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OCA2 (OCA2 melanosomal transmembrane protein)

Written2016-04Kunal 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

(Note : for Links provided by Atlas : click)

Identity

Alias_namesD15S12
P
EYCL3
EYCL2
eye color 3 (brown)
eye color 2 (central brown)
oculocutaneous albinism II (pink-eye dilution homolog, mouse)
Alias_symbol (synonym)BEY2
EYCL
BEY
BEY1
Other aliasMelanocyte-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
Oculocutaneous Albinism II [Pink-Eye Dilution (Murine) Homolog]
Total Brown Iris Pigmentation
Hair Color 3 (Brown)
SHEP1
BOCA
HCL3
PED
PEDH
HGNC (Hugo) OCA2
LocusID (NCBI) 4948
Atlas_Id 45789
Location 15q12  [Link to chromosome band 15q12]
Location_base_pair Starts at 27754876 and ends at 28099312 bp from pter ( according to hg19-Feb_2009)  [Mapping OCA2.png]
 
  Cytogenetic band showing OCA2 locus (Ref: http://www.genecards.org/cgi-bin/carddisp.pl?gene=OCA2&keywords=OCA2)

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 :
Ray K, Sengupta M, Ghosh S
OCA2 (OCA2 melanosomal transmembrane protein);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/OCA2ID45789ch15q12.html


Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ]
  Oculocutaneous Albinism


External links

Nomenclature
HGNC (Hugo)OCA2   8101
Cards
AtlasOCA2ID45789ch15q12
Entrez_Gene (NCBI)OCA2  4948  OCA2 melanosomal transmembrane protein
AliasesBEY; BEY1; BEY2; BOCA; 
D15S12; EYCL; EYCL2; EYCL3; HCL3; P; PED; SHEP1
GeneCards (Weizmann)OCA2
Ensembl hg19 (Hinxton)ENSG00000104044 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000104044 [Gene_View]  chr15:27754876-28099312 [Contig_View]  OCA2 [Vega]
ICGC DataPortalENSG00000104044
TCGA cBioPortalOCA2
AceView (NCBI)OCA2
Genatlas (Paris)OCA2
WikiGenes4948
SOURCE (Princeton)OCA2
Genetics Home Reference (NIH)OCA2
Genomic and cartography
GoldenPath hg38 (UCSC)OCA2  -     chr15:27754876-28099312 -  15q12-q13.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)OCA2  -     15q12-q13.1   [Description]    (hg19-Feb_2009)
EnsemblOCA2 - 15q12-q13.1 [CytoView hg19]  OCA2 - 15q12-q13.1 [CytoView hg38]
Mapping of homologs : NCBIOCA2 [Mapview hg19]  OCA2 [Mapview hg38]
OMIM203200   227220   611409   
Gene and transcription
Genbank (Entrez)BC012097 BX398277 M97901 M99564
RefSeq transcript (Entrez)NM_000275 NM_001300984
RefSeq genomic (Entrez)NC_000015 NC_018926 NG_009846 NT_187660 NW_011332701
Consensus coding sequences : CCDS (NCBI)OCA2
Cluster EST : UnigeneHs.654411 [ NCBI ]
CGAP (NCI)Hs.654411
Alternative Splicing GalleryENSG00000104044
Gene ExpressionOCA2 [ NCBI-GEO ]   OCA2 [ EBI - ARRAY_EXPRESS ]   OCA2 [ SEEK ]   OCA2 [ MEM ]
Gene Expression Viewer (FireBrowse)OCA2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4948
GTEX Portal (Tissue expression)OCA2
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ04671   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ04671  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ04671
Splice isoforms : SwissVarQ04671
PhosPhoSitePlusQ04671
Domains : Interpro (EBI)Cit_transptr-like_dom   
Domain families : Pfam (Sanger)CitMHS (PF03600)   
Domain families : Pfam (NCBI)pfam03600   
Conserved Domain (NCBI)OCA2
DMDM Disease mutations4948
Blocks (Seattle)OCA2
SuperfamilyQ04671
Human Protein AtlasENSG00000104044
Peptide AtlasQ04671
HPRD01945
IPIIPI00028627   IPI00150205   IPI00513686   IPI00795955   
Protein Interaction databases
DIP (DOE-UCLA)Q04671
IntAct (EBI)Q04671
FunCoupENSG00000104044
BioGRIDOCA2
STRING (EMBL)OCA2
ZODIACOCA2
Ontologies - Pathways
QuickGOQ04671
Ontology : AmiGOtransporter activity  L-tyrosine transmembrane transporter activity  protein binding  cytoplasm  lysosomal membrane  endoplasmic reticulum membrane  eye pigment biosynthetic process  spermatid development  cell proliferation  endosome membrane  tyrosine transport  integral component of membrane  melanocyte differentiation  melanosome membrane  melanin biosynthetic process  transmembrane transport  
Ontology : EGO-EBItransporter activity  L-tyrosine transmembrane transporter activity  protein binding  cytoplasm  lysosomal membrane  endoplasmic reticulum membrane  eye pigment biosynthetic process  spermatid development  cell proliferation  endosome membrane  tyrosine transport  integral component of membrane  melanocyte differentiation  melanosome membrane  melanin biosynthetic process  transmembrane transport  
REACTOMEQ04671 [protein]
REACTOME PathwaysR-HSA-5662702 [pathway]   
NDEx NetworkOCA2
Atlas of Cancer Signalling NetworkOCA2
Wikipedia pathwaysOCA2
Orthology - Evolution
OrthoDB4948
GeneTree (enSembl)ENSG00000104044
Phylogenetic Trees/Animal Genes : TreeFamOCA2
HOVERGENQ04671
HOGENOMQ04671
Homologs : HomoloGeneOCA2
Homology/Alignments : Family Browser (UCSC)OCA2
Gene fusions - Rearrangements
Fusion: TCGAGABRG3 15q12 OCA2 15q12 BRCA LUSC
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerOCA2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)OCA2
dbVarOCA2
ClinVarOCA2
1000_GenomesOCA2 
Exome Variant ServerOCA2
ExAC (Exome Aggregation Consortium)OCA2 (select the gene name)
Genetic variants : HAPMAP4948
Genomic Variants (DGV)OCA2 [DGVbeta]
DECIPHEROCA2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisOCA2 
Mutations
ICGC Data PortalOCA2 
TCGA Data PortalOCA2 
Broad Tumor PortalOCA2
OASIS PortalOCA2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICOCA2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDOCA2
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch OCA2
DgiDB (Drug Gene Interaction Database)OCA2
DoCM (Curated mutations)OCA2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)OCA2 (select a term)
intoGenOCA2
NCG5 (London)OCA2
Cancer3DOCA2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM203200    227220    611409   
Orphanet17992    17993    11458    13811    13771   
MedgenOCA2
Genetic Testing Registry OCA2
NextProtQ04671 [Medical]
TSGene4948
GENETestsOCA2
Target ValidationOCA2
Huge Navigator OCA2 [HugePedia]
snp3D : Map Gene to Disease4948
BioCentury BCIQOCA2
ClinGenOCA2 (curated)
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD4948
Chemical/Pharm GKB GenePA31890
Clinical trialOCA2
Miscellaneous
canSAR (ICR)OCA2 (select the gene name)
Probes
Litterature
PubMed108 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineOCA2
EVEXOCA2
GoPubMedOCA2
iHOPOCA2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Tue Aug 1 17:33:04 CEST 2017

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