rs1042602 — TYR S192Y

Common tyrosinase variant affecting melanin production, skin pigmentation, tanning ability, freckling, and melanoma risk

See your personal result for TYR

Upload your DNA data to find out which genotype you carry and what it means for you.

Upload your DNA data

Works with 23andMe, AncestryDNA, and other DNA test exports. Results in under 60 seconds.

Tyrosinase S192Y — Your Melanin Production Blueprint

Tyrosinase is the rate-limiting enzyme in melanin biosynthesis11 melanin biosynthesis
the production of melanin, the pigment that gives skin, hair, and eyes their color, functioning as a copper-containing oxidase that converts the amino acid tyrosine into dopaquinone22 dopaquinone
the first intermediate in melanin production, which then undergoes a series of reactions to form melanin. The S192Y variant (serine to tyrosine at position 192) is one of the most common polymorphisms in the TYR gene, particularly prevalent in European populations where the A allele frequency is approximately 35% (meaning ~58% of Europeans carry at least one copy), while the variant is virtually absent in East Asian populations (~0.1%) and present at low frequency in African populations (~5%)33 virtually absent in East Asian populations (~0.1%) and present at low frequency in African populations (~5%)
nearly fixed at the ancestral C allele in East Asian populations; found at ~5% in African populations per gnomAD.

The Mechanism

The S192Y substitution occurs at a critical position in the tyrosinase enzyme. While the variant enzyme retains catalytic activity, biochemical studies in primary melanocytes44 biochemical studies in primary melanocytes
functional analysis comparing melanocytes with different TYR genotypes demonstrate that the 192Y form exhibits reduced tyrosine hydroxylase and DOPA oxidase activities compared to the ancestral 192S form. This missense change affects post-translational regulation of the enzyme rather than transcription levels, meaning cells produce similar amounts of tyrosinase protein, but the Y192 variant functions less efficiently at converting tyrosine to dopaquinone, the committed step in melanin synthesis.

The variant appears to have undergone positive natural selection in European populations55 positive natural selection in European populations
evidence of recent positive selection with the derived A allele in Sulem et al. 2007, possibly as populations migrated to higher latitudes with lower UV exposure, where lighter pigmentation reduced vitamin D deficiency risk while maintaining adequate photoprotection.

The Evidence

Large-scale population studies66 Large-scale population studies
GWAS in 2,986 Icelanders with replication in 2,718 Icelanders and 1,214 Dutch individuals established that rs1042602 is strongly associated with freckling (OR=1.32, p=1.5×10⁻¹¹), with the A allele (192Y) associated with absence of freckles. Interestingly, no association was found with overall skin or eye color, suggesting this variant specifically affects the melanocytic response to UV exposure rather than constitutive pigmentation. In South Asian populations77 South Asian populations
GWAS of 737 South Asian individuals in the UK, the same variant showed strong association with skin pigmentation variation.

The most clinically significant finding emerged from melanoma risk studies88 melanoma risk studies
analysis of 1,025 melanoma patients and 773 healthy controls in Spain: the A allele (192Y) was significantly associated with increased melanoma susceptibility (p=0.0035) and, strikingly, with poorer disease-free survival, particularly in men. Carriers of the A allele99 Carriers of the A allele
patients with at least one A allele showed shorter disease-free survival periods, and in multivariate analysis adjusted for age, Breslow thickness, ulceration, and melanoma subtype, the association remained significant (HR=0.4, 95% CI 0.20-0.83, p=0.0139 for men).

Practical Implications

If you carry one or two copies of the A allele (192Y variant), your melanocytes produce less melanin in response to UV exposure, which translates to reduced tanning ability and altered freckling patterns. More importantly, this variant appears to increase melanoma risk beyond its effect on pigmentation alone—suggesting the variant may influence melanocyte biology in ways that affect both UV response and malignant transformation potential.

Functional studies1010 Functional studies
compound heterozygosity analysis in OCA1B patients have shown that when S192Y occurs in cis (on the same chromosome) with another TYR variant (R402Q), the compound haplotype can cause a mild but penetrant form of oculocutaneous albinism in homozygotes. However, the S192Y variant alone, even in homozygous form, produces only subtle pigmentation differences rather than clinical albinism.

Interactions

TYR S192Y interacts significantly with rs1126809 (R402Q), another common TYR variant. The two SNPs show high linkage disequilibrium (r²=0.86). R402Q drives the temperature-sensitive reduction in tyrosinase activity documented in biochemical studies — near wild-type activity can be recovered at lower culture temperature in 402Q/Q melanocytes — and when S192Y and R402Q are inherited together in cis, the compound haplotype functions as a pathogenic OCA1B allele that can lead to mild albinism phenotypes when homozygous or compound heterozygous with a pathogenic TYR variant in trans. This highlights the importance of considering both variants together when assessing pigmentation-related phenotypes.

The variant also shows epistatic interactions with other pigmentation genes including SLC45A2 (rs16891982, L374F) and SLC24A5 (rs1426654, A111T), as these genes encode proteins involved in melanosome pH regulation and trafficking, which affect the cellular environment where tyrosinase functions. Geographic correlation studies1111 Geographic correlation studies
analysis across Chinese populations demonstrate that rs1042602 allele frequencies correlate with latitude, sunshine hours, and temperature, confirming environmental selective pressure on this locus.

Genotype Interpretations

What each possible genotype means for this variant.

CC Normal Melanin Production Normal

Standard tyrosinase activity with normal tanning ability and baseline melanoma risk

You have two copies of the ancestral 192S form of tyrosinase, which provides normal melanin synthesis capacity. About 42% of Europeans share this genotype, while it is nearly universal (>99%) in East Asian populations and very common (~90%) in African populations. Your melanocytes respond to UV exposure with typical melanin production, supporting normal tanning ability and freckling patterns based on your other pigmentation genes. This genotype is associated with lower melanoma risk compared to A-allele carriers.

AC Intermediate Melanin Production Intermediate

Moderately reduced melanin synthesis with mildly increased melanoma risk

The heterozygous state produces both wild-type and variant tyrosinase enzymes. Studies suggest a gene-dosage effect where heterozygotes show intermediate melanin production capacity. Your melanocytes can mount a partial UV-protective response through the wild-type enzyme, but the presence of the less efficient Y192 variant somewhat limits your overall melanogenic capacity.

The melanoma risk for AC individuals falls between AA and CC genotypes, following a dose-dependent pattern. In survival analyses of melanoma patients, those carrying even one A allele showed reduced disease-free survival compared to CC patients, though the effect was less pronounced than in AA homozygotes.

AA Reduced Melanin Production Reduced

Lower melanin synthesis with increased melanoma risk and altered UV response

The homozygous AA genotype produces tyrosinase enzymes with serine replaced by tyrosine at position 192 on both chromosomes. Biochemical studies show this variant has measurably reduced tyrosine hydroxylase and DOPA oxidase activities compared to the wild-type enzyme. While this doesn't cause albinism (you still produce melanin), it does affect the melanocyte's ability to respond to UV radiation with protective melanin production.

The melanoma association is particularly notable. In a large Spanish cohort, AA individuals showed not only increased melanoma susceptibility but also significantly shorter disease-free survival periods after diagnosis. The mechanism appears to involve more than just reduced photoprotection—the variant may affect melanocyte stress responses or DNA repair capacity in ways that influence tumor behavior. This effect was most pronounced in men.