What you carry at this position in your DNA and what research says about it.
Autoimmune Disease Risk: 10/10 evidence, 115 publications.
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Sample genotype (not yours): G/G
Typical Autoimmune Risk
Standard immune regulation is maintained by this common genotype, resulting in a typical baseline risk for most autoimmune disorders.
What this genotype means: Typical baseline risk for rheumatoid arthritis; Typical baseline risk for type 1 diabetes; Slightly higher risk for Crohn's disease compared to A carriers.
Sample genotype (not yours): A/A
Highly Increased Risk of Autoimmune Disorders
Double copies of the A allele significantly increase the risk for multiple autoimmune conditions, particularly rheumatoid arthritis and type 1 diabetes.
What this genotype means: Significantly increased risk of rheumatoid arthritis; Significantly increased risk of type 1 diabetes; Lower risk of Crohn's disease.
Sample genotype (not yours): A/G
Increased Risk of Autoimmune Disorders
Presence of one copy of the A allele increases susceptibility to several autoimmune conditions, including rheumatoid arthritis and type 1 diabetes.
What this genotype means: Increased risk of rheumatoid arthritis; Increased risk of type 1 diabetes; Slightly lower risk of Crohn's disease.
Gene function and biological role
Gene Function: The PTPN22 gene encodes lymphoid tyrosine phosphatase, a powerful enzyme that acts as a natural brake on immune cell activation [1]. By dampening T-cell receptor signaling, this enzyme prevents the immune system from overreacting and attacking the body's own tissues [1]. When this gene functions normally, it helps maintain immune tolerance and prevents chronic inflammation. However, genetic variations in PTPN22 can disrupt this delicate balance, leading to either an overactive or underactive immune response. This makes PTPN22 one of the most critical non-HLA genes associated with human autoimmune diseases [1].
Variant Impact: The rs2476601 variant is a missense mutation in the PTPN22 gene that changes the amino acid at position 620 from arginine to tryptophan [1]. This specific structural change prevents the lymphoid tyrosine phosphatase enzyme from binding to its regulatory partner, Csk kinase [1]. Without this binding, the enzyme cannot properly shut down T-cell activation, leading to hyper-reactive immune cells [1]. Consequently, this single-nucleotide change is widely recognized as a major genetic risk factor for multiple autoimmune conditions [1]. Interestingly, while it increases susceptibility to many autoimmune disorders, it actually reduces the risk of Crohn's disease [2].
Key Insight: This single genetic variant acts as a master regulator of autoimmunity, raising the risk for several distinct diseases like rheumatoid arthritis and lupus while simultaneously lowering the risk for Crohn's disease.
Location: PTPN22. Chromosome 1 · 1p13.2 · 113.8 Mb
Estimated prevalence by population
Global 0.6%; European 1.0%; African < 0.1%; East Asian < 0.1%; South Asian < 0.1%; Americas 0.2%; Ashkenazi 0.3%; Finnish 2.1%; Middle Eastern < 0.1%; Amish 0.2%.
Estimated AA genotype frequency.
Global 11.9%; European 18.1%; African 3.0%; East Asian 0.1%; South Asian 2.5%; Americas 7.5%; Ashkenazi 10.6%; Finnish 25.0%; Middle Eastern 1.4%; Amish 7.6%.
Estimated AG genotype frequency.
Global 87.5%; European 80.9%; African 97.0%; East Asian 99.9%; South Asian 97.5%; Americas 92.4%; Ashkenazi 89.1%; Finnish 72.8%; Middle Eastern 98.6%; Amish 92.3%.
Estimated GG genotype frequency.
Showing effects for G/G genotype
Immunity & Inflammation
Autoimmune Diseases
Rheumatoid Arthritis. Evidence: 10/10. Source: PMID 17804836. Typical Risk.
Lupus. Evidence: 10/10. Source: PMID 19838195. Typical Risk.
Chronic Inflammatory Diseases
Crohn's Disease. Evidence: 10/10. Source: PMID 18587394. Increased Risk.
Cardiovascular & Metabolic
Diabetes & Glycemic Traits
Type 1 Diabetes. Evidence: 10/10. Source: PMID 17554260. Typical Risk.
Endocrine & Reproductive
Hormone Levels & Endocrine Regulation
Hypothyroidism. Evidence: 10/10. Source: PMID 27182965. Typical Risk.
Pharmacogenomics
Adverse Drug Reactions
Drug-Induced Liver Injury. Evidence: 6/10. Source: PMID 30664875. Typical Risk.
Showing effects for A/A genotype
Rheumatoid Arthritis. Evidence: 10/10. Source: PMID 17804836. ~2x Higher Risk.
Lupus. Evidence: 10/10. Source: PMID 19838195. Increased Risk.
Crohn's Disease. Evidence: 10/10. Source: PMID 18587394. Lower Risk.
Type 1 Diabetes. Evidence: 10/10. Source: PMID 17554260. Increased Risk.
Hypothyroidism. Evidence: 10/10. Source: PMID 27182965. Increased Risk.
Drug-Induced Liver Injury. Evidence: 6/10. Source: PMID 30664875. Increased Risk.
Showing effects for A/G genotype
Rheumatoid Arthritis. Evidence: 10/10. Source: PMID 17804836. Increased Risk.
Crohn's Disease. Evidence: 10/10. Source: PMID 18587394. Typical Risk.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Carrying the G/G genotype means your PTPN22 gene produces the standard arginine-containing version of the lymphoid tyrosine phosphatase enzyme [1]. This version of the enzyme successfully binds to its regulatory partner, Csk, allowing your body to properly downregulate T-cell activation when necessary [1]. As a result, you have a typical baseline risk for rheumatoid arthritis, type 1 diabetes, lupus, and autoimmune thyroid diseases [1]. However, because the G allele is associated with standard immune responses, it does carry a slightly higher risk for Crohn's disease compared to carriers of the A allele [2]. Overall, your immune system maintains a standard balance of activation and regulation. You also have a typical baseline risk of liver injury when taking the common antibiotic amoxicillin-clavulanate [3].
Typical baseline risk for rheumatoid arthritis; Typical baseline risk for type 1 diabetes; Slightly higher risk for Crohn's disease compared to A carriers.
Sample genotype: AA (Homozygous)
Having the A/A genotype means all of your PTPN22-derived enzymes contain tryptophan at position 620, severely disrupting their ability to regulate T-cell activation [1]. This lack of immune inhibition leads to a highly active immune system, which translates to roughly double the typical risk for rheumatoid arthritis and type 1 diabetes [1]. You also face significantly elevated risks for systemic lupus erythematosus, Hashimoto's thyroiditis, and Graves' disease [2]. Conversely, this hyper-reactive immune profile is protective against Crohn's disease, lowering your risk compared to the general population [3]. Additionally, you have a higher susceptibility to liver injury when taking the common antibiotic amoxicillin-clavulanate [4].
Significantly increased risk of rheumatoid arthritis; Significantly increased risk of type 1 diabetes; Lower risk of Crohn's disease; Increased risk of amoxicillin-clavulanate liver injury.
Sample genotype: AG (Heterozygous)
Having the A/G genotype means you produce both the standard and the hyper-reactive tryptophan-containing version of the lymphoid tyrosine phosphatase enzyme [1]. The variant enzyme cannot bind effectively to its regulatory partner, which reduces the immune system's ability to suppress T-cell activation [1]. This leads to an increased risk of developing rheumatoid arthritis, type 1 diabetes, and systemic lupus erythematosus [1]. On the positive side, this altered immune state appears to offer some protection against Crohn's disease [2]. You also have an increased likelihood of drug-induced liver injury if prescribed the common antibiotic amoxicillin-clavulanate [3].
Increased risk of rheumatoid arthritis; Increased risk of type 1 diabetes; Slightly lower risk of Crohn's disease; Increased risk of amoxicillin-clavulanate liver injury.
Variants with shared genetic architecture
rs6679677 · PTPN22 Gene · Chr 1 · Autoimmune Disease Risk
rs2488457 · AP4B1-AS1 Gene · Chr 1 · Autoimmune Disease Risk
rs3757387 · IRF5 Gene · Chr 7 · Autoimmune Disease Risk
PTPN22: the archetypal non-HLA autoimmunity gene.
Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease.
A Missense Variant in PTPN22 is a Risk Factor for Drug-induced Liver Injury.
Seven newly identified loci for autoimmune thyroid disease.
Content updated August 2026.
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