OCA2 (OCA2 melanosomal transmembrane protein)

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

Identity

HGNC

OCA2

LOCATION

15q12

IMAGE

LEGEND

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

LOCUSID

4948

ALIAS

BEY,BEY1,BEY2,BOCA,D15S12,EYCL,EYCL2,EYCL3,HCL3,P,PED,SHEP1

FUSION GENES

Show Gene Fusions

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)

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)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

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/oca2-(oca2-melanosomal-transmembrane-protein)