold protein superfamily

pfam00060
Location:293 → 562

Lig_chan; Ligand-gated ion channel

cl10011
Location:1 → 146

Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily

Alternate T2T-CHM13v2.0

Genomic

NC_060935.1 Alternate T2T-CHM13v2.0

Range

120535497..121012594

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054368569.1 → XP_054224544.1 glutamate receptor ionotropic, kainate 4 isoform X2

UniProtKB/TrEMBL

B2RAP6
XM_054368570.1 → XP_054224545.1 glutamate receptor ionotropic, kainate 4 isoform X3

UniProtKB/TrEMBL

B2RAP6
XM_054368568.1 → XP_054224543.1 glutamate receptor ionotropic, kainate 4 isoform X1

UniProtKB/TrEMBL

A0A8D9UJ88, B2RAP6
XM_054368571.1 → XP_054224546.1 glutamate receptor ionotropic, kainate 4 isoform X4
XM_054368572.1 → XP_054224547.1 glutamate receptor ionotropic, kainate 4 isoform X5
XM_054368573.1 → XP_054224548.1 glutamate receptor ionotropic, kainate 4 isoform X6