PTPN22 rs2476601: Autoimmune Risk Variant
The rs2476601 variant is a common genetic change in the PTPN22 gene associated with an increased risk for several autoimmune diseases. While it influences immune system function, it is not a diagnostic test and does not predict disease development.
What each genotype means
Typical autoimmune risk profile
This is the most common genotype for this variant. Research indicates that individuals with this genotype do not carry the specific risk-associated change linked to increased susceptibility for several autoimmune conditions, such as type 1 diabetes and rheumatoid arthritis.
This is the major genotype found in the vast majority of the global population.
Increased autoimmune risk
This genotype includes one copy of the T allele, also known as the R620W variant. Studies have associated this allele with an increased statistical risk for developing multiple autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus, likely due to its role in regulating immune cell signaling.
This genotype is carried by a significant portion of individuals of European ancestry, though it is much less common in East Asian populations.
Elevated autoimmune risk
This genotype includes two copies of the T allele, which is associated with altered PTPN22 protein function and immune system regulation. Individuals with this genotype may have a higher statistical predisposition to certain autoimmune conditions compared to those without the T allele, though this does not mean a disease will develop.
This is the least common genotype, occurring at a low frequency in most populations.
What is the rs2476601 Variant?
The rs2476601 variant is a single-nucleotide polymorphism (SNP) located within the PTPN22 gene on chromosome 1. It is often referred to in scientific literature as 'C1858T' or by its protein-level change, 'R620W', indicating an amino acid substitution from arginine to tryptophan at position 620. This genetic alteration modifies the structure of the PTPN22 protein. Its relatively high frequency across human populations has facilitated extensive research into its effects on immune system regulation. The specific notation (C/T or G/A) can vary depending on whether the coding or complementary strand is analyzed, but the biological significance of the variant remains consistent.
The Role of the PTPN22 Gene
The PTPN22 gene encodes a protein called lymphoid tyrosine phosphatase (LYP), a critical regulator of T cell activity within the immune system. LYP functions as an 'off switch' for certain signaling pathways, helping to maintain immune tolerance—the body's ability to distinguish self from non-self and avoid attacking its own tissues. By dephosphorylating key signaling molecules, LYP helps to dampen immune responses. When the PTPN22 protein's function is altered by the rs2476601 variant, this regulatory 'brake' may be less effective. This can lead to dysregulated immune signaling, potentially increasing the likelihood of the immune system mounting an inappropriate response against the body's own cells.
Research and Disease Association
Rs2476601 is recognized as a significant genetic risk factor for multiple autoimmune diseases, independent of HLA associations. Studies have consistently linked this variant to an increased susceptibility to conditions such as type 1 diabetes, rheumatoid arthritis, and Graves' disease. The evidence supporting these associations is considered moderate to strong, derived from numerous genome-wide association studies (GWAS) and meta-analyses. However, the relationship is complex; in some populations, this variant has been associated with a reduced risk of other conditions like Crohn's disease. It's crucial to understand that this SNP is just one piece of a larger puzzle, contributing a small part to the overall risk profile for these multifactorial diseases.
Population Frequency
The frequency of the rs2476601 variant differs considerably across global populations. The allele associated with increased autoimmune risk is most prevalent among individuals of European descent, estimated to occur in about 10–18% of this group. In many other ancestral populations, this variant is considerably rarer. These variations in prevalence highlight the importance of studying diverse populations to fully understand the role and impact of genetic factors in health and disease worldwide.
Understanding Your Genotype
Possessing a specific genotype for rs2476601 does not guarantee the development of an autoimmune disease. Many individuals with the risk-associated allele remain healthy throughout their lives. It is essential to consult with a healthcare professional for personalized health advice and risk assessment, as genetic information alone is not sufficient for diagnosis or medical decision-making. For any health concerns, always seek guidance from a qualified medical provider.
How common is this variant?
The risk-associated allele for rs2476601 is most common in European populations, where it is found in approximately 10-18% of individuals, and is much rarer in other global populations.
Frequently asked questions
Can a DNA test tell me if I have an autoimmune disease?
No, genetic variants like rs2476601 indicate susceptibility or risk, not a diagnosis. Autoimmune diseases are diagnosed by clinicians based on symptoms, physical exams, and specific diagnostic tests.
What should I do if I have the risk allele for rs2476601?
No specific action is required. This variant is common, and most carriers do not develop autoimmune conditions. Focus on a healthy lifestyle and discuss any health concerns with your doctor.
Is rs2476601 used for medication dosing?
No, this variant is not currently used to guide medication dosing. Always discuss your treatment plan and any questions about medication with your clinician or pharmacist.
Why is the risk allele for rs2476601 more common in some populations?
Genetic variations arise from human history, migration, and evolutionary pressures. Understanding these population-specific frequencies is key to global health research and understanding disease patterns.
What is the PTPN22 gene's function?
The PTPN22 gene produces a protein called lymphoid tyrosine phosphatase (LYP), which acts as a regulator, or 'brake,' for the immune system, particularly in T cells, helping to prevent autoimmune responses.
Sources & further reading
Educational information only, last refreshed 10/5/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This variant in PTPN22 is associated with autoimmune-related phenotypes in patients with chronic spontaneous urticaria.
This variant in the PTPN22 gene region is associated with altered risk for autoimmune conditions including type 1 diabetes and rheumatoid arthritis.
Located in the promoter region of PTPN22, this variant has been robustly associated via genome-wide association studies with altered risk for autoimmune disorders such as type 1 diabetes and rheumatoid arthritis.
Potent autoantigen-signaling variant R620W strongly associated with susceptibility to rheumatoid arthritis, type 1 diabetes, and systemic lupus erythematosus.
The C/C genotype at this locus is linked to the downregulation of PTPN22 mRNA expression and increased rheumatoid arthritis risk.