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Gene Review

HTR5A  -  5-hydroxytryptamine (serotonin) receptor...

Homo sapiens

Synonyms: 5-HT-5, 5-HT-5A, 5-HT5A, 5-hydroxytryptamine receptor 5A, Serotonin receptor 5A
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Disease relevance of HTR5A

  • Human serotonin 5A (5-HT5A) receptors were stably expressed in undifferentiated C6 glioma [1].
  • The 5-HT5A gene colocalized with the mouse mutation reeler and the human mutation holoprosencephaly type 3, which both result in abnormal brain development, raising the possibility that the 5-HT5A receptor plays a role in brain development [2].

Psychiatry related information on HTR5A


High impact information on HTR5A

  • We propose that REC17 and MR22, designated as 5-HT5 alpha and 5-HT5 beta, represent a distinct subfamily of 5-HT receptors [5].
  • Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase [6].
  • An intronless gene encoding an additional human serotonin (5-HT) 5-HT1-like receptor subtype was isolated from a human genomic library with probes obtained from degenerate PCR primers used to amplify 5-HT-receptor-specific sequences [6].
  • We also determined the chromosomal localization of the 5-HT5A and 5-HT5B genes and of their human counterparts [2].
  • It was concluded that in addition to the inhibition of cAMP accumulation and ADP-ribosyl cyclase activity, 5-HT5A receptors regulate intracellular Ca2+ mobilization which is probably a result of the IP3-sensitive Ca2+ store [1].

Chemical compound and disease context of HTR5A


Biological context of HTR5A

  • Assignment of the 5-hydroxytryptamine (serotonin) receptor 5A gene (HTR5A) to human chromosome band 7q36.1 [8].
  • The deduced amino acid sequence of the gene reveals a protein of 357 residues which shares 93% (nucleotide) and 84% (amino acid) identity to the cloned mouse 5-HT5A receptor [9].
  • As with the mouse and rat 5-HT5A receptors, the gene consists of two coding exons separated by a large intron [9].
  • 5. A ligand-stimulated reduction in the detectable level of the catalytic domain of protein kinase A (PKA) in nuclear extracts isolated from Human 5-HT5A expressing cells was observed [10].
  • Genetic variation in the 5-HT5A gene might be involved in susceptibility to depression, the major psychoses or in influencing clinical response to treatment [3].

Anatomical context of HTR5A


Associations of HTR5A with chemical compounds

  • No interaction was encountered between 2-methyl-5-HT and MDL72222, suggesting an absence of 5-HT3 receptors [13].
  • This action appears to be due to activation of a 5-HT1-like receptor as it is mimicked by some 5-HT1 receptor ligands (mCPP, TFMPP and 5-Me-O-DMT), but not by DOI (5-HT2) or 2-Me-5-HT (5-HT3) [14].
  • These properties distinguish this receptor from any previously characterized and establish a fifth 5-HT1-like receptor subtype (5-HT1F) coupled to the inhibition of adenylate cyclase [6].
  • On the other hand, activation of 5-HT5A receptors transiently opened the K+ channels, presumably due to the increase in intracellular Ca2+ after formation of inositol (1,4,5) trisphosphate [7].
  • In addition to this known signaling via Gi/Go, 5-HT5A receptors are coupled to the inhibition of ADP-ribosyl cyclase and cyclic ADP ribose formation [7].

Other interactions of HTR5A

  • The polymorphism studied for 5-HT5A, 5-HT6, alpha1A- and alpha2A-receptors give no clear associations with the response to clozapine [15].
  • This review was undertaken to summarize the results of structure-activity relationship studies with ligands of 5-HT5, 5-HT6 and 5-HT7 receptors [16].
  • This is the first study to describe such G-protein activation for the Human 5-HT5A receptor in any cell [10].
  • Two polymorphisms (-19G/C and 12A/T) in the 5-HT5A receptor gene were analyzed by polymerase chain reaction amplification and subsequent enzyme digestion [4].

Analytical, diagnostic and therapeutic context of HTR5A


  1. Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways. Noda, M., Yasuda, S., Okada, M., Higashida, H., Shimada, A., Iwata, N., Ozaki, N., Nishikawa, K., Shirasawa, S., Uchida, M., Aoki, S., Wada, K. J. Neurochem. (2003) [Pubmed]
  2. Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B receptors define a new family of serotonin receptors: cloning, functional expression, and chromosomal localization. Matthes, H., Boschert, U., Amlaiky, N., Grailhe, R., Plassat, J.L., Muscatelli, F., Mattei, M.G., Hen, R. Mol. Pharmacol. (1993) [Pubmed]
  3. Association analysis of the 5-HT5A gene in depression, psychosis and antipsychotic response. Birkett, J.T., Arranz, M.J., Munro, J., Osbourn, S., Kerwin, R.W., Collier, D.A. Neuroreport (2000) [Pubmed]
  4. Genetic variation in the 5-HT5A receptor gene in patients with bipolar disorder and major depression. Arias, B., Collier, D.A., Gastó, C., Pintor, L., Gutiérrez, B., Vallès, V., Fañanás, L. Neurosci. Lett. (2001) [Pubmed]
  5. Two members of a distinct subfamily of 5-hydroxytryptamine receptors differentially expressed in rat brain. Erlander, M.G., Lovenberg, T.W., Baron, B.M., de Lecea, L., Danielson, P.E., Racke, M., Slone, A.L., Siegel, B.W., Foye, P.E., Cannon, K. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  6. Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase. Adham, N., Kao, H.T., Schecter, L.E., Bard, J., Olsen, M., Urquhart, D., Durkin, M., Hartig, P.R., Weinshank, R.L., Branchek, T.A. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  7. Multiple signal transduction pathways mediated by 5-HT receptors. Noda, M., Higashida, H., Aoki, S., Wada, K. Mol. Neurobiol. (2004) [Pubmed]
  8. Assignment of the 5-hydroxytryptamine (serotonin) receptor 5A gene (HTR5A) to human chromosome band 7q36.1. Schanen, N.C., Scherer, S.W., Tsui, L.C., Francke, U. Cytogenet. Cell Genet. (1996) [Pubmed]
  9. Cloning and characterisation of the human 5-HT5A serotonin receptor. Rees, S., den Daas, I., Foord, S., Goodson, S., Bull, D., Kilpatrick, G., Lee, M. FEBS Lett. (1994) [Pubmed]
  10. Functional coupling of a recombinant human 5-HT5A receptor to G-proteins in HEK-293 cells. Hurley, P.T., McMahon, R.A., Fanning, P., O'Boyle, K.M., Rogers, M., Martin, F. Br. J. Pharmacol. (1998) [Pubmed]
  11. Identification of one of the least well understood 5-HT receptors (5-HT5A) in the spinal cord. Ramage, A.G. J. Comp. Neurol. (2004) [Pubmed]
  12. Distribution of the 5-HT5A serotonin receptor mRNA in the human brain. Pasqualetti, M., Ori, M., Nardi, I., Castagna, M., Cassano, G.B., Marazziti, D. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  13. 5-Hydroxytryptamine contracts human uterine artery smooth muscle predominantly via 5-HT2 receptors. Karlsson, C., Bodelsson, G., Bodelsson, M., Stjernquist, M. Hum. Reprod. (1997) [Pubmed]
  14. Interactions of descending serotonergic systems with other neurotransmitters in the modulation of nociception. Sawynok, J., Reid, A. Behav. Brain Res. (1996) [Pubmed]
  15. Pharmacogenetics as a tool in the therapy of schizophrenia. Wilffert, B., Zaal, R., Brouwers, J.R. Pharmacy world & science : PWS. (2005) [Pubmed]
  16. In the search for selective ligands of 5-HT5, 5-HT6 and 5-HT7 serotonin receptors. Wesołowska, A. Polish journal of pharmacology. (2002) [Pubmed]
  17. De novo 7q36 deletion: breakpoint analysis and types of holoprosencephaly. Frints, S.G., Schoenmakers, E.F., Smeets, E., Petit, P., Fryns, J.P. Am. J. Med. Genet. (1998) [Pubmed]
  18. Human 5-HT5A receptor gene: systematic screening for DNA sequence variation and linkage mapping on chromosome 7q34-q36 using a polymorphism in the 5' untranslated region. Shimron-Abarbanell, D., Erdmann, J., Vogt, I.R., Bryant, S.P., Spurr, N.K., Knapp, M., Propping, P., Nöthen, M.M. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
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