What you carry at this position in your DNA and what research says about it.
Autoimmune Disease Risk: 10/10 evidence, 28 publications.
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Sample genotype (not yours): C/C
Typical Autoimmune Disease Risk
Carrying two copies of the common C allele is associated with a baseline risk of developing autoimmune conditions. The immune system maintains a balanced inflammatory response because signaling pathways operate at typical levels.
What this genotype means: Standard baseline risk for rheumatoid arthritis; Typical levels of inflammatory signaling; Normal susceptibility to lupus and Sjogren's syndrome.
Sample genotype (not yours): C/T
Moderately Increased Autoimmune Disease Risk
Carrying one copy of the T allele is linked to a moderately increased risk of several autoimmune disorders. Altered regulatory binding in immune cells leads to slightly heightened inflammatory signaling.
What this genotype means: Moderately elevated risk of rheumatoid arthritis; Increased sensitivity to inflammatory triggers; Slightly higher susceptibility to lupus and Sjogren's syndrome.
Sample genotype (not yours): T/T
Significantly Increased Autoimmune Disease Risk
Carrying two copies of the T allele is associated with the highest genetic risk for multiple autoimmune diseases at this locus. This genotype leads to significantly increased inflammatory signaling due to altered gene regulation.
What this genotype means: Highest genetic risk for rheumatoid arthritis and lupus; Significantly elevated inflammatory pathway activity; Increased likelihood of developing multiple autoimmune conditions.
Gene function and biological role
Gene Function: The STAT4 gene encodes a critical transcription factor that acts as a master regulator within the immune system. It plays a central role in the Janus kinase and signal transducer and activator of transcription signaling pathway [1]. When activated by specific chemical messengers like interleukin-12, the STAT4 protein moves into the cell nucleus to drive the development of specialized inflammatory T cells [2]. This process is essential for defending the body against pathogens, but overactivation can lead to chronic inflammation [3]. Consequently, variations in this gene are heavily implicated in a wide range of autoimmune disorders [4].
Variant Impact: The rs11889341 variant is located within the third intron of the STAT4 gene, serving as a key regulatory switch rather than altering the protein structure directly [5]. The risk-associated T allele at this position alters transcription factor binding, which decreases repressor activity and leads to elevated expression of the neighboring STAT1 gene in immune cells [5]. This molecular change enhances inflammatory signaling pathways, making immune cells more reactive [2]. As a result, this single nucleotide change has been identified as a major shared genetic risk factor across multiple autoimmune conditions [1].
Key Insight: The risk allele of this variant actually increases the expression of a neighboring gene, STAT1, rather than STAT4 itself, by altering transcription factor binding. Smoking significantly amplifies the genetic risk of severe complications like nephritis and myocardial infarction in individuals carrying the risk allele.
Location: STAT4. Chromosome 2 · 2q32.2 · 191.1 Mb
Estimated prevalence by population
Global 62.5%; European 60.5%; African 75.7%; East Asian 42.9%; South Asian 56.8%; Americas 47.4%; Ashkenazi 59.1%; Finnish 59.2%; Middle Eastern 52.0%; Amish 65.4%.
Estimated CC genotype frequency.
Global 32.7%; European 34.6%; African 22.6%; East Asian 45.2%; South Asian 37.1%; Americas 42.9%; Ashkenazi 35.5%; Finnish 35.5%; Middle Eastern 40.2%; Amish 30.9%.
Estimated CT genotype frequency.
Global 4.9%; European 5.0%; African 1.7%; East Asian 11.9%; South Asian 6.1%; Americas 9.7%; Ashkenazi 5.3%; Finnish 5.3%; Middle Eastern 7.8%; Amish 3.7%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Immunity & Inflammation
Autoimmune Diseases
Rheumatoid Arthritis. Evidence: 8/10. Source: PMID 24390342. Typical Risk.
Lupus. Evidence: 10/10. Source: PMID 26502338. Typical Risk.
Sjogren's Syndrome. Evidence: 8/10. Source: PMID 28076899. Typical Risk.
Juvenile Arthritis. Evidence: 6/10. Source: PMID 33106285. Typical Risk.
Systemic Sclerosis. Evidence: 6/10. Source: PMID 38296975. Typical Risk.
Endocrine & Reproductive
Hormone Levels & Endocrine Regulation
Hypothyroidism. Evidence: 8/10. Source: PMID 41238958. Typical Risk.
Showing effects for C/T genotype
Rheumatoid Arthritis. Evidence: 8/10. Source: PMID 24390342. ~1.14x Risk.
Lupus. Evidence: 10/10. Source: PMID 26502338. Increased Risk.
Sjogren's Syndrome. Evidence: 8/10. Source: PMID 28076899. Increased Risk.
Juvenile Arthritis. Evidence: 6/10. Source: PMID 33106285. ~1.26x Risk.
Systemic Sclerosis. Evidence: 6/10. Source: PMID 38296975. ~1.49x Risk.
Hypothyroidism. Evidence: 8/10. Source: PMID 41238958. Increased Risk.
Showing effects for T/T genotype
Rheumatoid Arthritis. Evidence: 8/10. Source: PMID 24390342. ~1.30x Risk.
Lupus. Evidence: 10/10. Source: PMID 26502338. Highest Risk.
Sjogren's Syndrome. Evidence: 8/10. Source: PMID 28076899. Highest Risk.
Juvenile Arthritis. Evidence: 6/10. Source: PMID 33106285. ~1.58x Risk.
Systemic Sclerosis. Evidence: 6/10. Source: PMID 38296975. ~2.22x Risk.
Hypothyroidism. Evidence: 8/10. Source: PMID 41238958. Highest Risk.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Carrying two copies of the common C allele is associated with a baseline risk of developing autoimmune conditions. The immune system maintains a balanced inflammatory response because STAT4-mediated signaling operates at typical levels [1]. Large-scale genetic analyses show no elevated susceptibility to rheumatoid arthritis or systemic lupus erythematosus for this genotype. Similarly, the risk for other related conditions like Sjogren's syndrome and hypothyroidism remains at the standard population average. Maintaining a healthy lifestyle and avoiding environmental triggers like smoking can help support overall immune health. This genetic profile is the most common globally, representing the baseline state of immune reactivity.
Standard baseline risk for rheumatoid arthritis; Typical levels of inflammatory signaling; Normal susceptibility to lupus and Sjogren's syndrome.
Sample genotype: CT (Heterozygous)
Carrying one copy of the T allele is linked to a moderately increased risk of several autoimmune disorders. Having a single T allele alters regulatory binding in immune cells, leading to heightened inflammatory signaling [1]. Research associates this genotype with a slightly elevated risk of developing rheumatoid arthritis and systemic lupus erythematosus. It also moderately increases the likelihood of experiencing Sjogren's syndrome, juvenile idiopathic arthritis, and thyroid-related issues like hypothyroidism. Environmental factors, particularly smoking, can interact with this genetic background to further amplify the risk of severe inflammatory complications [2]. Awareness of early symptoms can help in timely discussions with healthcare providers.
Moderately elevated risk of rheumatoid arthritis; Increased sensitivity to inflammatory triggers; Slightly higher susceptibility to lupus and Sjogren's syndrome.
Sample genotype: TT (Homozygous)
Carrying two copies of the T allele is associated with the highest genetic risk for multiple autoimmune diseases at this locus. This genotype leads to significantly increased inflammatory signaling due to altered gene regulation in B and T cells [1]. Clinical studies demonstrate a strong association with an increased risk of rheumatoid arthritis, systemic lupus erythematosus, and Sjogren's syndrome. There is also a pronounced elevation in susceptibility to juvenile idiopathic arthritis, systemic sclerosis, and hypothyroidism. Individuals with this genetic profile may also have a higher likelihood of requiring thyroid medications or developing autoantibodies. Knowing this risk can encourage proactive discussions with a physician regarding joint and immune health.
Highest genetic risk for rheumatoid arthritis and lupus; Significantly elevated inflammatory pathway activity; Increased likelihood of developing multiple autoimmune conditions.
Variants with shared genetic architecture
rs7574865 · STAT4 Gene · Chr 2 · Autoimmune Disease Risk
rs3821236 · STAT4 Gene · Chr 2 · Autoimmune Disease Risk
rs7582694 · STAT4 Gene · Chr 2 · Autoimmune Disease Risk
Genetics of rheumatoid arthritis contributes to biology and drug discovery.
Association of STAT4 polymorphism with severe renal insufficiency in lupus nephritis.
Content updated August 2026.
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