rs1393350
badMag 4.5This is a intron variant variant in the TYR gene.
Key Literature Trait Associations
Melanoma
The A allele of rs1393350 in TYR is robustly associated with cutaneous melanoma risk. A landmark GWAS by Bishop et al. (2009) identified this locus at genome-wide significance (p=2.41×10⁻¹⁴, OR≈1.29–1.30) across European-ancestry cohorts, with consistent homogeneity of effect across geographically diverse populations. A 2011 systematic meta-analysis by Chatzinasiou et al. confirmed the 11q14.3 TYR locus as one of only four genome-wide significant melanoma susceptibility loci with strong epidemiological credibility. The biological basis involves TYR's central role in melanin synthesis and its recognized association with freckling, cutaneous sun sensitivity, and UV damage response—established melanoma risk factors.
Eye color
The A allele of rs1393350 is associated with lighter (blue/gray) eye color and is one of six SNPs forming the validated IrisPlex forensic eye-color prediction system. Walsh et al. (2011) established this panel using 6,168 Dutch Europeans, achieving >90% prediction accuracy for blue and brown eye colors. GWAS Catalog data reports OR≈1.52 (p=3×10⁻¹²) and a beta of −0.28 units decrease in eye darkness score per A allele (p=3×10⁻⁹). The association reflects TYR's enzymatic role in melanin deposition in the iris; reduced tyrosinase activity associated with the A allele produces less pigment and lighter iris appearance.
Skin sensitivity to sun
The A allele of rs1393350 is associated with greater skin sensitivity to sun exposure (OR≈1.26 per copy, p=2×10⁻⁶), consistent with the lower baseline melanin production conferred by this TYR allele. Individuals with reduced tyrosinase activity produce less photoprotective eumelanin, resulting in poorer tanning response, increased UV sensitivity, and higher risk of sunburn. GWAS Catalog data identifies the A allele as the risk allele at this locus for sun sensitivity phenotypes in European populations.
Suntan
The A allele of rs1393350 is associated with reduced tanning ability (beta=0.19 decrease in tanning score per allele, p=2×10⁻¹³), reflecting the role of TYR in eumelanin synthesis. Eumelanin is the primary pigment responsible for the facultative tanning response to UV radiation; reduced tyrosinase activity limits UV-induced melanin production. This tanning phenotype association reinforces the mechanistic link between rs1393350 and the broader cluster of TYR-related pigmentation traits.
Freckling
rs1393350 is an intronic variant in TYR (tyrosinase, the rate-limiting enzyme of melanin synthesis) that tags the coding variant rs1126809 (R402Q) via strong linkage disequilibrium (r2=0.86). The A allele is associated with reduced TYR activity, lighter skin, and increased freckling propensity. It also shows a modest shift toward blue versus green iris pigmentation.
▶GWAS Catalog Trait Associations (6)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
GWAS Catalog Trait Associations (6)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
▶Research that mentions this SNP (3)
▶Association of TGFβ1 and clinical factors with scar outcome following melanoma excisionAssociationN=202Ward SV et al.(2012)· Archives of Dermatological Research
Genetic association study of 202 melanoma patients examining SNPs in 24 candidate genes related to pigmentation and wound healing in relation to scar outcome. SNP rs8110090 in TGFβ1 was significantly associated with poorer scar outcomes (p=0.0002). Clinical factors including younger age, shorter time since surgery, and presence of infection or eczema were also associated with worse scarring.
▶Model-based prediction of human hair color using DNA variantsAssociationN=385Wojciech Branicki et al.(2011)· Human Genetics
This study demonstrates that human hair color can be predicted from DNA variants with high accuracy using a multinomial logistic regression model. A subset of 13 genetic markers from 11 genes (MC1R, HERC2, IRF4, TYR, EXOC2, SLC45A2, TYRP1, OCA2, SLC24A4, KITLG, ASIP) predicted hair color categories in Polish Europeans with AUC values of 0.93 for red hair, 0.87 for black hair, 0.82 for brown hair, and 0.81 for blond hair. MC1R variants showed the strongest association with red hair (OR=12.64 for R variants, P=2.5×10⁻¹⁷), while rs12913832 in HERC2 was significantly associated with darker hair colors (OR=3.33 for black, P=4.3×10⁻⁶).
▶Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in CaucasiansAssociationN=1,673Hongmei Nan et al.(2009)· International Journal of Cancer
Nested case-control study of 1,673 Caucasian women examining 15 SNPs in pigmentation genes. TYR Arg402Gln (rs1126809) and SLC45A2 Phe374Leu (rs16891982) were significantly associated with skin color and tanning ability. ASIP haplotype (rs4911414[T], rs1015362[G]) increased melanoma risk (OR 1.68) and SCC risk (OR 1.54), while TYRP1 rs1408799 and SLC45A2 -1721 C>G (rs13289) showed protective effects against melanoma (OR 0.77, 0.75 respectively). No associations remained significant after Bonferroni correction.
Gene information from NCBI Gene. Variant classifications from ClinVar.
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