IRF1

Chr 5AR

interferon regulatory factor 1

Also known as: IMD117, IRF-1, MAR

NCBI Gene: 3659 ENSG00000125347 UniProt: P10914 OMIM: 147575

The protein encoded by this gene is a transcriptional regulator and tumor suppressor, serving as an activator of genes involved in both innate and acquired immune responses. The encoded protein activates the transcription of genes involved in the body's response to viruses and bacteria, playing a role in cell proliferation, apoptosis, the immune response, and DNA damage response. This protein represses the transcription of several other genes. As a tumor suppressor, it both suppresses tumor cell growth and stimulates an immune response against tumor cells. Defects in this gene have been associated with gastric cancer, myelogenous leukemia, and lung cancer. [provided by RefSeq, Aug 2017]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Gastric cancer, somaticMIM #613659

Immunodeficiency 117, mycobacteriosis, autosomal recessiveMIM #620668

Nonsmall cell lung cancer, somaticMIM #211980

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Gastric cancer, somatic; Immunodeficiency 117, mycobacteriosis, autosomal recessive (+1); no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

386

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.26

LOEUF· LoF intol.

LOF

Mechanism· predicted

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GeneReview available — IRF1

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.26LOEUF

pLI 0.991

Z-score 3.77

OE 0.05 (0.02–0.26)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.35Z-score

OE missense 0.51 (0.43–0.60)

92 obs / 181.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.05 (0.02–0.26)

0≤0.351.4

Missense OE?0.51 (0.43–0.60)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 1 / 18.5Missense obs/exp: 92 / 181.1Syn Z: 0.61

Background carrier burden — how many people carry a rare variant somewhere in IRF1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 340

278 rare PASS variants

Rare truncating (LoF)

1 in 880

43 rare PASS variants

Rare synonymous (reference)

1 in 400

148 rare PASS variants

Rare missense and truncating variants are carried at similar rates in IRF1; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

Exome coverage (gnomAD): All 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓