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Aliases for TPH2 Gene

Aliases for TPH2 Gene

  • Tryptophan Hydroxylase 2 2 3 5
  • Neuronal Tryptophan Hydroxylase 3 4
  • Tryptophan 5-Monooxygenase 2 3 4
  • EC 4 58
  • NTPH 3 4
  • Tryptophan 5-Monooxygenase 2
  • Tryptophan 5-Hydroxylase 2 3
  • EC 1.14.16 58
  • 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. Mutations in this gene may be associated with psychiatric diseases such as bipolar affective disorder and major depression. [provided by RefSeq, Feb 2016]

GeneCards Summary for TPH2 Gene

TPH2 (Tryptophan Hydroxylase 2) is a Protein Coding gene. Diseases associated with TPH2 include Major Depressive Disorder And Accelerated Response To Antidepressant Drug Treatment and Tryptophan Hydroxylase Deficiency. Among its related pathways are Metabolism and Amine-derived hormones. 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

Additional gene information for TPH2 Gene

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

Genomics for TPH2 Gene

Regulatory Elements for TPH2 Gene

Enhancers for TPH2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH12H072293 0.9 FANTOM5 ENCODE 14.7 +357.0 357015 4.3 JUND FOS NFE2 MAFK NFE2L2 TRHDE TPH2 TRHDE-AS1 ENSG00000257287
GH12H072087 0.3 FANTOM5 31.1 +149.2 149199 0.2 TPH2 TRHDE GC12P072258
GH12H071972 0.6 ENCODE 11.6 +34.0 34030 0.2 NFIC LCORL NFIB SCRT2 REST RAD21 TPH2 ENSG00000258115
GH12H071780 0.6 ENCODE 11.3 -158.1 -158142 1.1 CTCF ZNF654 TRIM22 SMC3 ZNF143 REST RAD21 TBC1D15 RAB21 TPH2 ENSG00000257410
GH12H071787 0.6 ENCODE 10.4 -151.1 -151051 0.2 SMARCE1 ZNF766 SOX6 HMBOX1 NR2F2 SPI1 TBC1D15 TPH2 ENSG00000257410 RAB21
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around TPH2 on UCSC Golden Path with GeneCards custom track

Genomic Locations for TPH2 Gene

Genomic Locations for TPH2 Gene
247,773 bases
Plus strand

Genomic View for TPH2 Gene

Genes around TPH2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TPH2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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

Selected DME Specific Peptides for TPH2 Gene


Post-translational modifications for TPH2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for TPH2 Gene

ENSEMBL proteins:
REFSEQ proteins:

Domains & Families for TPH2 Gene

Gene Families for TPH2 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.
  • 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

Phenotypes From GWAS Catalog for TPH2 Gene

Gene Ontology (GO) - Molecular Function for TPH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004510 tryptophan 5-monooxygenase activity IEA --
GO:0005506 iron ion binding IEA --
GO:0016491 oxidoreductase activity 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 IEA --
GO:0046872 metal ion binding IEA --
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:

Clone Products

  • Addgene plasmids for TPH2

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

Localization for TPH2 Gene

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TPH2 gene
Compartment Confidence
cytosol 5
nucleus 3
extracellular 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 and Subcellular locations from the Human Protein Atlas (HPA) for TPH2 Gene

Pathways & Interactions for TPH2 Gene

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

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:0009072 aromatic amino acid family metabolic process IEA --
GO:0014823 response to activity IEA --
GO:0031667 response to nutrient levels IEA --
GO:0042427 serotonin biosynthetic process IEA --
genes like me logo Genes that share ontologies with TPH2: view

Drugs & Compounds for TPH2 Gene

(27) Drugs for TPH2 Gene - From: DrugBank, PharmGKB, ApexBio, DGIdb, IUPHAR, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
L-Tryptophan Approved, Withdrawn Nutra Positive, Allosteric regulator, Enzyme, substrate 0
Telotristat Approved Pharma Target, antagonist TPH inhibitor 0
Citalopram Approved Pharma 520
Mirtazapine Approved Pharma 95
Venlafaxine Approved Pharma Dual serotonin/noradrenalin re-uptake inhibitor 0

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

(4) Tocris Compounds for TPH2 Gene

Compound Action Cas Number
17-ODYA LTB omega-hydroxylase inhibitor 34450-18-5
DMOG Prolyl hydroxylase inhibitor 89464-63-1
Metyrapone 11-beta hydroxylase inhibitor 54-36-4
p-Chlorophenylalanine Tryptophan hydroxylase inhibitor 7424-00-2

(8) ApexBio Compounds for TPH2 Gene

Compound Action Cas Number
17-ODYA LTB4 ω-hydroxylase inhibitor 34450-18-5
LP533401 hcl Tph-1 inhibitor 1040526-12-2
LX1606 Tryptophan hydroxylase (TPH) inhibitor 1137608-69-5
Metyrapone 54-36-4
p-Chlorophenylalanine 7424-00-2
Ro 61-8048 199666-03-0
Telotristat TPH inhibitor 1033805-28-5
WWL 70 α/β-hydrolase domain 6 inhibitor 947669-91-2
genes like me logo Genes that share compounds with TPH2: view

Drug Products

Transcripts for TPH2 Gene

mRNA/cDNA for TPH2 Gene

(1) 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:

Clone Products

  • Addgene plasmids for TPH2

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 from GTEx, Illumina, BioGPS, and CGAP SAGE 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

Protein tissue co-expression partners for TPH2 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of TPH2 Gene:


SOURCE GeneReport for Unigene cluster for TPH2 Gene:


mRNA Expression by UniProt/SwissProt for TPH2 Gene:

Tissue specificity: Brain specific.

Evidence on tissue expression from TISSUES for TPH2 Gene

  • Nervous system(4.6)
  • Adrenal gland(2)
genes like me logo Genes that share expression patterns with TPH2: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for TPH2 Gene

Orthologs for TPH2 Gene

This gene was present in the common ancestor of animals.

Orthologs for TPH2 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia TPH2 33 34
  • 99.32 (n)
(Bos Taurus)
Mammalia TPH2 34
  • 90 (a)
(Rattus norvegicus)
Mammalia Tph2 33
  • 87.77 (n)
(Mus musculus)
Mammalia Tph2 33 16 34
  • 87.5 (n)
(Canis familiaris)
Mammalia TPH2 33 34
  • 84.83 (n)
(Ornithorhynchus anatinus)
Mammalia TPH2 34
  • 36 (a)
(Gallus gallus)
Aves TPH2 33 34
  • 81.15 (n)
(Anolis carolinensis)
Reptilia TPH2 34
  • 91 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia tph2 33
  • 74.16 (n)
(Danio rerio)
Actinopterygii tph2 33 34
  • 67.97 (n)
fruit fly
(Drosophila melanogaster)
Insecta Trh 34
  • 46 (a)
(Caenorhabditis elegans)
Secernentea tph-1 33 34
  • 58.58 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 62 (a)
Species where no ortholog for TPH2 was found in the sources mined by GeneCards:
  • 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
rs120074176 other, Attention deficit-hyperactivity disorder 7 (ADHD7) [MIM:613003] 71,979,053(+) ACATC(C/T)GGCAT reference, missense
rs11178998 Likely benign 71,938,935(+) CTGCT(A/G)CTGCC nc-transcript-variant, utr-variant-5-prime
rs139968591 Likely benign 71,944,686(+) CACCC(A/G)GTAAG nc-transcript-variant, reference, synonymous-codon
rs17110747 Likely benign 72,032,174(+) ACAAA(A/G)GTTCA utr-variant-3-prime
rs41317118 Likely benign 72,031,844(+) ACTGT(A/G)TTAGT utr-variant-3-prime

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

Variant ID Type Subtype PubMed ID
nsv826429 CNV loss 20364138
nsv826428 CNV loss 20364138
nsv821295 CNV deletion 20802225
nsv819959 CNV loss 19587683
nsv518498 CNV loss 19592680
nsv512284 CNV loss 21212237
nsv473226 CNV novel sequence insertion 20440878
nsv1068690 CNV deletion 25765185
nsv1054578 CNV loss 25217958
nsv1036178 CNV loss 25217958
esv996582 CNV deletion 20482838
esv9704 CNV loss 19470904
esv3629923 CNV loss 21293372
esv3629922 CNV loss 21293372
esv3580319 CNV loss 25503493
esv3580318 CNV loss 25503493
esv3549390 CNV deletion 23714750
esv3549389 CNV deletion 23714750
esv3280 CNV loss 18987735
esv3251940 CNV deletion 24192839
esv275101 CNV gain+loss 21479260
esv2746049 CNV deletion 23290073
esv2746048 CNV deletion 23290073
esv2746047 CNV deletion 23290073
esv2451960 CNV deletion 19546169
esv23023 CNV loss 19812545
esv2253374 CNV deletion 18987734
esv1137133 CNV deletion 17803354
esv1003596 CNV deletion 20482838
dgv832n106 CNV deletion 24896259
dgv47n73 CNV deletion 24416366
dgv301e199 CNV deletion 23128226
dgv295n67 CNV loss 20364138

Variation tolerance for TPH2 Gene

Residual Variation Intolerance Score: 28.8% 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

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

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

Disorders for TPH2 Gene

MalaCards: The human disease database

(19) MalaCards diseases for TPH2 Gene - From: HGMD, OMIM, GeneTests, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search TPH2 in MalaCards View complete list of genes associated with diseases


  • 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. {ECO:0000269 PubMed:15629698}. 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 VA … McMahon FJ (Biological psychiatry 2007) 3 22 25 45 60
  2. Involvement of tryptophan hydroxylase 2 (TPH2) gene polymorphisms in susceptibility to coronary artery lesions in Korean children with Kawasaki disease. (PMID: 19763617) Park SW … Chung JH (European journal of pediatrics 2010) 3 22 45 60
  3. Association of polymorphisms of the tryptophan hydroxylase 2 gene with risk for bipolar disorder or suicidal behavior. (PMID: 19800079) Campos SB … Correa H (Journal of psychiatric research 2010) 3 22 45 60
  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 CP … Reif A (European archives of psychiatry and clinical neuroscience 2010) 3 22 45 60
  5. Risk-taking behavior in a gambling task associated with variations in the tryptophan hydroxylase 2 gene: relevance to psychiatric disorders. (PMID: 20043001) Juhasz G … Anderson IM (Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 2010) 3 22 45 60

Products for TPH2 Gene

Sources for TPH2 Gene

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