OCA2 (OCA2 melanosomal transmembrane protein)

2016-04-01   Kunal Ray , Mainak Sengupta , Sampurna Ghosh 


Atlas Image
Cytogenetic band showing OCA2 locus (Ref: http://www.genecards.org/cgi-bin/carddisp.pl?gene=OCA2&keywords=OCA2)


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.



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.


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.



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.


Due to its localization in the melanosomal membrane, OCA2 is thought to be expressed in the melanocytes.


OCA2 is hypothesized to be present in the melanosomal membrane of the melanocytes.


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.


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 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 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

Entity name
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)


Pubmed IDLast YearTitleAuthors
219264162011Genome-wide association study identifies novel loci predisposing to cutaneous melanoma.Amos CI et al
197106842010Multiple pigmentation gene polymorphisms account for a substantial proportion of risk of cutaneous malignant melanoma.Duffy DL et al
231031112013Report of a novel OCA2 gene mutation and an investigation of OCA2 variants on melanoma risk in a familial melanoma pedigree.Hawkes JE et al
273806242017Impact of a Delayed Laparoscopic Appendectomy on the Risk of Complications in Acute Appendicitis: A Retrospective Study of 4,065 Patients.Kim HK et al
273805412016Viewing the Valence Electronic Structure of Ferric and Ferrous Hexacyanide in Solution from the Fe and Cyanide Perspectives.Kunnus K et al
193849532009Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians.Nan H et al

Other Information

Locus ID:

NCBI: 4948
MIM: 611409
HGNC: 8101
Ensembl: ENSG00000104044


dbSNP: 4948
ClinVar: 4948
TCGA: ENSG00000104044


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Metabolism of amino acids and derivativesREACTOMER-HSA-71291
Melanin biosynthesisREACTOMER-HSA-5662702


Pubmed IDYearTitleCitations
128175912003Control of confounding of genetic associations in stratified populations.228
179520752007Genetic determinants of hair, eye and skin pigmentation in Europeans.224
205856272010Web-based, participant-driven studies yield novel genetic associations for common traits.155
125794162003Skin pigmentation, biogeographical ancestry and admixture mapping.141
182522222008A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color.107
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
193849532009Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians.67
193849532009Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians.67
197106842010Multiple pigmentation gene polymorphisms account for a substantial proportion of risk of cutaneous malignant melanoma.66
182522212008Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene.65


Kunal Ray ; Mainak Sengupta ; Sampurna Ghosh

OCA2 (OCA2 melanosomal transmembrane protein)

Atlas Genet Cytogenet Oncol Haematol. 2016-04-01

Online version: http://atlasgeneticsoncology.org/gene/45789/oca2-(oca2-melanosomal-transmembrane-protein)