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Gene Review

SLC6A5  -  solute carrier family 6 (neurotransmitter...

Homo sapiens

Synonyms: GLYT-2, GLYT2, GlyT-2, GlyT2, HKPX3, ...
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Psychiatry related information on SLC6A5

  • No association between genetic variants at the GLYT2 gene and bipolar affective disorder and schizophrenia [1].

High impact information on SLC6A5


Biological context of SLC6A5


Anatomical context of SLC6A5

  • The GlyT-2 form is expressed mainly in the spinal cord, brainstem and cerebellum [7].
  • When stably expressed in CHO cells, human GlyT2 displays a dose-dependent uptake of glycine with an apparent Km of 108 microM [4].
  • Expression of the intact hGlyT2 transporter sequence in COS-7 cells resulted in a 10-fold increase in high-affinity uptake relative to control cells transfected with vector alone [5].
  • The role of N-glycosylation in transport to the plasma membrane and sorting of the neuronal glycine transporter GLYT2 [6].
  • In this study we have investigated the actions of Zn2+ on the glycine transporters, GLYT1b and GLYT2a, expressed in Xenopus laevis oocytes and we demonstrate that Zn2+ is a noncompetitive inhibitor of GLYT1 but has no effect on GLYT2 [8].

Associations of SLC6A5 with chemical compounds


Other interactions of SLC6A5


Analytical, diagnostic and therapeutic context of SLC6A5

  • Site-directed mutagenesis of the four glycosylation sites (Asn-345, Asn-355, Asn-360, and Asn-366), located in the large extracellular loop of GLYT2, produced an inactive protein that was retained in intracellular compartments when transiently transfected in COS cells or in nonpolarized MDCK cells [6].
  • Our findings further showed that the non-radioactive in situ hybridization technique for identifying GlyT2 mRNA in fixed free-floating sections is a highly efficient tool for identifying glycinergic neurons in the spinal cord [10].
  • Western analysis and immunocytochemistry in frozen sections of mouse brain demonstrated a clear caudal-rostral gradient of GLYT2 distribution, with massive accumulation in the spinal cord and brainstem and less in the cerebellum [11].


  1. No association between genetic variants at the GLYT2 gene and bipolar affective disorder and schizophrenia. Jamra, R.A., Villela, A.W., Klein, K., Becker, T., Schulze, T.G., Schmael, C., Deschner, M., Klopp, N., Illig, T., Propping, P., Cichon, S., Rietschel, M., Nöthen, M.M., Schumacher, J. Psychiatr. Genet. (2006) [Pubmed]
  2. Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease. Rees, M.I., Harvey, K., Pearce, B.R., Chung, S.K., Duguid, I.C., Thomas, P., Beatty, S., Graham, G.E., Armstrong, L., Shiang, R., Abbott, K.J., Zuberi, S.M., Stephenson, J.B., Owen, M.J., Tijssen, M.A., van den Maagdenberg, A.M., Smart, T.G., Supplisson, S., Harvey, R.J. Nat. Genet. (2006) [Pubmed]
  3. Phosphorylation of the norepinephrine transporter at threonine 258 and serine 259 is linked to protein kinase C-mediated transporter internalization. Jayanthi, L.D., Annamalai, B., Samuvel, D.J., Gether, U., Ramamoorthy, S. J. Biol. Chem. (2006) [Pubmed]
  4. Molecular cloning and functional expression of the human glycine transporter GlyT2 and chromosomal localisation of the gene in the human genome. Morrow, J.A., Collie, I.T., Dunbar, D.R., Walker, G.B., Shahid, M., Hill, D.R. FEBS Lett. (1998) [Pubmed]
  5. Characterization of multiple forms of the human glycine transporter type-2. Gallagher, M.J., Burgess, L.H., Brunden, K.R. Brain Res. Mol. Brain Res. (1999) [Pubmed]
  6. The role of N-glycosylation in transport to the plasma membrane and sorting of the neuronal glycine transporter GLYT2. Martínez-Maza, R., Poyatos, I., López-Corcuera, B., N úñez, E., Giménez, C., Zafra, F., Aragón, C. J. Biol. Chem. (2001) [Pubmed]
  7. Cloning, functional characterisation and population analysis of a variant form of the human glycine type 2 transporter. Evans, J., Herdon, H., Cairns, W., O'Brien, E., Chapman, C., Terrett, J., Gloger, I. FEBS Lett. (1999) [Pubmed]
  8. Zn2+ inhibits glycine transport by glycine transporter subtype 1b. Ju, P., Aubrey, K.R., Vandenberg, R.J. J. Biol. Chem. (2004) [Pubmed]
  9. Substrate-induced conformational changes of extracellular loop 1 in the glycine transporter GLYT2. López-Corcuera, B., Núñez, E., Martínez-Maza, R., Geerlings, A., Aragón, C. J. Biol. Chem. (2001) [Pubmed]
  10. Distribution of glycinergic neuronal somata in the rat spinal cord. Hossaini, M., French, P.J., Holstege, J.C. Brain Res. (2007) [Pubmed]
  11. Structure, function and brain localization of neurotransmitter transporters. Jursky, F., Tamura, S., Tamura, A., Mandiyan, S., Nelson, H., Nelson, N. J. Exp. Biol. (1994) [Pubmed]
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