• Gene: TYK2 (Tyrosine Kinase 2)

• Chromosome: 19p13.2

• Position (GRCh38): Chr19: 10350471

Location Within Gene: Exon 8 (missense coding variant)

• A allele

Causes a Valine to Phenylalanine substitution at position 362 (V362F)

• Alters the pseudokinase domain of TYK2

• Affects stability and function of TYK2 protein

• The A allele is associated with modulated cytokine signaling, especially Type I interferons, IL-12, and IL-23

• TYK2 is a key JAK family member—this SNP affects JAK-STAT pathway signaling

• Modifies responsiveness to multiple cytokines, particularly IFN-α, IL-6, IL-10, IL-12, and IL-23

• The A allele has been associated with both protective and risk-modifying effects depending on the disease and cytokine balance

• European (EUR): A allele ~45–55%

• East Asian (EAS): A allele ~80%

African (AFR): A allele ~60–65%
(Source: gnomAD, 1000 Genomes)

• TYK2, JAK1/STAT1/STAT3/STAT4

• JAK-STAT cytokine signaling

• Interferon signaling

• Th1 and Th17 cell development

• Immune regulation and antiviral defense

• Autoimmune Addison’s Disease

• Systemic Lupus Erythematosus (SLE)

• Multiple Sclerosis

• Type 1 Diabetes

• Psoriasis

• Rheumatoid Arthritis

• Inflammatory Bowel Disease

• rs2304256 is one of the most widely studied TYK2 SNPs in autoimmune disease genetics

• Some studies suggest the A allele may be protective in MS and RA, while increasing risk in Addison’s and T1D

• Functional analysis shows modulation of cytokine signaling, not a full gain or loss of function—more like a re-calibration of immune sensitivity

• Affects how strongly immune cells respond to inflammatory cues

• Adds nuance to disease risk—it can enhance or dampen immune responses depending on other genetic and environmental factors

• Important in therapeutic decision-making—TYK2 is a drug target for multiple autoimmune drugs (e.g., deucravacitinib)

rs2304256 is a functional missense SNP in TYK2 that tweaks the intensity of cytokine signaling via the JAK-STAT pathway. It’s implicated in Addison’s Disease and many other autoimmune conditions, making it one of the most important cross-disease SNPs in immunogenetics.

ItemThis SNP report is intended for informational and educational purposes only. It should not be used to diagnose or treat any health condition. All genetic findings must be interpreted by qualified medical professionals in the context of clinical and family history. description