SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Journal   Science. Citation   Science. 310(5755):1782-6 Publication date   2005 Dec 16 Authors   Lamason RL Mohideen MA Mest JR Wong AC Norton HL Aros MC Jurynec MJ Mao X Humphreville VR Humbert JE Sinha S Moore JL Jagadeeswaran P Zhao W Ning G Makalowska I McKeigue PM O'donnell D Kittles R Parra EJ Mangini NJ Grunwald DJ Shriver MD Canfield VA Cheng KC Investigators   Victor A. Canfield Keith C. Cheng Izabela Makalowska Mark Shriver Grant agencies   National Cancer Institute National Eye Institute National Institute of Child Health and Human Development National Human Genome Research Institute National Heart, Lung, and Blood Institute National Center for Research Resources Grants   NCI CA73935 NEI EY11308 NICHD HD37572 NICHD HD40179 NHGRI HG002154 NHLBI HL077910 NCRR RR017441 MeSH headings   Antiporters Skin Pigmentation Zebrafish Zebrafish Proteins MeSH qualifiers   genetics Abstract   Lighter variations of pigmentation in humans are associated with diminished number, size, and density of melanosomes, the pigmented organelles of melanocytes. Here we show that zebrafish golden mutants share these melanosomal changes and that golden encodes a putative cation exchanger slc24a5 (nckx5) that localizes to an intracellular membrane, likely the melanosome or its precursor. The human ortholog is highly similar in sequence and functional in zebrafish. The evolutionarily conserved ancestral allele of a human coding polymorphism predominates in African and East Asian populations. In contrast, the variant allele is nearly fixed in European populations, is associated with a substantial reduction in regional heterozygosity, and correlates with lighter skin pigmentation in admixed populations, suggesting a key role for the SLC24A5 gene in human pigmentation.