This gene encodes a member of the aromatic amino 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 have been associated with an elevated risk for a variety of diseases and disorders, including schizophrenia, somatic anxiety, anger-related tra... See more...

Aliases for TPH1 Gene

Aliases for TPH1 Gene

  • Tryptophan Hydroxylase 1 2 3 5
  • Tryptophan Hydroxylase (Tryptophan 5-Monooxygenase) 2 3
  • Tryptophan 5-Monooxygenase 1 3 4
  • Tryptophan 5-Hydroxylase 1 3 4
  • EC 4 50
  • TPRH 3 4
  • TRPH 3 4
  • Indoleacetic Acid-5-Hydroxylase 3
  • Tryptophan 5-Monooxygenase 2
  • L-Tryptophan Hydroxylase 3
  • EC 1.14.16 50
  • TPH1 5
  • TPH 4

External Ids for TPH1 Gene

Previous HGNC Symbols for TPH1 Gene

  • TPRH
  • TPH

Previous GeneCards Identifiers for TPH1 Gene

  • GC11M018984
  • GC11M018081
  • GC11M018006
  • GC11M018005
  • GC11M017997
  • GC11M017724

Summaries for TPH1 Gene

Entrez Gene Summary for TPH1 Gene

  • This gene encodes a member of the aromatic amino 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 have been associated with an elevated risk for a variety of diseases and disorders, including schizophrenia, somatic anxiety, anger-related traits, bipolar disorder, suicidal behavior, addictions, and others.[provided by RefSeq, Apr 2009]

GeneCards Summary for TPH1 Gene

TPH1 (Tryptophan Hydroxylase 1) is a Protein Coding gene. Diseases associated with TPH1 include Personality Disorder and Anxiety. Among its related pathways are Amine-derived hormones and Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics. 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 TPH2.

Tocris Summary for TPH1 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 TPH1 Gene

No data available for CIViC Summary , UniProtKB/Swiss-Prot Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TPH1 Gene

Genomics for TPH1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TPH1 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
GH11J018046 Promoter 0.5 EPDnew 250.7 0.0 -20 0.1 ZFHX2 EZH2 HSALNG0082970 HSALNG0082971 TPH1 SERGEF SAAL1
GH11J018105 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 4.8 -59.2 -59232 2.6 BCLAF1 SP1 ZNF207 NCOR1 MYC ZNF600 ZNF580 POLR2A NFIC ZBTB10 SAAL1 HIGD1AP5 lnc-SAAL1-2 lnc-MRGPRX3-1 GTF2H1 SPTY2D1 MRGPRX3 ENSG00000256282 TSG101 ENSG00000256361
GH11J018143 Enhancer 0.4 ENCODE 4.5 -98.0 -98021 1.4 JUND BHLHE40 CTCF ENSG00000285562 MRGPRX3 TPH1 lnc-MRGPRX3-2 MRGPRX4 ENSG00000255470
GH11J018080 Enhancer 0.3 Ensembl 4.8 -35.1 -35132 1.2 NFIC NFIB SAAL1 SERGEF TPH1 lnc-TPH1-1 lnc-MRGPRX3-3 lnc-SAAL1-2
GH11J018135 Enhancer 0.2 Ensembl 6.5 -87.3 -87332 0.4 MRGPRX3 MRGPRX13P SLC25A51P4 GLTPP1 ENSG00000255470 TPH1 ENSG00000285562 piR-57195-048 MRGPRX4
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TPH1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TPH1

Top Transcription factor binding sites by QIAGEN in the TPH1 gene promoter:
  • TBP

Genomic Locations for TPH1 Gene

Latest Assembly
28,715 bases
Minus strand

Previous Assembly
(GRCh37/hg19 by Entrez Gene)
28,715 bases
Minus strand

(GRCh37/hg19 by Ensembl)
24,863 bases
Minus strand

Genomic View for TPH1 Gene

Genes around TPH1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TPH1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TPH1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TPH1 Gene

Proteins for TPH1 Gene

  • Protein details for TPH1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Tryptophan 5-hydroxylase 1
    Protein Accession:
    Secondary Accessions:
    • D3DQX6
    • O95188
    • O95189
    • Q16736
    • Q3KPG8

    Protein attributes for TPH1 Gene

    444 amino acids
    Molecular mass:
    50985 Da
    Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
    Quaternary structure:
    • Homotetramer.

    Three dimensional structures from OCA and Proteopedia for TPH1 Gene

    Alternative splice isoforms for TPH1 Gene


neXtProt entry for TPH1 Gene

Selected DME Specific Peptides for TPH1 Gene


Post-translational modifications for TPH1 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for TPH1 Gene

Antibodies for research

Domains & Families for TPH1 Gene

Gene Families for TPH1 Gene

Human Protein Atlas (HPA):
  • Enzymes
  • FDA approved drug targets
  • Predicted intracellular proteins

Protein Domains for TPH1 Gene

Suggested Antigen Peptide Sequences for TPH1 Gene

GenScript: Design optimal peptide antigens:
  • Tryptophan hydroxylase 1 (B3VRW5_HUMAN)
  • Tryptophan hydroxylase 1 (B3VRX0_HUMAN)
  • Tryptophan hydroxylase 1 (B3VRX5_HUMAN)
  • Tryptophan hydroxylase 1 (B3VRY0_HUMAN)
  • Tryptophan hydroxylase 1 (B3VRY5_HUMAN)

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 TPH1: view

Function for TPH1 Gene

Molecular function for TPH1 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tryptophan + O2 = (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin + 5-hydroxy-L-tryptophan; Xref=Rhea:RHEA:16709, ChEBI:CHEBI:15379, ChEBI:CHEBI:15642, ChEBI:CHEBI:57912, ChEBI:CHEBI:58266, ChEBI:CHEBI:59560; EC=;.

Enzyme Numbers (IUBMB) for TPH1 Gene

Phenotypes From GWAS Catalog for TPH1 Gene

Gene Ontology (GO) - Molecular Function for TPH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004497 monooxygenase activity IEA --
GO:0004510 tryptophan 5-monooxygenase activity IBA 21873635
GO:0005506 iron ion binding IEA --
GO:0005515 protein binding IPI 32296183
GO:0016491 oxidoreductase activity IEA --
genes like me logo Genes that share ontologies with TPH1: view
genes like me logo Genes that share phenotypes with TPH1: view

Animal Models for TPH1 Gene

MGI Knock Outs for TPH1:

Animal Models for research

  • Taconic Biosciences Mouse Models for TPH1

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TPH1

No data available for Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for TPH1 Gene

Localization for TPH1 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 TPH1 gene
Compartment Confidence
cytosol 5
nucleus 3
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for TPH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
GO:0043005 neuron projection IEA,IBA 21873635
genes like me logo Genes that share ontologies with TPH1: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for TPH1 Gene

Pathways & Interactions for TPH1 Gene

genes like me logo Genes that share pathways with TPH1: view

UniProtKB/Swiss-Prot P17752-TPH1_HUMAN

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

SIGNOR curated interactions for TPH1 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for TPH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007623 circadian rhythm IEA --
GO:0009072 aromatic amino acid family metabolic process IEA --
GO:0030279 negative regulation of ossification IEA --
GO:0035902 response to immobilization stress IEA --
GO:0042427 serotonin biosynthetic process IEA --
genes like me logo Genes that share ontologies with TPH1: view

Drugs & Compounds for TPH1 Gene

(67) Drugs for TPH1 Gene - From: DrugBank, PharmGKB, ApexBio, DGIdb, IUPHAR, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Tetrahydrobiopterin Approved, Investigational Pharma Target, cofactor 0
Fenfluramine Approved, Illicit, Investigational, Withdrawn Pharma Inhibitor, Inhibition, antagonist 18
Tryptophan Approved, Withdrawn Nutra Enzyme, substrate 106
Metyrapone Approved, Investigational Pharma 11-beta hydroxylase inhibitor 15
Citalopram Approved Pharma 613

(27) Additional Compounds for TPH1 Gene - From: Novoseek, IUPHAR, and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Inhibitor, Inhibition
4a-Carbinolamine tetrahydrobiopterin
  • (6R)-2-Amino-6-[(1R,2S)-1,2-dihydroxypropyl]-7,8-dihydro-6H-pteridin-4-one
  • (6R)-6-[(1R,2S)-1,2-Dihydroxypropyl]-7,8-dihydro-6H-pterin
  • 6,7-Dihydrobiopterin
  • Q-H2BPT
  • Quinoid-dihydrobiopterin
  • (4AS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin
  • (6R)-6-(L-Erythro-1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4a-hydroxypterin
  • 4a-Hydroxy-5,6,4,8-tetrahydrobiopterin
  • 4a-HTHB
  • 4a-Hydroxy-5,6,7,8-tetrahydrobiopterin

(4) Tocris Compounds for TPH1 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

(7) ApexBio Compounds for TPH1 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
genes like me logo Genes that share compounds with TPH1: view

Drug products for research

Transcripts for TPH1 Gene

mRNA/cDNA for TPH1 Gene

7 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TPH1

Alternative Splicing Database (ASD) splice patterns (SP) for TPH1 Gene

No ASD Table

Relevant External Links for TPH1 Gene

GeneLoc Exon Structure for

Expression for TPH1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TPH1 Gene

mRNA differential expression in normal tissues according to GTEx for TPH1 Gene

This gene is overexpressed in Artery - Aorta (x14.1).

Protein differential expression in normal tissues from HIPED for TPH1 Gene

This gene is overexpressed in Brain (34.1), Spleen (18.7), and Liver (13.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for TPH1 Gene

Protein tissue co-expression partners for TPH1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TPH1

SOURCE GeneReport for Unigene cluster for TPH1 Gene:


mRNA Expression by UniProt/SwissProt for TPH1 Gene:

Tissue specificity: Isoform 2 seems to be less widely expressed than isoform 1.

Evidence on tissue expression from TISSUES for TPH1 Gene

  • Nervous system(4.8)
  • Intestine(2.6)
  • Adrenal gland(2.6)
  • Kidney(2.2)
  • Blood(2.2)
  • Pancreas(2.2)
  • Stomach(2.2)
  • Muscle(2.2)
  • Spleen(2.1)
  • Liver(2.1)
  • Skin(2.1)
  • Heart(2)
genes like me logo Genes that share expression patterns with TPH1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Phenotype-based relationships between genes and organs from Gene ORGANizer for TPH1 Gene

Orthologs for TPH1 Gene

This gene was present in the common ancestor of animals.

Orthologs for TPH1 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia TPH1 29 30
  • 99.85 (n)
(Canis familiaris)
Mammalia TPH1 29 30
  • 93.84 (n)
(Bos Taurus)
Mammalia TPH1 29 30
  • 93.24 (n)
(Rattus norvegicus)
Mammalia Tph1 29
  • 86.71 (n)
(Mus musculus)
Mammalia Tph1 29 16 30
  • 85.81 (n)
(Ornithorhynchus anatinus)
Mammalia TPH1 30
  • 85 (a)
(Monodelphis domestica)
Mammalia TPH1 30
  • 83 (a)
(Gallus gallus)
Aves TPH1 29 30
  • 80.2 (n)
(Anolis carolinensis)
Reptilia TPH1 30
  • 75 (a)
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia LOC100497239 29
  • 73.74 (n)
African clawed frog
(Xenopus laevis)
Amphibia tph1 29
(Danio rerio)
Actinopterygii tph1a 29 30
  • 70.46 (n)
tph1b 30
  • 70 (a)
tph 29
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP006020 29
  • 59.13 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta Trh 29 30
  • 58.51 (n)
(Caenorhabditis elegans)
Secernentea tph-1 30
  • 41 (a)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 63 (a)
Species where no ortholog for TPH1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • 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 Vase (Ciona intestinalis)
  • 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 TPH1 Gene

Gene Tree for TPH1 (if available)
Gene Tree for TPH1 (if available)
Evolutionary constrained regions (ECRs) for TPH1: view image
Alliance of Genome Resources:
Additional Orthologs for TPH1

Paralogs for TPH1 Gene

Paralogs for TPH1 Gene

(3) SIMAP similar genes for TPH1 Gene using alignment to 14 proteins:

  • B3VS00_HUMAN
  • B3VS05_HUMAN
  • B3VS10_HUMAN
  • E9PR49_HUMAN
  • Q08EN2_HUMAN
genes like me logo Genes that share paralogs with TPH1: view

Variants for TPH1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TPH1 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
rs143049345 Likely Benign: not provided 18,021,050(-) G/C
NM_004179.3(TPH1):c.1276C>G (p.His426Asp)
rs146455709 Benign: not provided 18,036,028(-) G/A
NM_004179.3(TPH1):c.232C>T (p.His78Tyr)
rs56151798 Benign: not provided 18,022,863(-) A/G
NM_004179.3(TPH1):c.1095T>C (p.Leu365=)

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for TPH1 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for TPH1 Gene

Variant ID Type Subtype PubMed ID
esv3625482 CNV loss 21293372
nsv832079 CNV loss 17160897

Variation tolerance for TPH1 Gene

Residual Variation Intolerance Score: 44.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.68; 46.06% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TPH1 Gene

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

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TPH1 Gene

Disorders for TPH1 Gene

MalaCards: The human disease database

(55) MalaCards diseases for TPH1 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
personality disorder
  • character disorder
  • anxiety disorder
bipolar disorder
  • bipolar depression
generalized anxiety disorder
  • anxiety generalized
major depressive disorder
  • mdd
- elite association - COSMIC cancer census association via MalaCards
Search TPH1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for TPH1

Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with TPH1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TPH1 Gene

Publications for TPH1 Gene

  1. Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin. (PMID: 12379098) Wang L … Stevens RC (Biochemistry 2002) 3 4 22 25
  2. 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 40
  3. Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder. (PMID: 18982004) Kato M … Serretti A (Molecular psychiatry 2010) 3 22 40
  4. The tryptophan hydroxylase 1 (TPH1) gene, schizophrenia susceptibility, and suicidal behavior: a multi-centre case-control study and meta-analysis. (PMID: 19526457) Saetre P … Jönsson EG (American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2010) 3 22 40
  5. Fluoxetine response in impulsive-aggressive behavior and serotonin transporter polymorphism in personality disorder. (PMID: 20010449) Silva H … Bustamante ML (Psychiatric genetics 2010) 3 22 40

Products for TPH1 Gene

Sources for TPH1 Gene