IRF1

Chr 5AR

interferon regulatory factor 1

Also known as: IMD117, IRF-1, MAR

NCBI Gene: 3659ENSG00000125347UniProt: P10914

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]

Primary Disease Associations & Inheritance

Gastric cancer, somaticMIM #613659
Immunodeficiency 117, mycobacteriosis, autosomal recessiveMIM #620668
AR
Nonsmall cell lung cancer, somaticMIM #211980
55
ClinVar variants
18
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— IRF1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 21 VUS of 55 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.05 (0.02–0.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.51 (0.43–0.60)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91
0≤1.21.6
LoF obs/exp: 1 / 18.5Missense obs/exp: 92 / 181.1Syn Z: 0.61

ClinVar Variant Classifications

55 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic1
VUS21
Likely Benign2
Benign14
17
Pathogenic
1
Likely Pathogenic
21
VUS
2
Likely Benign
14
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
15
0
17
Likely Pathogenic
0
0
1
0
1
VUS
0
19
2
0
21
Likely Benign
0
0
2
0
2
Benign
0
0
12
2
14
Total02132255

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

IRF1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Gastric cancer, somatic

MIM #613659

Molecular basis of disorder known

Immunodeficiency 117, mycobacteriosis, autosomal recessive

MIM #620668

Molecular basis of disorder known

Autosomal recessive

Nonsmall cell lung cancer, somatic

MIM #211980

Molecular basis of disorder known

📖
GeneReview available — IRF1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of key genes as diagnostic biomarkers for IBD using bioinformatics and machine learning.
Li T et al.·J Transl Med
2025
Mefloquine enhances the efficacy of anti-PD-1 immunotherapy via IFN-γ-STAT1-IRF1-LPCAT3-induced ferroptosis in tumors.
Tao Q et al.·J Immunother Cancer
2024
Multiplex cerebrospinal fluid proteomics identifies biomarkers for diagnosis and prediction of Alzheimer's disease.
Guo Y et al.·Nat Hum Behav
2024
Interferon regulatory factor-1-expressing astrocytes are epigenetically controlled and exacerbate TBI-associated pathology in mice.
Cui W et al.·Sci Transl Med
2025
Indoxyl sulfate induces intestinal barrier injury through IRF1-DRP1 axis-mediated mitophagy impairment.
Huang Y et al.·Theranostics
2020
PARP7-mediated ADP-ribosylation of FRA1 promotes cancer cell growth by repressing IRF1- and IRF3-dependent apoptosis.
Manetsch P et al.·Proc Natl Acad Sci U S A
2023
Targeting autophagy overcomes cancer-intrinsic resistance to CAR-T immunotherapy in B-cell malignancies.
Tang L et al.·Cancer Commun (Lond)
2024
NF-κB-dependent IRF1 activation programs cDC1 dendritic cells to drive antitumor immunity.
Ghislat G et al.·Sci Immunol
2021
FOXA1 enhances antitumor immunity via repressing interferon-induced PD-L1 expression in nasopharyngeal carcinoma.
Ge J et al.·J Immunother Cancer
2024
LATS1/2 loss promote tumor immune evasion in endometrial cancer through downregulating MHC-I expression.
Yang Q et al.·J Exp Clin Cancer Res
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools