TDO2 Gene: Tryptophan 2,3-Dioxygenase
Key enzyme in tryptophan catabolism and immune regulation
Gene Information Card
| Symbol | TDO2 |
|---|---|
| Full Name | tryptophan 2,3-dioxygenase |
| Gene Type | protein-coding |
| Chromosomal Location | 4q32.1 |
| NCBI Gene ID | 6999 ncbi.nlm.nih.gov/gene/6999 |
| Ensembl ID | ENSG00000100100 |
| UniProt ID | P48775 |
| OMIM ID | 191070 |
| HGNC ID | 11708 |
| Aliases | TDO, TPH2, TRPO |
Description
TDO2 encodes tryptophan 2,3-dioxygenase, the first and rate-limiting enzyme in the kynurenine pathway of tryptophan catabolism. It converts L-tryptophan to N-formylkynurenine. TDO2 is primarily expressed in the liver and plays a critical role in regulating systemic tryptophan levels. Dysregulation of TDO2 is implicated in cancer immune evasion, neurological disorders, and metabolic diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| TDO2 deficiency (tryptophanuria with dwarfism) | Loss-of-function mutations reduce tryptophan degradation, leading to elevated tryptophan and growth abnormalities. | OMIM #191070, case reports |
| Cancer (various) | Overexpression in tumors depletes local tryptophan, suppressing T-cell responses via kynurenine-AhR axis. | COSMIC, literature review |
| Huntington disease | Altered TDO2 activity may contribute to kynurenine pathway imbalance and neurotoxicity. | NCBI Gene, PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 45.2 | High |
| Brain | 1.8 | Low |
| Lung | 0.5 | Not detected |
| Kidney | 0.3 | Not detected |
| Heart | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 62.1 | Hepatocellular carcinoma cell line |
| HEK293 | 0.8 | Embryonic kidney cells |
| A549 | 0.2 | Lung carcinoma |
| MCF7 | 0.1 | Breast cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.100C>T (p.Arg34*) | Nonsense | Rare | Loss of function; associated with TDO2 deficiency |
| c.403G>A (p.Gly135Arg) | Missense | Rare | Loss of function; reduced enzyme activity |
| c.829C>T (p.Arg277Trp) | Missense | Rare | Loss of function; impaired substrate binding |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., p.Arg34*, p.Gly135Arg) reduce or abolish enzyme activity, leading to TDO2 deficiency.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in TDO2.
Dominant Negative (DN)
No evidence of dominant-negative effects for TDO2 mutations.
View complete mutation data：
Gene Ontology (GO)
| • tryptophan 2 (GO:0004833) | • tryptophan catabolic process (GO:0006569) |
| • cytoplasm (GO:0005737) | • cytosol (GO:0005829) |
| • kynurenine metabolic process (GO:0019443) |
Pathways
• KEGG: hsa00380 – Tryptophan metabolism
• Reactome: R-HSA-71240 – Tryptophan catabolism
• WikiPathways: WP465 – Tryptophan metabolism
Protein Summary
TDO2 is a 406-amino-acid heme-containing dioxygenase that exists as a homotetramer. It catalyzes the oxidative cleavage of the indole ring of L-tryptophan to form N-formylkynurenine. The enzyme is allosterically regulated by tryptophan and inhibited by nicotinamide adenine dinucleotide (NAD+). TDO2 is predominantly expressed in the liver and is induced by glucocorticoids and tryptophan. Its activity is critical for maintaining tryptophan homeostasis and modulating immune responses via the kynurenine pathway.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TDO2 Knockout HEK293 Cell Line | EDJ-KQ2779 | Human | 6999 | Details Get a Quote |
| TDO2 Knockout A-549 Cell Line | EDJ-KQ23694 | Human | 6999 | Details Get a Quote |
| TDO2 Knockout HeLa Cell Line | EDJ-KQ54638 | Human | 6999 | Details Get a Quote |
| TDO2 Knockout HCT 116 Cell Line | EDJ-KQ71591 | Human | 6999 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
