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Gene Review

SLC18A2  -  solute carrier family 18 (vesicular...

Homo sapiens

Synonyms: Monoamine transporter, SVAT, SVMT, Solute carrier family 18 member 2, Synaptic vesicular amine transporter, ...
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Disease relevance of SLC18A2


Psychiatry related information on SLC18A2


High impact information on SLC18A2


Chemical compound and disease context of SLC18A2


Biological context of SLC18A2


Anatomical context of SLC18A2


Associations of SLC18A2 with chemical compounds

  • Catecholamines exhibit a 3-fold higher affinity, and histamine exhibits a 30-fold higher affinity, for VMAT2 [20].
  • Reserpine and ketanserin are slightly more potent inhibitors of VMAT2-mediated transport than of VMAT1-mediated transport, whereas tetrabenazine binds to and inhibits only VMAT2 [20].
  • Cultures were pretreated with either corticosterone, a specific inhibitor of EMT, or reserpine, a specific inhibitor of VMAT-2 [21].
  • It has been shown that one-copy deletion of the VMAT2 gene increases locomotion activity significantly in response to drug treatments and dopamine neuron death rate in response to neurotoxin treatments in knockout mice [17].
  • We conclude that human VMAT2 Cys 126 in loop 1/2 and Cys 333 in loop 7/8 form a disulfide bond which contributes to efficient monoamine transport [22].

Physical interactions of SLC18A2

  • VMAT2 binding is elevated in dopa-responsive dystonia: visualizing empty vesicles by PET [23].
  • [3H]Dihydrotetrabenazine shows no detectable binding to CGAT but does bind to SVAT, accounting for the differential sensitivity [24].
  • CONCLUSIONS: Reduced striatal VMAT2 binding suggests nigrostriatal pathology in HD, most severely in the HDr phenotype [25].

Regulatory relationships of SLC18A2


Other interactions of SLC18A2

  • The contribution of the two transporter isoforms to monoamine storage in human neuroendocrine tissues was examined with isoform-specific polyclonal antibodies against hVMAT1 and hVMAT2 [20].
  • Three Types of Tyrosine Hydroxylase-Positive CNS Neurons Distinguished by Dopa Decarboxylase and VMAT2 Co-Expression [30].
  • After 4 weeks of differentiation in vitro, cortical and striatal NSCs gave rise to similar numbers of GABAergic and VMAT2- and parvalbumin-containing neurons [31].
  • Statistical analysis with the KCNMA1, HTR7 and SLC18A2 genes, which lie in the support region of interest revealed no evidence for association after correction for multiple comparisons [18].
  • Neurons containing VMAT2 constituted 14-20% of all intrinsic neurons in the upper GI tract, and there was an equal number of TH-positive neurons [32].

Analytical, diagnostic and therapeutic context of SLC18A2


  1. The effect of rare human sequence variants on the function of vesicular monoamine transporter 2. Burman, J., Tran, C.H., Glatt, C., Freimer, N.B., Edwards, R.H. Pharmacogenetics (2004) [Pubmed]
  2. Expression of the two isoforms of the vesicular monoamine transporter (VMAT1 and VMAT2) in the endocrine pancreas and pancreatic endocrine tumors. Anlauf, M., Eissele, R., Schäfer, M.K., Eiden, L.E., Arnold, R., Pauser, U., Klöppel, G., Weihe, E. J. Histochem. Cytochem. (2003) [Pubmed]
  3. Three-dimensional models of neurotransmitter transporters and their interactions with cocaine and S-citalopram. Ravna, A.W. World J. Biol. Psychiatry (2006) [Pubmed]
  4. Differential expression of vesicular monoamine transporter (VMAT) 1 and 2 in gastrointestinal endocrine tumours. Jakobsen, A.M., Andersson, P., Saglik, G., Andersson, E., Kölby, L., Erickson, J.D., Forssell-Aronsson, E., Wängberg, B., Ahlman, H., Nilsson, O. J. Pathol. (2001) [Pubmed]
  5. Genetic and epigenetic SLC18A2 silencing in prostate cancer is an independent adverse predictor of biochemical recurrence after radical prostatectomy. Sørensen, K.D., Wild, P.J., Mortezavi, A., Adolf, K., Tørring, N., Heebøll, S., Ulhøi, B.P., Ottosen, P., Sulser, T., Hermanns, T., Moch, H., Borre, M., Ørntoft, T.F., Dyrskjøt, L. Clin. Cancer Res. (2009) [Pubmed]
  6. Striatal monoaminergic terminals in Lewy body and Alzheimer's dementias. Suzuki, M., Desmond, T.J., Albin, R.L., Frey, K.A. Ann. Neurol. (2002) [Pubmed]
  7. Association of DNA polymorphisms in the synaptic vesicular amine transporter gene (SLC18A2) with alcohol and nicotine dependence. Schwab, S.G., Franke, P.E., Hoefgen, B., Guttenthaler, V., Lichtermann, D., Trixler, M., Knapp, M., Maier, W., Wildenauer, D.B. Neuropsychopharmacology (2005) [Pubmed]
  8. Variations in the Vesicular Monoamine Transporter 1 Gene (VMAT1/SLC18A1) are Associated with Bipolar I Disorder. Lohoff, F.W., Dahl, J.P., Ferraro, T.N., Arnold, S.E., Gallinat, J., Sander, T., Berrettini, W.H. Neuropsychopharmacology (2006) [Pubmed]
  9. Loss of striatal vesicular monoamine transporter protein (VMAT2) in human cocaine users. Little, K.Y., Krolewski, D.M., Zhang, L., Cassin, B.J. The American journal of psychiatry. (2003) [Pubmed]
  10. Gastric endocrine cells: gene expression, processing, and targeting of active products. Dockray, G.J., Varro, A., Dimaline, R. Physiol. Rev. (1996) [Pubmed]
  11. Screening a large reference sample to identify very low frequency sequence variants: comparisons between two genes. Glatt, C.E., DeYoung, J.A., Delgado, S., Service, S.K., Giacomini, K.M., Edwards, R.H., Risch, N., Freimer, N.B. Nat. Genet. (2001) [Pubmed]
  12. Striatal dopamine nerve terminal markers in human, chronic methamphetamine users. Wilson, J.M., Kalasinsky, K.S., Levey, A.I., Bergeron, C., Reiber, G., Anthony, R.M., Schmunk, G.A., Shannak, K., Haycock, J.W., Kish, S.J. Nat. Med. (1996) [Pubmed]
  13. Localization and dynamic regulation of biogenic amine transporters in the mammalian central nervous system. Hoffman, B.J., Hansson, S.R., Mezey, E., Palkovits, M. Frontiers in neuroendocrinology. (1998) [Pubmed]
  14. Expression of vesicular monoamine transporters in endocrine hyperplasia and endocrine tumors of the oxyntic stomach. Eissele, R., Anlauf, M., Schäfer, M.K., Eiden, L.E., Arnold, R., Weihe, E. Digestion (1999) [Pubmed]
  15. Dopamine transporters and neuronal injury. Miller, G.W., Gainetdinov, R.R., Levey, A.I., Caron, M.G. Trends Pharmacol. Sci. (1999) [Pubmed]
  16. Synthesis of [11C]tetrabenazine, a vesicular monoamine uptake inhibitor, for PET imaging studies. DaSilva, J.N., Kilbourn, M.R., Mangner, T.J. Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine. (1993) [Pubmed]
  17. SLC18A2 promoter haplotypes and identification of a novel protective factor against alcoholism. Lin, Z., Walther, D., Yu, X.Y., Li, S., Drgon, T., Uhl, G.R. Hum. Mol. Genet. (2005) [Pubmed]
  18. Autosomal linkage analysis for the level of response to alcohol. Schuckit, M.A., Wilhelmsen, K., Smith, T.L., Feiler, H.S., Lind, P., Lange, L.A., Kalmijn, J. Alcohol. Clin. Exp. Res. (2005) [Pubmed]
  19. Exon/intron boundaries, novel polymorphisms, and association analysis with schizophrenia of the human synaptic vesicle monoamine transporter (SVMT) gene. Kunugi, H., Ishida, S., Akahane, A., Nanko, S. Mol. Psychiatry (2001) [Pubmed]
  20. Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter. Erickson, J.D., Schafer, M.K., Bonner, T.I., Eiden, L.E., Weihe, E. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  21. Histamine uptake by human endometrial cells expressing the organic cation transporter EMT and the vesicular monoamine transporter-2. Noskova, V., Bottalico, B., Olsson, H., Ehinger, A., Pilka, R., Casslén, B., Hansson, S.R. Mol. Hum. Reprod. (2006) [Pubmed]
  22. Identification of human vesicle monoamine transporter (VMAT2) lumenal cysteines that form an intramolecular disulfide bond. Thiriot, D.S., Sievert, M.K., Ruoho, A.E. Biochemistry (2002) [Pubmed]
  23. VMAT2 binding is elevated in dopa-responsive dystonia: visualizing empty vesicles by PET. De La Fuente-Fernández, R., Furtado, S., Guttman, M., Furukawa, Y., Lee, C.S., Calne, D.B., Ruth, T.J., Stoessl, A.J. Synapse (2003) [Pubmed]
  24. The chromaffin granule and synaptic vesicle amine transporters differ in substrate recognition and sensitivity to inhibitors. Peter, D., Jimenez, J., Liu, Y., Kim, J., Edwards, R.H. J. Biol. Chem. (1994) [Pubmed]
  25. Decreased striatal monoaminergic terminals in Huntington disease. Bohnen, N.I., Koeppe, R.A., Meyer, P., Ficaro, E., Wernette, K., Kilbourn, M.R., Kuhl, D.E., Frey, K.A., Albin, R.L. Neurology (2000) [Pubmed]
  26. Biochemistry and molecular biology of the vesicular monoamine transporter from chromaffin granules. Henry, J.P., Botton, D., Sagne, C., Isambert, M.F., Desnos, C., Blanchard, V., Raisman-Vozari, R., Krejci, E., Massoulie, J., Gasnier, B. J. Exp. Biol. (1994) [Pubmed]
  27. The First Luminal Domain of Vesicular Monoamine Transporters Mediates G-protein-dependent Regulation of Transmitter Uptake. Brunk, I., Blex, C., Rachakonda, S., H??ltje, M., Winter, S., Pahner, I., Walther, D.J., Ahnert-Hilger, G. J. Biol. Chem. (2006) [Pubmed]
  28. Measurement of secretory vesicle pH reveals intravesicular alkalinization by vesicular monoamine transporter type 2 resulting in inhibition of prohormone cleavage. Blackmore, C.G., Varro, A., Dimaline, R., Bishop, L., Gallacher, D.V., Dockray, G.J. J. Physiol. (Lond.) (2001) [Pubmed]
  29. Electron microscopic immunolabeling of transporters and receptors identifies transmitter-specific functional sites envisioned in Cajal's neuron. Pickel, V.M., Garzón, M., Mengual, E. Prog. Brain Res. (2002) [Pubmed]
  30. Three Types of Tyrosine Hydroxylase-Positive CNS Neurons Distinguished by Dopa Decarboxylase and VMAT2 Co-Expression. Weihe, E., Depboylu, C., Sch??tz, B., Sch??fer, M.K., Eiden, L.E. Cell. Mol. Neurobiol. (2006) [Pubmed]
  31. Human fetal cortical and striatal neural stem cells generate region-specific neurons in vitro and differentiate extensively to neurons after intrastriatal transplantation in neonatal rats. Kallur, T., Darsalia, V., Lindvall, O., Kokaia, Z. J. Neurosci. Res. (2006) [Pubmed]
  32. Chemical coding of the human gastrointestinal nervous system: cholinergic, VIPergic, and catecholaminergic phenotypes. Anlauf, M., Schäfer, M.K., Eiden, L., Weihe, E. J. Comp. Neurol. (2003) [Pubmed]
  33. Functional identification and molecular cloning of a human brain vesicle monoamine transporter. Erickson, J.D., Eiden, L.E. J. Neurochem. (1993) [Pubmed]
  34. Identification of dopamine plasma membrane and vesicular transporters in human peripheral blood lymphocytes. Amenta, F., Bronzetti, E., Cantalamessa, F., El-Assouad, D., Felici, L., Ricci, A., Tayebati, S.K. J. Neuroimmunol. (2001) [Pubmed]
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