What you carry at this position in your DNA and what research says about it.
Skin Cancer Risk: 10/10 evidence, 59 publications.
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Sample genotype (not yours): C/C
Typical Skin Cancer Risk and Darker Pigmentation
You carry two copies of the common C allele, which is associated with typical skin cancer risk and darker hair and eye pigmentation. Your skin has a typical ability to tan and is less sensitive to sunburn.
What this genotype means: Typical skin cancer risk; Lower sensitivity to sunburn; Darker hair and eye pigmentation.
Sample genotype (not yours): C/T
Increased Skin Cancer Risk and Sun Sensitivity
Carrying one copy of the T allele increases your sensitivity to the sun and raises your risk of skin cancers. You are more likely to have freckles, lighter eyes, and a reduced ability to tan.
What this genotype means: Increased risk of skin cancers; Higher sensitivity to sunburn; Likelihood of freckles and lighter eyes.
Sample genotype (not yours): T/T
Significantly Increased Skin Cancer Risk and High Sun Sensitivity
Carrying two copies of the T allele significantly increases your risk of skin cancers and sunburns. You are highly likely to have freckles, light eyes, and a very limited ability to tan.
What this genotype means: Significantly increased risk of skin cancers; Very high sensitivity to sunburn; Strong likelihood of freckles and light eyes.
Gene function and biological role
Gene Function: The IRF4 gene encodes interferon regulatory factor 4, a transcription factor crucial for both immune system regulation and melanocyte development [1]. In immune cells, it guides the development and activation of B cells, T cells, and dendritic cells. In pigment-producing melanocytes, IRF4 works alongside other key factors to activate the expression of tyrosinase, the primary enzyme responsible for melanin synthesis [2]. This dual role makes the gene a central hub linking immune defense, skin pigmentation, and cancer susceptibility [1].
Variant Impact: The rs12203592 variant is located in an intronic enhancer region of the IRF4 gene [1]. The ancestral C allele allows strong binding of transcription factors, promoting robust IRF4 expression in melanocytes [2]. The variant T allele disrupts this binding site, leading to significantly reduced IRF4 levels and impaired melanin production [2]. This molecular change results in lighter skin, reduced tanning ability, and a higher vulnerability to ultraviolet radiation [1].
Read on the Burns or Tans page
Key Insight: This single genetic letter change acts as a molecular bridge between your immune system and your skin's natural sun defense.
Location: IRF4. Chromosome 6 · 6p25.3 · 0.4 Mb
Origin Story: The T allele is found almost exclusively in populations of European ancestry, particularly in Ireland, where it likely underwent positive selection to maximize vitamin D synthesis in low-sunlight northern climates despite the trade-off of increased skin cancer risk.
Estimated prevalence by population
Global 81.4%; European 69.2%; African 93.5%; East Asian 99.9%; South Asian 98.1%; Americas 85.0%; Ashkenazi 62.2%; Finnish 94.9%; Middle Eastern 91.4%; Amish 95.2%.
Estimated CC genotype frequency.
Global 17.2%; European 28.0%; African 6.3%; East Asian 0.1%; South Asian 1.9%; Americas 14.4%; Ashkenazi 33.4%; Finnish 5.1%; Middle Eastern 8.4%; Amish 4.7%.
Estimated CT genotype frequency.
Global 1.5%; European 2.8%; African 0.1%; East Asian < 0.1%; South Asian < 0.1%; Americas 0.6%; Ashkenazi 4.5%; Finnish 0.1%; Middle Eastern 0.2%; Amish 0.1%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Cancer & Oncology
Skin Cancer
Skin Cancer. Evidence: 10/10. Source: PMID 21270109. Typical Risk.
Blood Cancers
Leukemia. Evidence: 4/10. Source: PMID 34220922. Typical Risk.
Organ Systems
Pigmentation & Appearance
Sun Sensitivity. Evidence: 9/10. Source: PMID 23548203. Typical Sensitivity.
Freckles. Evidence: 6/10. Source: PMID 20585627. Fewer Freckles.
Eye Color. Evidence: 10/10. Source: PMID 20585627. Darker Eyes.
Hair Color. Evidence: 10/10. Source: PMID 18483556. Darker Hair.
Showing effects for C/T genotype
Skin Cancer. Evidence: 10/10. Source: PMID 21270109. ~1.5x Increased Risk.
Leukemia. Evidence: 4/10. Source: PMID 34220922. ~1.38x Increased Risk.
Sun Sensitivity. Evidence: 9/10. Source: PMID 23548203. Increased Sensitivity.
Freckles. Evidence: 6/10. Source: PMID 20585627. More Freckles.
Eye Color. Evidence: 10/10. Source: PMID 20585627. Lighter Eyes.
Hair Color. Evidence: 10/10. Source: PMID 18483556. Brown or Fair Hair.
Showing effects for T/T genotype
Skin Cancer. Evidence: 10/10. Source: PMID 21270109. ~1.6x Increased Risk.
Sun Sensitivity. Evidence: 9/10. Source: PMID 23548203. High Sensitivity.
Freckles. Evidence: 6/10. Source: PMID 20585627. Many Freckles.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Robust expression of the IRF4 gene in skin cells is maintained by the ancestral C allele [1]. This robust expression helps activate tyrosinase, the enzyme that produces protective melanin pigment [2]. As a result, your skin is naturally more resilient to ultraviolet radiation, with a lower risk of developing melanoma, basal cell carcinoma, and squamous cell carcinoma [1]. You are also less likely to experience severe sunburns or extensive freckling [2]. However, this genotype is associated with a slightly higher susceptibility to vitiligo, an autoimmune skin condition, and male-pattern baldness [3]. Overall, your genetic profile supports standard cellular defenses against sun-induced damage.
Typical skin cancer risk; Lower sensitivity to sunburn; Darker hair and eye pigmentation.
Sample genotype: CT (Heterozygous)
A single copy of the T allele reduces the binding efficiency of key transcription factors in skin cells [1]. This leads to lower levels of IRF4 expression, which in turn reduces the production of protective melanin [2]. Consequently, you have an increased risk of developing melanoma, basal cell carcinoma, and squamous cell carcinoma [1]. Your skin is more prone to sunburn and freckling when exposed to ultraviolet light [2]. This genetic variant is also linked to lighter eye colors and brown or fair hair [2]. Additionally, there is a moderately elevated risk for certain blood-related conditions like acute myeloid leukemia [3]. Taking proactive sun protection measures is highly beneficial for managing these risks.
Increased risk of skin cancers; Higher sensitivity to sunburn; Likelihood of freckles and lighter eyes.
Sample genotype: TT (Homozygous)
Disrupted transcription factor binding from two copies of the T allele leads to a substantial reduction in IRF4 expression [1]. This severely limits your skin's ability to synthesize protective melanin in response to sun exposure [2]. As a result, you face a significantly higher risk of melanoma, basal cell carcinoma, and squamous cell carcinoma [1]. Your skin is highly sensitive to ultraviolet radiation, making sunburns and freckling very common [2]. This genotype is strongly associated with blue or light eyes and brown or fair hair [2]. Furthermore, you have an elevated susceptibility to uveal melanoma and myeloid leukemias [3]. Diligent sun protection, including daily sunscreen and regular skin checks, is crucial for your long-term health.
Significantly increased risk of skin cancers; Very high sensitivity to sunburn; Strong likelihood of freckles and light eyes.
Variants with shared genetic architecture
rs872071 · IRF4 Gene · Chr 6 · Lymphatic Cancer Risk
rs4911414 · ASIP Gene · Chr 20 · Sun Sensitivity
rs16891982 · SLC45A2 Gene · Chr 5 · Skin Cancer Risk
A germline variant in the interferon regulatory factor 4 gene as a novel skin cancer risk locus.
Content updated August 2026.
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