IDO1
protein-codingindoleamine 2,3-dioxygenase 1
Gene summary
This gene encodes indoleamine 2,3-dioxygenase (IDO) - a heme enzyme that catalyzes the first and rate-limiting step in tryptophan catabolism to N-formyl-kynurenine. This enzyme acts on multiple tryptophan substrates including D-tryptophan, L-tryptophan, 5-hydroxy-tryptophan, tryptamine, and serotonin. This enzyme is thought to play a role in a variety of pathophysiological processes such as antimicrobial and antitumor defense, neuropathology, immunoregulation, and antioxidant activity. Through its expression in dendritic cells, monocytes, and macrophages this enzyme modulates T-cell behavior by its peri-cellular catabolization of the essential amino acid tryptophan.[provided by RefSeq, Feb 2011]
- IDO
- INDO
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~26.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to IDO1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002164.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 1 | 3 | |||
| missense | 55 | 3 | 2 | 60 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 61 | 3 | 3 | 67 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002155.1 | 10 | MANE Select | |
| Ensembl | ENSP00000430950.1 | 10 | MANE Select | |
| Ensembl | ENSP00000253513.7 | 5 | Standard | |
| Ensembl | ENSP00000429297.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Tryptophan metabolism - Homo sapiens (human)
- African trypanosomiasis - Homo sapiens (human)
- Tryptophan Metabolism
- NAD+ biosynthetic pathways
- Tryptophan metabolism
Biological Process
- immune system process
- cytokine production involved in inflammatory response
- positive regulation of T cell tolerance induction
- positive regulation of chronic inflammatory response
- positive regulation of type 2 immune response
Molecular Function
- tryptophan 2,3-dioxygenase activity
- electron transfer activity
- heme binding
- indoleamine 2,3-dioxygenase activity
- metal ion binding
Cellular Component
- cytoplasm
- cytosol
- smooth muscle contractile fiber
- stereocilium bundle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000518237
- Coding exons
- 10
- Length
- 26170
- Individuals with no LoFs
- 124625
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 27
- Defined
- 124652
- p
- 0.000108
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.403 | 229 | 212 | 1.08 | 0.0000112 | 2617 |
| Missense (PolyPhen) | 94 | 80.938 | 1.1614 | 1015 | ||
| Synonymous | -0.0732 | 77 | 76.2 | 1.01 | 0.00000391 | 763 |
| Loss of Function | 1.33 | 11 | 16.9 | 0.651 | 7.79e-7 | 208 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00019 | rare |
| Latino/Admixed American | 0.00032 | 0.00032 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000072 | 0.000071 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the first and rate limiting step of the catabolism of the essential amino acid tryptophan along the kynurenine pathway (PubMed:17671174). Involved in the peripheral immune tolerance, contributing to maintain homeostasis by preventing autoimmunity or immunopathology that would result from uncontrolled and overreacting immune responses (PubMed:25691885). Tryptophan shortage inhibits T lymphocytes division and accumulation of tryptophan catabolites induces T-cell apoptosis and differentiation of regulatory T-cells (PubMed:25691885). Acts as a suppressor of anti-tumor immunity (PubMed:23103127, PubMed:25157255, PubMed:14502282, PubMed:25691885). Limits the growth of intracellular pathogens by depriving tryptophan (PubMed:25691885). Protects the fetus from maternal immune rejection (PubMed:25691885). {ECO:0000269|PubMed:14502282, ECO:0000269|PubMed:17671174, ECO:0000303|PubMed:23103127, ECO:0000303|PubMed:25157255, ECO:0000303|PubMed:25691885}.;
Recessive Scores
- pRec
- 0.436
Intolerance Scores
- LoFtool
- 0.732
- RVIS EVS
- 0.35
- RVIS percentile EVS
- 74.37
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.978
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |