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Gene Review

OCA2  -  oculocutaneous albinism II

Homo sapiens

Synonyms: BEY, BEY1, BEY2, BOCA, D15S12, ...
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Disease relevance of OCA2

  • In the present study, we show that albinism in one Native American population, the Navajo, is caused by a LINE-mediated 122.5-kilobase deletion of the P gene, thus demonstrating that albinism in this population is OCA2 [1].
  • Most types of human oculocutaneous albinism (OCA) result from mutations in the gene for tyrosinase (OCA1) or the P protein (OCA2), although other types of OCA have been described but have not been mapped to specific loci [2].
  • Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma [3].
  • The occuloalbinism 2 (OCA2) gene, localized at 15q11, encodes a melanosomal transmembrane protein that is involved in the most common form of human occulo-cutaneous albinism, a human genetic disorder characterized by fair pigmentation and susceptibility to skin cancer [3].
  • The mouse pink-eyed dilution gene: association with hypopigmentation in Prader-Willi and Angelman syndromes and with human OCA2 [4].

Psychiatry related information on OCA2

  • Sildenafil refractory erectile dysfunction after RRP in men without PED is not predominantly associated with penile Doppler parameters consistent with arterial insufficiency [5].

High impact information on OCA2

  • The pathogen-inducible nitric oxide synthase (iNOS) in plants is a variant of the P protein of the glycine decarboxylase complex [6].
  • One of the two major autosomal recessive forms involves the tyrosinase gene (OCA1), while the other form (OCA2) has recently been associated with alterations of the P gene on chromosome 15 [7].
  • The P protein is a transmembrane polypeptide that may transport small molecules such as tyrosine, the precursor of melanin [8].
  • The human P gene corresponds to the D15S12 locus within the chromosome segment 15q11-q13, which is typically deleted in patients with Prader-Willi and Angelman syndrome (see ref. 5 for review) [9].
  • Moreover, lentiviral-mediated delivery of PED antisense DNA resulted in dramatic down-regulation of the endogenous gene expression and sensitization of primitive neural cells to apoptosis mediated by inflammatory cytokines and DRs [10].

Chemical compound and disease context of OCA2


Biological context of OCA2


Anatomical context of OCA2

  • The P protein, with 12 transmembrane domains localized to the melanosome, has no assigned function as of yet but is responsible for OCA2 when dysfunctional [18].
  • There was no difference in expression levels of biallelically expressed genes (for example, OCA2) from within 15q11-q13 when comparing UPD cell lines with controls [19].
  • Thus, absence of caspase 8 and high expression of PED constitute two levels of protection from apoptosis induced by DRs and inflammatory cytokines in neural stem and progenitor cells [10].
  • No P protein activity was detected when the mutant P protein with this amino acid substitution was expressed in COS 7 cells [20].
  • We looked at the outcome of doppler velocimetry of the umbilical artery in three groups of pregnancies: those with positive end diastolic velocities (PED; n = 214), absent end diastolic velocities (AED; n = 178) and reversed end diastolic velocities (RED; n = 67) [21].

Associations of OCA2 with chemical compounds

  • A Three-Single-Nucleotide Polymorphism Haplotype in Intron 1 of OCA2 Explains Most Human Eye-Color Variation [22].
  • To isolate the putative 15q11-q13 candidate AD gene, a genomic contig and physical map of the approximately 1.2-Mb region from the GABA receptor gene cluster to the OCA2 locus was generated [23].
  • Partial inactivation of P-protein could result secondarily from impaired metabolism of glycine resulting from deficiency in the activity of H-protein [24].
  • This is the first reported crystal structure of a P-protein, and it reveals that P-proteins do not involve the alpha(2)-type active dimer universally observed in the evolutionarily related pyridoxal 5'-phosphate (PLP)-dependent enzymes [12].
  • In the phlobaphene pathway, a subset of C1-regulated genes, including a1, are activated by the Myb domain P protein independently of B/R [25].

Physical interactions of OCA2

  • We replaced the L8 complex in E. coli 50 S subunits with the rat counterpart P protein complex consisting of P1, P2, and P0 [26].

Enzymatic interactions of OCA2

  • Active transcription could also be reconstituted using bacterially synthesized recombinant P protein provided the P protein was phosphorylated by cellular casein kinase II [27].

Regulatory relationships of OCA2

  • The P-protein complex of eukaryotic ribosomes forms a lateral stalk structure in the active site of the large ribosomal subunit and is thought to assist in the elongation phase of translation by stimulating GTPase activity of elongation factor-2 and removal of deacylated tRNA [28].

Other interactions of OCA2

  • We have also applied two methods of admixture mapping to test for the effects of three candidate genes (TYR, OCA2, MC1R) on pigmentation [16].
  • The two loci, GABRA5 and D15S24, flanking D15S12, are both hypervariable, and many different haplotypes were observed with the alleles at the three loci on both ty-pos OCA-associated chromosomes and "normal" chromosomes.(ABSTRACT TRUNCATED AT 250 WORDS)[29]
  • Furthermore, the role of LC8 in cellular mechanisms other than transport, e.g., inhibition of neuronal nitric oxide synthase, suggests that the P protein interactions could be involved in physiopathological mechanisms of rabies virus-induced pathogenesis [30].
  • Using fluorescence in situ hybridization and YAC mapping, we have found that at least one D15F37 locus is centromeric to D15S9 and at least two are between OCA2 and D15S24 [31].
  • In addition, a second gamma-aminobutyric acid (GABAA) receptor, the alpha 5 subunit, has been localized within the reference map to between GABRB3 and D15S12 [32].

Analytical, diagnostic and therapeutic context of OCA2


  1. A 122.5-kilobase deletion of the P gene underlies the high prevalence of oculocutaneous albinism type 2 in the Navajo population. Yi, Z., Garrison, N., Cohen-Barak, O., Karafet, T.M., King, R.A., Erickson, R.P., Hammer, M.F., Brilliant, M.H. Am. J. Hum. Genet. (2003) [Pubmed]
  2. Mutation in and lack of expression of tyrosinase-related protein-1 (TRP-1) in melanocytes from an individual with brown oculocutaneous albinism: a new subtype of albinism classified as "OCA3". Boissy, R.E., Zhao, H., Oetting, W.S., Austin, L.M., Wildenberg, S.C., Boissy, Y.L., Zhao, Y., Sturm, R.A., Hearing, V.J., King, R.A., Nordlund, J.J. Am. J. Hum. Genet. (1996) [Pubmed]
  3. Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma. Jannot, A.S., Meziani, R., Bertrand, G., Gérard, B., Descamps, V., Archimbaud, A., Picard, C., Ollivaud, L., Basset-Seguin, N., Kerob, D., Lanternier, G., Lebbe, C., Saiag, P., Crickx, B., Clerget-Darpoux, F., Grandchamp, B., Soufir, N., Melan-Cohort, n.u.l.l. Eur. J. Hum. Genet. (2005) [Pubmed]
  4. The mouse pink-eyed dilution gene: association with hypopigmentation in Prader-Willi and Angelman syndromes and with human OCA2. Brilliant, M.H., King, R., Francke, U., Schuffenhauer, S., Meitinger, T., Gardner, J.M., Durham-Pierre, D., Nakatsu, Y. Pigment Cell Res. (1994) [Pubmed]
  5. Is sildenafil failure in men after radical retropubic prostatectomy (RRP) due to arterial disease? Penile duplex Doppler findings in 174 men after RRP. McCullough, A., Woo, K., Telegrafi, S., Lepor, H. Int. J. Impot. Res. (2002) [Pubmed]
  6. The pathogen-inducible nitric oxide synthase (iNOS) in plants is a variant of the P protein of the glycine decarboxylase complex. Klessig, D.F., Ytterberg, A.J., van Wijk, K.J. Cell (2004) [Pubmed]
  7. African origin of an intragenic deletion of the human P gene in tyrosinase positive oculocutaneous albinism. Durham-Pierre, D., Gardner, J.M., Nakatsu, Y., King, R.A., Francke, U., Ching, A., Aquaron, R., del Marmol, V., Brilliant, M.H. Nat. Genet. (1994) [Pubmed]
  8. Mutations of the P gene in oculocutaneous albinism, ocular albinism, and Prader-Willi syndrome plus albinism. Lee, S.T., Nicholls, R.D., Bundey, S., Laxova, R., Musarella, M., Spritz, R.A. N. Engl. J. Med. (1994) [Pubmed]
  9. A gene for the mouse pink-eyed dilution locus and for human type II oculocutaneous albinism. Rinchik, E.M., Bultman, S.J., Horsthemke, B., Lee, S.T., Strunk, K.M., Spritz, R.A., Avidano, K.M., Jong, M.T., Nicholls, R.D. Nature (1993) [Pubmed]
  10. Absence of caspase 8 and high expression of PED protect primitive neural cells from cell death. Ricci-Vitiani, L., Pedini, F., Mollinari, C., Condorelli, G., Bonci, D., Bez, A., Colombo, A., Parati, E., Peschle, C., De Maria, R. J. Exp. Med. (2004) [Pubmed]
  11. Albinism in Africa as a public health issue. Hong, E.S., Zeeb, H., Repacholi, M.H. BMC public health [electronic resource]. (2006) [Pubmed]
  12. Structure of P-protein of the glycine cleavage system: implications for nonketotic hyperglycinemia. Nakai, T., Nakagawa, N., Maoka, N., Masui, R., Kuramitsu, S., Kamiya, N. EMBO J. (2005) [Pubmed]
  13. Ligation-state hydrogen exchange: Coupled binding and folding equilibria in ribonuclease P protein. Henkels, C.H., Oas, T.G. J. Am. Chem. Soc. (2006) [Pubmed]
  14. Role of NH(2)- and COOH-terminal domains of the P protein of human parainfluenza virus type 3 in transcription and replication. De, B.P., Hoffman, M.A., Choudhary, S., Huntley, C.C., Banerjee, A.K. J. Virol. (2000) [Pubmed]
  15. C-terminal phosphorylation of human respiratory syncytial virus P protein occurs mainly at serine residue 232. Sánchez-Seco, M.P., Navarro, J., Martínez, R., Villanueva, N. J. Gen. Virol. (1995) [Pubmed]
  16. Skin pigmentation, biogeographical ancestry and admixture mapping. Shriver, M.D., Parra, E.J., Dios, S., Bonilla, C., Norton, H., Jovel, C., Pfaff, C., Jones, C., Massac, A., Cameron, N., Baron, A., Jackson, T., Argyropoulos, G., Jin, L., Hoggart, C.J., McKeigue, P.M., Kittles, R.A. Hum. Genet. (2003) [Pubmed]
  17. Interactive effects of MC1R and OCA2 on melanoma risk phenotypes. Duffy, D.L., Box, N.F., Chen, W., Palmer, J.S., Montgomery, G.W., James, M.R., Hayward, N.K., Martin, N.G., Sturm, R.A. Hum. Mol. Genet. (2004) [Pubmed]
  18. Molecular basis of congenital hypopigmentary disorders in humans: a review. Boissy, R.E., Nordlund, J.J. Pigment Cell Res. (1997) [Pubmed]
  19. Microarray analysis of gene/transcript expression in Prader-Willi syndrome: deletion versus UPD. Bittel, D.C., Kibiryeva, N., Talebizadeh, Z., Butler, M.G. J. Med. Genet. (2003) [Pubmed]
  20. Identification of a common mutation in Finnish patients with nonketotic hyperglycinemia. Kure, S., Takayanagi, M., Narisawa, K., Tada, K., Leisti, J. J. Clin. Invest. (1992) [Pubmed]
  21. Clinical significance of absent or reversed end diastolic velocity waveforms in umbilical artery. Karsdorp, V.H., van Vugt, J.M., van Geijn, H.P., Kostense, P.J., Arduini, D., Montenegro, N., Todros, T. Lancet (1994) [Pubmed]
  22. A Three-Single-Nucleotide Polymorphism Haplotype in Intron 1 of OCA2 Explains Most Human Eye-Color Variation. Duffy, D.L., Montgomery, G.W., Chen, W., Zhao, Z.Z., Le, L., James, M.R., Hayward, N.K., Martin, N.G., Sturm, R.A. Am. J. Hum. Genet. (2007) [Pubmed]
  23. Autistic disorder and chromosome 15q11-q13: construction and analysis of a BAC/PAC contig. Maddox, L.O., Menold, M.M., Bass, M.P., Rogala, A.R., Pericak-Vance, M.A., Vance, J.M., Gilbert, J.R. Genomics (1999) [Pubmed]
  24. Defective glycine cleavage system in nonketotic hyperglycinemia. Occurrence of a less active glycine decarboxylase and an abnormal aminomethyl carrier protein. Hiraga, K., Kochi, H., Hayasaka, K., Kikuchi, G., Nyhan, W.L. J. Clin. Invest. (1981) [Pubmed]
  25. Evidence for direct activation of an anthocyanin promoter by the maize C1 protein and comparison of DNA binding by related Myb domain proteins. Sainz, M.B., Grotewold, E., Chandler, V.L. Plant Cell (1997) [Pubmed]
  26. Replacement of L7/L12.L10 protein complex in Escherichia coli ribosomes with the eukaryotic counterpart changes the specificity of elongation factor binding. Uchiumi, T., Hori, K., Nomura, T., Hachimori, A. J. Biol. Chem. (1999) [Pubmed]
  27. Requirement of casein kinase II-mediated phosphorylation for the transcriptional activity of human respiratory syncytial viral phosphoprotein P: transdominant negative phenotype of phosphorylation-defective P mutants. Mazumder, B., Barik, S. Virology (1994) [Pubmed]
  28. Evolutionary analyses of the 12-kDa acidic ribosomal P-proteins reveal a distinct protein of higher plant ribosomes. Szick, K., Springer, M., Bailey-Serres, J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  29. The tyrosinase-positive oculocutaneous albinism gene shows locus homogeneity on chromosome 15q11-q13 and evidence of multiple mutations in southern African negroids. Kedda, M.A., Stevens, G., Manga, P., Viljoen, C., Jenkins, T., Ramsay, M. Am. J. Hum. Genet. (1994) [Pubmed]
  30. Cytoplasmic dynein LC8 interacts with lyssavirus phosphoprotein. Jacob, Y., Badrane, H., Ceccaldi, P.E., Tordo, N. J. Virol. (2000) [Pubmed]
  31. Expressed copies of the MN7 (D15F37) gene family map close to the common deletion breakpoints in the Prader-Willi/Angelman syndromes. Buiting, K., Gross, S., Ji, Y., Senger, G., Nicholls, R.D., Horsthemke, B. Cytogenet. Cell Genet. (1998) [Pubmed]
  32. FISH ordering of reference markers and of the gene for the alpha 5 subunit of the gamma-aminobutyric acid receptor (GABRA5) within the Angelman and Prader-Willi syndrome chromosomal regions. Knoll, J.H., Sinnett, D., Wagstaff, J., Glatt, K., Wilcox, A.S., Whiting, P.M., Wingrove, P., Sikela, J.M., Lalande, M. Hum. Mol. Genet. (1993) [Pubmed]
  33. The role of carrier protein in the sensitivity of enzyme-linked immunosorbent assay for antiribosomal P protein antibodies: further comment on the article by Yoshio et al. Hirohata, S., Isshi, K., Toyoshima, S. Arthritis Rheum. (1999) [Pubmed]
  34. Prevalence of autoantibodies to ribosomal P proteins in juvenile-onset systemic lupus erythematosus compared with the adult disease. Reichlin, M., Broyles, T.F., Hubscher, O., James, J., Lehman, T.A., Palermo, R., Stafford, H.A., Taylor-Albert, E., Wolfson-Reichlin, M. Arthritis Rheum. (1999) [Pubmed]
  35. Glycine decarboxylase multienzyme complex. Purification and partial characterization from pea leaf mitochondria. Walker, J.L., Oliver, D.J. J. Biol. Chem. (1986) [Pubmed]
  36. Accuracy of anti-ribosomal P protein antibody testing for the diagnosis of neuropsychiatric systemic lupus erythematosus: an international meta-analysis. Karassa, F.B., Afeltra, A., Ambrozic, A., Chang, D.M., De Keyser, F., Doria, A., Galeazzi, M., Hirohata, S., Hoffman, I.E., Inanc, M., Massardo, L., Mathieu, A., Mok, C.C., Morozzi, G., Sanna, G., Spindler, A.J., Tzioufas, A.G., Yoshio, T., Ioannidis, J.P. Arthritis Rheum. (2006) [Pubmed]
  37. Antibody response to P-protein in patients with Branhamella catarrhalis infections. Chi, D.S., Verghese, A., Moore, C., Hamati, F., Berk, S.L. Am. J. Med. (1990) [Pubmed]
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