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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
  • NTPH 3 4
  • Tryptophan 5-Hydroxylase 2 3
  • Tryptophan 5-Monooxygenase 2
  • EC 4
  • 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 Depression. Among its related pathways are Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways and Amine-derived hormones. Gene Ontology (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

GeneHancer (GH) Regulatory Elements for TPH2 Gene

Promoters and enhancers for TPH2 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH12J071938 Promoter/Enhancer 1.4 EPDnew ENCODE 650.7 +0.0 37 0.2 ARNT ZFP64 ARID4B SIN3A ZNF48 SLC30A9 ZNF766 CBX5 ZNF213 ZNF143 TPH2 ENSG00000258115
GH12J072293 Enhancer 0.8 FANTOM5 ENCODE 14.7 +357.0 357014 4.3 JUND NFE2 FOS MAFK NFE2L2 TRHDE TPH2 TRHDE-AS1 ENSG00000257287
GH12J072088 Enhancer 0.3 FANTOM5 31.1 +149.2 149199 0.2 TRHDE TPH2 GC12P072258
GH12J071780 Enhancer 0.6 ENCODE 11.3 -158.1 -158142 1.1 CTCF ZNF654 TRIM22 REST ELF1 RAD21 SMC3 ZNF143 TBC1D15 RAB21 TPH2 ENSG00000257410
GH12J071972 Enhancer 0.5 ENCODE 11.6 +34.0 34030 0.2 LCORL NFIC NFIB SCRT2 REST RAD21 TPH2 ENSG00000258115
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TPH2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the TPH2 gene promoter:
  • NRSF form 2
  • NRSF form 1
  • SEF-1 (1)
  • POU3F2
  • POU3F2 (N-Oct-5a)
  • POU3F2 (N-Oct-5b)
  • Sox5

Genomic Locations for TPH2 Gene

Genomic Locations for TPH2 Gene
247,773 bases
Plus strand
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

Post-translational modifications for TPH2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for TPH2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for TPH2 Gene

Domains & Families for TPH2 Gene

Gene Families for TPH2 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • FDA approved 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 CatalyticActivity:
L-tryptophan + tetrahydrobiopterin + O(2) = 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin.
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};

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:

Animal Model Products

  • Taconic Biosciences Mouse Models 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

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

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
L-Tryptophan Approved, Withdrawn Nutra Positive, Allosteric regulator, Inhibition, Inhibitor, Enzyme, substrate 0
Metyrapone Approved, Investigational Pharma 11-beta hydroxylase inhibitor 13
Fenfluramine Approved, Illicit, Investigational, Withdrawn Pharma Inhibition, Inhibitor, antagonist 12
Telotristat ethyl Approved, Investigational Pharma Target, antagonist 0
Citalopram Approved Pharma 526

(7) 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
  • 6,7-Dihydrobiopterin
  • Quinoid-dihydrobiopterin
  • (6R)-6-(L-erythro-1,2-Dihydroxypropyl)-7,8-dihydro-6H-pterin
  • 1,3,5-Benzenetriol
  • 1,3,5-Trihydroxybenzene
  • (6R)-6-(L-erythro-1,2-Dihydroxypropyl)-5,6,7,8-tetrahydro-4a-hydroxypterin
  • 4a-Hydroxy-5,6,4,8-tetrahydrobiopterin
  • 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
  • FE (II) ion
  • Fe(II)
  • Fe(2+)
  • Ferrous ion
  • Iron ion(2+)

(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
genes like me logo Genes that share compounds with TPH2: view

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 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 34 33
  • 99.32 (n)
(Bos Taurus)
Mammalia TPH2 34
  • 90 (a)
(Rattus norvegicus)
Mammalia Tph2 33
  • 87.77 (n)
(Mus musculus)
Mammalia Tph2 16 34 33
  • 87.5 (n)
(Canis familiaris)
Mammalia TPH2 34 33
  • 84.83 (n)
(Ornithorhynchus anatinus)
Mammalia TPH2 34
  • 36 (a)
(Gallus gallus)
Aves TPH2 34 33
  • 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 34 33
  • 67.97 (n)
fruit fly
(Drosophila melanogaster)
Insecta Trh 34
  • 46 (a)
(Caenorhabditis elegans)
Secernentea tph-1 34 33
  • 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)
Evolutionary constrained regions (ECRs) for TPH2: view image

Paralogs for TPH2 Gene

Paralogs for TPH2 Gene

(3) SIMAP similar genes for TPH2 Gene using alignment to 13 proteins:

  • B3VS15_HUMAN
  • B3VS20_HUMAN
  • B3VS25_HUMAN
  • B3VS30_HUMAN
  • B3VS35_HUMAN
  • B3VS40_HUMAN
  • B3VS45_HUMAN
  • B3VS50_HUMAN
  • B3VS55_HUMAN
  • B3VS60_HUMAN
  • B3VS65_HUMAN
  • Q14CC5_HUMAN
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 Variation AA Info Type
rs11178998 likely-benign, Tryptophan 5-monooxygenase deficiency 71,938,935(+) A/G 5_prime_UTR_variant, non_coding_transcript_variant
rs120074175 risk-factor, Unipolar depression, susceptibility to 72,031,544(+) G/A coding_sequence_variant, genic_downstream_transcript_variant, missense_variant
rs120074176 risk-factor, Attention deficit-hyperactivity disorder 7, Attention deficit-hyperactivity disorder 7 (ADHD7) [MIM:613003] 71,979,053(+) C/T coding_sequence_variant, genic_downstream_transcript_variant, missense_variant
rs139968591 likely-benign, Tryptophan 5-monooxygenase deficiency 71,944,686(+) A/G coding_sequence_variant, non_coding_transcript_variant, synonymous_variant
rs146131690 uncertain-significance, Tryptophan 5-monooxygenase deficiency 72,032,426(+) G/C 3_prime_UTR_variant, genic_downstream_transcript_variant

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

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

Additional Variant Information for TPH2 Gene

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

SNP Genotyping and Copy Number Assay Products

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

Disorders for TPH2 Gene

MalaCards: The human disease database

(21) MalaCards diseases for TPH2 Gene - From: HGMD, OMIM, ClinVar, GTR, DISEASES, Novoseek, and GeneCards

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


  • 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.
  • 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.

Additional Disease Information for TPH2

Genetic Association Database
Human Genome Epidemiology 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 44 58
  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 44 58
  3. 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 44 58
  4. Simultaneous analysis of serotonin transporter, tryptophan hydroxylase 1 and 2 gene expression in the ventral prefrontal cortex of suicide victims. (PMID: 20052688) Perroud N … Guipponi M (American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2010) 3 22 44 58
  5. Alternative splicing and extensive RNA editing of human TPH2 transcripts. (PMID: 20126463) Grohmann M … Walther DJ (PloS one 2010) 3 4 22 58

Products for TPH2 Gene

Sources for TPH2 Gene

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