Details for: GRIK3

Gene ID: 2899

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: GRIK3

Ensembl ID: ENSG00000163873

Description: glutamate ionotropic receptor kainate type subunit 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Activation of ca-permeable kainate receptor
    (R-HSA-451308)
  • Activation of kainate receptors upon glutamate binding
    (R-HSA-451326)
  • Ionotropic activity of kainate receptors
    (R-HSA-451306)
  • Neuronal system
    (R-HSA-112316)
  • Neurotransmitter receptors and postsynaptic signal transmission
    (R-HSA-112314)
  • Presynaptic function of kainate receptors
    (R-HSA-500657)
  • Transmission across chemical synapses
    (R-HSA-112315)
  • Adenylate cyclase-inhibiting g protein-coupled glutamate receptor signaling pathway
    (GO:0007196)
  • Adenylate cyclase inhibiting g protein-coupled glutamate receptor activity
    (GO:0001640)
  • Axon
    (GO:0030424)
  • Calcium-mediated signaling
    (GO:0019722)
  • Dendrite
    (GO:0030425)
  • Dendrite cytoplasm
    (GO:0032839)
  • Glutamate-gated calcium ion channel activity
    (GO:0022849)
  • Glutamate-gated receptor activity
    (GO:0004970)
  • Glutamate receptor activity
    (GO:0008066)
  • Glutamate receptor signaling pathway
    (GO:0007215)
  • Glutamatergic synapse
    (GO:0098978)
  • G protein-coupled glutamate receptor signaling pathway
    (GO:0007216)
  • Ionotropic glutamate receptor signaling pathway
    (GO:0035235)
  • Kainate selective glutamate receptor activity
    (GO:0015277)
  • Kainate selective glutamate receptor complex
    (GO:0032983)
  • Ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential
    (GO:0099507)
  • Modulation of chemical synaptic transmission
    (GO:0050804)
  • Monoatomic ion transmembrane transport
    (GO:0034220)
  • Negative regulation of synaptic transmission, glutamatergic
    (GO:0051967)
  • Perikaryon
    (GO:0043204)
  • Plasma membrane
    (GO:0005886)
  • Postsynaptic density membrane
    (GO:0098839)
  • Presynaptic membrane
    (GO:0042734)
  • Regulation of membrane potential
    (GO:0042391)
  • Regulation of postsynaptic membrane potential
    (GO:0060078)
  • Regulation of presynaptic membrane potential
    (GO:0099505)
  • Synaptic transmission, glutamatergic
    (GO:0035249)
  • Terminal bouton
    (GO:0043195)
  • Transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
    (GO:1904315)

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • sst GABAergic cortical interneuron CL4023017
    CSI 54.46
    rCSI 70.2%
    PRS 95.59
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 48.36
    rCSI 60.16%
    PRS 94.22
  • L6b glutamatergic cortical neuron CL4023038
    CSI 20.59
    rCSI 64.36%
    PRS 95.22
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 14.43
    rCSI 51.93%
    PRS 94.08
  • Mueller cell CL0000636
    CSI 13.33
    rCSI 30.42%
    PRS 96.34
  • interneuron CL0000099
    CSI 13.33
    rCSI 26.76%
    PRS 96.83
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 13.19
    rCSI 49.87%
    PRS 94.58
  • VIP GABAergic cortical interneuron CL4023016
    CSI 12.11
    rCSI 14.47%
    PRS 94.96
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 11.85
    rCSI 13.68%
    PRS 95.92
  • Schwann cell CL0002573
    CSI 11.34
    rCSI 32.25%
    PRS 96.93
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 11.26
    rCSI 19.88%
    PRS 94.98
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 11.08
    rCSI 65.26%
    PRS 94.75
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 10.24
    rCSI 24.88%
    PRS 93.74
  • inhibitory interneuron CL0000498
    CSI 9.58
    rCSI 22.12%
    PRS 95.26
  • neural cell CL0002319
    CSI 9.1
    rCSI 34.34%
    PRS 92.5
  • cardiac neuron CL0010022
    CSI 8.64
    rCSI 27.64%
    PRS 98.03
  • glutamatergic neuron CL0000679
    CSI 7.53
    rCSI 15.47%
    PRS 92.76
  • neural crest cell CL0011012
    CSI 6.97
    rCSI 5.51%
    PRS 97.31
  • central nervous system neuron CL2000029
    CSI 6.88
    rCSI 50.59%
    PRS 95.65
  • glycinergic amacrine cell CL4030028
    CSI 6.88
    rCSI 17.92%
    PRS 95.15
  • retinal ganglion cell CL0000740
    CSI 6.28
    rCSI 13.87%
    PRS 94.85
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 5.38
    rCSI 9.77%
    PRS 95.74
  • dopaminergic neuron CL0000700
    CSI 5.29
    rCSI 29.9%
    PRS 93.9
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 5.16
    rCSI 16.96%
    PRS 93.43
  • GABAergic neuron CL0000617
    CSI 4.85
    rCSI 16.26%
    PRS 92.44
  • enteroglial cell CL4040002
    CSI 4.56
    rCSI 23.97%
    PRS 97.99
  • glial cell CL0000125
    CSI 4.5
    rCSI 17.14%
    PRS 95.75
  • serotonergic neuron CL0000850
    CSI 4.37
    rCSI 19.52%
    PRS 91.08
  • basket cell CL0000118
    CSI 3.22
    rCSI 20.2%
    PRS 88.7
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 3
    rCSI 7.17%
    PRS 94.01
  • melanocyte of skin CL1000458
    CSI 2.55
    rCSI 3.48%
    PRS 83.95
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.48
    rCSI 59.91%
    PRS 92.64
  • Bergmann glial cell CL0000644
    CSI 2.46
    rCSI 3.37%
    PRS 95.54
  • basal cell of epidermis CL0002187
    CSI 2.24
    rCSI 3.97%
    PRS 82.81
  • GABAergic amacrine cell CL4030027
    CSI 1.72
    rCSI 5.88%
    PRS 92.73
  • medium spiny neuron CL1001474
    CSI 0.85
    rCSI 7.32%
    PRS 95.28

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [GRIK3](/details-gene/2899) (glutamate ionotropic receptor kainate type subunit 3) is a protein-coding gene located on chromosome 1p34.3. It encodes a crucial subunit of the kainate-type ionotropic glutamate receptors, which are ligand-gated ion channels that mediate a significant portion of excitatory neurotransmission in the central nervous system. The expression profile of [GRIK3](/details-gene/2899) is highly specific to the nervous system, with its most significant expression observed in diverse neuronal populations, including key cortical interneurons such as [sst GABAergic cortical interneuron](/details-cell/CL4023017) and [pvalb GABAergic cortical interneuron](/details-cell/CL4023018). This distinct cellular localization suggests a fundamental role for [GRIK3](/details-gene/2899) in modulating neural circuit activity and synaptic plasticity. The gene is clinically associated with neurological function, as noted in OMIM ([153245](https://omim.org/entry/153245)). ## Cellular Roles and Expression Landscape The **Overall** expression data strongly establishes [GRIK3](/details-gene/2899) as a gene with a specialized function within the nervous system. Its highest significance scores are found in a variety of neuronal subtypes, indicating a broad yet specific role in neurotransmission. Notably, [GRIK3](/details-gene/2899) is a defining marker for several types of inhibitory GABAergic interneurons, including [sst GABAergic cortical interneuron](/details-cell/CL4023017) (CSI: 54.46) and [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) (CSI: 48.36). Its high significance in these cells suggests it plays a key role in modulating the release of GABA, thereby controlling the excitatory-inhibitory balance within cortical circuits. The gene is also highly significant in excitatory neuron populations, such as [L6b glutamatergic cortical neuron](/details-cell/CL4023038) (CSI: 20.59) and [L5 extratelencephalic projecting glutamatergic cortical neuron](/details-cell/CL4023041) (CSI: 14.43), where it likely functions in postsynaptic signal reception. Beyond central neurons, its expression in glial cells like [Mueller cell](/details-cell/CL0000636) and [Schwann cell](/details-cell/CL0002573) suggests a broader involvement in neural function and support. The highly restricted expression pattern, with an absence of significant scores in non-neural cell types, underscores its specialized role in the nervous system. ## Pathways and Molecular Function [GRIK3](/details-gene/2899) is integral to glutamatergic signaling pathways. It functions as a core component of the [kainate selective glutamate receptor complex](/details-go/GO:0032983), which is essential for [synaptic transmission, glutamatergic](/details-go/GO:0035249). The encoded protein contributes to [kainate selective glutamate receptor activity](/details-go/GO:0015277), forming an ion channel that, upon binding glutamate, allows the influx of cations, as described in the Reactome pathway '[Activation of ca-permeable kainate receptor](/details-pathway/R-HSA-451308)'. This ionotropic activity is fundamental to the [regulation of membrane potential](/details-go/GO:0042391) and is implicated in the function of both the [presynaptic membrane](/details-go/GO:0042734) and the [postsynaptic density membrane](/details-go/GO:0098839). Its role in presynaptic function ([R-HSA-500657](https://reactome.org/content/detail/R-HSA-500657)) is consistent with its high expression in GABAergic interneurons, where it may modulate neurotransmitter release. Additionally, some annotations suggest a role in G protein-coupled signaling pathways ([GO:0007216](https://www.ebi.ac.uk/QuickGO/term/GO:0007216)), indicating that [GRIK3](/details-gene/2899)-containing receptors may have more complex, metabotropic-like signaling capabilities beyond their primary ion channel function. ## Research Directions The specific expression patterns and known functions of [GRIK3](/details-gene/2899) provide a basis for several testable hypotheses regarding its role in neural circuit function and disease. 1. **Hypothesis 1:** The high significance of [GRIK3](/details-gene/2899) in distinct classes of GABAergic interneurons ([sst GABAergic cortical interneuron](/details-cell/CL4023017) and [pvalb GABAergic cortical interneuron](/details-cell/CL4023018)) suggests that it differentially regulates GABA release from these subtypes. Receptors containing the [GRIK3](/details-gene/2899) subunit may act as presynaptic autoreceptors or heteroreceptors that fine-tune the timing and strength of inhibition within cortical microcircuits. 2. **Hypothesis 2:** Based on reports of unequal allelic expression ([Link](https://pubmed.ncbi.nlm.nih.gov/11124978/)) and potential RNA editing ([Link](https://pubmed.ncbi.nlm.nih.gov/7719709/)), it is hypothesized that post-transcriptional and epigenetic regulation of [GRIK3](/details-gene/2899) creates functional diversity in kainate receptors across individuals, contributing to variability in synaptic plasticity and susceptibility to neurological disorders like epilepsy or temporal lobe sclerosis. ### Experimental Approach To test Hypothesis 1, one could employ a cell type-specific gene knockout strategy. By crossing a `Grik3`-floxed mouse line with Sst-Cre or Pvalb-Cre driver lines, [GRIK3](/details-gene/2899) can be selectively deleted from either SST-positive or PVALB-positive interneurons. Electrophysiological recordings (whole-cell patch-clamp) from connected pyramidal neurons in cortical slices would allow for precise measurement of inhibitory postsynaptic currents (IPSCs). A significant change in the frequency or kinetics of IPSCs in the conditional knockout animals compared to controls would provide direct evidence for the role of [GRIK3](/details-gene/2899) in modulating GABA release from specific interneuron populations. ### Therapeutic Potential As a key component of a major neurotransmitter receptor, [GRIK3](/details-gene/2899) represents a plausible therapeutic target for conditions involving excitatory/inhibitory imbalance, such as epilepsy, anxiety disorders, and schizophrenia. Its highly specific expression within the central nervous system suggests that pharmacological agents targeting [GRIK3](/details-gene/2899)-containing receptors could achieve circuit-specific modulation with a lower risk of systemic side effects. The therapeutic strategy would likely focus on developing selective negative or positive allosteric **modulators** to restore physiological balance, rather than direct agonists or antagonists, which could cause widespread neuronal disruption.

Genular Protein ID: 2350861067

Symbol: GRIK3_HUMAN

Name: Glutamate receptor ionotropic, kainate 3

UniProtKB Accession Codes:

Q13003 A9Z1Z8 B1AMS6 Q13004 Q16136

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChEBI 7 ChEMBL 1 ChiTaRS 1 ComplexPortal 9 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 3 DrugCentral 1 EMBL 9 EMDB 2 Ensembl 2 GO 22 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 2 RefSeq 1 Rhea 1 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 7719709

Title: Molecular characterization of the human EAA5 (GluR7) receptor: a high-affinity kainate receptor with novel potential RNA editing sites.

PubMed ID: 7719709

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 8128318

Title: Chromosomal localization of gene for human glutamate receptor subunit-7.

PubMed ID: 8128318

DOI: 10.1007/bf01233385

PubMed ID: 11124978

Title: Unequal expression of allelic kainate receptor GluR7 mRNAs in human brains.

PubMed ID: 11124978

DOI: 10.1523/jneurosci.20-24-09025.2000

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 919
  • Mass: 104037
  • Checksum: 0F68F6CF33E4CE71
  • Sequence:
    • MTAPWRRLRS LVWEYWAGLL VCAFWIPDSR GMPHVIRIGG IFEYADGPNA QVMNAEEHAF 
RFSANIINRN RTLLPNTTLT YDIQRIHFHD SFEATKKACD QLALGVVAIF GPSQGSCTNA 
VQSICNALEV PHIQLRWKHH PLDNKDTFYV NLYPDYASLS HAILDLVQYL KWRSATVVYD 
DSTGLIRLQE LIMAPSRYNI RLKIRQLPID SDDSRPLLKE MKRGREFRII FDCSHTMAAQ 
ILKQAMAMGM MTEYYHFIFT TLDLYALDLE PYRYSGVNLT GFRILNVDNP HVSAIVEKWS 
MERLQAAPRS ESGLLDGVMM TDAALLYDAV HIVSVCYQRA PQMTVNSLQC HRHKAWRFGG 
RFMNFIKEAQ WEGLTGRIVF NKTSGLRTDF DLDIISLKED GLEKVGVWSP ADGLNITEVA 
KGRGPNVTDS LTNRSLIVTT VLEEPFVMFR KSDRTLYGND RFEGYCIDLL KELAHILGFS 
YEIRLVEDGK YGAQDDKGQW NGMVKELIDH KADLAVAPLT ITHVREKAID FSKPFMTLGV 
SILYRKPNGT NPSVFSFLNP LSPDIWMYVL LAYLGVSCVL FVIARFSPYE WYDAHPCNPG 
SEVVENNFTL LNSFWFGMGS LMQQGSELMP KALSTRIIGG IWWFFTLIII SSYTANLAAF 
LTVERMESPI DSADDLAKQT KIEYGAVKDG ATMTFFKKSK ISTFEKMWAF MSSKPSALVK 
NNEEGIQRAL TADYALLMES TTIEYVTQRN CNLTQIGGLI DSKGYGIGTP MGSPYRDKIT 
IAILQLQEED KLHIMKEKWW RGSGCPEEEN KEASALGIQK IGGIFIVLAA GLVLSVLVAV 
GEFVYKLRKT AEREQRSFCS TVADEIRFSL TCQRRVKHKP QPPMMVKTDA VINMHTFNDR 
RLPGKDSMAC STSLAPVFP