MC1Rvariant

MC1R variant refers to any allele of the MC1R gene that alters the function or expression of the melanocortin 1 receptor. The MC1R gene, located on chromosome 16, encodes a G protein-coupled receptor expressed in melanocytes. Its normal function is to mediate signaling from α-melanocyte-stimulating hormone to increase intracellular cAMP and promote eumelanin production, resulting in darker pigmentation.

Many MC1R variants are missense mutations, but there are also nonsense and frameshift variants. The most studied variants include R151C, R160W, D294H, among others. The frequency and spectrum of variants vary by population; certain alleles are enriched in individuals with red hair or pale skin, particularly in European populations.

Phenotypically, carrying one or more MC1R variants can influence hair color, skin type, and tanning response. Individuals with bi-allelic loss-of-function MC1R variants are more likely to have red hair, pale skin, freckles, and poor tanning ability. However, genotype-phenotype relationships are imperfect; some people with MC1R variants do not have red hair and not all redheads carry the common variants.

Clinical relevance: MC1R variants are associated with increased risk of sunburn and UV damage, and a modestly elevated risk of cutaneous melanoma, independent of hair and skin color. The effect is polygenic and interacts with environmental factors such as sun exposure. Testing for MC1R variants can aid in research and risk assessment but does not determine cancer risk on its own.

Ongoing research explores the broader roles of MC1R signaling in pigmentation biology, pain sensitivity, and evolutionary variation.