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Aliases for TPH2 Gene

Aliases for TPH2 Gene

  • Tryptophan Hydroxylase 2 2 3
  • Neuronal Tryptophan Hydroxylase 3 4
  • Tryptophan 5-Monooxygenase 2 3 4
  • EC 4 63
  • NTPH 3 4
  • EC 1.14.16 63
  • ADHD7 3

External Ids for TPH2 Gene

Previous GeneCards Identifiers for TPH2 Gene

  • GC12P072284
  • GC12P072049
  • GC12P070618
  • GC12P069382
  • GC12P072332

Summaries for TPH2 Gene

Entrez Gene Summary for TPH2 Gene

  • This gene encodes a member of the pterin-dependent aromatic acid hydroxylase family. The encoded protein catalyzes the first and rate limiting step in the biosynthesis of serotonin, an important hormone and neurotransmitter. The human genome contains two related tryptophan hydroxylases, one on chromosome 11p15-p14 and one on chromosome 12q21. This gene is expressed predominantly in the brain stem. Mutations in this gene may be associated with psychiatric diseases such as bipolar affective disorder and major depression. [provided by RefSeq, Jul 2008]

GeneCards Summary for TPH2 Gene

TPH2 (Tryptophan Hydroxylase 2) is a Protein Coding gene. Diseases associated with TPH2 include tryptophan hydroxylase deficiency and major depressive disorder and accelerated response to antidepressant drug treatment. Among its related pathways are Metabolism and CDK-mediated phosphorylation and removal of Cdc6. GO annotations related to this gene include iron ion binding and oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced pteridine as one donor, and incorporation of one atom of oxygen. An important paralog of this gene is TPH1.

Tocris Summary for TPH2 Gene

  • Hydroxylases are enzymes that catalyze the addition of hydroxyl groups to substrates during oxidation reactions. This diverse group of enzymes includes tryptophan hydroxylase (E.C., steroid 11-beta hydroxylase (E.C., and LTB4 omega-hydroxylase (E.C.

Gene Wiki entry for TPH2 Gene

No data available for UniProtKB/Swiss-Prot , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TPH2 Gene

Genomics for TPH2 Gene

Regulatory Elements for TPH2 Gene

Genomic Location for TPH2 Gene

71,938,846 bp from pter
72,186,618 bp from pter
247,773 bases
Plus strand

Genomic View for TPH2 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for TPH2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TPH2 Gene

Proteins for TPH2 Gene

  • Protein details for TPH2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Tryptophan 5-hydroxylase 2
    Protein Accession:
    Secondary Accessions:
    • A6NGA4
    • Q14CB0

    Protein attributes for TPH2 Gene

    490 amino acids
    Molecular mass:
    56057 Da
    Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for TPH2 Gene

    Alternative splice isoforms for TPH2 Gene


neXtProt entry for TPH2 Gene

Proteomics data for TPH2 Gene at MOPED

Post-translational modifications for TPH2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for TPH2 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • R&D Systems Antibodies for TPH2 (Tryptophan Hydroxylase 2)

Domains & Families for TPH2 Gene

Gene Families for TPH2 Gene

Graphical View of Domain Structure for InterPro Entry



  • Contains 1 ACT domain.
  • Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.
  • Contains 1 ACT domain.
  • Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.
genes like me logo Genes that share domains with TPH2: view

Function for TPH2 Gene

Molecular function for TPH2 Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=41.3 uM for L-tryptophan {ECO:0000269 PubMed:17905754}; Vmax=833 nmol/min/mg enzyme {ECO:0000269 PubMed:17905754};
UniProtKB/Swiss-Prot CatalyticActivity:
L-tryptophan + tetrahydrobiopterin + O(2) = 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin

Enzyme Numbers (IUBMB) for TPH2 Gene

Gene Ontology (GO) - Molecular Function for TPH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004497 monooxygenase activity --
GO:0004510 tryptophan 5-monooxygenase activity IEA --
GO:0005506 iron ion binding IEA --
GO:0016597 amino acid binding IEA --
GO:0016714 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced pteridine as one donor, and incorporation of one atom of oxygen --
genes like me logo Genes that share ontologies with TPH2: view
genes like me logo Genes that share phenotypes with TPH2: view

Animal Models for TPH2 Gene

MGI Knock Outs for TPH2:

Animal Model Products

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for TPH2

In Situ Assay Products

Flow Cytometry Products

No data available for miRNA , Transcription Factor Targets and HOMER Transcription for TPH2 Gene

Localization for TPH2 Gene

Subcellular locations from

Jensen Localization Image for TPH2 Gene COMPARTMENTS Subcellular localization image for TPH2 gene
Compartment Confidence
cytosol 4
extracellular 1
nucleus 1

Gene Ontology (GO) - Cellular Components for TPH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
GO:0043005 neuron projection IEA --
genes like me logo Genes that share ontologies with TPH2: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for TPH2 Gene

Pathways & Interactions for TPH2 Gene

genes like me logo Genes that share pathways with TPH2: view

PCR Array Products

  • Pathway & Disease-focused RT² Profiler PCR Arrays

UniProtKB/Swiss-Prot Q8IWU9-TPH2_HUMAN

  • Pathway: Aromatic compound metabolism; serotonin biosynthesis; serotonin from L-tryptophan: step 1/2

SIGNOR curated interactions for TPH2 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for TPH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007623 circadian rhythm IEA --
GO:0008152 metabolic process --
GO:0009072 aromatic amino acid family metabolic process IEA --
GO:0014823 response to activity IEA --
GO:0031667 response to nutrient levels IEA --
genes like me logo Genes that share ontologies with TPH2: view

Drugs & Compounds for TPH2 Gene

(20) Drugs for TPH2 Gene - From: HMDB, IUPHAR, DGIdb, PharmGKB, ApexBio, NovoSeek, DrugBank, and Tocris

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
L-Tryptophan Approved Nutra Inhibition, Inhibitor, Enzyme, substrate 0
Citalopram Approved Pharma 485
Mirtazapine Approved Pharma 74
Venlafaxine Approved Pharma Dual serotonin/noradrenalin re-uptake inhibitor 181
Tetrahydrobiopterin Approved, Investigational Pharma 0

(10) Additional Compounds for TPH2 Gene - From: HMDB, IUPHAR, Tocris, and NovoSeek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Inhibition, Inhibitor
Inhibition, Inhibitor
4a-Carbinolamine tetrahydrobiopterin
  • 1,3,5-Benzenetriol
  • 1,3,5-Trihydroxybenzene
  • 1,3,5-Trihydroxybenzene anhydrate
  • 1,3,5-Trihydroxybenzene anhydrous
  • 1,3,5-Trihydroxybenzene dihydrate
  • (6R)-6-(L-erythro-1,2-Dihydroxypropyl)-5,6,7,8-tetrahydro-4a-hydroxypterin
  • 2-Amino-6-(1,2-dihydroxypropyl)-4a-hydroxy-5,6,7,8-tetrahydropteridin-4(4aH)-one
  • 2-Amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4a-hydroxy-4(4aH)-Pteridinone
  • 2-Amino-6-[(1R,2S)-1,2-dihydroxypropyl]-4a-hydroxy-1,5,6,7-tetrahydropteridin-4-one
  • 4a-Hydroxy-5,6,7,8-tetrahydrobiopterin
  • Armco iron
  • Carbonyl iron
  • FE
  • Ferrovac e
  • Hematite
genes like me logo Genes that share compounds with TPH2: view

Transcripts for TPH2 Gene

mRNA/cDNA for TPH2 Gene

(2) REFSEQ mRNAs :
(4) Additional mRNA sequences :
(6) Selected AceView cDNA sequences:
(6) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for TPH2 Gene

Tryptophan hydroxylase 2:
Representative Sequences:

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for TPH2

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for TPH2 Gene

No ASD Table

Relevant External Links for TPH2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for TPH2 Gene

mRNA expression in normal human tissues for TPH2 Gene

mRNA differential expression in normal tissues according to GTEx for TPH2 Gene

This gene is overexpressed in Pituitary (x8.6), Brain - Hippocampus (x7.1), Brain - Anterior cingulate cortex (BA24) (x5.1), Brain - Hypothalamus (x4.8), Brain - Frontal Cortex (BA9) (x4.7), and Testis (x4.3).

Protein differential expression in normal tissues from HIPED for TPH2 Gene

This gene is overexpressed in Spinal cord (68.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for TPH2 Gene

SOURCE GeneReport for Unigene cluster for TPH2 Gene Hs.736576

mRNA Expression by UniProt/SwissProt for TPH2 Gene

Tissue specificity: Brain specific
genes like me logo Genes that share expression patterns with TPH2: view

Protein tissue co-expression partners for TPH2 Gene

- Elite partner

Primer Products

In Situ Assay Products

Orthologs for TPH2 Gene

This gene was present in the common ancestor of animals.

Orthologs for TPH2 Gene

Organism Taxonomy Gene Similarity Type Details
(Canis familiaris)
Mammalia TPH2 35
  • 84.83 (n)
  • 90.61 (a)
TPH2 36
  • 90 (a)
(Mus musculus)
Mammalia Tph2 35
  • 87.5 (n)
  • 93.44 (a)
Tph2 16
Tph2 36
  • 94 (a)
(Pan troglodytes)
Mammalia TPH2 35
  • 99.32 (n)
  • 99.59 (a)
TPH2 36
  • 100 (a)
(Rattus norvegicus)
Mammalia Tph2 35
  • 87.77 (n)
  • 94.23 (a)
(Bos Taurus)
Mammalia TPH2 36
  • 90 (a)
(Ornithorhynchus anatinus)
Mammalia TPH2 36
  • 36 (a)
(Gallus gallus)
Aves TPH2 35
  • 81.15 (n)
  • 91.6 (a)
TPH2 36
  • 87 (a)
(Anolis carolinensis)
Reptilia TPH2 36
  • 91 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia tph2 35
  • 74.16 (n)
  • 80.82 (a)
(Danio rerio)
Actinopterygii tph2 35
  • 67.97 (n)
  • 76.3 (a)
tph2 36
  • 77 (a)
fruit fly
(Drosophila melanogaster)
Insecta Trh 36
  • 46 (a)
(Caenorhabditis elegans)
Secernentea tph-1 35
  • 58.58 (n)
  • 58.13 (a)
tph-1 36
  • 42 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 62 (a)
Species with no ortholog for TPH2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for TPH2 Gene

Gene Tree for TPH2 (if available)
Gene Tree for TPH2 (if available)

Paralogs for TPH2 Gene

Paralogs for TPH2 Gene

genes like me logo Genes that share paralogs with TPH2: view

Variants for TPH2 Gene

Sequence variations from dbSNP and Humsavar for TPH2 Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type MAF
rs763541 -- 71,961,392(-) GTGCA(A/G)ATTAA intron-variant
rs990234 -- 72,004,337(+) GGAGA(C/T)GGCAT intron-variant
rs990235 -- 72,004,373(+) ATCTA(C/T)GTCAT intron-variant
rs1005691 -- 71,996,614(-) CAAGG(C/T)CAGAC intron-variant
rs1007023 -- 71,994,594(+) CCAGT(G/T)CTATT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for TPH2 Gene

Variant ID Type Subtype PubMed ID
nsv518498 CNV Loss 19592680
esv2746047 CNV Deletion 23290073
esv1003596 CNV Deletion 20482838
esv2451960 CNV Deletion 19546169
esv2253374 CNV Deletion 18987734
nsv512284 CNV Loss 21212237
esv996582 CNV Deletion 20482838
esv2746048 CNV Deletion 23290073
esv9704 CNV Loss 19470904
esv1137133 CNV Deletion 17803354
nsv819959 CNV Loss 19587683
dgv295n67 CNV Loss 20364138
nsv821295 CNV Deletion 20802225
nsv826428 CNV Loss 20364138
esv23023 CNV Loss 19812545
nsv826429 CNV Loss 20364138
esv275101 CNV Gain+Loss 21479260
esv3280 CNV Deletion 18987735
esv2746049 CNV Deletion 23290073
dgv301e199 CNV Deletion 23128226
nsv899256 CNV Gain 21882294

Variation tolerance for TPH2 Gene

Residual Variation Intolerance Score: 28.82% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.78; 33.60% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for TPH2 Gene

HapMap Linkage Disequilibrium report
Human Gene Mutation Database (HGMD)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TPH2 Gene

Disorders for TPH2 Gene

MalaCards: The human disease database

(18) MalaCards diseases for TPH2 Gene - From: OMIM, GeneTests, DISEASES, NovoSeek, and GeneCards


  • Attention deficit-hyperactivity disorder 7 (ADHD7) [MIM:613003]: A neurobehavioral developmental disorder primarily characterized by the coexistence of attentional problems and hyperactivity, with each behavior occurring infrequently alone. {ECO:0000269 PubMed:18347598}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Naturally occurring variants of TPH2 with impaired enzyme activity could cause deficiency of serotonin production and result in an increased risk of developing behavioral disorders.
  • Major depressive disorder (MDD) [MIM:608516]: A common psychiatric disorder. It is a complex trait characterized by one or more major depressive episodes without a history of manic, mixed, or hypomanic episodes. A major depressive episode is characterized by at least 2 weeks during which there is a new onset or clear worsening of either depressed mood or loss of interest or pleasure in nearly all activities. Four additional symptoms must also be present including changes in appetite, weight, sleep, and psychomotor activity; decreased energy; feelings of worthlessness or guilt; difficulty thinking, concentrating, or making decisions; or recurrent thoughts of death or suicidal ideation, plans, or attempts. The episode must be accompanied by distress or impairment in social, occupational, or other important areas of functioning. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Relevant External Links for TPH2

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with TPH2: view

No data available for Genatlas for TPH2 Gene

Publications for TPH2 Gene

  1. Nested association between genetic variation in tryptophan hydroxylase II, bipolar affective disorder, and suicide attempts. (PMID: 16806105) Lopez V.A. … McMahon F.J. (Biol. Psychiatry 2007) 23 25 26 67
  2. Serotonin-1A receptor gene HTR1A variation predicts interferon-induced depression in chronic hepatitis C. (PMID: 17408646) Kraus M.R. … Scheurlen M. (Gastroenterology 2007) 25 26 67
  3. Association of polymorphisms of the tryptophan hydroxylase 2 gene with risk for bipolar disorder or suicidal behavior. (PMID: 19800079) Campos S.B. … Correa H. (J Psychiatr Res 2010) 23 67
  4. A gene-environment investigation on personality traits in two independent clinical sets of adult patients with personality disorder and attention deficit/hyperactive disorder. (PMID: 19894072) Jacob C.P. … Reif A. (Eur Arch Psychiatry Clin Neurosci 2010) 23 67
  5. The effect of rearing experience and TPH2 genotype on HPA axis function and aggression in rhesus monkeys: a retrospective analysis. (PMID: 19900455) Chen G.L. … Miller G.M. (Horm Behav 2010) 23 67

Products for TPH2 Gene

Sources for TPH2 Gene

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