| Written | 2016-04 | Kunal Ray, Mainak Sengupta, Sampurna Ghosh |
| Academy of Scientific and Innovative Research (AcSIR), Campus at CSIR - Central Road Research Institute, Mathura Road, New Delhi - 110 025, kunalray@gmail.com (KR); University of Calcutta, Department of Genetics, 35, Ballygunge Circular Road, Kolkata - 700 019, sengupta.mainak@gmail.com); sampurna_ghosh@yahoo.in (MS, SG) India. |
| Abstract | OCA2 gene (OCA2), having a chromosomal location of 15q12-q13, encodes an integral membrane transporter protein playing a role in regulating the pH of melanosomes. OCA2 is hypothesized to be involved in the transport of tyrosine, the precursor to melanin synthesis, within the melanocyte. Defects in this gene are the cause of oculocutaneous albinism type II; OCA II. |
| Keywords | OCA2, albinism, OCA II |
| Identity |
| Alias (NCBI) | Melanocyte-Specific Transporter Protein | Oculocutaneous Albinism II (Pink-Eye Dilution Homolog, Mouse) | Pink-Eyed Dilution Protein Homolog | Eye Color 2 (Central Brown) | Eye Color 3 (Brown) | P-Protein | P | Oculocutaneous Albinism II [Pink-Eye Dilution (Murine) Homolog] | Total Brown Iris Pigmentation | Hair Color 3 (Brown) | SHEP1 | EYCL2 | EYCL3 | BOCA | BEY1 | BEY2 | EYCL | HCL3 | PED | BEY | D15S12 | PEDH |
| HGNC (Hugo) | OCA2 |
| HGNC Alias symb | BEY2 | EYCL | BEY | BEY1 |
| HGNC Alias name | melanocyte-specific transporter protein | P-protein |
| HGNC Previous name | D15S12 | P | EYCL3 | EYCL2 |
| HGNC Previous name | "eye color 3 (brown) | eye color 2 (central brown) | oculocutaneous albinism II (pink-eye dilution homolog, mouse)" |
| LocusID (NCBI) | 4948 |
| Atlas_Id | 45789 |
| Location | 15q12 [Link to chromosome band 15q12] |
| Location_base_pair | Starts at 27754876 and ends at 28099315 bp from pter ( according to GRCh38/hg38-Dec_2013) [Mapping OCA2.png] |
 | |
| Cytogenetic band showing OCA2 locus (Ref: http://www.genecards.org/cgi-bin/carddisp.pl?gene=OCA2&keywords=OCA2) | |
| Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| GABRG3 (15q12) / OCA2 (15q12) |
| DNA/RNA |
| Description | In Chromosome: 15, the 344,486 bases long gene starts from 27,754,873 bp from pter and ends at 28,099,358 bp from pter; Orientation: Minus strand. It contains 24 exons and spans ~344.5 kb of the genome. |
| Transcription | The gene encodes a 3154 bp transcript. Alternative splicing results in at least two transcript variants. Variant 2 lacks an alternate in-frame exon in the central coding region, compared to variant 1, resulting in an isoform that is shorter than isoform 1. |
| Protein |
| Description | The gene encodes a protein containing 838 amino acids with molecular mass of 92850 Da. The OCA2 is thought to be a melanosomal multipass integral membrane protein (with 12 predicted transmembrane domains). OCA2 is characterized by the presence of a conserved consensus acidic dileucine-based sorting motif within the cytoplasmic N-terminal region. A second dileucine signal within this region confers steady-state lysosomal localization in melanocytes. It belongs to the CitM (TC 2.A.11) transporter family. |
| Expression | Due to its localization in the melanosomal membrane, OCA2 is thought to be expressed in the melanocytes. |
| Localisation | OCA2 is hypothesized to be present in the melanosomal membrane of the melanocytes. |
| Function | The precise function of OCA2 has not been elucidated till date. However, the potential functions include: a) normal biogenesis of melanosomes, b) for normal processing and transport of tyrosinase and other melanosomal proteins, and c) maintenance of an acidic pH in melanosomes. |
| Homology | Its sequence predicts that OCA2 has a homology to a superfamily of permeases. It has been proposed that OCA2 also regulates the post-translational processing of tyrosinase, which catalyzes the rate limiting steps in melanin biosynthesis and is a major determinant of brown and/or blue eye color. |
| Mutations |
| Germinal | Mutations in OCA2 are responsible for albinism known also as OCA2. A few OCA2 mutations have been associated also with autosomal recessive ocular albinism. While the degree of cutaneous pigment and iris color may vary, the newborn with OCA2 nearly always have pigmented hair. Nevi and freckles are common. Visual acuity is better than in OCA1 and reaches 3/10. Africans with OCA2 appear with light brown hair and skin, and gray irises. Eighty six mutations in OCA2 have been reported in Albinism Database (http://www.ifpcs.org/albinism/oca2mut.html). It is to be noted that Albinism Database has been updated till 2009. |
| Somatic | Somatic mutations in OCA2 have been identified in cancers (http://www.cancerindex.org/geneweb/OCA2.htm, http://cancer.sanger.ac.uk/cosmic/search?q=OCA2), but no causality have been reported. |
| Implicated in |
| Note | |
| Entity | Melanoma |
| Note | In 2005, Jannot et al reported, based on allelic distribution between cases and controls, that malignant melanoma and OCA2 are associated (p value=0.030 after correction for multiple testing). In 2010 Duffy et al claimed the OCA2 variant Arg419Gln (rs1800407) to be a significant risk factor for cutaneous malignant melanoma based on a genome wide association study (GWAS). In 2011, another GWAS identified a locus at chromosome 15q13.1 (HERC2/OCA2 region) in a discovery cohort of 1804 melanoma cases and 1026 controls, to be associated with melanoma (Amos et al., 2011). Co-segregation analysis in an OCA2 affected pedigree containing individuals diagnosed with both cutaneous and iris melanoma, revealed that OCA2 variants could act as contributors towards melanoma predisposition (Hawkes et al., 2013). The OCA2 Arg419Gln SNP has also been found to be associated with basal cell carcinoma of skin (OR, 1.50; 95% CI, 1.06-2.13) (Nan et al., 2009) |
| Bibliography |
| Genome-wide association study identifies novel loci predisposing to cutaneous melanoma |
| Amos CI, Wang LE, Lee JE, Gershenwald JE, Chen WV, Fang S, Kosoy R, Zhang M, Qureshi AA, Vattathil S, Schacherer CW, Gardner JM, Wang Y, Bishop DT, Barrett JH; GenoMEL Investigators, MacGregor S, Hayward NK, Martin NG, Duffy DL; Q-Mega Investigators, Mann GJ, Cust A, Hopper J; AMFS Investigators, Brown KM, Grimm EA, Xu Y, Han Y, Jing K, McHugh C, Laurie CC, Doheny KF, Pugh EW, Seldin MF, Han J, Wei Q |
| Hum Mol Genet 2011 Dec 15;20(24):5012-23 |
| PMID 21926416 |
| Multiple pigmentation gene polymorphisms account for a substantial proportion of risk of cutaneous malignant melanoma |
| Duffy DL, Zhao ZZ, Sturm RA, Hayward NK, Martin NG, Montgomery GW |
| J Invest Dermatol 2010 Feb;130(2):520-8 |
| PMID 19710684 |
| Report of a novel OCA2 gene mutation and an investigation of OCA2 variants on melanoma risk in a familial melanoma pedigree |
| Hawkes JE, Cassidy PB, Manga P, Boissy RE, Goldgar D, Cannon-Albright L, Florell SR, Leachman SA |
| J Dermatol Sci 2013 Jan;69(1):30-7 |
| PMID 23103111 |
| Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma |
| Jannot AS, 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 |
| Eur J Hum Genet 2005 Aug;13(8):913-20 |
| Impact of a Delayed Laparoscopic Appendectomy on the Risk of Complications in Acute Appendicitis: A Retrospective Study of 4,065 Patients |
| Kim HK, Kim YS, Lee SH, Lee HH |
| Dig Surg 2016 Jul 6;34(1):25-29 |
| PMID 27380624 |
| Viewing the Valence Electronic Structure of Ferric and Ferrous Hexacyanide in Solution From the Fe and Cyanide Perspectives |
| Kunnus K, Zhang W, Delcey MG, Pinjari RV, Miedema PS, Schreck S, Quevedo W, Schroeder H, Foehlisch A, Gaffney KJ, Lundberg M, Odelius M, Wernet P |
| J Phys Chem B 2016 Jul 5 |
| PMID 27380541 |
| Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians |
| Nan H, Kraft P, Hunter DJ, Han J |
| Int J Cancer 2009 Aug 15;125(4):909-17 |
| PMID 19384953 |
| Citation |
| This paper should be referenced as such : |
| Kunal Ray, Mainak Sengupta, Sampurna Ghosh |
| OCA2 (OCA2 melanosomal transmembrane protein) |
| Atlas Genet Cytogenet Oncol Haematol. 2016;20(12):592-594. |
| Free journal version : [ pdf ] [ DOI ] |
| Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ] |
| Oculocutaneous Albinism |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Feb 19 17:56:40 CET 2021 |
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