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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. [provided by RefSeq, Jul 2008]
GRM3 (Glutamate Metabotropic Receptor 3) is a Protein Coding gene. Diseases associated with GRM3 include Bipolar I Disorder and Bipolar Disorder. Among its related pathways are Signaling by GPCR and Peptide ligand-binding receptors. Gene Ontology (GO) annotations related to this gene include G protein-coupled receptor activity and glutamate receptor activity. An important paralog of this gene is GRM2.
Metabotropic Glutamate (mGlu) group II receptors are members of the metabotropic class of glutamate receptors, which also includes mGlu group I and mGlu group III receptors. Group II receptors are divided into two subtypes, mGlu2 and mGlu3.
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 |
---|---|---|---|---|---|---|---|---|---|---|
GH07J086643 | Promoter/Enhancer | 1.9 | EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER | 250.7 | +0.1 | 92 | 2 | SIN3A ZNF341 ZBTB48 REST TAF1 ZBTB21 GLIS1 GATA2 L3MBTL2 ZNF560 | GRM3 HSALNG0059351 CROT TP53TG1 ELAPOR2 | |
GH07J086653 | Promoter/Enhancer | 0.7 | Ensembl dbSUPER | 250.7 | +1.4 | 1392 | 0.2 | EGR2 EZH2 ZFHX2 | GRM3 HSALNG0059351 ENSG00000231255 ELAPOR2 | |
GH07J086665 | Promoter/Enhancer | 0.5 | EPDnew dbSUPER | 261.8 | +21.7 | 21693 | 0.1 | GRM3 HSALNG0059351 ENSG00000231255 ELAPOR2 | ||
GH07J086651 | Promoter/Enhancer | 0.7 | FANTOM5 Ensembl dbSUPER | 21.1 | +2.2 | 2191 | 1 | HSALNG0059351 GRM3 ELAPOR2 ENSG00000231255 | ||
GH07J086667 | Enhancer | 0.7 | Ensembl ENCODE dbSUPER | 11.6 | +24.4 | 24392 | 1.8 | CTCF RAD21 ZNF654 | GRM3 HSALNG0059351 ENSG00000231255 ELAPOR2 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001640 | adenylate cyclase inhibiting G protein-coupled glutamate receptor activity | IBA | 21873635 |
GO:0001641 | group II metabotropic glutamate receptor activity | IBA | 21873635 |
GO:0004930 | G protein-coupled receptor activity | IEA,TAS | 8840013 |
GO:0005246 | calcium channel regulator activity | IEA | -- |
GO:0008066 | glutamate receptor activity | TAS | 8840013 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005886 | plasma membrane | TAS | -- |
GO:0005887 | integral component of plasma membrane | TAS,IBA | 21873635 |
GO:0014069 | postsynaptic density | IEA | -- |
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 | Amphetamine addiction | ||
5 | Phospholipase D signaling pathway |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0007165 | signal transduction | IEA | -- |
GO:0007186 | G protein-coupled receptor signaling pathway | IEA,TAS | -- |
GO:0007194 | negative regulation of adenylate cyclase activity | TAS | 8840013 |
GO:0007196 | adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway | IEA | -- |
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, antagonist | 320 | ||
Risperidone | Approved, Investigational | Pharma | SR-2A inhibitor | 545 | ||
L-Glutamine | Approved, Investigational | Nutra | 0 | |||
Spaglumic acid | Experimental | Pharma | Selective mGlu3 agonist | 0 | ||
(S)-MCPG | Experimental | Pharma | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs |
---|
Compound | Action | Cas Number |
---|---|---|
DCG IV | Very potent, selective group II mGlu agonist. Also NMDA agonist | 147782-19-2 |
L-CCG-l | Potent group II mGlu agonist | 117857-93-9 |
MAP4 | Potent group II mGlu agonist. Also specific group III mGlu antagonist | 157381-42-5 |
Spaglumic acid | Selective mGlu3 agonist | 3106-85-2 |
Xanthurenic acid | Selectively activates group II mGlu receptors | 59-00-7 |
ExUns: | 1a | · | 1b | · | 1c | · | 1d | · | 1e | ^ | 2 | ^ | 3a | · | 3b | · | 3c | · | 3d | · | 3e | ^ | 4a | · | 4b | · | 4c | ^ | 5 | ^ | 6 | ^ | 7 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | |||||||||||||||||||||||||||||||
SP2: | - | - | - | - | - | - | - | ||||||||||||||||||||||||||
SP3: | - | - | - | ||||||||||||||||||||||||||||||
SP4: | - | ||||||||||||||||||||||||||||||||
SP5: |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | GRM3 30 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | GRM3 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | GRM3 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | GRM3 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Grm3 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Grm3 30 17 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | GRM3 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | GRM3 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | GRM3 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | grm3 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | grm3 30 31 |
|
OneToOne | |
Fruit Fly (Drosophila melanogaster) |
Insecta | mGluRA 30 31 |
|
OneToMany | |
Glu-RA 32 |
|
|
|||
CG30361 32 |
|
|
|||
Worm (Caenorhabditis elegans) |
Secernentea | mgl-1 30 31 32 |
|
OneToMany |
SNP ID | Clinical significance and condition | Chr 07 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
rs112184476 | Benign: not provided | 86,839,542(+) |
C/T NM_000840.2(GRM3):c.2028C>T (p.Gly676=) |
SYNONYMOUS_VARIANT,INTRON | |
rs112722806 | Likely Benign: not provided | 86,838,987(+) |
G/A NM_000840.2(GRM3):c.1473G>A (p.Ser491=) |
SYNONYMOUS_VARIANT,INTRON | |
rs138568176 | Likely Benign: not provided | 86,839,743(+) |
C/T NM_000840.2(GRM3):c.2229C>T (p.Tyr743=) |
SYNONYMOUS_VARIANT,INTRON | |
rs17161027 | Likely Benign: not provided | 86,839,434(+) |
C/T NM_000840.2(GRM3):c.1920C>T (p.Ile640=) |
SYNONYMOUS_VARIANT,INTRON | |
rs56763064 | Benign: not provided | 86,765,277(+) |
G/A NM_000840.2(GRM3):c.132G>A (p.Leu44=) |
SYNONYMOUS |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
dgv1310e214 | CNV | gain | 21293372 |
esv2504097 | CNV | deletion | 19546169 |
esv2667611 | CNV | deletion | 23128226 |
esv3305507 | CNV | mobile element insertion | 20981092 |
esv3307636 | CNV | mobile element insertion | 20981092 |
esv3309610 | CNV | mobile element insertion | 20981092 |
esv3326124 | CNV | insertion | 20981092 |
esv3360307 | CNV | insertion | 20981092 |
esv3373913 | CNV | insertion | 20981092 |
esv3614018 | CNV | loss | 21293372 |
esv3614020 | CNV | loss | 21293372 |
esv7104 | CNV | gain | 19470904 |
nsv478422 | CNV | novel sequence insertion | 20440878 |
nsv824201 | CNV | loss | 20364138 |
nsv831053 | CNV | gain | 17160897 |
Disorder | Aliases | PubMed IDs |
---|---|---|
bipolar i disorder |
|
|
bipolar disorder |
|
|
schizophrenia |
|
|
status epilepticus |
|
|
major depressive disorder |
|
|