What you carry at this position in your DNA and what research says about it.
Psoriatic Arthritis Risk: 9/10 evidence, 17 publications.
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Sample genotype (not yours): C/C
Typical Risk of Psoriatic Arthritis
Possession of two copies of the common C allele is associated with a baseline risk for developing psoriatic arthritis and psoriasis.
What this genotype means: Normal Act1-TRAF6 protein binding; Typical baseline risk of psoriatic arthritis; Typical baseline risk of psoriasis.
Sample genotype (not yours): C/T
~1.6x Higher Risk of Psoriatic Arthritis
Inheriting one copy of the T allele is associated with an increased risk of developing psoriatic arthritis and cutaneous psoriasis.
What this genotype means: Disrupted Act1-TRAF6 protein binding; Elevated risk of psoriatic arthritis; Elevated risk of cutaneous psoriasis.
Sample genotype (not yours): T/T
Inheriting two copies of the T allele is associated with an increased risk of developing psoriatic arthritis and cutaneous psoriasis.
Gene function and biological role
Gene Function: The TRAF3IP2 gene encodes a vital immune signaling adapter protein known as Act1 or CIKS [1]. This protein plays a central role in regulating cellular responses to interleukin-17 (IL-17), a key cytokine involved in inflammation and defense against pathogens [1]. Act1 acts as a bridge, connecting interleukin receptors to downstream signaling pathways that activate inflammatory genes [2]. Proper functioning of this pathway is essential for maintaining skin barrier integrity and controlling fungal infections [3]. However, overactivity or dysregulation of this pathway can trigger chronic inflammatory and autoimmune conditions [2].
Variant Impact: A missense mutation at rs33980500 in the TRAF3IP2 gene changes the amino acid at position 10 from aspartate to asparagine [1]. This specific change, often referred to as p.Asp10Asn, occurs in the amino-terminal domain of the Act1 protein [1]. Functional studies show that this alteration severely disrupts the protein's ability to bind to its signaling partner, TRAF6 [2]. By impairing this interaction, the variant alters the modulation of immunoregulatory signals and downstream inflammatory pathways [1]. Despite this functional impairment, the variant is common in many populations and acts as a major genetic risk factor rather than a direct cause of disease [1].
Key Insight: The risk-increasing T allele actually reduces the binding of the Act1 protein to its signaling partner, showing that a loss of normal immune signaling can paradoxically promote chronic inflammation.
Location: TRAF3IP2. Chromosome 6 · 6q21 · 111.6 Mb
Estimated prevalence by population
Global 82.0%; European 85.8%; African 73.1%; East Asian 98.7%; South Asian 88.6%; Americas 78.9%; Ashkenazi 75.8%; Finnish 87.3%; Middle Eastern 80.6%; Amish 84.8%.
Estimated CC genotype frequency.
Global 17.0%; European 13.6%; African 24.8%; East Asian 1.3%; South Asian 11.1%; Americas 19.8%; Ashkenazi 22.5%; Finnish 12.2%; Middle Eastern 18.3%; Amish 14.5%.
Estimated CT genotype frequency.
Global 1.0%; European 0.5%; African 2.1%; East Asian < 0.1%; South Asian 0.3%; Americas 1.2%; Ashkenazi 1.7%; Finnish 0.4%; Middle Eastern 1.0%; Amish 0.6%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Immunity & Inflammation
Autoimmune Diseases
Psoriatic Arthritis. Evidence: 9/10. Source: PMID 20953186. Typical Risk.
Lupus. Evidence: 3/10. Source: PMID 23836313. Typical Risk.
Chronic Inflammatory Diseases
Inflammatory Bowel Disease. Evidence: 6/10. Source: PMID 38616254. Typical Risk.
Organ Systems
Skin & Hair Conditions
Psoriasis. Evidence: 10/10. Source: PMID 20953188. Typical Risk.
Showing effects for C/T genotype
Psoriatic Arthritis. Evidence: 9/10. Source: PMID 20953186. ~1.6x Increased Risk.
Lupus. Evidence: 3/10. Source: PMID 23836313. Increased Risk.
Inflammatory Bowel Disease. Evidence: 6/10. Source: PMID 38616254. Increased Risk.
Psoriasis. Evidence: 10/10. Source: PMID 20953188. Increased Risk.
Showing effects for T/T genotype
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Possessing two copies of the standard genetic sequence encodes aspartate at position 10 of the Act1 protein [1]. This configuration allows the Act1 protein to interact normally with its signaling partner, TRAF6, ensuring proper transmission of inflammatory signals [2]. Consequently, immune responses mediated by interleukin-17 function as expected, maintaining healthy skin barrier defenses [3]. Individuals with this genotype do not experience the elevated risk of chronic autoimmune joint and skin inflammation associated with the variant allele [1]. While this genotype represents the typical baseline risk in the general population, it does not guarantee complete immunity from developing inflammatory conditions, as environmental factors and other genetic loci also play significant roles [4].
Normal Act1-TRAF6 protein binding; Typical baseline risk of psoriatic arthritis; Typical baseline risk of psoriasis.
Sample genotype: CT (Heterozygous)
Inheriting one copy of the T allele leads to the production of an altered Act1 protein where aspartate is replaced by asparagine at position 10 [1]. This structural change impairs the protein's ability to bind with TRAF6, disrupting normal interleukin-17 signaling pathways [2]. Although the molecular mechanism involves a loss of interaction, the downstream effect paradoxically predisposes individuals to chronic inflammatory states [3]. Large-scale genetic studies have consistently linked this heterozygous genotype to a roughly 1.6-fold increase in the risk of developing psoriatic arthritis [1]. It is also associated with a higher susceptibility to plaque psoriasis and other autoimmune manifestations [4]. Knowing this risk can help individuals recognize early signs of joint stiffness or skin lesions, allowing for prompt clinical evaluation [1].
Disrupted Act1-TRAF6 protein binding; Elevated risk of psoriatic arthritis; Elevated risk of cutaneous psoriasis.
Sample genotype: TT (Homozygous)
Inheriting two copies of the T allele means all produced Act1 proteins have the asparagine substitution at position 10 [1]. This complete substitution severely impairs the protein's interaction with TRAF6, leading to altered modulation of immunoregulatory signals [2]. The resulting disruption in interleukin-17 signaling pathways is strongly associated with chronic inflammatory diseases [3]. Clinical studies show that this genotype carries a 1.6-fold or higher risk of developing psoriatic arthritis compared to the common genotype [1]. It also elevates susceptibility to cutaneous psoriasis, systemic lupus erythematosus, and other inflammatory conditions [4]. While this genetic profile increases susceptibility, many individuals with this genotype never develop these conditions, highlighting the importance of environmental triggers [1].
Variants with shared genetic architecture
rs12191877 · HLA-C Gene · Chr 6 · Psoriasis Risk
rs10484554 · HLA-C Gene · Chr 6 · Psoriasis Risk
rs12188300 · IL12B Gene · Chr 5 · Psoriasis Risk
Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis.
Content updated August 2026.
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