OCA2 gene

The OCA2 gene (OCA2 stands for "oculocutaneous albinimus type 2" or "melanosomal transmembrane protein") is a protein-coding gene located on chromosome 15q12-q13.1. Alternative splicing leads to several transcript variants. An important paralog of this gene is SLC13A3.

The OCA2 gene encodes the human homolog of the mouse P gene (pink-eyed dilution). The encoded protein is thought to be an integral membrane protein involved in the transport of small molecules, in particular tyrosine, a precursor of melanin synthesis. It is involved in mammalian pigmentation, where it may control skin color variation and is responsible for brown or blue eye color.

Mutations in this gene lead to oculocutaneous albinism type 2.

The encoded "Melanosomal Transmembrane Protein" contributes to a melanosome-specific anion (chloride) current that modulates melanosomal pH for optimal tyrosinase activity required for melanogenesis and melanosome maturation.

Intracellular ion channels are essential regulators of organellar and cellular functions. In particular, no ion channel has been characterized in melanosomes, the organelles that produce and store the main pigment melanin in mammals. Direct patch-clamp measurements of skin and eye melanosomes identified a chloride-selective anion conductance mediated by OCA2 that is required for melanin production. Expression of OCA2 increases the pH of the organelle, suggesting that the chloride channel regulates melanin synthesis by modulating melanosome pH. This finding suggests that a melanosomal anion channel exists that requires OCA2 and is essential for skin and eye pigmentation (Bellono NW et al. 2014).

One of the components of the mammalian pigmentation system (Visser M et al. 2012). May serve as a key control point by which ethnic variation in skin color is determined. Main determinant of brown and/or blue eye color. The protein appears to regulate the post-translational processing of tyrosinase, which catalyzes the limiting reaction in melanin synthesis.

1. Bellono NW et al. (2014) An intracellular anion channel critical for pigmentation. Elife: e04543).
2. Brilliant MH (2001) The mouse p (pink-eyed dilution) and human P genes, oculocutaneous albinism type 2 (OCA2), and melanosomal pH. Pigment Cell Res 14:86-93.
3. Lee ST et al. (1995) Organization and sequence of the human P gene and identification of a new family of transport proteins. Genomics 26:354-363.
4. Visser M et al. (2012) HERC2 rs12913832 modulates human pigmentation by attenuating chromatin-loop formation between a long-range enhancer and the OCA2 promoter. Genome Res 22:446-455.
5. Zhang X et al. (2023) Identification of Polymorphisms in the HERC2-OCA2 Gene Locus and their Association with Feather Color in Quail. J Poult Sci 60:2023013.