GRIK2 (glutamate ionotropic receptor kainate type subunit 2)

Gene

• Entrez ID: 2898
• Gene name: Glutamate ionotropic receptor kainate type subunit 2
• Gene symbol: GRIK2
• Synonyms (NCBI Gene): EAA4, GLR6, GLUK6, GLUR6, GluK2, MRT6, NEDLAS
• Chromosome: 6
• Chromosome location: 6q16.3
• 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 com

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs749995448	C>A,T	Pathogenic	Synonymous variant, non coding transcript variant, coding sequence variant, stop gained
rs1265340906	C>A,T	Likely-pathogenic	Coding sequence variant, synonymous variant, stop gained, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT029019	hsa-miR-26b-5p	Microarray	19088304
MIRT1034228	hsa-miR-101	CLIP-seq
MIRT1034229	hsa-miR-1206	CLIP-seq
MIRT1034230	hsa-miR-144	CLIP-seq
MIRT1034231	hsa-miR-214	CLIP-seq
MIRT1034232	hsa-miR-3120-3p	CLIP-seq
MIRT1034233	hsa-miR-3619-5p	CLIP-seq
MIRT1034234	hsa-miR-3647-3p	CLIP-seq
MIRT1034235	hsa-miR-4753-3p	CLIP-seq
MIRT1034236	hsa-miR-4768-5p	CLIP-seq
MIRT1034237	hsa-miR-567	CLIP-seq
MIRT1034238	hsa-miR-582-5p	CLIP-seq
MIRT1034239	hsa-miR-761	CLIP-seq
MIRT1034240	hsa-miR-873	CLIP-seq
MIRT2006751	hsa-miR-153	CLIP-seq
MIRT2006752	hsa-miR-2052	CLIP-seq
MIRT1034232	hsa-miR-3120-3p	CLIP-seq
MIRT2006753	hsa-miR-33a	CLIP-seq
MIRT2006754	hsa-miR-33b	CLIP-seq
MIRT2006755	hsa-miR-3692	CLIP-seq
MIRT2006756	hsa-miR-4320	CLIP-seq
MIRT2006757	hsa-miR-448	CLIP-seq
MIRT2006758	hsa-miR-4496	CLIP-seq
MIRT2006759	hsa-miR-450b-5p	CLIP-seq
MIRT2006760	hsa-miR-507	CLIP-seq
MIRT2006761	hsa-miR-543	CLIP-seq
MIRT2006762	hsa-miR-545	CLIP-seq
MIRT2006763	hsa-miR-548g	CLIP-seq
MIRT2006764	hsa-miR-557	CLIP-seq
MIRT2239156	hsa-miR-34b	CLIP-seq
MIRT2239157	hsa-miR-4420	CLIP-seq
MIRT2239158	hsa-miR-4724-5p	CLIP-seq
MIRT2239159	hsa-miR-4760-3p	CLIP-seq
MIRT2239160	hsa-miR-548ae	CLIP-seq
MIRT2239161	hsa-miR-548aj	CLIP-seq
MIRT2239162	hsa-miR-548am	CLIP-seq
MIRT2239163	hsa-miR-548x	CLIP-seq
MIRT2388759	hsa-miR-323-5p	CLIP-seq
MIRT2388760	hsa-miR-876-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000149	Function	SNARE binding	IEA
GO:0001662	Process	Behavioral fear response	IEA
GO:0004970	Function	Glutamate-gated receptor activity	IDA	7536611, 8730589, 14511640
GO:0004970	Function	Glutamate-gated receptor activity	IEA
GO:0004970	Function	Glutamate-gated receptor activity	IMP	34375587
GO:0005216	Function	Monoatomic ion channel activity	IEA
GO:0005234	Function	Extracellularly glutamate-gated ion channel activity	IMP	28180184
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA	14511640
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	IMP	34375587
GO:0005886	Component	Plasma membrane	TAS	7536611
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0006874	Process	Intracellular calcium ion homeostasis	IEA
GO:0007215	Process	Glutamate receptor signaling pathway	TAS	7536611
GO:0007268	Process	Chemical synaptic transmission	IEA
GO:0007268	Process	Chemical synaptic transmission	IEA
GO:0007268	Process	Chemical synaptic transmission	TAS	7536611
GO:0008066	Function	Glutamate receptor activity	IEA
GO:0008328	Component	Ionotropic glutamate receptor complex	IEA
GO:0014069	Component	Postsynaptic density	IEA
GO:0015276	Function	Ligand-gated monoatomic ion channel activity	IEA
GO:0015277	Function	Kainate selective glutamate receptor activity	IBA
GO:0015277	Function	Kainate selective glutamate receptor activity	IDA	15537878
GO:0015277	Function	Kainate selective glutamate receptor activity	IEA
GO:0015277	Function	Kainate selective glutamate receptor activity	TAS	7536611
GO:0016020	Component	Membrane	IEA
GO:0019228	Process	Neuronal action potential	IEA
GO:0019722	Process	Calcium-mediated signaling	IEA
GO:0022849	Function	Glutamate-gated calcium ion channel activity	IEA
GO:0030165	Function	PDZ domain binding	IEA
GO:0030424	Component	Axon	IEA
GO:0030425	Component	Dendrite	IEA
GO:0031624	Function	Ubiquitin conjugating enzyme binding	IEA
GO:0031625	Function	Ubiquitin protein ligase binding	IEA
GO:0032839	Component	Dendrite cytoplasm	IEA
GO:0032983	Component	Kainate selective glutamate receptor complex	IBA
GO:0032983	Component	Kainate selective glutamate receptor complex	IEA
GO:0034220	Process	Monoatomic ion transmembrane transport	IEA
GO:0035235	Process	Ionotropic glutamate receptor signaling pathway	IEA
GO:0035249	Process	Synaptic transmission, glutamatergic	IBA
GO:0035249	Process	Synaptic transmission, glutamatergic	IEA
GO:0038023	Function	Signaling receptor activity	IEA
GO:0042391	Process	Regulation of membrane potential	IEA
GO:0042734	Component	Presynaptic membrane	IBA
GO:0042734	Component	Presynaptic membrane	IEA
GO:0042802	Function	Identical protein binding	IEA
GO:0043025	Component	Neuronal cell body	IEA
GO:0043113	Process	Receptor clustering	IEA
GO:0043195	Component	Terminal bouton	IEA
GO:0043204	Component	Perikaryon	IEA
GO:0043524	Process	Negative regulation of neuron apoptotic process	IEA
GO:0043525	Process	Positive regulation of neuron apoptotic process	IEA
GO:0045202	Component	Synapse	IEA
GO:0045211	Component	Postsynaptic membrane	IEA
GO:0046328	Process	Regulation of JNK cascade	IEA
GO:0048169	Process	Regulation of long-term neuronal synaptic plasticity	IEA
GO:0048172	Process	Regulation of short-term neuronal synaptic plasticity	IEA
GO:0048172	Process	Regulation of short-term neuronal synaptic plasticity	IMP	15537878
GO:0050804	Process	Modulation of chemical synaptic transmission	IBA
GO:0050804	Process	Modulation of chemical synaptic transmission	IDA	15537878
GO:0050806	Process	Positive regulation of synaptic transmission	IMP	15537878
GO:0051402	Process	Neuron apoptotic process	IEA
GO:0051402	Process	Neuron apoptotic process	IEA
GO:0051967	Process	Negative regulation of synaptic transmission, glutamatergic	IEA
GO:0051967	Process	Negative regulation of synaptic transmission, glutamatergic	IEA
GO:0060079	Process	Excitatory postsynaptic potential	IEA
GO:0060080	Process	Inhibitory postsynaptic potential	IEA
GO:0097110	Function	Scaffold protein binding	IEA
GO:0097471	Component	Mossy fiber rosette	IEA
GO:0098686	Component	Hippocampal mossy fiber to CA3 synapse	IEA
GO:0098815	Process	Modulation of excitatory postsynaptic potential	IEA
GO:0098839	Component	Postsynaptic density membrane	IBA
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0099171	Process	Presynaptic modulation of chemical synaptic transmission	IEA
GO:0099505	Process	Regulation of presynaptic membrane potential	IEA
GO:0099507	Function	Ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential	IEA
GO:0120169	Process	Detection of cold stimulus involved in thermoception	IEA
GO:0120169	Process	Detection of cold stimulus involved in thermoception	ISS
GO:1904315	Function	Transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	IBA
GO:1904315	Function	Transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	IEA

Other IDs

• MIM: 138244
• HGNC: 4580
• e!Ensembl: ENSG00000164418

Protein

• UniProt ID: Q13002
• Protein name: Glutamate receptor ionotropic, kainate 2 (GluK2) (Excitatory amino acid receptor 4) (EAA4) (Glutamate receptor 6) (GluR-6) (GluR6)
• Protein function: Ionotropic glutamate receptor that functions as a cation permeable ligand-gated ion channel, gated by L-glutamate and the glutamatergic agonist kainic acid. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervo
• PDB: 3QXM, 5CMM
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01094	ANF_receptor	52 → 398	Receptor family ligand binding region	Family
  PF10613	Lig_chan-Glu_bd	431 → 546	Ligated ion channel L-glutamate- and glycine-binding site	Domain
  PF00060	Lig_chan	560 → 831	Ligand-gated ion channel	Family

• Tissue specificity: TISSUE SPECIFICITY: Expression is higher in cerebellum than in cerebral cortex. {ECO:0000269|PubMed:20230879}.
• Sequence:

  MKIIFPILSNPVFRRTVKLLLCLLWIGYSQGTTHVLRFGGIFEYVESGPMGAEELAFRFA
  VNTINRNRTLLPNTTLTYDTQKINLYDSFEASKKACDQLSLGVAAIFGPSHSSSANAVQS
  ICNALGVPHIQTRWKHQVSDNKDSFYVSLYPDFSSLSRAILDLVQFFKWKTVTVVYDDST
  GLIRLQELIKAPSRYNLRLKIRQLPADTKDAKPLLKEMKRGKEFHVIFDCSHEMAAGILK
  QALAMGMMTEYYHYIFTTLDLFALDVEPYRYSGVNMTGFRILNTENTQVSSIIEKWSMER
  LQAPPKPDSGLLDGFMTTDAALMYDAVHVVSVAVQQFPQMTVSSLQCNRHKPWRFGTRFM
  SLIKEAHWEGLTGRITFNKTNGLRTDFDLDVISLKEEGLEKIGTWDPASGLNMTESQKGK
  PANITDSLSNRSLIVTTILEEPYVLFKKSDKPLYGNDRFEGYCIDLLRELSTILGFTYEI
  RLVEDGKYGAQDDANGQWNGMVRELIDHKADLAVAPLAITYVREKVIDFSKPFMTLGISI
  LYRKPNGTNPGVFSFLNPLSPDIWMYILLAYLGVSCVLFVIARFSPYEWYNPHPCNPDSD
  VVENNFTLLNSFWFGVGALMQQGSELMPKALSTRIVGGIWWFFTLIIISSYTANLAAFLT
  VERMESPIDSADDLAKQTKIEYGAVEDGATMTFFKKSKISTYDKMWAFMSSRRQSVLVKS
  NEEGIQRVLTSDYAFLMESTTIEFVTQRNCNLTQIGGLIDSKGYGVGTPMGSPYRDKITI
  AILQLQEEGKLHMMKEKWWRGNGCPEEESKEASALGVQNIGGIFIVLAAGLVLSVFVAVG
  EFLYKSKKNAQLEKRSFCSAMVEELRMSLKCQRRLKHKPQAPVIVKTEEVINMHTFNDRR
  LPGKETMA

• Sequence length: 908

Pathways

KEGG:

Neuroactive ligand-receptor interaction
Glutamatergic synapse

Reactome:

Activation of Na-permeable kainate receptors
Activation of Ca-permeable Kainate Receptor

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Autistic behavior	Likely pathogenic	rs2128471643	RCV001568409	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Gait ataxia	Pathogenic	rs1790057505	RCV001568406	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
GRIK2-related neurodevelopmental disorder	Pathogenic	rs1790058081	RCV001089950	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hyperintensity of cerebral white matter on MRI	Pathogenic	rs1790058081	RCV001568408	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual disability	Pathogenic; Likely pathogenic	rs1790058081, rs1265340906, rs1790057505	RCV001568408 RCV000790433 RCV001568406	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual disability, autosomal recessive 6	Pathogenic	rs749995448	RCV000169686	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neurodevelopmental disorder with impaired language and ataxia and with or without seizures	Pathogenic; Likely pathogenic	rs1790058081, rs2483041289, rs2484177690, rs1790057505	RCV001751791 RCV003333433 RCV003990011 RCV001759860 RCV001751535	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Severe global developmental delay	Pathogenic	rs1790058081, rs1790057505	RCV001568408 RCV001568406	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISTIC DISORDER	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL RECESSIVE NON-SYNDROMIC INTELLECTUAL DISABILITY	—	Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BELL'S PALSY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	CTD, Disgenet, GWAS catalog CTD, Disgenet, GWAS catalog CTD, Disgenet, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR I DISORDER, MOST RECENT EPISODE MANIC	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARCINOMA, NON-SMALL-CELL LUNG	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CAROTID ARTERY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CENTRAL NERVOUS SYSTEM CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CEREBRAL AMYLOID ANGIOPATHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLON CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLONIC NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLOR VISION DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLORECTAL CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMPLEX NEURODEVELOPMENTAL DISORDER	—	ClinGen, ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEMENTIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEPRESSION, BIPOLAR	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Developmental disorder	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EBV-positive nodal T- and NK-cell lymphoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ENDOMETRIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ESOPHAGEAL NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLAUCOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOBLASTOMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GRIK2-related disorder	Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HUNTINGTON DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INFLAMMATORY BOWEL DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INSOMNIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 6	—	Disgenet, HPO Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IRRITABLE BOWEL SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LATE-ONSET ALZHEIMER'S DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lip and oral cavity carcinoma	association	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LYMPHATIC METASTASIS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 6	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MIXED BIPOLAR I DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MOOD DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NERVOUS SYSTEM DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-SPECIFIC SYNDROMIC INTELLECTUAL DISABILITY	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBESITY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBSESSIVE-COMPULSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OVARIAN NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TREATMENT-RESISTANT HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VASCULAR DEMENTIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations