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Gene Review

HTR2A  -  5-hydroxytryptamine (serotonin) receptor...

Homo sapiens

Synonyms: 5-HT-2, 5-HT-2A, 5-HT2A, 5-hydroxytryptamine receptor 2A, HTR2, ...
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Disease relevance of HTR2A


Psychiatry related information on HTR2A

  • Several case-control association studies have raised the possibility that the A allele of a -1438 G/A polymorphism in the type 2A serotonin receptor (HTR2A) gene may be a risk factor for anorexia nervosa [5].
  • Genetic association has been reported between a synonymous 102T/C polymorphism in the gene encoding HTR2A and a number of clinical phenotypes, including schizophrenia, clozapine response, psychotic symptoms in Alzheimer's disease and certain features of depression [6].
  • Nominally significant association was found at the HTR2A rs6311 polymorphism in subjects with tic disorder and OCD (p = .05), replicating a previous finding in Tourette syndrome and OCD [7].
  • We report here a case-control association study with T102C polymorphism in the serotonin 2A receptor gene (HTR2A) in patients affected by unipolar affective disorder (UPAD) and in controls [8].
  • The study showed a positive association between panic disorder and the HTR2A gene, suggesting that HTR2A plays an important role in the pathogenesis of panic disorder [9].

High impact information on HTR2A


Chemical compound and disease context of HTR2A


Biological context of HTR2A


Anatomical context of HTR2A


Associations of HTR2A with chemical compounds


Physical interactions of HTR2A

  • Molecular dynamics (MD) simulations of ligand-receptor complexes were performed for each investigated analogue, docked twice into the central cavity of 5-HT1A/5-HT2A, each time in a different orientation [31].
  • Decreased hippocampal 5-HT2A receptor binding in major depressive disorder: in vivo measurement with [18F]altanserin positron emission tomography [32].
  • IFN did not alter either [3H]ketanserin binding to 5-HT2A receptors or [3H]paroxetine binding to 5-HT transporters [33].
  • Furthermore, we demonstrated using glutathione S-transferase (GST)-fusion proteins of receptor domains that ARF1 and ARF6 bind to the third intracellular loop (i3) and the carboxy terminal tail (ct) of the 5-HT2AR [34].
  • The inhibitory effect of preincubation with MRS2365 was circumvented by activation of the Gq-coupled 5-HT2A receptor suggesting that MRS2365 induces loss of the ADP response as a consequence of desensitization of the Gq-coupled P2Y1 receptor [35].

Co-localisations of HTR2A

  • We propose that the spectral data following the lower ipsapirone dose reflect a net decrease of neuronal activity at 5-HT2 receptors, mediated through stimulation of somatodendritic autoreceptors in the raphe nuclei (presynaptic) and/or through stimulation of postsynaptic 5-HT1A receptors colocalized with 5-HT2 receptors [36].

Regulatory relationships of HTR2A

  • Variable participation of 5-HT1-like receptors and 5-HT2 receptors in serotonin-induced contraction of human isolated coronary arteries. 5-HT1-like receptors resemble cloned 5-HT1D beta receptors [37].
  • 5-HT1B/1D and 5-HT2B receptors are expressed since day 2 of the serotonergic differentiation while 5-HT2A receptors are induced at day 4 [38].
  • 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 [39].
  • Nefazodone's potent 5-HT2 antagonism in combination with 5-HT reuptake inhibition appears to enhance 5-HT1A-mediated neurotransmission [40].
  • The coapplication of 5-HT1A and 5-HT2 receptor agonists inhibited the induction of NMDAR-dependent LTP in 5-HT-depleted slices [41].

Other interactions of HTR2A

  • RESULTS: Statistically significant positive associations were found for HTR2A and hSERT polymorphisms [42].
  • When comparing specific response to nonspecific response, we found significant negative associations in three SNPs in the HTR2A gene (P=0.001-0.03) and two SNPs in the MAOA gene (P=0.03-0.05) [43].
  • In the specific response vs nonspecific and nonresponse comparison, three SNPs in the TPH2 gene (P=0.02-0.04) were positively associated and one SNP in the HTR2A gene (P=0.02) was negatively associated [43].
  • Serotonin 5-HT1A, 5-HT1B, and 5-HT2A receptor mRNA expression in subjects with major depression, bipolar disorder, and schizophrenia [44].
  • 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 [22].

Analytical, diagnostic and therapeutic context of HTR2A

  • Although the association of schizophrenia with the C allele of HTR2A was confirmed by a meta-analysis 5 years ago, there was a continuous debate because negative findings were also considerable, which may have been due to ethnic differences in association [45].
  • Multiple regression analysis showed that age and body mass index (BMI) were significantly associated with OSA, but HTR2A polymorphisms were not [2].
  • Acute vascular constriction by 5-HT is usually shared by 5-HT1B and 5-HT2A receptors, except in intracranial arteries which constrict only through 5-HT1B receptors [3].
  • Reverse transcription-polymerase chain reaction (RT-PCR) and ribonuclease protection assays were performed to identify 5-HT1 and 5-HT2 receptor mRNA expression in human coronary artery [46].
  • PCR products corresponding to 5-HT2A and 5-HT2B, but not 5-HT2C, receptor mRNA could readily be detected [47].


  1. Amplicon melting analysis with labeled primers: a closed-tube method for differentiating homozygotes and heterozygotes. Gundry, C.N., Vandersteen, J.G., Reed, G.H., Pryor, R.J., Chen, J., Wittwer, C.T. Clin. Chem. (2003) [Pubmed]
  2. Serotonin-2A and 2C receptor gene polymorphisms in Japanese patients with obstructive sleep apnea. Sakai, K., Takada, T., Nakayama, H., Kubota, Y., Nakamata, M., Satoh, M., Suzuki, E., Akazawa, K., Gejyo, F. Intern. Med. (2005) [Pubmed]
  3. 5-hydroxytryptamine receptors in the human cardiovascular system. Kaumann, A.J., Levy, F.O. Pharmacol. Ther. (2006) [Pubmed]
  4. Attenuation of haloperidol-induced catalepsy by a 5-HT2C receptor antagonist. Reavill, C., Kettle, A., Holland, V., Riley, G., Blackburn, T.P. Br. J. Pharmacol. (1999) [Pubmed]
  5. The 5-HT(2A) -1438G/A polymorphism in anorexia nervosa: a combined analysis of 316 trios from six European centres. Gorwood, P., Adès, J., Bellodi, L., Cellini, E., Collier, D.A., Di Bella, D., Di Bernardo, M., Estivill, X., Fernandez-Aranda, F., Gratacos, M., Hebebrand, J., Hinney, A., Hu, X., Karwautz, A., Kipman, A., Mouren-Siméoni, M.C., Nacmias, B., Ribasés, M., Remschmidt, H., Ricca, V., Rotella, C.M., Sorbi, S., Treasure, J. Mol. Psychiatry (2002) [Pubmed]
  6. The serotonin-2A receptor gene locus does not contain common polymorphism affecting mRNA levels in adult brain. Bray, N.J., Buckland, P.R., Hall, H., Owen, M.J., O'Donovan, M.C. Mol. Psychiatry (2004) [Pubmed]
  7. Association Studies of Serotonin System Candidate Genes in Early-onset Obsessive-Compulsive Disorder. Dickel, D.E., Veenstra-Vanderweele, J., Bivens, N.C., Wu, X., Fischer, D.J., Van Etten-Lee, M., Himle, J.A., Leventhal, B.L., Cook, E.H., Hanna, G.L. Biol. Psychiatry (2007) [Pubmed]
  8. Lack of association between the 5HT2A receptor polymorphism (T102C) and unipolar affective disorder in a multicentric European study. Oswald, P., Souery, D., Massat, I., Del-Favero, J., Linotte, S., Papadimitriou, G., Dikeos, D., Kaneva, R., Milanova, V., Oruc, L., Ivezic, S., Serretti, A., Lilli, R., Van Broeckhoven, C., Mendlewicz, J. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. (2003) [Pubmed]
  9. 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]
  10. International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Hoyer, D., Clarke, D.E., Fozard, J.R., Hartig, P.R., Martin, G.R., Mylecharane, E.J., Saxena, P.R., Humphrey, P.P. Pharmacol. Rev. (1994) [Pubmed]
  11. Monoaminergic regulation of neuroendocrine function and its modification by cocaine. Levy, A.D., Baumann, M.H., Van de Kar, L.D. Frontiers in neuroendocrinology. (1994) [Pubmed]
  12. 5-HT2A gene promoter polymorphism and anorexia nervosa. Ziegler, A., Görg, T. Lancet (1999) [Pubmed]
  13. 5-HT2A promoter polymorphism -1438G/A, anorexia nervosa, and obsessive-compulsive disorder. Enoch, M.A., Kaye, W.H., Rotondo, A., Greenberg, B.D., Murphy, D.L., Goldman, D. Lancet (1998) [Pubmed]
  14. Coexpression of 5-HT2A and 5-HT4 receptors coupled to distinct signaling pathways in human intestinal muscle cells. Kuemmerle, J.F., Murthy, K.S., Grider, J.R., Martin, D.C., Makhlouf, G.M. Gastroenterology (1995) [Pubmed]
  15. Allelic association analysis of the dopamine D2, D3, 5-HT2A, and GABA(A)gamma2 receptors and serotonin transporter genes with heroin abuse in Chinese subjects. Li, T., Liu, X., Zhao, J., Hu, X., Ball, D.M., Loh, e.l.-.W., Sham, P.C., Collier, D.A. Am. J. Med. Genet. (2002) [Pubmed]
  16. Serotonin receptor 2A, 2C, 1A genes and response to lithium prophylaxis in mood disorders. Serretti, A., Lorenzi, C., Lilli, R., Smeraldi, E. Journal of psychiatric research. (2000) [Pubmed]
  17. 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]
  18. A novel class of 5-HT2A receptor antagonists: aryl aminoguanidines. Bryant, H.U., Nelson, D.L., Button, D., Cole, H.W., Baez, M.B., Lucaites, V.L., Wainscott, D.B., Whitesitt, C., Reel, J., Simon, R., Koppel, G.A. Life Sci. (1996) [Pubmed]
  19. Serotonin 2A receptor antagonist treatment reduces dopamine D1 receptor-mediated rotational behavior but not l-DOPA-induced abnormal involuntary movements in the unilateral dopamine-depleted rat. Taylor, J.L., Bishop, C., Ullrich, T., Rice, K.C., Walker, P.D. Neuropharmacology (2006) [Pubmed]
  20. Pharmacogenetics of antidepressant medication intolerance. Murphy, G.M., Kremer, C., Rodrigues, H.E., Schatzberg, A.F. The American journal of psychiatry. (2003) [Pubmed]
  21. Serotonin subtype 2 receptor genes and clinical response to clozapine in schizophrenia patients. Masellis, M., Basile, V., Meltzer, H.Y., Lieberman, J.A., Sevy, S., Macciardi, F.M., Cola, P., Howard, A., Badri, F., Nöthen, M.M., Kalow, W., Kennedy, J.L. Neuropsychopharmacology (1998) [Pubmed]
  22. 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]
  23. Human trabecular meshwork cells express functional serotonin-2A (5HT2A) receptors: role in IOP reduction. Sharif, N.A., Kelly, C.R., McLaughlin, M. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  24. 5-HT1B receptor-mediated contractions in human temporal artery: evidence from selective antagonists and 5-HT receptor mRNA expression. Verheggen, R., Hundeshagen, A.G., Brown, A.M., Schindler, M., Kaumann, A.J. Br. J. Pharmacol. (1998) [Pubmed]
  25. 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]
  26. RBI-257: a highly potent dopamine D4 receptor-selective ligand. Kula, N.S., Baldessarini, R.J., Kebabian, J.W., Bakthavachalam, V., Xu, L. Eur. J. Pharmacol. (1997) [Pubmed]
  27. Serotonin and dopamine receptor gene polymorphisms and the risk of extrapyramidal side effects in perphenazine-treated schizophrenic patients. Gunes, A., Scordo, M.G., Jaanson, P., Dahl, M.L. Psychopharmacology (Berl.) (2007) [Pubmed]
  28. Antisocial alcoholism and serotonin-related polymorphisms: association tests. Hill, E.M., Stoltenberg, S.F., Bullard, K.H., Li, S., Zucker, R.A., Burmeister, M. Psychiatr. Genet. (2002) [Pubmed]
  29. The association between the T102C polymorphism of the HTR2A serotonin receptor gene and HDL cholesterol level in Koreans. Choi, J.H., Zhang, S.Y., Park, K.W., Cho, Y.S., Oh, B.H., Lee, M.M., Park, Y.B., Kim, H.S. J. Biochem. Mol. Biol. (2005) [Pubmed]
  30. The serotonin-2A receptor polymorphism and smoking behavior in Japan. Terayama, H., Itoh, M., Fukunishi, I., Iwahashi, K. Psychiatr. Genet. (2004) [Pubmed]
  31. Molecular dynamics of 5-HT1A and 5-HT2A serotonin receptors with methylated buspirone analogues. Bronowska, A., Chilmonczyk, Z., Leś, A., Edvardsen, O., Ostensen, R., Sylte, I. J. Comput. Aided Mol. Des. (2001) [Pubmed]
  32. Decreased hippocampal 5-HT2A receptor binding in major depressive disorder: in vivo measurement with [18F]altanserin positron emission tomography. Mintun, M.A., Sheline, Y.I., Moerlein, S.M., Vlassenko, A.G., Huang, Y., Snyder, A.Z. Biol. Psychiatry (2004) [Pubmed]
  33. Effects of chronic administration of interferon alpha A/D on serotonergic receptors in rat brain. Abe, S., Hori, T., Suzuki, T., Baba, A., Shiraishi, H., Yamamoto, T. Neurochem. Res. (1999) [Pubmed]
  34. Selective interaction of ARF1 with the carboxy-terminal tail domain of the 5-HT2A receptor. Robertson, D.N., Johnson, M.S., Moggach, L.O., Holland, P.J., Lutz, E.M., Mitchell, R. Mol. Pharmacol. (2003) [Pubmed]
  35. (N)-methanocarba-2MeSADP (MRS2365) is a subtype-specific agonist that induces rapid desensitization of the P2Y1 receptor of human platelets. Bourdon, D.M., Mahanty, S.K., Jacobson, K.A., Boyer, J.L., Harden, T.K. J. Thromb. Haemost. (2006) [Pubmed]
  36. The 5-HT1A agonist ipsapirone enhances EEG slow wave activity in human sleep and produces a power spectrum similar to 5-HT2 blockade. Seifritz, E., Moore, P., Trachsel, L., Bhatti, T., Stahl, S.M., Gillin, J.C. Neurosci. Lett. (1996) [Pubmed]
  37. Variable participation of 5-HT1-like receptors and 5-HT2 receptors in serotonin-induced contraction of human isolated coronary arteries. 5-HT1-like receptors resemble cloned 5-HT1D beta receptors. Kaumann, A.J., Frenken, M., Posival, H., Brown, A.M. Circulation (1994) [Pubmed]
  38. Cross-talk between 5-hydroxytryptamine receptors in a serotonergic cell line. Involvement of arachidonic acid metabolism. Tournois, C., Mutel, V., Manivet, P., Launay, J.M., Kellermann, O. J. Biol. Chem. (1998) [Pubmed]
  39. 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]
  40. Novel serotonergic mechanisms and clinical experience with nefazodone. Fontaine, R. Clinical neuropharmacology. (1993) [Pubmed]
  41. Serotonin inhibits the induction of NMDA receptor-dependent long-term potentiation in the rat primary visual cortex. Kim, H.S., Jang, H.J., Cho, K.H., Hahn, S.J., Kim, M.J., Yoon, S.H., Jo, Y.H., Kim, M.S., Rhie, D.J. Brain Res. (2006) [Pubmed]
  42. Genetic association analysis of serotonin system genes in bipolar affective disorder. Vincent, J.B., Masellis, M., Lawrence, J., Choi, V., Gurling, H.M., Parikh, S.V., Kennedy, J.L. The American journal of psychiatry. (1999) [Pubmed]
  43. 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]
  44. Serotonin 5-HT1A, 5-HT1B, and 5-HT2A receptor mRNA expression in subjects with major depression, bipolar disorder, and schizophrenia. López-Figueroa, A.L., Norton, C.S., López-Figueroa, M.O., Armellini-Dodel, D., Burke, S., Akil, H., López, J.F., Watson, S.J. Biol. Psychiatry (2004) [Pubmed]
  45. Meta-analysis of association between the T102C polymorphism of the 5HT2a receptor gene and schizophrenia. Abdolmaleky, H.M., Faraone, S.V., Glatt, S.J., Tsuang, M.T. Schizophr. Res. (2004) [Pubmed]
  46. Identification of mRNA for 5-HT1 and 5-HT2 receptor subtypes in human coronary arteries. Ishida, T., Hirata, K., Sakoda, T., Kawashima, S., Akita, H., Yokoyama, M. Cardiovasc. Res. (1999) [Pubmed]
  47. 5-HT2B receptor mRNA in guinea pig superior cervical ganglion. Newberry, N.R., Watkins, C.J., Volenec, A., Flanigan, T.P. Neuroreport (1996) [Pubmed]
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