What you carry at this position in your DNA and what research says about it.
Autoimmunity and Infection Risk: 10/10 evidence, 44 publications.
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Sample genotype (not yours): G/G
Typical Autoimmune and Infection Risk
Standard immune signaling pathways operate at normal levels. This results in baseline population risks for both autoimmune diseases and infectious pathogens.
What this genotype means: Standard immune system signaling; Baseline risk for autoimmune diseases; Typical defense against tuberculosis.
Sample genotype (not yours): C/C
Autoimmune Protection but High Tuberculosis Risk
Strong protection against multiple autoimmune diseases is offset by a significantly increased vulnerability to tuberculosis and severe viral infections.
What this genotype means: Strong protection against autoimmune diseases; Significantly increased susceptibility to tuberculosis; Higher risk of severe COVID-19 complications.
Sample genotype (not yours): G/C
Reduced Autoimmune Risk
A single copy of the protective allele slightly dampens inflammatory signaling. This provides moderate protection against several autoimmune disorders without compromising general infection defense.
What this genotype means: Slightly lowered risk of rheumatoid arthritis; Slightly lowered risk of psoriasis; Maintained defense against infections.
Gene function and biological role
Gene Function: The TYK2 gene encodes tyrosine kinase 2, an enzyme that plays a critical role in the human immune system [1]. It acts as an essential signaling chemical transducer downstream of receptors for several key cytokines, including type I interferons, interleukin-12, and interleukin-23 [1]. These cytokine pathways are vital for activating immune cells to fight off viral and bacterial pathogens [2]. However, overactive signaling through these same pathways can drive chronic inflammation and lead to autoimmune diseases where the body attacks its own tissues [2].
Variant Impact: The rs34536443 variant is a missense mutation in the TYK2 gene that changes the amino acid proline to alanine at position 1104, commonly referred to as the P1104A alteration [1]. This molecular change results in a hypomorphic protein, meaning the TYK2 enzyme is partially disabled and exhibits significantly reduced catalytic activity [1]. Because of this dampening effect, immune cells show decreased signaling in response to inflammatory cytokines [2]. While this reduction in immune signaling protects against several autoimmune conditions, it simultaneously compromises the body's defense against certain intracellular pathogens [1].
Key Insight: This variant represents a classic evolutionary trade-off where a genetic change that protects against modern autoimmune diseases also makes the body highly vulnerable to ancient infectious diseases like tuberculosis.
Location: TYK2. Chromosome 19 · 19p13.2 · 10.4 Mb
Origin Story: Tuberculosis has exerted strong negative selective pressure on this variant in Europe over the last 2,000 years, keeping the protective but infection-susceptible C allele relatively rare in the population.
Estimated prevalence by population
Global 94.5%; European 91.4%; African 98.2%; East Asian 100.0%; South Asian 97.7%; Americas 95.8%; Ashkenazi 93.5%; Finnish 94.3%; Middle Eastern 94.0%; Amish 97.2%.
Estimated GG genotype frequency.
Global 5.4%; European 8.4%; African 1.8%; East Asian 0.0%; South Asian 2.3%; Americas 4.2%; Ashkenazi 6.4%; Finnish 5.6%; Middle Eastern 5.9%; Amish 2.8%.
Estimated GC genotype frequency.
Global 0.1%; European 0.2%; African < 0.1%; East Asian 0.0%; South Asian < 0.1%; Americas < 0.1%; Ashkenazi 0.1%; Finnish 0.1%; Middle Eastern 0.1%; Amish < 0.1%.
Estimated CC genotype frequency.
Showing effects for G/G genotype
Immunity & Inflammation
Autoimmune Diseases
Rheumatoid Arthritis. Evidence: 10/10. Source: PMID 24390342. Typical Risk.
Multiple Sclerosis. Evidence: 8/10. Source: PMID 21354972. Typical Risk.
Infection Susceptibility & Resistance
Tuberculosis. Evidence: 3/10. Source: PMID 30578352. Typical Risk.
COVID-19 Severity. Evidence: 9/10. Source: PMID 37198478. Typical Risk.
Organ Systems
Skin & Hair Conditions
Psoriasis. Evidence: 10/10. Source: PMID 23143594. Typical Risk.
Endocrine & Reproductive
Hormone Levels & Endocrine Regulation
Hypothyroidism. Evidence: 10/10. Source: PMID 36093044. Typical Risk.
Showing effects for C/C genotype
Rheumatoid Arthritis. Evidence: 10/10. Source: PMID 24390342. Strongly Protected.
Multiple Sclerosis. Evidence: 8/10. Source: PMID 21354972. Strongly Protected.
Tuberculosis. Evidence: 3/10. Source: PMID 30578352. ~90x Higher Risk.
COVID-19 Severity. Evidence: 9/10. Source: PMID 37198478. ~1.5x Higher Risk.
Psoriasis. Evidence: 10/10. Source: PMID 23143594. Strongly Protected.
Hypothyroidism. Evidence: 10/10. Source: PMID 36093044. Strongly Protected.
Showing effects for G/C genotype
Rheumatoid Arthritis. Evidence: 10/10. Source: PMID 24390342. Reduced Risk.
Multiple Sclerosis. Evidence: 8/10. Source: PMID 21354972. Reduced Risk.
Psoriasis. Evidence: 10/10. Source: PMID 23143594. Reduced Risk.
Hypothyroidism. Evidence: 10/10. Source: PMID 36093044. Reduced Risk.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Standard TYK2 enzyme activity is maintained, allowing the immune system to respond fully to viral and bacterial threats [1]. This normal signaling capacity ensures robust defense mechanisms against intracellular pathogens such as Mycobacterium tuberculosis [1]. However, this fully active state also means there is no genetic protection against common autoimmune conditions [2]. Baseline susceptibility remains for rheumatoid arthritis, psoriasis, and multiple sclerosis [2]. Most people globally carry this genotype, representing the evolutionary baseline for human immune function.
Standard immune system signaling; Baseline risk for autoimmune diseases; Typical defense against tuberculosis.
Sample genotype: CC (Homozygous)
Highly dampened TYK2 signaling provides powerful genetic protection against autoimmune conditions like rheumatoid arthritis, psoriasis, and multiple sclerosis [1]. However, this profound reduction in cytokine signaling severely compromises the body's ability to fight off certain pathogens [2]. A dramatically elevated risk of developing active tuberculosis exists if exposed to the bacterium [2]. Additionally, a higher risk of experiencing severe complications from viral infections like COVID-19 is present [3]. This genotype represents a stark evolutionary trade-off between inflammatory protection and infectious vulnerability.
Strong protection against autoimmune diseases; Significantly increased susceptibility to tuberculosis; Higher risk of severe COVID-19 complications.
Sample genotype: GC (Heterozygous)
A partial reduction in TYK2 signaling activity helps lower the risk of developing autoimmune diseases [1]. Moderate protection is conferred against rheumatoid arthritis, psoriasis, and multiple sclerosis [1]. Because the second copy of the gene remains fully functional, overall immune defense is preserved [2]. General resistance to viral and bacterial infections remains comparable to the baseline population [2]. This heterozygous state successfully balances autoimmune protection with robust pathogen defense.
Slightly lowered risk of rheumatoid arthritis; Slightly lowered risk of psoriasis; Maintained defense against infections.
Variants with shared genetic architecture
rs12720356 · TYK2 Gene · Chr 19 · Autoimmune Disease Risk
rs2304256 · TYK2 Gene · Chr 19 · Autoimmune Disease Risk
rs280519 · TYK2 Gene · Chr 19 · Autoimmune Disease Risk
Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity.
GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19.
Content updated August 2026.
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