This phenotype is caused by a loss-of-function mutation in the melanocortin 1 receptor (MC1R) gene.[43][44] However, variations in the MC1R gene sequence only have considerable influence on pigmentation in populations where red hair and extremely fair skin is prevalent.[3] The gene variation’s primary effect is to promote eumelanin synthesis at the expense of pheomelanin synthesis, although this contributes to very little variation in skin reflectance between different ethnic groups.[45] Melanocytes from light skin cells cocultured with keratinocytes give rise to a distribution pattern characteristic of light skin.[46]