IRF5

Chr 7AD

interferon regulatory factor 5

Also known as: SLEB10

NCBI Gene: 3663ENSG00000128604UniProt: Q13568

This gene encodes a member of the interferon regulatory factor (IRF) family, a group of transcription factors with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conserved N-terminal DNA-binding domain containing tryptophan (W) repeats. Alternative promoter use and alternative splicing result in multiple transcript variants, and a 30-nt indel polymorphism (SNP rs60344245) can result in loss of a 10-aa segment. [provided by RefSeq, Dec 2016]

Primary Disease Associations & Inheritance

{Inflammatory bowel disease 14}MIM #612245
{Systemic lupus erythematosus, susceptibility to, 10}MIM #612251
AD
UniProtRheumatoid arthritis
96
ClinVar variants
26
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— IRF5
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 56 VUS of 96 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.59LOEUF
pLI 0.009
Z-score 3.06
OE 0.33 (0.19–0.59)
Moderately constrained

More LoF-intolerant than ~75% 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.
1.92Z-score
OE missense 0.69 (0.62–0.78)
214 obs / 308.9 exp
Tolerant

Mild missense constraint

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.0.33 (0.19–0.59)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.69 (0.62–0.78)
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.0.94
0≤1.21.6
LoF obs/exp: 8 / 24.3Missense obs/exp: 214 / 308.9Syn Z: 0.55

ClinVar Variant Classifications

96 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic1
VUS56
Likely Benign9
Benign5
25
Pathogenic
1
Likely Pathogenic
56
VUS
9
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
25
0
25
Likely Pathogenic
0
0
1
0
1
VUS
1
52
3
0
56
Likely Benign
0
1
2
6
9
Benign
0
0
2
3
5
Total15333996

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

View in ClinVar →

Protein Context — Lollipop Plot

IRF5 · 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

{Inflammatory bowel disease 14}

MIM #612245

Molecular basis of disorder known

{Systemic lupus erythematosus, susceptibility to, 10}

MIM #612251

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Precision medicine in systemic lupus erythematosus.
Fasano S et al.·Nat Rev Rheumatol
2023Review
Inhibition of IRF5 hyperactivation protects from lupus onset and severity.
Song S et al.·J Clin Invest
2020Clinical trial
An autoimmune pleiotropic SNP modulates IRF5 alternative promoter usage through ZBTB3-mediated chromatin looping.
Wang Z et al.·Nat Commun
2023
Association of Fusobacterium nucleatum with Specific T-cell Subsets in the Colorectal Carcinoma Microenvironment.
Borowsky J et al.·Clin Cancer Res
2021
Molecular mechanisms controlling age-associated B cells in autoimmunity.
Phalke S et al.·Immunol Rev
2022Review
Interferon regulatory factor-5-dependent CD11c+ macrophages contribute to the formation of rupture-prone atherosclerotic plaques.
Edsfeldt A et al.·Eur Heart J
2022
Regulating IRFs in IFN Driven Disease.
Jefferies CA·Front Immunol
2019Review
Macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation.
Zec K et al.·J Exp Med
2023
Role of interferon regulatory factor 5 (IRF5) in tumor progression: Prognostic and therapeutic potential.
Roberts BK et al.·Biochim Biophys Acta Rev Cancer
2024Review
Interferon regulatory factor 5: a potential target for therapeutic intervention in inflammatory diseases.
Yu X et al.·Front Immunol
2025Review
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