Details for: GRM5

Gene ID: 2915

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: GRM5

Ensembl ID: ENSG00000168959

Description: glutamate metabotropic receptor 5

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • pvalb GABAergic cortical interneuron CL4023018
    CSI 79.12
    rCSI 98.43%
    PRS 99.5
  • sst GABAergic cortical interneuron CL4023017
    CSI 67.85
    rCSI 87.47%
    PRS 99.69
  • VIP GABAergic cortical interneuron CL4023016
    CSI 65.62
    rCSI 78.38%
    PRS 99.53
  • Bergmann glial cell CL0000644
    CSI 61.81
    rCSI 84.58%
    PRS 99.61
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 55.83
    rCSI 93.72%
    PRS 99.57
  • oligodendrocyte precursor cell CL0002453
    CSI 51.68
    rCSI 100%
    PRS 99.28
  • retinal bipolar neuron CL0000748
    CSI 51.22
    rCSI 95.93%
    PRS 99.5
  • sncg GABAergic cortical interneuron CL4023015
    CSI 50.91
    rCSI 81.87%
    PRS 99.4
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 49.74
    rCSI 90.38%
    PRS 99.78
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 48.95
    rCSI 86.45%
    PRS 99.49
  • inhibitory interneuron CL0000498
    CSI 48.93
    rCSI 100%
    PRS 99.69
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 45.35
    rCSI 98.38%
    PRS 99.62
  • neuron CL0000540
    CSI 38.81
    rCSI 100%
    PRS 99.36
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 38.07
    rCSI 91.04%
    PRS 99.59
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 36.45
    rCSI 88.58%
    PRS 99.21
  • glutamatergic neuron CL0000679
    CSI 31.27
    rCSI 64.26%
    PRS 98.65
  • L6b glutamatergic cortical neuron CL4023038
    CSI 29.41
    rCSI 91.92%
    PRS 99.5
  • rod bipolar cell CL0000751
    CSI 28.62
    rCSI 51.42%
    PRS 99.68
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 28.07
    rCSI 87.78%
    PRS 99.61
  • interneuron CL0000099
    CSI 28.04
    rCSI 56.31%
    PRS 99.8
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 26.47
    rCSI 87.01%
    PRS 99.5
  • cerebral cortex neuron CL0010012
    CSI 25.02
    rCSI 100%
    PRS 99.7
  • neural cell CL0002319
    CSI 24.99
    rCSI 94.31%
    PRS 99.33
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 24.83
    rCSI 89.37%
    PRS 99.33
  • glycinergic amacrine cell CL4030028
    CSI 24.44
    rCSI 63.66%
    PRS 99.64
  • serotonergic neuron CL0000850
    CSI 24.14
    rCSI 100%
    PRS 99.14
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 23.92
    rCSI 90.39%
    PRS 99.3
  • cerebellar granule cell CL0001031
    CSI 23.17
    rCSI 34.06%
    PRS 99.74
  • GABAergic neuron CL0000617
    CSI 22.73
    rCSI 76.14%
    PRS 98.54
  • dopaminergic neuron CL0000700
    CSI 21.04
    rCSI 100%
    PRS 99.41
  • GABAergic amacrine cell CL4030027
    CSI 19.87
    rCSI 68.06%
    PRS 99.45
  • ON-bipolar cell CL0000749
    CSI 19.16
    rCSI 28.48%
    PRS 99.75
  • lung ciliated cell CL1000271
    CSI 18.82
    rCSI 21.77%
    PRS 99.62
  • diffuse bipolar 6 cell CL4033032
    CSI 17.84
    rCSI 93.81%
    PRS 99.6
  • amacrine cell CL0000561
    CSI 17.21
    rCSI 49.87%
    PRS 99.66
  • glial cell CL0000125
    CSI 16.56
    rCSI 63.06%
    PRS 99.4
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 15.05
    rCSI 88.6%
    PRS 99.42
  • invaginating midget bipolar cell CL4033034
    CSI 13.93
    rCSI 82.24%
    PRS 99.47
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 12.13
    rCSI 17.2%
    PRS 99.78
  • cerebral cortex endothelial cell CL1001602
    CSI 12.11
    rCSI 20.94%
    PRS 99.75
  • macroglial cell CL0000126
    CSI 11.32
    rCSI 29.11%
    PRS 99.86
  • Schwann cell CL0002573
    CSI 10.83
    rCSI 30.79%
    PRS 99.77
  • medium spiny neuron CL1001474
    CSI 10.28
    rCSI 88.57%
    PRS 99.69
  • vascular leptomeningeal cell CL4023051
    CSI 9.47
    rCSI 16.61%
    PRS 99.83
  • central nervous system neuron CL2000029
    CSI 9.34
    rCSI 68.67%
    PRS 99.75
  • astrocyte of the cerebral cortex CL0002605
    CSI 8.77
    rCSI 19.67%
    PRS 99.51
  • glioblast CL0000030
    CSI 8.36
    rCSI 13.34%
    PRS 99.59
  • parietal epithelial cell CL1000452
    CSI 8.35
    rCSI 22.32%
    PRS 99.77
  • flat midget bipolar cell CL4033033
    CSI 7.81
    rCSI 55.84%
    PRS 99.62
  • retinal ganglion cell CL0000740
    CSI 7.04
    rCSI 15.56%
    PRS 99.46
  • OFFx cell CL4033036
    CSI 6.98
    rCSI 32.84%
    PRS 99.46
  • diffuse bipolar 1 cell CL4033027
    CSI 6.25
    rCSI 47.01%
    PRS 99.43
  • diffuse bipolar 4 cell CL4033031
    CSI 5.74
    rCSI 65.78%
    PRS 99.27
  • diffuse bipolar 3a cell CL4033029
    CSI 5.41
    rCSI 36.86%
    PRS 99.53
  • diffuse bipolar 2 cell CL4033028
    CSI 5.19
    rCSI 40.18%
    PRS 99.63
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 4.74
    rCSI 10.8%
    PRS 99.43
  • starburst amacrine cell CL0004232
    CSI 4.14
    rCSI 34.86%
    PRS 99.47
  • direct pathway medium spiny neuron CL4023026
    CSI 3.48
    rCSI 83.41%
    PRS 98.94
  • indirect pathway medium spiny neuron CL4023029
    CSI 3.45
    rCSI 83.13%
    PRS 98.88
  • neural progenitor cell CL0011020
    CSI 2.2
    rCSI 9.7%
    PRS 97.81

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.

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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 [GRM5](/details-gene/2915) (glutamate metabotropic receptor 5) encodes a G protein-coupled receptor that acts as a receptor for the excitatory neurotransmitter glutamate. As a member of the Class C GPCR family, it plays a central role in modulating neuronal excitability, synaptic plasticity, and higher-order cognitive functions. Expression data from the **Overall** context indicates that [GRM5](/details-gene/2915) is a highly significant gene within the central nervous system, showing prominent expression in a diverse array of both inhibitory and excitatory [neurons](/details-cell/CL0000540) as well as glial cells. Its function is tightly linked to processes such as [learning and memory](/details-ontology/GO:0007611) and the regulation of synaptic transmission, and its dysfunction has been implicated in several neurological and psychiatric disorders. ## Cellular Roles and Expression Landscape The expression profile of [GRM5](/details-gene/2915) firmly establishes its importance in the central nervous system. In the **Overall** context, it is most significantly expressed in various subtypes of inhibitory interneurons, including [pvalb GABAergic cortical interneurons](/details-cell/CL4023018) (CSI: 79.12), [sst GABAergic cortical interneurons](/details-cell/CL4023017) (CSI: 67.85), and [VIP GABAergic cortical interneurons](/details-cell/CL4023016) (CSI: 65.62). This suggests a critical role in modulating GABAergic signaling and maintaining the excitatory/inhibitory balance within cortical circuits. Concurrently, [GRM5](/details-gene/2915) is also significantly expressed in excitatory [neurons](/details-cell/CL0000540), such as [L2/3 intratelencephalic projecting glutamatergic neurons](/details-cell/CL4030059) (CSI: 45.35), underscoring its canonical role in postsynaptic glutamatergic signaling. Beyond its neuronal roles, the gene shows notable significance in glial populations, including [Bergmann glial cells](/details-cell/CL0000644) (CSI: 61.81) and [oligodendrocyte precursor cells](/details-cell/CL0002453) (CSI: 51.68). This expression pattern suggests that [GRM5](/details-gene/2915) may also participate in neuron-glia communication, glial development, or myelination processes. The broad yet specific distribution across these key neural cell types highlights [GRM5](/details-gene/2915) as a fundamental modulator of brain circuitry and function. ## Pathways and Molecular Function The functions of [GRM5](/details-gene/2915) are primarily mediated through its activity as a [glutamate receptor](/details-ontology/GO:0008066) that couples to Gq/G11 proteins. Consistent with this, it is a key component of the [G alpha (q) signalling events](/details-pathway/R-HSA-416476) pathway. Upon glutamate binding, [GRM5](/details-gene/2915) initiates the [phospholipase c-activating g protein-coupled glutamate receptor signaling pathway](/details-ontology/GO:0007206), leading to the generation of inositol trisphosphate and diacylglycerol. This cascade results in the mobilization of intracellular calcium and activation of protein kinase C, influencing a wide range of cellular processes. This signaling is integral to its role in [chemical synaptic transmission](/details-ontology/GO:0007268) and the [positive regulation of long-term neuronal synaptic plasticity](/details-ontology/GO:0048170), which are the molecular underpinnings of [learning](/details-ontology/GO:0007612) and [cognition](/details-ontology/GO:0050890). Cellular component annotations place the [GRM5](/details-gene/2915) protein at critical sites for these functions, including the [dendritic spine](/details-ontology/GO:0043197) and the [postsynaptic density membrane](/details-ontology/GO:0098839). Furthermore, its involvement in pathways like [trans-synaptic signaling by endocannabinoid](/details-ontology/GO:0099553) suggests it participates in complex feedback mechanisms that fine-tune synaptic strength. Structurally, the receptor's function has been explored in studies detailing its transmembrane domain ([Link](https://doi.org/10.1038/nature13396)), and its activity can be modulated by interactions with other proteins, such as neuronal Ca2+-binding protein 2 ([Link](https://doi.org/10.1111/j.1471-4159.2009.06348.x)). ## Research Directions The central role of [GRM5](/details-gene/2915) in synaptic function and its high expression in specific neuronal subtypes make it a compelling subject for further investigation, particularly in the context of neurological disorders. One publication has demonstrated that a mutation in this gene can disrupt dendritic morphology and cause ASD-related behaviors, highlighting its importance in neurodevelopment ([Link](https://doi.org/10.1523/jneurosci.2068-16.2017)). Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis on Cortical Inhibition:** Given its exceptionally high significance in [pvalb GABAergic cortical interneurons](/details-cell/CL4023018), we hypothesize that cell-type-specific loss of [GRM5](/details-gene/2915) function in these fast-spiking interneurons impairs their ability to regulate pyramidal cell activity, leading to a network hyperexcitability that contributes to the pathophysiology of epilepsy. 2. **Hypothesis on Synaptic Plasticity in Neurodevelopmental Disorders:** We hypothesize that dysregulation of [GRM5](/details-gene/2915)-mediated signaling in developing glutamatergic [neurons](/details-cell/CL0000540) disrupts experience-dependent synaptic plasticity (e.g., long-term depression), leading to aberrant circuit formation and the cognitive and behavioral deficits associated with autism spectrum disorders. A key experiment to test the second hypothesis would involve using a conditional knockout mouse model to specifically delete *Grm5* in forebrain excitatory [neurons](/details-cell/CL0000540) during early postnatal development. Electrophysiological recordings from acute hippocampal or cortical slices could then be used to measure mGluR-dependent long-term depression (LTD) at Schaffer collateral synapses. These functional data could be correlated with behavioral assays assessing social interaction, repetitive behaviors, and learning to directly link synaptic deficits with ASD-like phenotypes. As a therapeutic target, [GRM5](/details-gene/2915) holds significant potential. Being a G protein-coupled receptor located on the cell surface, it is highly accessible to small-molecule drugs. Its complex role suggests that nuanced modulation, rather than simple antagonism or agonism, is the most promising therapeutic strategy. Allosteric modulators (both positive and negative) that can fine-tune receptor activity are being actively investigated for conditions ranging from Fragile X syndrome and depression to schizophrenia. Its widespread but specific expression pattern in the CNS necessitates careful consideration of off-target effects, but also offers the potential to correct fundamental circuit imbalances in a range of brain disorders.

Genular Protein ID: 3910795295

Symbol: GRM5_HUMAN

Name: Metabotropic glutamate receptor 5

UniProtKB Accession Codes:

Database IDs:

Citations:

PubMed ID: 7908515

Title: Molecular cloning and the functional expression of two isoforms of human metabotropic glutamate receptor subtype 5.

PubMed ID: 7908515

DOI: 10.1006/bbrc.1994.1349

PubMed ID: 16554811

Title: Human chromosome 11 DNA sequence and analysis including novel gene identification.

PubMed ID: 16554811

DOI: 10.1038/nature04632

PubMed ID: 7688218

Title: A variant of metabotropic glutamate receptor subtype 5: an evolutionally conserved insertion with no termination codon.

PubMed ID: 7688218

DOI: 10.1006/bbrc.1993.1866

PubMed ID: 19694902

Title: The association of metabotropic glutamate receptor type 5 with the neuronal Ca2+-binding protein 2 modulates receptor function.

PubMed ID: 19694902

DOI: 10.1111/j.1471-4159.2009.06348.x

PubMed ID: 28130356

Title: Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and Causes ASD-Related Behaviors.

PubMed ID: 28130356

DOI: 10.1523/jneurosci.2068-16.2017

PubMed ID: 25042998

Title: Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain.

PubMed ID: 25042998

DOI: 10.1038/nature13396

Sequence Information:

  • Length: 1212
  • Mass: 132469
  • Checksum: A3C73606681C6A25
  • Sequence:
  • MVLLLILSVL LLKEDVRGSA QSSERRVVAH MPGDIIIGAL FSVHHQPTVD KVHERKCGAV 
    REQYGIQRVE AMLHTLERIN SDPTLLPNIT LGCEIRDSCW HSAVALEQSI EFIRDSLISS 
    EEEEGLVRCV DGSSSSFRSK KPIVGVIGPG SSSVAIQVQN LLQLFNIPQI AYSATSMDLS 
    DKTLFKYFMR VVPSDAQQAR AMVDIVKRYN WTYVSAVHTE GNYGESGMEA FKDMSAKEGI 
    CIAHSYKIYS NAGEQSFDKL LKKLTSHLPK ARVVACFCEG MTVRGLLMAM RRLGLAGEFL 
    LLGSDGWADR YDVTDGYQRE AVGGITIKLQ SPDVKWFDDY YLKLRPETNH RNPWFQEFWQ 
    HRFQCRLEGF PQENSKYNKT CNSSLTLKTH HVQDSKMGFV INAIYSMAYG LHNMQMSLCP 
    GYAGLCDAMK PIDGRKLLES LMKTNFTGVS GDTILFDENG DSPGRYEIMN FKEMGKDYFD 
    YINVGSWDNG ELKMDDDEVW SKKSNIIRSV CSEPCEKGQI KVIRKGEVSC CWTCTPCKEN 
    EYVFDEYTCK ACQLGSWPTD DLTGCDLIPV QYLRWGDPEP IAAVVFACLG LLATLFVTVV 
    FIIYRDTPVV KSSSRELCYI ILAGICLGYL CTFCLIAKPK QIYCYLQRIG IGLSPAMSYS 
    ALVTKTNRIA RILAGSKKKI CTKKPRFMSA CAQLVIAFIL ICIQLGIIVA LFIMEPPDIM 
    HDYPSIREVY LICNTTNLGV VTPLGYNGLL ILSCTFYAFK TRNVPANFNE AKYIAFTMYT 
    TCIIWLAFVP IYFGSNYKII TMCFSVSLSA TVALGCMFVP KVYIILAKPE RNVRSAFTTS 
    TVVRMHVGDG KSSSAASRSS SLVNLWKRRG SSGETLRYKD RRLAQHKSEI ECFTPKGSMG 
    NGGRATMSSS NGKSVTWAQN EKSSRGQHLW QRLSIHINKK ENPNQTAVIK PFPKSTESRG 
    LGAGAGAGGS AGGVGATGGA GCAGAGPGGP ESPDAGPKAL YDVAEAEEHF PAPARPRSPS 
    PISTLSHRAG SASRTDDDVP SLHSEPVARS SSSQGSLMEQ ISSVVTRFTA NISELNSMML 
    STAAPSPGVG APLCSSYLIP KEIQLPTTMT TFAEIQPLPA IEVTGGAQPA AGAQAAGDAA 
    RESPAAGPEA AAAKPDLEEL VALTPPSPFR DSVDSGSTTP NSPVSESALC IPSSPKYDTL 
    IIRDYTQSSS SL

Genular Protein ID: 1988594725

Symbol: A8K5P7_HUMAN

Name: N/A

UniProtKB Accession Codes:

Database IDs:

Sequence Information:

  • Length: 905
  • Mass: 101417
  • Checksum: 078564EFCC85E93B
  • Sequence:
  • MVLLLILSVL LLKEDVRGSA QSSERRVVAH MPGDIIIGAL FSVHHQPTVD KVHERKCGAV 
    REQYGIQRVE AMLHTLERIN SDPTLLPNIT LGCEIRDSCW HSAVALEQSI EFIRDSLISS 
    EEEEGLVRCV DGSSSSFRSK KPIVGVIGPG SSSVAIQVQN LLQLFNIPQI AYSATSMDLS 
    DKTLFKYFMR VVPSDAQQAR AMVDIVKRYN WTYVSAVHTE GNYGESGMEA FKDMSAKEGI 
    CIAHSYKIYS NAGEQSFDKL LKKLTSHLPK ARVVACFCEG MTVRGLLMAM RRLGLAGEFL 
    LLGSDGWADR YDVTDGYQRE AVGGITIKLQ SPDVKWFDDY YLKLRPETNH RNPWFQEFWQ 
    HRFQCRLEGF PQENSKYNKT CNSSLTLKTH HVQDSKMGFV INAIYSMAYG LHNMQMSLCP 
    GYAGLCDAMK PIDGRKLLES LMKTNFTGVS GDTILFDENG DSPGRYEIMN FKEMGKDYFD 
    YINVGSWDNG ELKMDDDEVW SKKSNIIRSV CSEPCEKGQI KVIRKGEVSC CWTCTPCKEN 
    EYVFDEYTCK ACQLGSWPTD DLTGCDLIPV QYLRWGDPEP IAAVVFACLG LLATLFVTVV 
    FIIYRDTPVV KSSSRELCYI ILAGICLGYL CTFCLIAKPK QIYCYLQRIG IGLSPAMSYS 
    ALVTKTNRIA RILAGSKKKI CTKKPRFMSA CAQLVIAFIL ICIQLGIIVA LFIMEPPDIM 
    HDYPSIREVY LICNTTNLGV VTPLGYNGLL ILSCTFYAFK TRNVPANFNE AKYIAFTMYT 
    TCIIWLAFVP IYFGSNYKII TMCFSVSLSA TVALGCMFVP KVYIILAKPE RNVRSAFTTS 
    TVVRMHVGDG KSSSAASRSS SLVNLWKRRG SSGETLSSNG KSVTWAQNEK SSRGQHLWQR 
    LSIHI