rs4988235

rs4988235 is a human single-nucleotide polymorphism (SNP) located in an intronic region of the MCM6 gene on chromosome 2, about 15 kilobases upstream of the LCT gene, which encodes lactase. The ancestral allele is C, while the derived allele is T. The T allele is strongly associated with lactase persistence, the continued expression of lactase into adulthood.

Function and phenotype: The rs4988235 T allele is linked to adult lactase persistence, enabling digestion of lactose beyond the weaning period. In individuals with the T allele, LCT expression in the small intestine often remains high, whereas individuals with the C allele more commonly experience lactase non-persistence and lactose intolerance as adults.

Population distribution and evolution: The T allele shows a clinal pattern in Europe, being more frequent in Northern European populations and gradually less common toward the south. In many populations outside Europe, the T allele is rare or absent. The distribution of rs4988235 T has been interpreted as a signal of recent positive selection coinciding with the rise of dairy farming in Europe during the last 10,000 years. Studies of linkage disequilibrium and extended haplotype homozygosity support this selective history.

Global context: While rs4988235 is the best-characterized European marker for lactase persistence, other regulatory variants associated with lactase persistence exist in non-European populations. Nonetheless, rs4988235 remains a widely used proxy in studies of human adaptation to dairy consumption and lactase regulation.