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Gene Review

GRM6  -  glutamate receptor, metabotropic 6

Homo sapiens

Synonyms: CSNB1B, GPRC1F, MGLUR6, Metabotropic glutamate receptor 6, mGlu6, ...
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Disease relevance of GRM6

  • Mutations in GRM6 cause autosomal recessive congenital stationary night blindness with a distinctive scotopic 15-Hz flicker electroretinogram [1].

High impact information on GRM6


Chemical compound and disease context of GRM6


Biological context of GRM6


Anatomical context of GRM6

  • Analysis of an agonist selectivity and an expression pattern of mGluR6 has indicated that mGluR6 is responsible for synaptic neurotransmission from photoreceptor cells to ON-bipolar cells in the visual system [6].
  • All mGluR subtypes are found in the cerebellar cortex with the exception of mGluR6 which is exclusively expressed in the retina [7].
  • These studies demonstrated that [3H]LY341495 is a useful radioligand for studying the pharmacology and expression of recombinant mGlu6, 7a and 8a receptors in cell lines [8].
  • In contrast, we demonstrated sufficient specific binding of [3H]LY341495 to human mGlu6, mGlu7a and mGlu8a receptor-expressing cell membranes to allow for further characterizations [8].
  • To determine which specific G proteins from the Galphai/o family are able to couple to mGluR6, a Galpha reconstitution system was employed using PTX-insensitive Galpha mutants expressed with mGluR6 in PTX-treated sympathetic neurons from the rat superior cervical ganglion (SCG) [9].

Associations of GRM6 with chemical compounds


Other interactions of GRM6

  • In addition, GRIN2A and GRM6 loci were successfully localized on Chr 10 linkage maps by linkage analyses [13].
  • When tested at group II and III receptors, MPEP did not show agonist or antagonist activity at 100 microM on human mGlu2, -3, -4a, -7b, and -8a receptors nor at 10 microM on the human mGlu6 receptor [14].
  • [3H]L-AP4 binding was present in human embryonic kidney cells transfected with the high-affinity mGluR4 receptor but not in cells transfected with mGluR6 or the low-affinity mGluR7 receptor [15].
  • The efficiency of coupling to mGluR6 was Goa > Gob, Gi1 > Gi2, Gi3, whereas no coupling was observed with Galphaz, nor with the retinal Galpha proteins, rod (GNAT2) or cone (GNAT1) transducin (GalphaTr-R, GalphaTr-C) [9].
  • G protein coupling profile of mGluR6 and expression of G[alpha] proteins in retinal ON bipolar cells [9].

Analytical, diagnostic and therapeutic context of GRM6

  • Gene targeting of mGluR6 results in a loss of ON responses without changing OFF responses and severely impairs detecting visual contrasts [16].
  • Novel splice variants of metabotropic glutamate receptor type 6 (mGlu6 receptor) were identified by reverse transcription-polymerase chain reaction (RT-PCR) amplification and sequence analysis of rat and human retina cDNAs [11].
  • We prepared antibodies selective for the C-terminus of the human mGluR6 receptor and used confocal and electron microscopy to study the patterns of immunostaining in retina of monkey, cat, and rabbit [17].


  1. Mutations in GRM6 cause autosomal recessive congenital stationary night blindness with a distinctive scotopic 15-Hz flicker electroretinogram. Zeitz, C., van Genderen, M., Neidhardt, J., Luhmann, U.F., Hoeben, F., Forster, U., Wycisk, K., Mátyás, G., Hoyng, C.B., Riemslag, F., Meire, F., Cremers, F.P., Berger, W. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  2. Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6. Dryja, T.P., McGee, T.L., Berson, E.L., Fishman, G.A., Sandberg, M.A., Alexander, K.R., Derlacki, D.J., Rajagopalan, A.S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  3. The metabotropic receptor mGluR6 may signal through G(o), but not phosphodiesterase, in retinal bipolar cells. Nawy, S. J. Neurosci. (1999) [Pubmed]
  4. Congenital stationary night blindness associated with mutations in GRM6 encoding glutamate receptor MGluR6. O'Connor, E., Allen, L.E., Bradshaw, K., Boylan, J., Moore, A.T., Trump, D. The British journal of ophthalmology. (2006) [Pubmed]
  5. The whole nucleotide sequence and chromosomal localization of the gene for human metabotropic glutamate receptor subtype 6. Hashimoto, T., Inazawa, J., Okamoto, N., Tagawa, Y., Bessho, Y., Honda, Y., Nakanishi, S. Eur. J. Neurosci. (1997) [Pubmed]
  6. Molecular diversity of glutamate receptors and their physiological functions. Nakanishi, S., Masu, M., Bessho, Y., Nakajima, Y., Hayashi, Y., Shigemoto, R. EXS. (1994) [Pubmed]
  7. Metabotropic glutamate receptors in the cerebellum with a focus on their function in Purkinje cells. Knöpfel, T., Grandes, P. Cerebellum (2002) [Pubmed]
  8. Binding of [3H](2S,1'S,2'S)-2-(9-xanthylmethyl)-2-(2'-carboxycyclopropyl) glycine ([3H]LY341495) to cell membranes expressing recombinant human group III metabotropic glutamate receptor subtypes. Wright, R.A., Arnold, M.B., Wheeler, W.J., Ornstein, P.L., Schoepp, D.D. Naunyn Schmiedebergs Arch. Pharmacol. (2000) [Pubmed]
  9. G protein coupling profile of mGluR6 and expression of G[alpha] proteins in retinal ON bipolar cells. Tian, L., Kammermeier, P.J. Vis. Neurosci. (2006) [Pubmed]
  10. A new highly selective metabotropic excitatory amino acid agonist: 2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid. Bräuner-Osborne, H., Sløk, F.A., Skjaerbaek, N., Ebert, B., Sekiyama, N., Nakanishi, S., Krogsgaard-Larsen, P. J. Med. Chem. (1996) [Pubmed]
  11. Identification of novel alternatively-spliced mRNA isoforms of metabotropic glutamate receptor 6 gene in rat and human retina. Valerio, A., Ferraboli, S., Paterlini, M., Spano, P., Barlati, S. Gene (2001) [Pubmed]
  12. Transmitter concentration at a three-dimensional synapse. Rao-Mirotznik, R., Buchsbaum, G., Sterling, P. J. Neurophysiol. (1998) [Pubmed]
  13. Gene mapping of NMDA receptors and metabotropic glutamate receptors in the rat (Rattus norvegicus). Kuramoto, T., Maihara, T., Masu, M., Nakanishi, S., Serikawa, T. Genomics (1994) [Pubmed]
  14. 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Gasparini, F., Lingenhöhl, K., Stoehr, N., Flor, P.J., Heinrich, M., Vranesic, I., Biollaz, M., Allgeier, H., Heckendorn, R., Urwyler, S., Varney, M.A., Johnson, E.C., Hess, S.D., Rao, S.P., Sacaan, A.I., Santori, E.M., Veliçelebi, G., Kuhn, R. Neuropharmacology (1999) [Pubmed]
  15. Molecular basis for the differential agonist affinities of group III metabotropic glutamate receptors. Rosemond, E., Wang, M., Yao, Y., Storjohann, L., Stormann, T., Johnson, E.C., Hampson, D.R. Mol. Pharmacol. (2004) [Pubmed]
  16. Glutamate receptors: brain function and signal transduction. Nakanishi, S., Nakajima, Y., Masu, M., Ueda, Y., Nakahara, K., Watanabe, D., Yamaguchi, S., Kawabata, S., Okada, M. Brain Res. Brain Res. Rev. (1998) [Pubmed]
  17. Localization of mGluR6 to dendrites of ON bipolar cells in primate retina. Vardi, N., Duvoisin, R., Wu, G., Sterling, P. J. Comp. Neurol. (2000) [Pubmed]
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