The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

TPH2  -  tryptophan hydroxylase 2

Homo sapiens

Synonyms: ADHD7, FLJ37295, NTPH, Neuronal tryptophan hydroxylase, Tryptophan 5-hydroxylase 2, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of TPH2


Psychiatry related information on TPH2


High impact information on TPH2


Chemical compound and disease context of TPH2


Biological context of TPH2


Anatomical context of TPH2

  • Previously, we reported elevated levels of TPH protein in the dorsal raphe nucleus (DRN) of depressed suicides and now examine expression of neuronal TPH2 mRNA in a cohort of matched controls and depressed suicides (n = 11 pairs) [14].
  • TPH2 is the predominant enzyme form expressed in brain extracts from mesencephalic tegmentum, striatum, and hippocampus with a molecular weight of 56 kDa [12].
  • Due to the lack of data about its anatomic expression in humans we performed a mRNA expression analysis comparing TPH1 and TPH2 mRNA in several regions of the human brain (cortex, thalamus, hypothalamus, hippocampus, amygdala, cerebellum and raphe nuclei) [15].
  • TPH2 and beta-actin mRNA levels in postmortem brain were quantified using real-time PCR. mRNA samples provided by the Stanley Foundation Array Collection were derived from the dorsolateral prefrontal cortex (Brodmann Area 46) of 35 bipolar, 35 schizophrenic, and 35 control subjects [16].
  • OBJECTIVE: To determine the association of TPH2 with suicide attempt, major depression, and a neurochemical intermediate phenotype, cerebrospinal fluid 5-hydroxyindoleacetic acid [9].

Associations of TPH2 with chemical compounds

  • Recent studies have indicated that a newly identified second isoform of the tryptophan hydroxylase gene (TPH2) is preferentially involved in the rate-limiting synthesis of neuronal serotonin [17].
  • TPH2 is more soluble than TPH1, has a higher molecular weight and different kinetic properties, including a lower catalytic efficiency towards phenylalanine than TPH1 [18].
  • OBJECTIVE: We screened the complete protein coding sequence of the newly identified neuronal form of tryptophan hydroxylase (TPH2) for genetic variants [19].
  • Two-week fluoxetine treatment also significantly reduced expression of tryptophan hydroxylase-2 (TPH2) and 5-HT transporter mRNAs as determined by RT-PCR in the brainstem [20].
  • The results indicate that none of the SNPs in the TPH2 gene examined in this study associate with the cocaine-dependent phenotype [21].

Regulatory relationships of TPH2

  • Serotonin signaling has long been implicated in both BPAD and suicide, and the gene encoding the brain-expressed isoform of tryptophan hydroxlyase (TPH2) has been described [22].

Other interactions of TPH2

  • The major finding of this study was the high expression level of TPH2 mRNA in the raphe nuclei ( approximately 4-fold more abundant than that of TPH1) [15].
  • Further confirmation, preferably from different ethnic groups, is required to firmly implicate TPH2 in the pathophysiology of ADHD [10].
  • 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 [23].
  • This study was designed to examine whether the -473T > A and -8396G > C polymorphisms of the TPH2 gene may be associated with completed suicide in subjects with major psychoses from the Stanley Foundation Brain Bank sample [24].
  • We conclude that TPH2 may play a modest role in autism susceptibility, perhaps relating specifically to repetitive behaviors, pending replication of this result [25].

Analytical, diagnostic and therapeutic context of TPH2


  1. Functional Domains of Human Tryptophan Hydroxylase 2 (hTPH2). Carkaci-Salli, N., Flanagan, J.M., Martz, M.K., Salli, U., Walther, D.J., Bader, M., Vrana, K.E. J. Biol. Chem. (2006) [Pubmed]
  2. Postmortem parietal cortex TPH2 expression is not altered in schizophrenic, unipolar-depressed, and bipolar patients vs control subjects. Shamir, A., Shaltiel, G., Levi, I., Belmaker, R.H., Agam, G. J. Mol. Neurosci. (2005) [Pubmed]
  3. Analysis of the novel TPH2 gene in bipolar disorder and suicidality. De Luca, V., Mueller, D.J., Tharmalingam, S., King, N., Kennedy, J.L. Mol. Psychiatry (2004) [Pubmed]
  4. Transmission disequilibrium of polymorphic variants in the tryptophan hydroxylase-2 gene in attention-deficit/hyperactivity disorder. Walitza, S., Renner, T.J., Dempfle, A., Konrad, K., Wewetzer, C.h., Halbach, A., Herpertz-Dahlmann, B., Remschmidt, H., Smidt, J., Linder, M., Flierl, L., Knölker, U., Friedel, S., Schäfer, H., Gross, C., Hebebrand, J., Warnke, A., Lesch, K.P. Mol. Psychiatry (2005) [Pubmed]
  5. Association study of tryptophan hydroxylase 2 gene polymorphisms in panic disorder. Maron, E., T??ru, I., Must, A., Tasa, G., Toover, E., Vasar, V., Lang, A., Shlik, J. Neurosci. Lett. (2007) [Pubmed]
  6. The novel brain-specific tryptophan hydroxylase-2 gene in panic disorder. Mössner, R., Freitag, C.M., Gutknecht, L., Reif, A., Tauber, R., Franke, P., Fritze, J., Wagner, G., Peikert, G., Wenda, B., Sand, P., Rietschel, M., Garritsen, H., Jacob, C., Lesch, K.P., Deckert, J. J. Psychopharmacol. (Oxford) (2006) [Pubmed]
  7. Loss-of-function mutation in tryptophan hydroxylase-2 identified in unipolar major depression. Zhang, X., Gainetdinov, R.R., Beaulieu, J.M., Sotnikova, T.D., Burch, L.H., Williams, R.B., Schwartz, D.A., Krishnan, K.R., Caron, M.G. Neuron (2005) [Pubmed]
  8. Association of Brain-Specific Tryptophan Hydroxylase, TPH2, With Unipolar and Bipolar Disorder in a Northern Swedish, Isolated Population. Van Den Bogaert, A., Sleegers, K., De Zutter, S., Heyrman, L., Norrback, K.F., Adolfsson, R., Van Broeckhoven, C., Del-Favero, J. Arch. Gen. Psychiatry (2006) [Pubmed]
  9. Haplotype-based linkage of tryptophan hydroxylase 2 to suicide attempt, major depression, and cerebrospinal fluid 5-hydroxyindoleacetic acid in 4 populations. Zhou, Z., Roy, A., Lipsky, R., Kuchipudi, K., Zhu, G., Taubman, J., Enoch, M.A., Virkkunen, M., Goldman, D. Arch. Gen. Psychiatry (2005) [Pubmed]
  10. Tryptophan hydroxylase 2 (TPH2) gene variants associated with ADHD. Sheehan, K., Lowe, N., Kirley, A., Mullins, C., Fitzgerald, M., Gill, M., Hawi, Z. Mol. Psychiatry (2005) [Pubmed]
  11. A unique central tryptophan hydroxylase isoform. Walther, D.J., Bader, M. Biochem. Pharmacol. (2003) [Pubmed]
  12. Differential tissue distribution of tryptophan hydroxylase isoforms 1 and 2 as revealed with monospecific antibodies. Sakowski, S.A., Geddes, T.J., Thomas, D.M., Levi, E., Hatfield, J.S., Kuhn, D.M. Brain Res. (2006) [Pubmed]
  13. SNP and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene provide evidence for association with major depression. Zill, P., Baghai, T.C., Zwanzger, P., Schüle, C., Eser, D., Rupprecht, R., Möller, H.J., Bondy, B., Ackenheil, M. Mol. Psychiatry (2004) [Pubmed]
  14. Neuronal tryptophan hydroxylase mRNA expression in the human dorsal and median raphe nuclei: major depression and suicide. Bach-Mizrachi, H., Underwood, M.D., Kassir, S.A., Bakalian, M.J., Sibille, E., Tamir, H., Mann, J.J., Arango, V. Neuropsychopharmacology (2006) [Pubmed]
  15. Analysis of tryptophan hydroxylase I and II mRNA expression in the human brain: A post-mortem study. Zill, P., B??ttner, A., Eisenmenger, W., M??ller, H.J., Ackenheil, M., Bondy, B. Journal of psychiatric research (2007) [Pubmed]
  16. Tryptophan hydroxylase 2 gene expression and promoter polymorphisms in bipolar disorder and schizophrenia. De Luca, V., Likhodi, O., Van Tol, H.H., Kennedy, J.L., Wong, A.H. Psychopharmacology (Berl.) (2005) [Pubmed]
  17. A regulatory variant of the human tryptophan hydroxylase-2 gene biases amygdala reactivity. Brown, S.M., Peet, E., Manuck, S.B., Williamson, D.E., Dahl, R.E., Ferrell, R.E., Hariri, A.R. Mol. Psychiatry (2005) [Pubmed]
  18. Different properties of the central and peripheral forms of human tryptophan hydroxylase. McKinney, J., Knappskog, P.M., Haavik, J. J. Neurochem. (2005) [Pubmed]
  19. Identification of genetic variants in the neuronal form of tryptophan hydroxylase (TPH2). Breidenthal, S.E., White, D.J., Glatt, C.E. Psychiatr. Genet. (2004) [Pubmed]
  20. Effect of repeated treatment with fluoxetine on tryptophan hydroxylase-2 gene expression in the rat brainstem. Dygalo, N.N., Shishkina, G.T., Kalinina, T.S., Yudina, A.M., Ovchinnikova, E.S. Pharmacol. Biochem. Behav. (2006) [Pubmed]
  21. Analysis of variations in the tryptophan hydroxylase-2 (TPH2) gene in cocaine dependence. Dahl, J.P., Cubells, J.F., Ray, R., Weller, A.E., Lohoff, F.W., Ferraro, T.N., Oslin, D.W., Kampman, K.M., Dackis, C., Tang, Y., Gelernter, J., Kranzler, H.R., O'Brien, C.P., Berrettini, W.H. Addiction biology. (2006) [Pubmed]
  22. Nested association between genetic variation in tryptophan hydroxylase II, bipolar affective disorder, and suicide attempts. Lopez, V.A., Detera-Wadleigh, S., Cardona, I., Kassem, L., McMahon, F.J. Biol. Psychiatry (2007) [Pubmed]
  23. 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]
  24. The interaction between TPH2 promoter haplotypes and clinical-demographic risk factors in suicide victims with major psychoses. De Luca, V., Hlousek, D., Likhodi, O., Van Tol, H.H., Kennedy, J.L., Wong, A.H. Genes Brain Behav. (2006) [Pubmed]
  25. Possible association between autism and variants in the brain-expressed tryptophan hydroxylase gene (TPH2). Coon, H., Dunn, D., Lainhart, J., Miller, J., Hamil, C., Battaglia, A., Tancredi, R., Leppert, M.F., Weiss, R., McMahon, W. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2005) [Pubmed]
  26. Amygdala responsiveness is modulated by tryptophan hydroxylase-2 gene variation. Canli, T., Congdon, E., Gutknecht, L., Constable, R.T., Lesch, K.P. Journal of neural transmission (Vienna, Austria : 1996) (2005) [Pubmed]
WikiGenes - Universities