OCA2 (OCA2 melanosomal transmembrane protein)
2016-04-01 Kunal Ray , Mainak Sengupta , Sampurna Ghosh AffiliationIdentity
HGNC
LOCATION
15q12
IMAGE
LEGEND
Cytogenetic band showing OCA2 locus (Ref: http://www.genecards.org/cgi-bin/carddisp.pl?gene=OCA2&keywords=OCA2)
LOCUSID
ALIAS
BEY,BEY1,BEY2,BOCA,D15S12,EYCL,EYCL2,EYCL3,HCL3,P,PED,SHEP1
FUSION GENES
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.
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.
Proteins
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
Entity name
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)
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)
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 21926416 | 2011 | Genome-wide association study identifies novel loci predisposing to cutaneous melanoma. | Amos CI et al |
| 19710684 | 2010 | Multiple pigmentation gene polymorphisms account for a substantial proportion of risk of cutaneous malignant melanoma. | Duffy DL et al |
| 23103111 | 2013 | Report of a novel OCA2 gene mutation and an investigation of OCA2 variants on melanoma risk in a familial melanoma pedigree. | Hawkes JE et al |
| 27380624 | 2017 | Impact of a Delayed Laparoscopic Appendectomy on the Risk of Complications in Acute Appendicitis: A Retrospective Study of 4,065 Patients. | Kim HK et al |
| 27380541 | 2016 | Viewing the Valence Electronic Structure of Ferric and Ferrous Hexacyanide in Solution from the Fe and Cyanide Perspectives. | Kunnus K et al |
| 19384953 | 2009 | Genetic 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
Variants:
dbSNP: 4948
ClinVar: 4948
TCGA: ENSG00000104044
COSMIC: OCA2
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000104044 | ENST00000353809 | Q04671 |
| ENSG00000104044 | ENST00000354638 | Q04671 |
| ENSG00000104044 | ENST00000431101 | C9JDV3 |
| ENSG00000104044 | ENST00000445578 | C9JLG9 |
Expression (GTEx)
Pathways
| Pathway | Source | External ID |
|---|---|---|
| Metabolism | REACTOME | R-HSA-1430728 |
| Metabolism of amino acids and derivatives | REACTOME | R-HSA-71291 |
| Melanin biosynthesis | REACTOME | R-HSA-5662702 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37882226 | 2024 | Novel compound heterozygous mutations in OCA2 gene were identified in a Chinese family with oculocutaneous albinism. | 1 |
| 37882226 | 2024 | Novel compound heterozygous mutations in OCA2 gene were identified in a Chinese family with oculocutaneous albinism. | 1 |
| 37294081 | 2023 | Native American genetic ancestry and pigmentation allele contributions to skin color in a Caribbean population. | 1 |
| 37294081 | 2023 | Native American genetic ancestry and pigmentation allele contributions to skin color in a Caribbean population. | 1 |
| 34155719 | 2022 | Identification of OCA2 as a novel locus for the co-morbidity of asthma-plus-eczema. | 4 |
| 35328057 | 2022 | Delineating Novel and Known Pathogenic Variants in TYR, OCA2 and HPS-1 Genes in Eight Oculocutaneous Albinism (OCA) Pakistani Families. | 2 |
| 36059514 | 2022 | Key molecules associated with thyroid carcinoma prognosis: A study based on transcriptome sequencing and GEO datasets. | 3 |
| 34155719 | 2022 | Identification of OCA2 as a novel locus for the co-morbidity of asthma-plus-eczema. | 4 |
| 35328057 | 2022 | Delineating Novel and Known Pathogenic Variants in TYR, OCA2 and HPS-1 Genes in Eight Oculocutaneous Albinism (OCA) Pakistani Families. | 2 |
| 36059514 | 2022 | Key molecules associated with thyroid carcinoma prognosis: A study based on transcriptome sequencing and GEO datasets. | 3 |
| 33800529 | 2021 | Genetic Causes of Oculocutaneous Albinism in Pakistani Population. | 2 |
| 33974259 | 2021 | [Analysis of genetic variation for a child affected with congenital insensitivity to pain with anhidrosis and albinism by whole genome sequencing]. | 0 |
| 34246199 | 2021 | A custom capture sequence approach for oculocutaneous albinism identifies structural variant alleles at the OCA2 locus. | 4 |
| 34795370 | 2021 | Further insight into the global variability of the OCA2-HERC2 locus for human pigmentation from multiallelic markers. | 1 |
| 33800529 | 2021 | Genetic Causes of Oculocutaneous Albinism in Pakistani Population. | 2 |
Citation
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/chromosome-explorer/gene-explorer/
