P protein, also known asmelanocyte-specific transporter protein orpink-eyed dilution protein homolog, is aprotein that in humans is encoded by theoculocutaneous albinism II (OCA2)gene.[5] The P protein is believed to be anintegral membrane protein involved in small molecule transport, specifically oftyrosine—a precursor ofmelanin. Certain mutations in OCA2 result in type 2oculocutaneous albinism.[5] OCA2 encodes the human homologue of the mouse p (pink-eyed dilution) gene.
In human, the OCA2 gene is located on the long (q) arm ofchromosome 15 between positions 12 and 13.1
The human OCA2 gene is located on the long arm (q) of chromosome 15, specifically from base pair 28,000,020 to base pair 28,344,457 on chromosome 15.
OCA2 provides instructions for making the protein called P protein which is located inmelanocytes which are specialized cells that producemelanin, and in the cells of theretinal pigment epithelium. Melanin is responsible for giving color to the skin, hair, and eyes. Moreover, melanin is found in the light-sensitive tissue of the retina of the eye which plays a role in normal vision.
The exact function of protein P is unknown, but it has been found that it is essential for the normal coloring ofskin,eyes, andhair; and likely involved inmelanin production. This gene seems to be the main determinant of eye color depending on the amount of melanin production in theiris stroma (large amounts giving rise to brown eyes; little to no melanin giving rise toblue eyes).
This gene is mutated inAstyanax mexicanus, a Mexican fish which is characterized by a chronicalbinism in cave-dwelling individuals. It exists as a deletion in fish from the Pachón and Molino caves, which produces albinism.[6]
Mutations in the OCA2 gene cause a disruption in the normal production of melanin; therefore, causing vision problems and reductions inhair,skin, andeye color.Oculocutaneous albinism caused by mutations in the OCA2 gene is calledoculocutaneous albinism type 2. The prevalence of OCA type 2 is estimated at 1/38,000-1/40,000 in most populations throughout the world, with a higher prevalence in the African population of 1/3,900–1/1,500.[7] Other diseases associated with the deletion of the OCA2 gene areAngelman syndrome (light-colored hair and fair skin) andPrader–Willi syndrome (unusually light-colored hair and fair skin). With both these syndromes, the deletion often occurs in individuals with either syndrome.[8][9]
A mutation in theHERC2 gene adjacent to OCA2, affecting OCA2's expression in the human iris, is found common to nearly all people withblue eyes. It has been hypothesized that all blue-eyed humans share a single common ancestor with whom the mutation originated.[10][11][12]
TheHis615Argallele of OCA2 is involved in the light skin tone and the derived allele is restricted to East Asia with high frequencies, with highest frequencies in Eastern East Asia (49-63%), midrange frequencies in Southeast Asia, and the lowest frequencies in Western China and some Eastern European populations.[13][14]
^"OCA2 - oculocutaneous albinism II".Genetics Home Reference - Your guide to understanding genetic conditions. U.S. National Library of Medicine. Retrieved30 March 2013.
^Eiberg H, Troelsen J, Nielsen M, Mikkelsen A, Mengel-From J, Kjaer KW, et al. (March 2008). "Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression".Human Genetics.123 (2):177–187.doi:10.1007/s00439-007-0460-x.PMID18172690.S2CID9886658.
Lee ST, Nicholls RD, Jong MT, Fukai K, Spritz RA (March 1995). "Organization and sequence of the human P gene and identification of a new family of transport proteins".Genomics.26 (2):354–363.doi:10.1016/0888-7543(95)80220-G.PMID7601462.
Lee ST, Nicholls RD, Schnur RE, Guida LC, Lu-Kuo J, Spinner NB, et al. (November 1994). "Diverse mutations of the P gene among African-Americans with type II (tyrosinase-positive) oculocutaneous albinism (OCA2)".Human Molecular Genetics.3 (11):2047–2051.PMID7874125.
Durham-Pierre D, Gardner JM, Nakatsu Y, King RA, Francke U, Ching A, et al. (June 1994). "African origin of an intragenic deletion of the human P gene in tyrosinase positive oculocutaneous albinism".Nature Genetics.7 (2):176–179.doi:10.1038/ng0694-176.PMID7920637.S2CID6185436.
Rinchik EM, Bultman SJ, Horsthemke B, Lee ST, Strunk KM, Spritz RA, et al. (January 1993). "A gene for the mouse pink-eyed dilution locus and for human type II oculocutaneous albinism".Nature.361 (6407):72–76.Bibcode:1993Natur.361...72R.doi:10.1038/361072a0.PMID8421497.S2CID21794972.
Passmore LA, Kaesmann-Kellner B, Weber BH (September 1999). "Novel and recurrent mutations in the tyrosinase gene and the P gene in the German albino population".Human Genetics.105 (3):200–210.doi:10.1007/s004390051090 (inactive 12 July 2025).PMID10987646.{{cite journal}}: CS1 maint: DOI inactive as of July 2025 (link)
Manga P, Orlow SJ (October 2001). "Inverse correlation between pink-eyed dilution protein expression and induction of melanogenesis by bafilomycin A1".Pigment Cell Research.14 (5):362–367.doi:10.1034/j.1600-0749.2001.140508.x.PMID11601658.
Toyofuku K, Valencia JC, Kushimoto T, Costin GE, Virador VM, Vieira WD, et al. (June 2002). "The etiology of oculocutaneous albinism (OCA) type II: the pink protein modulates the processing and transport of tyrosinase".Pigment Cell Research.15 (3):217–224.doi:10.1034/j.1600-0749.2002.02007.x.PMID12028586.
