IDO1

Chr 8

indoleamine 2,3-dioxygenase 1

Also known as: IDO, IDO-1, INDO

NCBI Gene: 3620 ENSG00000131203 UniProt: P14902 OMIM: 147435

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

588

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.08

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.08LOEUF

pLI 0.000

Z-score 1.33

OE 0.65 (0.41–1.08)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.40Z-score

OE missense 1.08 (0.97–1.20)

229 obs / 212.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.65 (0.41–1.08)

0≤0.351.4

Missense OE?1.08 (0.97–1.20)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 11 / 16.9Missense obs/exp: 229 / 212.5Syn Z: -0.07

Background carrier burden — how many people carry a rare variant somewhere in IDO1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

550 rare PASS variants

Rare truncating (LoF)

1 in 2,400

90 rare PASS variants

Rare synonymous (reference)

1 in 420

182 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IDO1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 210	1 in 2,600
South Asian	~43k	1 in 140	1 in 1,200
Remaining (unassigned)	~30k	1 in 120	1 in 4,300
European (Finnish)	~27k	1 in 980	≈ 1 in 27,000
Admixed American	~22k	1 in 100	1 in 980
African / African American	~21k	1 in 120	1 in 1,400
East Asian	~20k	1 in 140	1 in 1,300
Ashkenazi Jewish	~13k	1 in 400	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 140	≈ 1 in 950

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 10 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: all 10.? see exons ↓