TPH2 Gene

Name tryptophan hydroxylase 2
Description 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]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTryptophan hydroxylase‐2 (TPH2) is the brain‐exclusive, rate‐limiting enzyme for serotonin biosynthesis. Multiple studies have detailed its biochemical and regulatory features – for example, a loss‐of‐function mutation (G1463A) that slashes serotonin production by around 80% illustrates its pivotal catalytic role."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Brain‐selective expression of TPH2, undetectable in peripheral tissues, further emphasizes its central role in neuromodulation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", with postmortem examinations confirming its unique distribution and absence of compensatory expression of the non‐neuronal isoform."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In depressed suicide cases, elevated TPH2 expression in the dorsal raphe suggests a compensatory upregulation in response to serotonin deficiency"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", while regulatory studies indicate that vitamin D–mediated mechanisms via vitamin D–responsive elements can significantly induce TPH2 expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In vitro investigations also show that the TPH2 promoter and 5′-UTR, including evidence of allelic mRNA imbalances and RNA editing, play critical roles in dictating gene expression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "11"}]}, {"type": "t", "text": " Moreover, analyses of alternative splicing and RNA editing have revealed additional layers of TPH2 regulation that modulate enzyme activity in the human brain"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", and even observations from serotonergic anomalies in conditions such as sudden infant death syndrome provide further context"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": ").\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies of TPH2 have linked common polymorphisms to an array of psychiatric phenotypes. Candidate gene meta‐analyses and family–based association studies in attention–deficit/hyperactivity disorder (ADHD) have flagged TPH2 variants as showing significant, though heterogeneous, associations."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "20"}]}, {"type": "t", "text": " Beyond ADHD, TPH2 variants have been repeatedly implicated in mood disorders: associations with major depression and bipolar disorder – including functionally detrimental substitutions like Pro206Ser that compromise enzyme stability – underline its contribution to affective dysregulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "31"}]}, {"type": "t", "text": " These findings support a model in which TPH2 gene variation can predispose individuals to affective disturbances, suicidal behavior, and even aspects of impulse control.\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA complementary body of research has focused on how TPH2 variability influences neural circuits and clinical responses. Functional magnetic resonance imaging and electrophysiological paradigms have shown that regulatory variants in TPH2 – such as the G(–703)T polymorphism – modulate amygdala reactivity to emotional stimuli, with measurable impacts on both negative and positive affect."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "32", "end_ref": "35"}]}, {"type": "t", "text": " Reviews and studies on treatment response further suggest that TPH2 polymorphisms may influence antidepressant outcomes and even placebo responsiveness"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "36"}]}, {"type": "t", "text": ", while electrophysiological recordings have identified additive effects of TPH2 and other serotonergic genes on early neural processing of emotional information."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "37", "end_ref": "39"}]}, {"type": "t", "text": " Additionally, TPH2 variants have been linked to altered decision-making and cognitive control in tasks assessing executive function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "40", "end_ref": "45"}]}, {"type": "t", "text": " Finally, studies in specific populations – such as Korean women with social anxiety – underscore how TPH2 variation can affect amygdala responsiveness, with broader implications for understanding the neural basis of anxiety disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "46"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xiaodong Zhang, Raul R Gainetdinov, Jean-Martin Beaulieu, et al. 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Synonyms NTPH, ADHD7
Proteins TPH2_HUMAN
NCBI Gene ID 121278
API
Download Associations
Predicted Functions View TPH2's ARCHS4 Predicted Functions.
Co-expressed Genes View TPH2's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View TPH2's ARCHS4 Predicted Functions.

Functional Associations

TPH2 has 4,361 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 91 datasets.

Click the + buttons to view associations for TPH2 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles tissues with high or low expression of TPH2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles tissues with high or low expression of TPH2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray tissue samples with high or low expression of TPH2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles tissues with high or low expression of TPH2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
BioGPS Human Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of TPH2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
BioGPS Mouse Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of TPH2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of TPH2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
CCLE Cell Line Gene Expression Profiles cell lines with high or low expression of TPH2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
ChEA Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of TPH2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of TPH2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores cellular components containing TPH2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 cellular components containing TPH2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores cellular components co-occuring with TPH2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 cellular components co-occuring with TPH2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
COSMIC Cell Line Gene CNV Profiles cell lines with high or low copy number of TPH2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with TPH2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
CTD Gene-Chemical Interactions chemicals interacting with TPH2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
CTD Gene-Disease Associations diseases associated with TPH2 gene/protein from the curated CTD Gene-Disease Associations dataset.
dbGAP Gene-Trait Associations traits associated with TPH2 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
DepMap CRISPR Gene Dependency cell lines with fitness changed by TPH2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores diseases co-occuring with TPH2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with TPH2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
DisGeNET Gene-Disease Associations diseases associated with TPH2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
DisGeNET Gene-Phenotype Associations phenotypes associated with TPH2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
DrugBank Drug Targets interacting drugs for TPH2 protein from the curated DrugBank Drug Targets dataset.
ENCODE Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at TPH2 gene from the ENCODE Histone Modification Site Profiles dataset.
ENCODE Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of TPH2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of TPH2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
ESCAPE Omics Signatures of Genes and Proteins for Stem Cells PubMedIDs of publications reporting gene signatures containing TPH2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
GAD Gene-Disease Associations diseases associated with TPH2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
GAD High Level Gene-Disease Associations diseases associated with TPH2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with TPH2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
GeneSigDB Published Gene Signatures PubMedIDs of publications reporting gene signatures containing TPH2 from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Diseases disease perturbations changing expression of TPH2 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
GEO Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of TPH2 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Kinase Perturbations kinase perturbations changing expression of TPH2 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of TPH2 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations transcription factor perturbations changing expression of TPH2 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Viral Infections virus perturbations changing expression of TPH2 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GO Biological Process Annotations 2015 biological processes involving TPH2 gene from the curated GO Biological Process Annotations 2015 dataset.
GO Cellular Component Annotations 2015 cellular components containing TPH2 protein from the curated GO Cellular Component Annotations 2015 dataset.
GO Cellular Component Annotations 2025 cellular components containing TPH2 protein from the curated GO Cellular Component Annotations 2025 dataset.
GO Molecular Function Annotations 2015 molecular functions performed by TPH2 gene from the curated GO Molecular Function Annotations 2015 dataset.
GO Molecular Function Annotations 2025 molecular functions performed by TPH2 gene from the curated GO Molecular Function Annotations 2025 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of TPH2 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
Guide to Pharmacology Chemical Ligands of Receptors ligands (chemical) binding TPH2 receptor from the curated Guide to Pharmacology Chemical Ligands of Receptors dataset.
GWAS Catalog SNP-Phenotype Associations phenotypes associated with TPH2 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations dataset.
GWASdb SNP-Disease Associations diseases associated with TPH2 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset.
GWASdb SNP-Phenotype Associations phenotypes associated with TPH2 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset.
Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles cell lines with high or low expression of TPH2 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset.
HMDB Metabolites of Enzymes interacting metabolites for TPH2 protein from the curated HMDB Metabolites of Enzymes dataset.
HPA Tissue Gene Expression Profiles tissues with high or low expression of TPH2 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset.
HPA Tissue Protein Expression Profiles tissues with high or low expression of TPH2 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset.
Hub Proteins Protein-Protein Interactions interacting hub proteins for TPH2 from the curated Hub Proteins Protein-Protein Interactions dataset.
HuBMAP ASCT+B Annotations cell types associated with TPH2 gene from the HuBMAP ASCT+B dataset.
HuBMAP ASCT+B Augmented with RNA-seq Coexpression cell types associated with TPH2 gene from the HuBMAP ASCT+B Augmented with RNA-seq Coexpression dataset.
HuGE Navigator Gene-Phenotype Associations phenotypes associated with TPH2 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset.
HumanCyc Pathways pathways involving TPH2 protein from the HumanCyc Pathways dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for TPH2 protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of TPH2 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
KEA Substrates of Kinases kinases that phosphorylate TPH2 protein from the curated KEA Substrates of Kinases dataset.
KEGG Pathways pathways involving TPH2 protein from the KEGG Pathways dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of TPH2 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
KnockTF Gene Expression Profiles with Transcription Factor Perturbations transcription factor perturbations changing expression of TPH2 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain TPH2 protein from the LOCATE Predicted Protein Localization Annotations dataset.
MGI Mouse Phenotype Associations 2023 phenotypes of transgenic mice caused by TPH2 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset.
MotifMap Predicted Transcription Factor Targets transcription factors regulating expression of TPH2 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset.
MPO Gene-Phenotype Associations phenotypes of transgenic mice caused by TPH2 gene mutations from the MPO Gene-Phenotype Associations dataset.
OMIM Gene-Disease Associations phenotypes associated with TPH2 gene from the curated OMIM Gene-Disease Associations dataset.
PANTHER Pathways pathways involving TPH2 protein from the PANTHER Pathways dataset.
Pathway Commons Protein-Protein Interactions interacting proteins for TPH2 from the Pathway Commons Protein-Protein Interactions dataset.
PFOCR Pathway Figure Associations 2023 pathways involving TPH2 protein from the PFOCR Pathway Figure Associations 2023 dataset.
PFOCR Pathway Figure Associations 2024 pathways involving TPH2 protein from the Wikipathways PFOCR 2024 dataset.
Phosphosite Textmining Biological Term Annotations biological terms co-occuring with TPH2 protein in abstracts of publications describing phosphosites from the Phosphosite Textmining Biological Term Annotations dataset.
PhosphoSitePlus Substrates of Kinases kinases that phosphorylate TPH2 protein from the curated PhosphoSitePlus Substrates of Kinases dataset.
Reactome Pathways 2014 pathways involving TPH2 protein from the Reactome Pathways dataset.
Reactome Pathways 2024 pathways involving TPH2 protein from the Reactome Pathways 2024 dataset.
Roadmap Epigenomics Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at TPH2 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of TPH2 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of TPH2 gene from the RummaGEO Gene Perturbation Signatures dataset.
TargetScan Predicted Conserved microRNA Targets microRNAs regulating expression of TPH2 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of TPH2 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset.
TCGA Signatures of Differentially Expressed Genes for Tumors tissue samples with high or low expression of TPH2 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores tissues with high expression of TPH2 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of TPH2 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores tissues with high expression of TPH2 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 tissues with high expression of TPH2 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with TPH2 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with TPH2 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.
WikiPathways Pathways 2014 pathways involving TPH2 protein from the Wikipathways Pathways 2014 dataset.
WikiPathways Pathways 2024 pathways involving TPH2 protein from the WikiPathways Pathways 2024 dataset.