OCA2

P protein, also known as melanocyte-specific transporter protein or pink-eyed dilution protein homolog, is a protein that in humans is encoded by the oculocutaneous albinism II (OCA2) gene.[5] The P protein is believed to be an integral membrane protein involved in small molecule transport, specifically of tyrosine - a precursor of melanin. Certain mutations in OCA2 result in type 2 oculocutaneous 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 of chromosome 15 between positions 12 and 13.1
OCA2
Identifiers
AliasesOCA2, BEY, BEY1, BEY2, BOCA, D15S12, EYCL, EYCL2, EYCL3, HCL3, PED, SHEP1, OCA2 melanosomal transmembrane protein, P
External IDsOMIM: 611409 MGI: 97454 HomoloGene: 37281 GeneCards: OCA2
Gene location (Human)
Chr.Chromosome 15 (human)[1]
Band15q12-q13.1Start27,754,875 bp[1]
End28,099,315 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

4948

18431

Ensembl

ENSG00000104044
ENSG00000277361

ENSMUSG00000030450

UniProt

Q04671

Q62052

RefSeq (mRNA)

NM_000275
NM_001300984

NM_021879

RefSeq (protein)

NP_000266
NP_001287913

NP_068679

Location (UCSC)Chr 15: 27.75 – 28.1 MbChr 7: 56.24 – 56.54 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.

Function

OCA2 provides instructions for making the protein called P protein which is located in melanocytes which are specialized cells that produce melanin, and in the cells of the retinal 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 of skin, eyes, and hair; and likely involved in melanin production. This gene seems to be the main determinant of eye color depending on the amount of melanin production in the iris stroma (large amounts giving rise to brown eyes; little to no melanin giving rise to blue eyes).

Clinical significance

Mutations in the OCA2 gene cause a disruption in the normal production of melanin; therefore, causing vision problems and reductions in hair, skin, and eye color. Oculocutaneous albinism caused by mutations in the OCA2 gene is called oculocutaneous 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.[6] Other diseases associated with the deletion of the OCA2 gene are Angelman syndrome (light-colored hair and fair skin) and Prader-Willi syndrome (unusually light-colored hair and fair skin). With both these syndromes, the deletion often occurs in individuals with either syndrome.[7][8]

A mutation in the HERC2 gene adjacent to OCA2, affecting OCA2's expression in the human iris, is found common to nearly all people with blue eyes. It has been hypothesized that all blue-eyed humans share a single common ancestor with whom the mutation originated.[9][10][11]

The His615Arg allele 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.[12][13]

References
  1. ENSG00000277361 GRCh38: Ensembl release 89: ENSG00000104044, ENSG00000277361 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000030450 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: OCA2 oculocutaneous albinism II (pink-eye dilution homolog, mouse)". Retrieved 2015-03-12.
  6. Hayashi, Masahiro; Suzuki, Tamio (April 2013). "Oculocutaneous albinism type 2". Orphanet. Retrieved 2014-11-09.
  7. "OCA2 - oculocutaneous albinism II". Genetics Home Reference - Your guide to understanding genetic conditions. U.S. National Library of Medicine. Retrieved 30 March 2013.
  8. "Don't it make your brown eyes blue?". Understanding Genetics. Understanding Genetics. Retrieved 30 March 2013.
  9. Bryner J (2008-01-31). "Here's what made those brown eyes blue". Health News. NBC News. Retrieved 2008-11-06.; Bryner J (2008-01-31). "One Common Ancestor Behind Blue Eyes". LiveScience. Imaginova Corp. Retrieved 2008-11-06.; "Blue-eyed humans have a single, common ancestor". News. University of Copenhagen. 2008-01-30. Retrieved 2008-11-06.
  10. Eiberg H, Troelsen J, Nielsen M, Mikkelsen A, Mengel-From J, Kjaer KW, Hansen L (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". Hum. Genet. 123 (2): 177–87. doi:10.1007/s00439-007-0460-x. PMID 18172690. S2CID 9886658.
  11. Sturm RA, Duffy DL, Zhao ZZ, Leite FP, Stark MS, Hayward NK, Martin NG, Montgomery GW (2008). "A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color". Am. J. Hum. Genet. 82 (2): 424–31. doi:10.1016/j.ajhg.2007.11.005. PMC 2427173. PMID 18252222.
  12. Donnelly MP, Paschou P, Grigorenko E, Gurwitz D, Barta C, Lu RB, Zhukova OV, Kim JJ, Siniscalco M, New M, Li H, Kajuna SL, Manolopoulos VG, Speed WC, Pakstis AJ, Kidd JR, Kidd KK (2012). "A global view of the OCA2-HERC2 region and pigmentation". Hum. Genet. 131 (5): 683–96. doi:10.1007/s00439-011-1110-x. PMC 3325407. PMID 22065085.
  13. Edwards M, Bigham A, Tan J, Li S, Gozdzik A, Ross K, Jin L, Parra EJ (2010). "Association of the OCA2 polymorphism His615Arg with melanin content in east Asian populations: further evidence of convergent evolution of skin pigmentation". PLOS Genet. 6 (3): e1000867. doi:10.1371/journal.pgen.1000867. PMC 2832666. PMID 20221248.

Further reading
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