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L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]
GRM8 (Glutamate Metabotropic Receptor 8) is a Protein Coding gene. Diseases associated with GRM8 include Chromosome 17Q21.31 Duplication Syndrome and Creutzfeldt-Jakob Disease. Among its related pathways are Signaling by GPCR and Taste transduction. Gene Ontology (GO) annotations related to this gene include G protein-coupled receptor activity and group III metabotropic glutamate receptor activity. An important paralog of this gene is GRM4.
Metabotropic Glutamate (mGlu) group III receptors are members of the metabotropic class of glutamate receptors, which also includes mGlu group I and mGlu group II receptors. Group III receptors are divided into four subtypes, mGlu4, mGlu6, mGlu7 and mGlu8.
GeneHancer (GH) Identifier | GH Type | GH Score |
GH Sources | Gene Association Score | Total Score | TSS distance (kb) | Number of Genes Away | Size (kb) | Transcription Factor Binding Sites |
Gene Targets |
---|---|---|---|---|---|---|---|---|---|---|
GH07J127252 | Promoter/Enhancer | 1.7 | FANTOM5 Ensembl ENCODE CraniofacialAtlas | 607.6 | +0.1 | 104 | 2.8 | CTCF PRDM10 PRDM1 ZNF143 ZIC2 PATZ1 REST RAD21 ZNF501 TRIM22 | GRM8 GRM8-AS1 | |
GH07J127447 | Enhancer | 0.8 | ENCODE | 9.9 | -194.4 | -194449 | 0.2 | CTCF ZNF512 FOXA1 ZNF143 REST RAD21 TRIM22 CBX3 HMBOX1 ZNF10 | ENSG00000224138 ZNF800 SND1 RBM28 GRM8 PAX4 piR-48222-336 lnc-ARF5-10 ARF5 | |
GH07J127224 | Enhancer | 0.3 | Ensembl | 11.5 | +25.8 | 25793 | 0.2 | CTCF ZNF652 | GRM8 GRM8-AS1 | |
GH07J127215 | Enhancer | 0.2 | Ensembl | 11.1 | +37.7 | 37692 | 0.4 | GRM8-AS1 GRM8 | ||
GH07J127322 | Enhancer | 0.2 | Ensembl | 10.6 | -68.6 | -68608 | 0.2 | GRM8 GRM8-AS1 piR-48965-136 ENSG00000224138 ZNF800 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001642 | group III metabotropic glutamate receptor activity | IBA | 21873635 |
GO:0004930 | G protein-coupled receptor activity | IEA,IMP | 9473604 |
GO:0008066 | glutamate receptor activity | IMP | 9473604 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005886 | plasma membrane | TAS | -- |
GO:0005887 | integral component of plasma membrane | TAS,IBA | 21873635 |
GO:0016020 | membrane | IEA | -- |
GO:0016021 | integral component of membrane | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Peptide ligand-binding receptors | ||
2 | Signaling by GPCR | ||
3 | Circadian entrainment | ||
4 | Phospholipase D signaling pathway | ||
5 | CREB Pathway |
CREB Pathway
.68
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0007165 | signal transduction | IEA | -- |
GO:0007186 | G protein-coupled receptor signaling pathway | IEA,TAS | -- |
GO:0007193 | adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway | IDA | 11166323 |
GO:0007196 | adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway | IMP | 9473604 |
GO:0007216 | G protein-coupled glutamate receptor signaling pathway | IBA | 21873635 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Glutamic acid | Approved | Nutra | Agonist, Full agonist, Target, antagonist | 304 | ||
L-AP4 | Pharma | Agonist, Full agonist | Selective group III mGlu agonist | 0 | ||
(<i>R,S</i>)-4-PPG | Pharma | Agonist, Full agonist | 0 | |||
(<i>S</i>)-3,4-DCPG | Pharma | Agonist, Full agonist | 0 | |||
(1<i>S</i>,3<i>R</i>)-ACPD | Pharma | Agonist, Full agonist | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
L-SOP |
|
Agonist, Full agonist |
|
Compound | Action | Cas Number |
---|---|---|
(RS)-PPG | Potent, selective mGlu8 agonist | 120667-15-4 |
(S)-3,4-DCPG | Potent, selective mGlu8a agonist | 201730-11-2 |
ACPT-I | Group III mGlu agonist | 194918-76-8 |
L-AP4 | Selective group III mGlu agonist | 23052-81-5 |
O-Phospho-L-serine | Group III mGlu agonist | 407-41-0 |
ExUns: | 1a | · | 1b | ^ | 2 | ^ | 3 | ^ | 4 | ^ | 5 | ^ | 6 | ^ | 7 | ^ | 8 | ^ | 9 | ^ | 10 | ^ | 11 | ^ | 12a | · | 12b | ^ | 13a | · | 13b |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | ||||||||||||||||||||||||||||
SP2: | - | - | - | - | |||||||||||||||||||||||||||
SP3: | - | - | - | ||||||||||||||||||||||||||||
SP4: |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | GRM8 30 |
|
||
Oppossum (Monodelphis domestica) |
Mammalia | GRM8 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | GRM8 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | GRM8 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | GRM8 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Grm8 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Grm8 30 |
|
||
Chicken (Gallus gallus) |
Aves | GRM8 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | GRM8 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | LOC100497088 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | grm8a 31 |
|
OneToMany | |
GRM8 (1 of 2) 31 |
|
OneToMany | |||
LOC569768 30 |
|
||||
Dr.26085 30 |
|
||||
Fruit Fly (Drosophila melanogaster) |
Insecta | mtt 30 |
|
||
Glu-RA 32 |
|
|
|||
CG30361 32 |
|
|
|||
African malaria mosquito (Anopheles gambiae) |
Insecta | GPRMGL5 30 |
|
||
Worm (Caenorhabditis elegans) |
Secernentea | mgl-1 32 |
|
|
|
mgl-3 31 |
|
OneToOne |
SNP ID | Clinical significance and condition | Chr 07 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
712683 | Benign: not provided | 126,533,896(-) | A/G | INTRON_VARIANT | |
712684 | Benign: not provided | 127,243,109(-) | G/C | MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT,INTRON_VARIANT | |
722089 | Likely Benign: not provided | 126,533,195(-) | C/A | NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT | |
722342 | Benign: not provided | 126,533,165(-) | C/T | NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT | |
722343 | Benign: not provided | 126,533,387(-) | G/A | NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT |
Disorder | Aliases | PubMed IDs |
---|---|---|
chromosome 17q21.31 duplication syndrome |
|
|
creutzfeldt-jakob disease |
|
|
juvenile absence epilepsy |
|
|
alcohol dependence |
|
|
schizophrenia |
|