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Gene Review

HTR2C  -  5-hydroxytryptamine (serotonin) receptor...

Homo sapiens

Synonyms: 5-HT-1C, 5-HT-2C, 5-HT1C, 5-HT2C, 5-HTR2C, ...
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Disease relevance of HTR2C


Psychiatry related information on HTR2C

  • These results indicate that the HTR2C promoter polymorphism does not contribute significantly to the etiopathogenesis of bipolar disorder in females [4].
  • The subjects were 63 biologically unrelated patients with panic disorder and 100 biologically unrelated normal control subjects who were native Japanese living in the western area of Japan. HTR1A and HTR2C showed no significant association with panic disorder [5].
  • Slow wave sleep in humans: role of 5-HT2A and 5-HT2C receptors [6].
  • This study investigated possible associations between selected polymorphisms in the serotonin receptor genes, 5-HT2A and 5-HT2C, with the presence of co-morbid depressive illness at baseline in a community based cohort of 158 patients with late onset patients with Alzheimer's disease (AD) [7].
  • In addition, another common polymorphic variation in the 5-HT2A and 5-HT2C serotonin receptor genes previously analyzed in schizophrenic patients was associated with auditory and visual hallucinations in AD [8].

High impact information on HTR2C

  • Disruption of PTEN coupling with 5-HT2C receptors suppresses behavioral responses induced by drugs of abuse [9].
  • Among the multiple serotonin receptors that exist in brain, at least two--5HT1A and 5HT2 or 5HT1C receptors--seem to mediate activation of pituitary-adrenocortical function [10].
  • Five adenosines within the coding sequence of the serotonin 2C receptor (5-HT2C) pre-mRNA are converted to inosines by RNA editing (named A, B, C' (E), C, and D sites) [11].
  • Thus, one outcome of fluoxetine treatment may be to reverse the abnormalities in 5-HT2C pre-mRNA editing seen in depressed suicide victims [11].
  • In human prefrontal cortex (PFC), the most abundant 5-HT2C mRNA sequences result from editing at the A site, or from the editing combinations AC'C, ABCD, and ABD [11].

Chemical compound and disease context of HTR2C


Biological context of HTR2C

  • Significant haplotype associations were found in all but the HTR1A and HTR2C genes [15].
  • We suggest that inconsistent associations between HTR2C and several phenotypes, including obesity, may be due to the LD pattern across the gene in which recombination and gene conversion have been influential [1].
  • We report a detailed investigation of linkage disequilibrium (LD) within and between the HTR2C promoter and the flanking sequences around a commonly utilized marker in the second coding exon of HTR2C [1].
  • HTR2C is also located on the X chromosome [16].
  • Although promoter-associated microsatellites have previously been shown to regulate expression of different genes, we did not find any significant influence of distinct HTR2C promoter microsatellite alleles on transcriptional efficiency as measured by luciferase activity and receptor availability as assayed by [(3)H]-mesulergine binding [4].

Anatomical context of HTR2C


Associations of HTR2C with chemical compounds

  • In the current investigation, we examined, in the original cohort of 120 normal volunteers, two additional coding region polymorphisms, a glycine to serine substitution in the dopamine D3 receptor (D3DR) and a cysteine to serine substitution in the 5-HT2C serotonin receptor (HTR2C) [20].
  • The current study examined the association between adolescent outcome in ADHD and serotonin system genes, including the -1438A>G polymorphism of the serotonin 2A receptor gene (HTR2A) and the -759C>T polymorphism of the serotonin 2C receptor gene (HTR2C) [21].
  • The cyclopropylamine moiety therefore appears to be a good strategy for rigidification of the ethylamine side chain only for tryptamines that bind to the 5-HT2C receptor isoform [22].
  • Distinct functional profiles of aripiprazole and olanzapine at RNA edited human 5-HT2C receptor isoforms [12].
  • In studies using the fluorescent cytoplasmic Ca2+ indicator FLUO-3AM, xanomeline induced an increase in cytoplasmic Ca2+ concentration in SH-SY5Y cells expressing recombinant human 5-HT2C receptors [23].

Physical interactions of HTR2C

  • Editing events at four major positions, termed A, B, C and D, as well as one minor site termed C', are predicted to alter amino acids within the second intracellular loop of the G-protein coupled 5-HT2C receptor [24].
  • In view of evidence that 5HT2A and 5HT2C sites functionally interact with 5HT1A receptors, we also examined the influence of these agents upon the actions of S 15535, but no significant alteration was seen in its enhancement of rhythms [25].

Regulatory relationships of HTR2C

  • 1. SB 206553 (5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2 ,3-f]indole) displays a high affinity (pK1 7.9) for the cloned human 5-HT2C receptor expressed in HEK 293 cells and the 5-HT2B receptor (pA2 8.9) as measured in the rat stomach fundus preparation [26].
  • We selected 42 patients with bipolar disorder type I (BPI) and 40 healthy controls for genetic analysis of DNA polymorphisms in the serotonin receptor 2c (5-HTR2c) and serotonin transporter (5-HTT) genes [27].
  • 5. Prior exposure of SH-SY5Y/5-HT2C cells to 5-HT (1 microM/15 min) caused a significant decrease in the 5-HT-stimulated peak in Ins(1,4,5)P3 levels whereas no such change occurred in SH-SY5Y/5-HT2A cells following exposure to 10 microM 5-HT for 15 min [28].

Other interactions of HTR2C

  • Furthermore, the maximal response to 5-carboxytryptamine was reduced in a concentration-dependent manner by the 5-HT2A/5-HT2C-selective partial agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [29].
  • The reduction of 5-HT1B-like responsiveness produced by 5-HT2C receptor activation was independent of protein kinase C activation and increases in the intracellular calcium concentration [29].
  • In the current study, we examined the relationship between the C-759T and G-697C polymorphisms of HTR2C and ADHD in 488 Han Chinese families [16].
  • Negative results for transmission disequilibrium of polymorphisms of HTR2C and MAOA with autism were provided from German and Austrian families [30].
  • The agonist-induced [Ca2+]i mobilization in h-CM cells was potently blocked by the 5-HT2A-selective antagonist M-100907 (IC50=1.2+/-0.4 nM) but less potently by the antagonists for 5-HT2B (RS-127445, IC50>10 microM) and 5-HT2C (RS-102221, IC50=5.8+/-2.3 microM) receptors [31].

Analytical, diagnostic and therapeutic context of HTR2C


  1. Complex HTR2C linkage disequilibrium and promoter associations with body mass index and serum leptin. McCarthy, S., Mottagui-Tabar, S., Mizuno, Y., Sennblad, B., Hoffstedt, J., Arner, P., Wahlestedt, C., Andersson, B. Hum. Genet. (2005) [Pubmed]
  2. A 5-HT2C receptor promoter polymorphism (HTR2C - 759C/T) is associated with obesity in women, and with resistance to weight loss in heterozygotes. Pooley, E.C., Fairburn, C.G., Cooper, Z., Sodhi, M.S., Cowen, P.J., Harrison, P.J. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2004) [Pubmed]
  3. The role of 5-HT2C receptor polymorphisms in the pharmacogenetics of antipsychotic drug treatment. Reynolds, G.P., Templeman, L.A., Zhang, Z.J. Prog. Neuropsychopharmacol. Biol. Psychiatry (2005) [Pubmed]
  4. Evolutionary conserved microsatellites in the promoter region of the 5-hydroxytryptamine receptor 2C gene (HTR2C) are not associated with bipolar disorder in females. Meyer, J., Saam, W., Mössner, R., Cangir, O., Ortega, G.R., Tatschner, T., Riederer, P., Wienker, T.F., Lesch, K.P. Journal of neural transmission (Vienna, Austria : 1996) (2002) [Pubmed]
  5. Positive association between panic disorder and polymorphism of the serotonin 2A receptor gene. Inada, Y., Yoneda, H., Koh, J., Sakai, J., Himei, A., Kinoshita, Y., Akabame, K., Hiraoka, Y., Sakai, T. Psychiatry research. (2003) [Pubmed]
  6. Slow wave sleep in humans: role of 5-HT2A and 5-HT2C receptors. Sharpley, A.L., Elliott, J.M., Attenburrow, M.J., Cowen, P.J. Neuropharmacology (1994) [Pubmed]
  7. Depression in Alzheimer's disease: the effect of serotonin receptor gene variation. Holmes, C., Arranz, M., Collier, D., Powell, J., Lovestone, S. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2003) [Pubmed]
  8. The study of genetic polymorphisms related to serotonin in Alzheimer's disease: a new perspective in a heterogenic disorder. Oliveira, J.R., Zatz, M. Braz. J. Med. Biol. Res. (1999) [Pubmed]
  9. Disruption of PTEN coupling with 5-HT2C receptors suppresses behavioral responses induced by drugs of abuse. Ji, S.P., Zhang, Y., Van Cleemput, J., Jiang, W., Liao, M., Li, L., Wan, Q., Backstrom, J.R., Zhang, X. Nat. Med. (2006) [Pubmed]
  10. The involvement of serotonin in regulation of pituitary-adrenocortical function. Fuller, R.W. Frontiers in neuroendocrinology. (1992) [Pubmed]
  11. Altered editing of serotonin 2C receptor pre-mRNA in the prefrontal cortex of depressed suicide victims. Gurevich, I., Tamir, H., Arango, V., Dwork, A.J., Mann, J.J., Schmauss, C. Neuron (2002) [Pubmed]
  12. Distinct functional profiles of aripiprazole and olanzapine at RNA edited human 5-HT2C receptor isoforms. Zhang, J.Y., Kowal, D.M., Nawoschik, S.P., Lou, Z., Dunlop, J. Biochem. Pharmacol. (2006) [Pubmed]
  13. BW 723C86, a 5-HT2B receptor agonist, causes hyperphagia and reduced grooming in rats. Kennett, G.A., Ainsworth, K., Trail, B., Blackburn, T.P. Neuropharmacology (1997) [Pubmed]
  14. Pharmacogenetics as a tool in the therapy of schizophrenia. Wilffert, B., Zaal, R., Brouwers, J.R. Pharmacy world & science : PWS. (2005) [Pubmed]
  15. Investigation of serotonin-related genes in antidepressant response. Peters, E.J., Slager, S.L., McGrath, P.J., Knowles, J.A., Hamilton, S.P. Mol. Psychiatry (2004) [Pubmed]
  16. Association between polymorphisms in serotonin 2C receptor gene and attention-deficit/hyperactivity disorder in Han Chinese subjects. Li, J., Wang, Y., Zhou, R., Zhang, H., Yang, L., Wang, B., Faraone, S.V. Neurosci. Lett. (2006) [Pubmed]
  17. 5-HT2B receptor-mediated calcium release from ryanodine-sensitive intracellular stores in human pulmonary artery endothelial cells. Ullmer, C., Boddeke, H.G., Schmuck, K., Lübbert, H. Br. J. Pharmacol. (1996) [Pubmed]
  18. Direct activation by dopamine of recombinant human 5-HT1A receptors: comparison with human 5-HT2C and 5-HT3 receptors. Oz, M., Zhang, L., Rotondo, A., Sun, H., Morales, M. Synapse (2003) [Pubmed]
  19. Inhibition of serotonin 5-hydroxytryptamine2c receptor function through heterodimerization: receptor dimers bind two molecules of ligand and one G-protein. Herrick-Davis, K., Grinde, E., Harrigan, T.J., Mazurkiewicz, J.E. J. Biol. Chem. (2005) [Pubmed]
  20. 5-HT2C (HTR2C) serotonin receptor gene polymorphism associated with the human personality trait of reward dependence: interaction with dopamine D4 receptor (D4DR) and dopamine D3 receptor (D3DR) polymorphisms. Ebstein, R.P., Segman, R., Benjamin, J., Osher, Y., Nemanov, L., Belmaker, R.H. Am. J. Med. Genet. (1997) [Pubmed]
  21. Contribution of 5-HT2A receptor gene -1438A>G polymorphism to outcome of attention-deficit/hyperactivity disorder in adolescents. Li, J., Kang, C., Wang, Y., Zhou, R., Wang, B., Guan, L., Yang, L., Faraone, S.V. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2006) [Pubmed]
  22. Synthesis and serotonin receptor affinities of a series of trans-2-(indol-3-yl)cyclopropylamine derivatives. Vangveravong, S., Kanthasamy, A., Lucaites, V.L., Nelson, D.L., Nichols, D.E. J. Med. Chem. (1998) [Pubmed]
  23. Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. Watson, J., Brough, S., Coldwell, M.C., Gager, T., Ho, M., Hunter, A.J., Jerman, J., Middlemiss, D.N., Riley, G.J., Brown, A.M. Br. J. Pharmacol. (1998) [Pubmed]
  24. Identification and characterization of RNA editing events within the 5-HT2C receptor. Niswender, C.M., Sanders-Bush, E., Emeson, R.B. Ann. N. Y. Acad. Sci. (1998) [Pubmed]
  25. Serotonin1A autoreceptor activation by S 15535 enhances circadian activity rhythms in hamsters: evaluation of potential interactions with serotonin2A and serotonin2C receptors. Gannon, R.L., Millan, M.J. Neuroscience (2006) [Pubmed]
  26. In vitro and in vivo profile of SB 206553, a potent 5-HT2C/5-HT2B receptor antagonist with anxiolytic-like properties. Kennett, G.A., Wood, M.D., Bright, F., Cilia, J., Piper, D.C., Gager, T., Thomas, D., Baxter, G.S., Forbes, I.T., Ham, P., Blackburn, T.P. Br. J. Pharmacol. (1996) [Pubmed]
  27. Association analysis of the 5-HT2C receptor and 5-HT transporter genes in bipolar disorder. Oruc, L., Verheyen, G.R., Furac, I., Jakovljević, M., Ivezić, S., Raeymaekers, P., Van Broeckhoven, C. Am. J. Med. Genet. (1997) [Pubmed]
  28. Comparative desensitization of the human 5-HT2A and 5-HT2C receptors expressed in the human neuroblastoma cell line SH-SY5Y. Briddon, S.J., Leslie, R.A., Elliott, J.M. Br. J. Pharmacol. (1998) [Pubmed]
  29. Signal transduction differences between 5-hydroxytryptamine type 2A and type 2C receptor systems. Berg, K.A., Clarke, W.P., Sailstad, C., Saltzman, A., Maayani, S. Mol. Pharmacol. (1994) [Pubmed]
  30. Sixth World Congress of Psychiatric Genetics X Chromosome Workshop. Paterson, A.D. Am. J. Med. Genet. (1999) [Pubmed]
  31. Serotonin-2 (5-HT2) receptor-mediated signal transduction in human ciliary muscle cells: role in ocular hypotension. Sharif, N.A., Kelly, C.R., Crider, J.Y., Davis, T.L. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics (2006) [Pubmed]
  32. Hallucinogens, serotonin and obsessive-compulsive disorder. Delgado, P.L., Moreno, F.A. Journal of psychoactive drugs. (1998) [Pubmed]
  33. Development of homogeneous high-affinity agonist binding assays for 5-HT2 receptor subtypes. Song, J., Hanniford, D., Doucette, C., Graham, E., Poole, M.F., Ting, A., Sherf, B., Harrington, J., Brunden, K., Stricker-Krongrad, A. Assay and drug development technologies. (2005) [Pubmed]
  34. RNA editing of serotonin 2C receptor in human postmortem brains of major mental disorders. Iwamoto, K., Kato, T. Neurosci. Lett. (2003) [Pubmed]
  35. Contribution of a helix 5 locus to selectivity of hallucinogenic and nonhallucinogenic ligands for the human 5-hydroxytryptamine2A and 5-hydroxytryptamine2C receptors: direct and indirect effects on ligand affinity mediated by the same locus. Almaula, N., Ebersole, B.J., Ballesteros, J.A., Weinstein, H., Sealfon, S.C. Mol. Pharmacol. (1996) [Pubmed]
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