TDO2 Gene

Name	tryptophan 2,3-dioxygenase
Description	This gene encodes a heme enzyme that plays a critical role in tryptophan metabolism by catalyzing the first and rate-limiting step of the kynurenine pathway. Increased activity of the encoded protein and subsequent kynurenine production may also play a role in cancer through the suppression of antitumor immune responses, and single nucleotide polymorphisms in this gene may be associated with autism. [provided by RefSeq, Feb 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTryptophan‐2,3‐dioxygenase (TDO2) is a heme‐dependent enzyme that catalyzes the oxidation of L‐tryptophan to N‐formylkynurenine—the first and rate‐limiting step of the kynurenine pathway. This enzymatic activity, which has been elucidated through structural, spectroscopic, and kinetic studies showing cooperative substrate binding and distinct stereoselectivity relative to other tryptophan‐degrading enzymes, plays a critical role in regulating both systemic and local tryptophan levels and generating bioactive metabolites that can activate receptors such as the aryl hydrocarbon receptor."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its catalytic function, TDO2‐derived kynurenine serves as a key immunomodulatory and neuroactive metabolite. Elevated or deregulated TDO2 expression has been implicated in promoting immune tolerance by depleting tryptophan and suppressing T‐cell proliferation, thereby facilitating tumor immune evasion. Aberrant TDO2 activity is reported in a wide range of pathological settings—including psychiatric disorders such as autism, various solid tumors (colorectal, esophageal, ovarian, pancreatic, melanoma, breast, and hepatocellular carcinomas), and even conditions linked to ethanol‐induced behavioral alterations—highlighting its role in driving malignant cell proliferation, invasion, metastasis, and the creation of an immunosuppressive microenvironment."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic investigations have further revealed that TDO2 function is precisely regulated—ranging from its cooperative subunit dynamics and substrate stereoselectivity to modulation by genetic polymorphisms and microRNAs (e.g., miR‑126‑5p). Therapeutic strategies targeting TDO2, including small‐molecule inhibitors, have shown promise in preclinical studies by disrupting downstream kynurenine–aryl hydrocarbon receptor signaling and reversing immunosuppressive states in the tumor microenvironment, although its activity may be diminished under hypoxic conditions. Collectively, these insights position TDO2 as a pivotal link between amino acid metabolism, immune regulation, and oncogenesis, and they suggest that TDO2 represents a promising target for innovative interventions across a spectrum of diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rafiqun Nabi, Fatema J Serajee, Diane C Chugani, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "TDO2 Was Downregulated in Hepatocellular Carcinoma and Inhibited Cell Proliferation by Upregulating the Expression of p21 and p27."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res Int (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2021/4708439"}], "href": "https://doi.org/10.1155/2021/4708439"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34423034"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34423034"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Heng Liang, Tianqi Li, Xin Fang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IDO1/TDO dual inhibitor RY103 targets Kyn-AhR pathway and exhibits preclinical efficacy on pancreatic cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2021.09.012"}], "href": "https://doi.org/10.1016/j.canlet.2021.09.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34520819"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34520819"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Yang Ai, Sang Luo, Ben Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-126-5p Promotes Tumor Cell Proliferation, Metastasis and Invasion by Targeting TDO2 in Hepatocellular Carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Molecules (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/molecules27020443"}], "href": "https://doi.org/10.3390/molecules27020443"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35056756"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35056756"}]}]}]}
Synonyms	TRPO, TPH2, HYPTRP, TO
Proteins	T23O_HUMAN
NCBI Gene ID	6999
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TDO2 has 6,038 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 115 datasets.

Click the + buttons to view associations for TDO2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

TDO2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of TDO2 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 TDO2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of TDO2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of TDO2 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 TDO2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of TDO2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of TDO2 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 TDO2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of TDO2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of TDO2 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 TDO2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with TDO2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of TDO2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TDO2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of TDO2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of TDO2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing TDO2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing TDO2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing TDO2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with TDO2 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 TDO2 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 TDO2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TDO2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with TDO2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with TDO2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by TDO2 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 TDO2 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 TDO2 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 TDO2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with TDO2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for TDO2 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at TDO2 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 TDO2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TDO2 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 TDO2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with TDO2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with TDO2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of TDO2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with TDO2 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 TDO2 from the GeneSigDB Published Gene Signatures dataset.