| Tbio | Metabotropic glutamate receptor 6 |
G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity (By similarity). Signaling stimulates TRPM1 channel activity and Ca(2+) uptake. Required for normal vision.
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, Feb 2012]
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, Feb 2012]
Comments
| Disease | Target Count |
|---|---|
| NIGHT BLINDNESS, CONGENITAL STATIONARY, TYPE 1B | 1 |
| Night blindness, congenital stationary | 14 |
| Disease | Target Count | P-value |
|---|---|---|
| psoriasis | 6685 | 1.16148233312891E-22 |
| medulloblastoma, large-cell | 6234 | 9.84812436641867E-4 |
| Disease | Target Count |
|---|---|
| Congenital stationary night blindness | 28 |
| Congenital stationary night blindness, type 1B | 1 |
| Disease | Target Count |
|---|---|
| Night blindness, congenital stationary, 1B | 1 |
| Disease | log2 FC | p |
|---|---|---|
| medulloblastoma, large-cell | 1.100 | 0.001 |
| psoriasis | -1.700 | 0.000 |
| Species | Source |
|---|---|
| Chimp | OMA EggNOG Inparanoid |
| Macaque | OMA EggNOG Inparanoid |
| Mouse | OMA EggNOG Inparanoid |
| Rat | OMA EggNOG Inparanoid |
| Cow | OMA EggNOG Inparanoid |
| Opossum | OMA EggNOG Inparanoid |
| Platypus | OMA EggNOG Inparanoid |
| Anole lizard | OMA Inparanoid |
| AID | Type | Active / Inconclusive / Inactive | Description |
|---|---|---|---|
| 2191 | confirmatory |
2 / 0 / 0 | Modulation of the Metabotropic Glutamate Receptor mGluR4: Selectivity at mGluR6 |
| 588730 | other |
0 / 0 / 2 | hmGluR6_Thallium_Fold_Shift (GIRK) |
| 623891 | other |
1 / 0 / 0 | Chemical Optimization of Advanced mGlu4 Lead Candidates (human_mGlu6_Selectivity) |
| PMID | Text |
|---|---|
| 26628857 | Two mutations in GRM6 gene have been identified in two consanguineous Pakistani families with congenital stationary night blindness. |
| 23714322 | We found 5 different mutations in GRM6, in congenital stationary night blindness. |
| 23452348 | These data suggest differences in coupling of TRPM1 function to mGluR6 signaling explain different cellular responses to glutamate in the retina and the skin. |
| 22959359 | The selective thinning of the inner retinal layers in patients with GRM6 mutations suggests either reduced bipolar or ganglion cell numbers or altered synaptic structure in the inner retina. |
| 22735794 | The results expand the mutation spectrum of NYX, CACNA1F and GRM6. They also suggest that NYX mutations are a common cause of congenital stationary night blindness (CSNB). |
| 22008250 | The phenotype associated with GRM6 mutation is variable in terms of presentation, refractive error, visual acuity and macular function. ERGs are electronegative and suggest ON-pathway dysfunction. |
| 20801516 | Observational study of genetic testing. (HuGE Navigator) |
| 20560679 | A positive association was observed between response to methadone and two variants in the genes MYOCD and GRM6. |
| 20560679 | Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) |
| 20379614 | Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator) |
| More... |
MARPRRAREPLLVALLPLAWLAQAGLARAAGSVRLAGGLTLGGLFPVHARGAAGRACGQLKKEQGVHRLE 1 - 70 AMLYALDRVNADPELLPGVRLGARLLDTCSRDTYALEQALSFVQALIRGRGDGDEVGVRCPGGVPPLRPA 71 - 140 PPERVVAVVGASASSVSIMVANVLRLFAIPQISYASTAPELSDSTRYDFFSRVVPPDSYQAQAMVDIVRA 141 - 210 LGWNYVSTLASEGNYGESGVEAFVQISREAGGVCIAQSIKIPREPKPGEFSKVIRRLMETPNARGIIIFA 211 - 280 NEDDIRRVLEAARQANLTGHFLWVGSDSWGAKTSPILSLEDVAVGAITILPKRASIDGFDQYFMTRSLEN 281 - 350 NRRNIWFAEFWEENFNCKLTSSGTQSDDSTRKCTGEERIGRDSTYEQEGKVQFVIDAVYAIAHALHSMHQ 351 - 420 ALCPGHTGLCPAMEPTDGRMLLQYIRAVRFNGSAGTPVMFNENGDAPGRYDIFQYQATNGSASSGGYQAV 421 - 490 GQWAETLRLDVEALQWSGDPHEVPSSLCSLPCGPGERKKMVKGVPCCWHCEACDGYRFQVDEFTCEACPG 491 - 560 DMRPTPNHTGCRPTPVVRLSWSSPWAAPPLLLAVLGIVATTTVVATFVRYNNTPIVRASGRELSYVLLTG 561 - 630 IFLIYAITFLMVAEPGAAVCAARRLFLGLGTTLSYSALLTKTNRIYRIFEQGKRSVTPPPFISPTSQLVI 631 - 700 TFSLTSLQVVGMIAWLGARPPHSVIDYEEQRTVDPEQARGVLKCDMSDLSLIGCLGYSLLLMVTCTVYAI 701 - 770 KARGVPETFNEAKPIGFTMYTTCIIWLAFVPIFFGTAQSAEKIYIQTTTLTVSLSLSASVSLGMLYVPKT 771 - 840 YVILFHPEQNVQKRKRSLKATSTVAAPPKGEDAEAHK 841 - 877 //
| PMID | Year | Title |
|---|---|---|
| 26628857 | 2015 | Mutations in GRM6 identified in consanguineous Pakistani families with congenital stationary night blindness. |
| 23714322 | 2013 | Genotype and phenotype of 101 dutch patients with congenital stationary night blindness. |
| 23452348 | 2013 | Metabotropic glutamate receptor 6 signaling enhances TRPM1 calcium channel function and increases melanin content in human melanocytes. |
| 23449627 | 2013 | Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity. |
| 22959359 | 2012 | Assessing retinal structure in complete congenital stationary night blindness and Oguchi disease. |
| 22735794 | 2012 | Mutation screening of TRPM1, GRM6, NYX and CACNA1F genes in patients with congenital stationary night blindness. |
| 22008250 | 2012 | A phenotypic study of congenital stationary night blindness (CSNB) associated with mutations in the GRM6 gene. |
| 20801516 | 2011 | Simultaneous mutation detection in 90 retinal disease genes in multiple patients using a custom-designed 300-kb retinal resequencing chip. |
| 20560679 | 2010 | Response to methadone maintenance treatment is associated with the MYOCD and GRM6 genes. |
| 20379614 | Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. | |
| More... |
