What you carry at this position in your DNA and what research says about it.
Autoimmune Disease Risk: 9/10 evidence, 21 publications.
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Sample genotype (not yours): C/C
Higher Autoimmune Risk and Stronger Viral Defense
Two copies of the common C allele are linked to an increased risk of developing autoimmune conditions like lupus and type 1 diabetes. However, this genotype maintains robust interferon signaling, which helps protect against severe viral infections.
What this genotype means: Increased susceptibility to systemic lupus erythematosus; Stronger immune defense against severe viral infections; Slightly elevated risk for type 1 diabetes.
Sample genotype (not yours): A/A
Lower Autoimmune Risk but Higher Severe Viral Risk
Two copies of the minor A allele offer significant protection against several autoimmune diseases, including lupus and type 1 diabetes. However, this comes at the cost of weaker interferon signaling, which increases susceptibility to severe viral infections.
What this genotype means: Significantly lower risk of systemic lupus erythematosus; Increased susceptibility to severe viral infections; Reduced risk of type 1 diabetes.
Sample genotype (not yours): C/A
Higher Autoimmune Risk and Increased Viral Susceptibility
Carrying one copy of each allele is associated with an elevated risk of autoimmune diseases such as lupus. At the same time, the presence of the A allele slightly compromises viral defense, raising the risk of severe viral outcomes.
What this genotype means: Increased risk of systemic lupus erythematosus; Slightly higher risk of severe viral infection outcomes; Elevated susceptibility to type 1 diabetes.
Gene function and biological role
Gene Function: TYK2 encodes tyrosine kinase 2, a member of the Janus kinase family that plays a critical role in intracellular signaling for various cytokines and type I interferons [1]. This signaling pathway is essential for activating immune responses against viral infections [1]. However, overactive TYK2 signaling can lead to excessive inflammation and the production of autoantibodies, contributing to autoimmune disorders [2]. Consequently, TYK2 is a major therapeutic target, with inhibitors used to treat conditions like plaque psoriasis and inflammatory bowel disease [2].
Variant Impact: The rs2304256 variant is a missense mutation in exon 8 of the TYK2 gene that changes the amino acid valine to phenylalanine at position 362 [1]. This specific change is located within the JH4 domain, which is crucial for TYK2 to bind to interferon receptors at the cell membrane [1]. In addition to altering the protein structure, this nucleotide change acts as a splicing modifier that influences how the TYK2 transcript is processed [1]. The minor A allele reduces the overall signaling efficiency of the TYK2 protein, which dampens the immune system's inflammatory response [3].
Key Insight: The same genetic variant that protects against autoimmune diseases like lupus also makes the body more vulnerable to severe viral infections like COVID-19.
Location: TYK2. Chromosome 19 · 19p13.2 · 10.4 Mb
Estimated prevalence by population
Global 59.7%; European 52.2%; African 79.3%; East Asian 23.9%; South Asian 52.8%; Americas 59.8%; Ashkenazi 45.9%; Finnish 58.7%; Middle Eastern 52.0%; Amish 34.2%.
Estimated CC genotype frequency.
Global 34.1%; European 40.1%; African 19.5%; East Asian 50.0%; South Asian 39.7%; Americas 35.0%; Ashkenazi 43.7%; Finnish 35.8%; Middle Eastern 40.2%; Amish 48.5%.
Estimated CA genotype frequency.
Global 6.2%; European 7.7%; African 1.2%; East Asian 26.1%; South Asian 7.5%; Americas 5.1%; Ashkenazi 10.4%; Finnish 5.5%; Middle Eastern 7.8%; Amish 17.2%.
Estimated AA genotype frequency.
Showing effects for C/C genotype
Immunity & Inflammation
Autoimmune Diseases
Lupus. Evidence: 9/10. Source: PMID 36750564. ~1.6x Increased Risk.
Infection Susceptibility & Resistance
COVID-19 Severity. Evidence: 9/10. Source: PMID 36762574. Lower Risk.
Cardiovascular & Metabolic
Diabetes & Glycemic Traits
Type 1 Diabetes. Evidence: 7/10. Source: PMID 19966805. ~1.16x Increased Risk.
Organ Systems
Liver Function & Disease
Biliary Cholangitis. Evidence: 8/10. Source: PMID 26394269. Increased Risk.
Showing effects for A/A genotype
Lupus. Evidence: 9/10. Source: PMID 36750564. Typical Risk.
COVID-19 Severity. Evidence: 9/10. Source: PMID 36762574. Highest Risk.
Type 1 Diabetes. Evidence: 7/10. Source: PMID 19966805. Lower Risk.
Biliary Cholangitis. Evidence: 8/10. Source: PMID 26394269. Lower Risk.
Showing effects for C/A genotype
COVID-19 Severity. Evidence: 9/10. Source: PMID 36762574. Increased Risk.
Type 1 Diabetes. Evidence: 7/10. Source: PMID 19966805. Increased Risk.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Inheriting the C/C genotype means having the standard, fully functional version of the TYK2 enzyme. This active state ensures strong type I interferon signaling, which is highly effective at clearing viral pathogens and reducing the risk of severe COVID-19 hospitalization [1]. However, this heightened immune vigilance comes with a significant trade-off, as persistent inflammatory signaling increases susceptibility to autoimmune attacks. Large-scale genetic studies show a clear association between the C allele and an elevated risk of systemic lupus erythematosus [2]. Additionally, this genotype is linked to higher rates of type 1 diabetes and primary biliary cholangitis [3]. Managing overall inflammation through lifestyle choices remains a practical focus for individuals with this common genetic profile.
Increased susceptibility to systemic lupus erythematosus; Stronger immune defense against severe viral infections; Slightly elevated risk for type 1 diabetes.
Sample genotype: AA (Homozygous)
The homozygous A/A genotype significantly alters the splicing and function of the TYK2 protein, leading to reduced interferon signaling. This dampened immune response is highly protective against autoimmune diseases, resulting in a much lower risk of developing systemic lupus erythematosus [1]. It also provides strong protection against other inflammatory conditions, such as type 1 diabetes [2] and primary biliary cholangitis [3]. However, the critical trade-off is a compromised ability to fight off certain viruses. Individuals with this genotype have a significantly higher risk of severe COVID-19 outcomes and hospitalization due to weakened viral clearance [4]. Prioritizing timely vaccinations and robust hygiene practices is especially important to compensate for this genetic vulnerability.
Significantly lower risk of systemic lupus erythematosus; Increased susceptibility to severe viral infections; Reduced risk of type 1 diabetes.
Sample genotype: CA (Heterozygous)
The heterozygous C/A genotype represents a complex immunological middle ground. Having one C allele maintains a higher susceptibility to autoimmune conditions, including systemic lupus erythematosus [1] and type 1 diabetes [2]. Concurrently, the single A allele alters TYK2 splicing, which can reduce the efficiency of interferon-mediated antiviral defenses. This reduction in signaling capacity is associated with an increased risk of severe COVID-19 complications compared to the C/C genotype [3]. Because both autoimmune and viral risks are slightly elevated, maintaining a balanced immune system is key. Regular health checkups and standard preventive measures against respiratory infections are highly relevant for individuals with this genotype.
Increased risk of systemic lupus erythematosus; Slightly higher risk of severe viral infection outcomes; Elevated susceptibility to type 1 diabetes.
Variants with shared genetic architecture
rs34536443 · TYK2 Gene · Chr 19 · Autoimmunity and Infection Risk
rs12720356 · TYK2 Gene · Chr 19 · Autoimmune Disease Risk
rs280519 · TYK2 Gene · Chr 19 · Autoimmune Disease Risk
Influence of TYK2 in systemic sclerosis susceptibility: a new locus in the IL-12 pathway.
Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases.
Content updated August 2026.
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