TDO2 (tryptophan 2,3-dioxygenase)

Gene

• Entrez ID: 6999
• Gene name: Tryptophan 2,3-dioxygenase
• Gene symbol: TDO2
• Synonyms: HYPTRP, TDO, TO, TPH2, TRPO
• Chromosome: 4
• Chromosome location: 4q32.1
• Summary: 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 ro

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs767123432	->A	Pathogenic	Coding sequence variant, frameshift variant
rs1553957997	G>C	Pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT2347492	hsa-miR-4272	CLIP-seq
MIRT2347493	hsa-miR-4719	CLIP-seq
MIRT2347494	hsa-miR-4742-3p	CLIP-seq
MIRT2347495	hsa-miR-548g	CLIP-seq
MIRT2640430	hsa-miR-1245	CLIP-seq
MIRT2640431	hsa-miR-1264	CLIP-seq
MIRT2640432	hsa-miR-1266	CLIP-seq
MIRT2640433	hsa-miR-140-5p	CLIP-seq
MIRT2640434	hsa-miR-155	CLIP-seq
MIRT2640435	hsa-miR-3166	CLIP-seq
MIRT2640436	hsa-miR-323-3p	CLIP-seq
MIRT2640437	hsa-miR-338-5p	CLIP-seq
MIRT2640438	hsa-miR-3647-3p	CLIP-seq
MIRT2640439	hsa-miR-3655	CLIP-seq
MIRT2640440	hsa-miR-3664-3p	CLIP-seq
MIRT2640441	hsa-miR-3678-3p	CLIP-seq
MIRT2640442	hsa-miR-376a	CLIP-seq
MIRT2640443	hsa-miR-376b	CLIP-seq
MIRT2640444	hsa-miR-3907	CLIP-seq
MIRT2640445	hsa-miR-409-5p	CLIP-seq
MIRT2347492	hsa-miR-4272	CLIP-seq
MIRT2640446	hsa-miR-4474-5p	CLIP-seq
MIRT2640447	hsa-miR-450b-5p	CLIP-seq
MIRT2640448	hsa-miR-4518	CLIP-seq
MIRT2640449	hsa-miR-4668-3p	CLIP-seq
MIRT2347493	hsa-miR-4719	CLIP-seq
MIRT2347494	hsa-miR-4742-3p	CLIP-seq
MIRT2640450	hsa-miR-4771	CLIP-seq
MIRT2640451	hsa-miR-4777-5p	CLIP-seq
MIRT2640452	hsa-miR-494	CLIP-seq
MIRT2640453	hsa-miR-507	CLIP-seq
MIRT2640454	hsa-miR-518d-5p	CLIP-seq
MIRT2640455	hsa-miR-519b-5p	CLIP-seq
MIRT2640456	hsa-miR-519c-5p	CLIP-seq
MIRT2640457	hsa-miR-520c-5p	CLIP-seq
MIRT2640458	hsa-miR-526a	CLIP-seq
MIRT2347495	hsa-miR-548g	CLIP-seq
MIRT2640459	hsa-miR-557	CLIP-seq
MIRT2640460	hsa-miR-586	CLIP-seq
MIRT2640461	hsa-miR-630	CLIP-seq
MIRT2640435	hsa-miR-3166	CLIP-seq
MIRT2640437	hsa-miR-338-5p	CLIP-seq
MIRT2640438	hsa-miR-3647-3p	CLIP-seq
MIRT2640441	hsa-miR-3678-3p	CLIP-seq
MIRT2640442	hsa-miR-376a	CLIP-seq
MIRT2640443	hsa-miR-376b	CLIP-seq
MIRT2640444	hsa-miR-3907	CLIP-seq
MIRT2692861	hsa-miR-3929	CLIP-seq
MIRT2347492	hsa-miR-4272	CLIP-seq
MIRT2692862	hsa-miR-4419b	CLIP-seq
MIRT2692863	hsa-miR-4478	CLIP-seq
MIRT2640447	hsa-miR-450b-5p	CLIP-seq
MIRT2640449	hsa-miR-4668-3p	CLIP-seq
MIRT2347493	hsa-miR-4719	CLIP-seq
MIRT2347494	hsa-miR-4742-3p	CLIP-seq
MIRT2640450	hsa-miR-4771	CLIP-seq
MIRT2640451	hsa-miR-4777-5p	CLIP-seq
MIRT2640453	hsa-miR-507	CLIP-seq
MIRT2640454	hsa-miR-518d-5p	CLIP-seq
MIRT2640455	hsa-miR-519b-5p	CLIP-seq
MIRT2640456	hsa-miR-519c-5p	CLIP-seq
MIRT2640457	hsa-miR-520c-5p	CLIP-seq
MIRT2640458	hsa-miR-526a	CLIP-seq
MIRT2347495	hsa-miR-548g	CLIP-seq
MIRT2640459	hsa-miR-557	CLIP-seq
MIRT2640460	hsa-miR-586	CLIP-seq
MIRT2640461	hsa-miR-630	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
YY1	Unknown	10580097

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004833	Function	Tryptophan 2,3-dioxygenase activity	IBA	21873635
GO:0004833	Function	Tryptophan 2,3-dioxygenase activity	IDA	27762317, 28285122
GO:0005515	Function	Protein binding	IPI	16189514, 24722188, 25416956, 25910212, 28514442, 31515488, 32296183, 32814053
GO:0005829	Component	Cytosol	TAS
GO:0006569	Process	Tryptophan catabolic process	TAS
GO:0016597	Function	Amino acid binding	IEA
GO:0019441	Process	Tryptophan catabolic process to kynurenine	IDA	27762317
GO:0019441	Process	Tryptophan catabolic process to kynurenine	IEA
GO:0019442	Process	Tryptophan catabolic process to acetyl-CoA	IBA	21873635
GO:0019825	Function	Oxygen binding	IEA
GO:0020037	Function	Heme binding	IBA	21873635
GO:0020037	Function	Heme binding	IDA	27762317, 28285122
GO:0042802	Function	Identical protein binding	IPI	24722188, 25416956, 32296183
GO:0046872	Function	Metal ion binding	IEA
GO:0051289	Process	Protein homotetramerization	IDA	27762317, 28285122
GO:1904842	Process	Response to nitroglycerin	IEA

Other IDs

• MIM: 191070
• HGNC: 11708
• e!Ensembl: ENSG00000151790

Protein

• UniProt ID: P48775
• Protein name: Tryptophan 2,3-dioxygenase (TDO) (EC 1.13.11.11) (Tryptamin 2,3-dioxygenase) (Tryptophan oxygenase) (TO) (TRPO) (Tryptophan pyrrolase) (Tryptophanase)
• Protein function: Heme-dependent dioxygenase that catalyzes the oxidative cleavage of the L-tryptophan (L-Trp) pyrrole ring and converts L-tryptophan to N-formyl-L-kynurenine. Catalyzes the oxidative cleavage of the indole moiety. {ECO:0000255|HAMAP-Rule:MF_03020
• PDB: 4PW8, 5TI9, 5TIA, 6A4I, 6PYY, 6PYZ, 6UD5, 6VBN, 7LU7, 7UI3, 8QV7, 8R5Q, 8R5R, 8VTQ, 8VUG, 8VZV, 8W1H, 8W2K, 9AT2, 9B17, 9B1Q, 9EZJ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF03301	Trp_dioxygenase	26 → 372	Tryptophan 2,3-dioxygenase	Family

• Sequence:

  MSGCPFLGNNFGYTFKKLPVEGSEEDKSQTGVNRASKGGLIYGNYLHLEKVLNAQELQSE
  TKGNKIHDEHLFIITHQAYELWFKQILWELDSVREIFQNGHVRDERNMLKVVSRMHRVSV
  ILKLLVQQFSILETMTALDFNDFREYLSPASGFQSLQFRLLENKIGVLQNMRVPYNRRHY
  RDNFKGEENELLLKSEQEKTLLELVEAWLERTPGLEPHGFNFWGKLEKNITRGLEEEFIR
  IQAKEESEEKEEQVAEFQKQKEVLLSLFDEKRHEHLLSKGERRLSYRALQGALMIYFYRE
  EPRFQVPFQLLTSLMDIDSLMTKWRYNHVCMVHRMLGSKAGTGGSSGYHYLRSTVSDRYK
  VFVDLFNLSTYLIPRHWIPKMNPTIHKFLYTAEYCDSSYFSSDESD

• Sequence length: 406

Pathways

KEGG:

Tryptophan metabolism
Metabolic pathways
Biosynthesis of cofactors

Reactome:

Tryptophan catabolism

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Autism	Autistic Disorder	rs121964908, rs121912597, rs2710102, rs7794745, rs142990298, rs62643608, rs181327458, rs797046134, rs869312704, rs1555013332, rs876657679, rs1057518999, rs1057518658, rs771827120, rs1555187899, rs773080572, rs753871454, rs1684130791, rs1684180699, rs1553510219, rs1684182454, rs1559060428, rs1553510677, rs1576352885, rs1574152522, rs1574152672, rs1696658542, rs1751123722, rs1750373491, rs1751075634	14755447
Hypertryptophanemia	Familial hypertryptophanemia, Hypertryptophanemia	rs767123432, rs1553957997	28285122
Schizophrenia	Schizophrenia, SCHIZOPHRENIA 1 (disorder)	rs74315508, rs74315509, rs13447324, rs1558507406, rs387906932, rs387906933, rs863223354, rs863223355, rs776061422, rs863223349, rs748809996, rs759748655, rs863223353, rs863223350, rs863223356, rs781821239, rs863223348, rs863223346, rs863223347, rs863223351, rs863223352, rs61734270, rs797045205, rs869312829, rs869312830, rs770913157, rs869312832, rs869312831, rs781720548, rs1262969313	16448631

Unknown
Disease name	Disease term	dbSNP ID	References
Bipolar disorder	Bipolar Disorder		21396719, 21085052, 21438144, 25152196, 24196946
Mental depression	Unipolar Depression, Major Depressive Disorder	rs587778876, rs587778877	24196946, 23336047, 23467366, 24376086, 26057341, 24376086, 23336047, 26057341, 23467366, 24196946
Nonorganic psychosis	Nonorganic psychosis		16448631
Psychosis	Psychotic Disorders		16448631