rs33932559

This is a variant in the MC1R gene that changes a isoleucine to an threonine.

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GWAS Catalog Trait Associations (1)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

Abnormality of skin pigmentation

Kim B et al. “Mapping and annotating genomic loci to prioritize genes and implicate distinct polygenic adaptations for skin color.” Nature Communications 15(1):4874 (2024)

Allele C

OR 0.12

p 6.0e-10

N 48,433

Large GWAS

East Asian

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ClinVar annotation

Pathogenic★☆☆☆

6 submitters6 publications

Melanoma, cutaneous malignant, susceptibility to, 5; not specified

View on ClinVar →

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Research that mentions this SNP (1)

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Identification of novel functional variants of the melanocortin 1 receptor gene originated from Asians

FunctionalN=995Kazuhiro Nakayama et al.(2006)· Human Genetics

This functional genetics study identified three novel MC1R gene variants with Asian origins: Phe147Δ, Thr157Ile, and Pro159Thr. In vitro cAMP assays demonstrated that these variants showed impaired signaling similar to or more severe than the European red-hair variant Arg151Cys, suggesting functional constraint on MC1R varies geographically, possibly due to UV light adaptation in Eurasian populations.

Traits studied:Fair skinRed hairSkin pigmentationUV light sensitivity

PubMed DOI Metascience Observatory

About MC1R

This intronless gene encodes the receptor protein for melanocyte-stimulating hormone (MSH). The encoded protein, a seven pass transmembrane G protein coupled receptor, controls melanogenesis. Two types of melanin exist: red pheomelanin and black eumelanin. Gene mutations that lead to a loss in function are associated with increased pheomelanin production, which leads to lighter skin and hair color. Eumelanin is photoprotective but pheomelanin may contribute to UV-induced skin damage by generating free radicals upon UV radiation. Binding of MSH to its receptor activates the receptor and stimulates eumelanin synthesis. This receptor is a major determining factor in sun sensitivity and is a genetic risk factor for melanoma and non-melanoma skin cancer. Over 30 variant alleles have been identified which correlate with skin and hair color, providing evidence that this gene is an important component in determining normal human pigment variation. [provided by RefSeq, Jul 2008]