What you carry at this position in your DNA and what research says about it.
Autoimmune Disease Risk: 10/10 evidence, 26 publications.
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Sample genotype (not yours): G/G
Lower Autoimmune Risk but Slightly Higher Blood Pressure
Carrying two copies of the G allele provides strong protection against several autoimmune disorders. However, it is associated with a tiny increase in blood pressure.
What this genotype means: Lower risk of lupus and rheumatoid arthritis; Lower risk of ulcerative colitis; Slightly higher blood pressure.
Sample genotype (not yours): A/A
Elevated Risk of Autoimmune Diseases
Carrying two copies of the A allele significantly increases the susceptibility to multiple autoimmune disorders. This genotype is also linked to slightly lower blood pressure.
What this genotype means: Significantly higher risk of lupus; Increased risk of rheumatoid arthritis and colitis; Slightly lower blood pressure.
Sample genotype (not yours): G/A
Moderately Increased Risk of Autoimmune Conditions
Carrying one copy of the A allele moderately increases the risk of several autoimmune diseases. It also offers slight protection against high blood pressure.
What this genotype means: Moderately increased risk of lupus; Slightly increased risk of rheumatoid arthritis and colitis; Typical blood pressure levels.
Gene function and biological role
Gene Function: The IRF5 gene encodes interferon regulatory factor 5, a crucial transcription factor in the immune system. It plays a central role in activating the type I interferon pathway and regulating inflammatory cytokines [1]. When immune cells detect pathogens, this protein helps trigger the defense response by signaling downstream of toll-like receptors [1]. Because of its powerful role in driving inflammation, variations in this gene are heavily linked to autoimmune conditions [2]. Proper regulation of this pathway is essential to prevent the immune system from attacking healthy tissues [2].
Variant Impact: This intergenic variant is located in the promoter region of the IRF5 gene, where it directly influences gene expression. The risk allele alters the binding of specific transcription factors, such as ZBTB3, to the promoter [2]. This change in binding alters how the gene is transcribed, leading to increased expression of IRF5 and heightened immune activity [2]. Consequently, the variant acts as a genetic switch that predisposes carriers to several chronic inflammatory diseases [3]. Conversely, the alternative allele is associated with a very slight increase in blood pressure [4].
Key Insight: This single genetic spelling change acts as a molecular pivot, where the allele that increases the risk of multiple autoimmune diseases simultaneously offers a tiny protective effect against high blood pressure.
Location: IRF5. Chromosome 7 · 7q32.1 · 128.9 Mb
Estimated prevalence by population
Global 39.6%; European 31.2%; African 52.5%; East Asian 77.1%; South Asian 36.9%; Americas 36.9%; Ashkenazi 24.5%; Finnish 36.4%; Middle Eastern 27.8%; Amish 29.4%.
Estimated GG genotype frequency.
Global 45.5%; European 49.3%; African 39.9%; East Asian 21.4%; South Asian 47.7%; Americas 47.7%; Ashkenazi 50.0%; Finnish 47.8%; Middle Eastern 49.8%; Amish 49.7%.
Estimated GA genotype frequency.
Global 14.9%; European 19.5%; African 7.6%; East Asian 1.5%; South Asian 15.4%; Americas 15.4%; Ashkenazi 25.5%; Finnish 15.7%; Middle Eastern 22.3%; Amish 21.0%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Immunity & Inflammation
Autoimmune Diseases
Lupus. Evidence: 10/10. Source: PMID 36750564. Typical Risk.
Rheumatoid Arthritis. Evidence: 7/10. Source: PMID 24532676. Typical Risk.
Systemic Sclerosis. Evidence: 6/10. Source: PMID 38296975. Typical Risk.
Chronic Inflammatory Diseases
Ulcerative Colitis. Evidence: 7/10. Source: PMID 21297633. Typical Risk.
Cardiovascular & Metabolic
Hypertension
Blood Pressure. Evidence: 7/10. Source: PMID 27618447. Slightly Higher.
Showing effects for A/A genotype
Lupus. Evidence: 10/10. Source: PMID 36750564. ~1.5x Increased Risk.
Rheumatoid Arthritis. Evidence: 7/10. Source: PMID 24532676. ~1.13x Increased Risk.
Systemic Sclerosis. Evidence: 6/10. Source: PMID 38296975. Increased Risk.
Ulcerative Colitis. Evidence: 7/10. Source: PMID 21297633. ~1.1x Increased Risk.
Blood Pressure. Evidence: 7/10. Source: PMID 27618447. Slightly Lower.
Showing effects for G/A genotype
Lupus. Evidence: 10/10. Source: PMID 36750564. Increased Risk.
Rheumatoid Arthritis. Evidence: 7/10. Source: PMID 24532676. Slightly Increased.
Systemic Sclerosis. Evidence: 6/10. Source: PMID 38296975. Slightly Increased.
Ulcerative Colitis. Evidence: 7/10. Source: PMID 21297633. Slightly Increased.
Blood Pressure. Evidence: 7/10. Source: PMID 27618447. Typical.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Inheriting two copies of the G allele means the promoter region of the IRF5 gene maintains typical, baseline activity levels. This lower expression of the transcription factor helps prevent the overactivation of the type I interferon pathway [1]. As a result, there is a significantly lower risk of developing systemic lupus erythematosus, rheumatoid arthritis, and ulcerative colitis. The protective effect is particularly notable for lupus, where this genotype avoids a substantial risk increase [2]. On the other hand, large-scale genetic analyses show that the G allele is linked to a very small increase in blood pressure [3]. This blood pressure effect is extremely minor, typically amounting to less than a fraction of a millimeter of mercury [3]. For most people, the benefit of reduced autoimmune susceptibility far outweighs this minor cardiovascular influence.
Lower risk of lupus and rheumatoid arthritis; Lower risk of ulcerative colitis; Slightly higher blood pressure.
Sample genotype: AA (Homozygous)
Inheriting two copies of the A allele causes the highest level of IRF5 gene expression due to altered promoter activity [1]. This overexpression drives chronic, low-grade inflammation by overactivating the type I interferon system [1]. Large-scale genomic studies demonstrate that this genotype is strongly associated with systemic lupus erythematosus, raising the odds by over 1.5 times [2]. It also significantly increases the risk of other inflammatory conditions, including rheumatoid arthritis and ulcerative colitis [3]. Interestingly, the A allele is associated with a minor protective effect against high blood pressure [4]. However, this blood pressure reduction is clinically very small and does not offset the substantial autoimmune risks.
Significantly higher risk of lupus; Increased risk of rheumatoid arthritis and colitis; Slightly lower blood pressure.
Sample genotype: GA (Heterozygous)
Having one copy of the A allele alters transcription factor binding in the promoter region of the IRF5 gene [1]. This molecular change leads to increased expression of the IRF5 protein, which can overstimulate inflammatory pathways [1]. Clinical studies show that carriers have an elevated risk of developing systemic lupus erythematosus [2]. Additionally, this genotype is associated with moderate increases in the risk of rheumatoid arthritis and ulcerative colitis [3]. While the immune system is more active, the presence of one G allele is linked to a very slight reduction in blood pressure compared to the G/G genotype [4]. This minor cardiovascular benefit is generally considered secondary to the increased autoimmune risk.
Moderately increased risk of lupus; Slightly increased risk of rheumatoid arthritis and colitis; Typical blood pressure levels.
Variants with shared genetic architecture
rs3757387 · IRF5 Gene · Chr 7 · Autoimmune Disease Risk
rs2004640 · IRF5 Gene · Chr 7 · Autoimmune Disease Risk
rs729302 · IRF5 Gene · Chr 7 · Autoimmune Disease Risk
Content updated August 2026.
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