Sodium/potassium/calcium exchanger 5

283652317750ENSG00000188467ENSMUSG00000035183Q71RS6Q8C261NM_205850NM_175034NP_995322NP_778199Sodium/potassium/calcium exchanger 5 (NCKX5), also known as solute carrier family 24 member 5 (SLC24A5), is a protein that in humans is encoded by the SLC24A5 gene that has a major influence on natural skin colour variation.

Sequence variation in the SLC24A5 gene, particularly a non-synonymous SNP changing the amino acid at position 111 in NCKX5 from alanine to threonine, has been associated with differences in skin pigmentation.

[10][11][12] It was introduced into Khoisan people via "back-to-Africa" migration around 2,000 years ago is partly responsible for their differing skin tone to most other African populations.

Removal of the NCKX5 protein disrupts melanogenesis in human and mouse melanocytes, causing a significant reduction in melanin pigment production.

Site-directed mutagenesis corresponding to a non-synonymous single nucleotide polymorphism in SLC24A5 alters a residue in NCKX5 (A111T) that is important for NCKX5 sodium-calcium exchanger activity.

In human, the SLC24A5 gene is located on the long (q) arm of chromosome 15 at position 21.1.
Global frequency distribution of the SLC24A5 gene's ancestral Ala111 allele (yellow) and its derived Ala111Thr allele (blue).
Origins of the SLC24A5 and SLC45A2 based on Archaeogenetics . Derived variants are said to have come from the Caucasus 28,000 years ago