PTPN22 rs2488457: Understanding Your Genetic Variant
The rs2488457 variant is a single-nucleotide polymorphism located in the promoter region of the PTPN22 gene. It is statistically associated with the regulation of PTPN22 expression and has been studied for its potential link to an increased risk of several autoimmune conditions.
What each genotype means
Typical PTPN22 expression
This is the most common genotype at this locus. Research indicates that individuals with this genotype do not show the specific downregulation of PTPN22 mRNA expression associated with the risk-linked G allele.
This is the most frequent genotype observed in most global populations.
Slightly increased autoimmune risk
Carrying one copy of the G allele has been associated in some studies with a slightly increased risk for certain autoimmune conditions, including rheumatoid arthritis. Research suggests this variant may influence PTPN22 mRNA expression levels, though the clinical significance varies by ancestry.
This heterozygous genotype is found at varying frequencies across different ethnic groups.
Increased autoimmune risk profile
Individuals with this genotype may have a higher statistical association with certain autoimmune diseases compared to those with the C/C genotype. Studies have linked this variant to the downregulation of PTPN22 mRNA expression, which may play a role in immune system regulation.
This genotype is less common than the C/C genotype and its prevalence varies significantly by ancestry.
What is rs2488457?
The rs2488457 variant is a specific genetic change located on chromosome 1 within the promoter region of the PTPN22 gene. In genetic literature, this variant is sometimes referred to as c.-1123C>G. A promoter region is a segment of DNA that acts as a control switch, determining how much of a gene's product is created by the cell. Because rs2488457 sits in this regulatory area, researchers investigate whether the presence of different alleles (the C or G versions of the DNA letter) changes the activity of the PTPN22 gene. This variant is distinct from other well-known PTPN22 variants, such as the R620W missense mutation, and is studied independently to understand its specific contribution to gene expression levels.
The Role of the PTPN22 Gene
The PTPN22 gene provides the blueprint for a protein known as lymphoid-specific tyrosine phosphatase (LYP). This protein is primarily expressed in hematopoietic cells, which include the various types of immune cells in your body. Its main function is to act as a negative regulator of T-cell receptor signaling. By controlling these signals, the PTPN22 protein helps maintain immune homeostasis, ensuring that T cells—the body's primary defense against infection—do not become overactive or attack the body's own healthy tissues. When the expression or function of this protein is altered, it may disrupt the delicate balance of the immune system, which is why variants in this gene are frequently investigated in the context of autoimmune research.
Research and Autoimmune Associations
Scientific studies have explored the association between the rs2488457 variant and various autoimmune diseases, including rheumatoid arthritis, type 1 diabetes, and systemic lupus erythematosus. Research suggests that the G allele may be linked to the downregulation of PTPN22 mRNA expression. In some populations, individuals carrying the G allele have shown a statistically higher risk for certain autoimmune conditions compared to those with the C/C genotype. However, it is important to note that the evidence for this association is moderate and can vary significantly between different ethnic groups. Autoimmune diseases are complex, multifactorial conditions influenced by a combination of numerous genetic variants and environmental triggers, meaning that possessing a specific genotype does not guarantee the development of any disease.
Interpreting Your Genetic Information
Genetic information regarding variants like rs2488457 is intended for educational purposes and should not be used for medical diagnosis or to predict personal health outcomes. While statistical associations exist in large population studies, they do not account for the unique interplay of your entire genome, lifestyle, or environmental history. If you are concerned about your risk for autoimmune conditions or have questions about your health, it is essential to consult with a qualified healthcare professional or a genetic counselor. They can provide context based on your personal and family medical history. Never use genetic data to make decisions about medications or treatments; always discuss any health-related concerns or potential changes to your care with your clinician or pharmacist.
How common is this variant?
The frequency of the rs2488457 variant is variable across different ethnic populations, with the minor G allele appearing at different rates in global cohorts.
Frequently asked questions
Does having the G allele mean I will get an autoimmune disease?
No. Genetic variants like rs2488457 only represent a small statistical increase in risk within a population. Most people with the G allele will never develop an autoimmune condition, as these diseases are complex and involve many other genetic and environmental factors.
Is rs2488457 the same as the R620W variant?
No. rs2488457 is a promoter variant located in the regulatory region of the PTPN22 gene, while R620W (rs2476601) is a missense variant that changes the amino acid sequence of the PTPN22 protein. They are distinct genetic markers.
Can I change my PTPN22 expression levels?
There is no known way to specifically alter the expression of the PTPN22 gene based on your genotype. Genetic expression is a complex biological process regulated by your body's internal systems.
Where can I find more information about my specific risk?
If you are concerned about your health, you should speak with a doctor or a genetic counselor. They can evaluate your personal and family medical history to provide a meaningful assessment of your health risks.
Sources & further reading
Educational information only, last refreshed 9/16/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Get my report — $29Related variants in PTPN22
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.
This variant in the PTPN22 gene region is associated with altered risk for autoimmune conditions including type 1 diabetes and rheumatoid arthritis.
This variant is a major risk factor for several autoimmune diseases, including type 1 diabetes and rheumatoid arthritis.