Human skin pigmentation is a complex and tightly regulated process. Using a transcriptome analysis performed in pigmented skin compared to skin devoid of melanocytes, we identified CLEC12B as a new melanocytic gene. We demonstrated that CLEC12B is selectively expressed in melanocytes, and that its expression is decreased in highly pigmented skin compared to white skin. CLEC12B directly recruits and activates SHP-1 and SHP-2 through its ITIM domain and promotes CREB degradation, leading to a downregulation of the downstream MITF pathway and ultimately controls melanin production and pigmentation in vitro and in reconstructed human epidermis model. The identification of CLEC12B fosters a new therapeutic target for the development of melanogenic agents in the clinical and cosmetic fields, but it also provides novel insights in the understanding of the melanocyte biology and regulation of melanogenesis.

Identification of a new gene involved in human skin pigmentation: CLEC12B