Q04671Q15211Q15212Q96EN1Q9UMI5P_HUMANP proteinMelanocyte-specific transporter proteinPink-eyed dilution protein homologOCA2D15S12PHomo sapiensHumanEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomoA gene for the mouse pink-eyed dilution locus and for human type II oculocutaneous albinism.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3)VARIANT ASP-257Organization and sequence of the human P gene and identification of a new family of transport proteins.NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3)FUNCTIONSUBCELLULAR LOCATIONVARIANTS TRP-305; GLN-419; PHE-440; ARG-615 AND THR-722The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)The mouse pink-eyed dilution gene: association with human Prader-Willi and Angelman syndromes.NUCLEOTIDE SEQUENCE [MRNA] OF 288-419DISEASEThe mouse p (pink-eyed dilution) and human P genes, oculocutaneous albinism type 2 (OCA2), and melanosomal pH.FUNCTIONInverse correlation between pink-eyed dilution protein expression and induction of melanogenesis by bafilomycin A1.POSSIBLE INVOLVEMENT IN SKIN COLOR VARIATIONEye colour: portals into pigmentation genes and ancestry.FUNCTIONMolecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism.REVIEW ON OCA2 VARIANTSHERC2 rs12913832 modulates human pigmentation by attenuating chromatin-loop formation between a long-range enhancer and the OCA2 promoter.FUNCTIONINDUCTIONSLC45A2 protein stability and regulation of melanosome pH determine melanocyte pigmentation.FUNCTIONDEVELOPMENTAL STAGETISSUE SPECIFICITYDiverse mutations of the P gene among African-Americans with type II (tyrosinase-positive) oculocutaneous albinism (OCA2).VARIANTS OCA2Frequent intragenic deletion of the P gene in Tanzanian patients with type II oculocutaneous albinism (OCA2).VARIANTS OCA2Novel mutations of the P gene in type II oculocutaneous albinism (OCA2).VARIANTS OCA2Mutations of the human P gene associated with type II oculocutaneous albinism (OCA2).VARIANTS OCA2 ARG-86; PHE-112; VAL-368; ILE-592; PRO-724 AND VAL-787VARIANT ASP-257Novel and recurrent mutations in the tyrosinase gene and the P gene in the German albino population.VARIANTS OCA2 GLY-290; ILE-443; GLU-614; LEU-617; CYS-679; CYS-720; ARG-795 AND VAL-833 DELVARIANTS TRP-305 AND GLN-419Identification of P gene mutations in individuals with oculocutaneous albinism in sub-Saharan Africa.VARIANT OCA2 VAL-334VARIANTS UNCLASSIFIED OCA MET-350; THR-370; LYS-678; PHE-688 AND LEU-743P gene as an inherited biomarker of human eye color.VARIANTS TRP-305 AND GLN-419INVOLVEMENT IN DETERMINATION OF EYE COLORMC1R mutations modify the classic phenotype of oculocutaneous albinism type 2 (OCA2).VARIANTS OCA2 GLY-290; ILE-443; ASP-489; CYS-679 AND LEU-743A novel P gene missense mutation in a Japanese patient with oculocutaneous albinism type II (OCA2).VARIANTS OCA2 THR-481 AND HIS-799Six novel P gene mutations and oculocutaneous albinism type 2 frequency in Japanese albino patients.VARIANTS OCA2 TRP-10; LEU-198; LEU-211; ILE-394 AND THR-481VARIANTS MET-387 AND ARG-615Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma.VARIANTS TRP-305 AND GLN-419INVOLVEMENT IN SUSCEPTIBILITY TO MELANOMAA three-single-nucleotide polymorphism haplotype in intron 1 of OCA2 explains most human eye-color variation.INVOLVEMENT IN SHEP1POLYMORPHISMThe consensus coding sequences of human breast and colorectal cancers.VARIANT [LARGE SCALE ANALYSIS] THR-773Genetic determinants of hair, eye and skin pigmentation in Europeans.INVOLVEMENT IN SHEP1POLYMORPHISMPrenatal diagnosis of oculocutaneous albinism type II and novel mutations in two Chinese families.VARIANTS OCA2 ILE-443; ASP-476; ARG-775 AND HIS-827Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene.INVOLVEMENT IN SHEP1POLYMORPHISMA single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color.VARIANT GLN-419FUNCTIONINDUCTIONINVOLVEMENT IN SHEP1INVOLVEMENT IN SUSCEPTIBILITY TO MELANOMAPOLYMORPHISMBlue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression.INVOLVEMENT IN SHEP1POLYMORPHISMINDUCTIONDNA variations in oculocutaneous albinism: an updated mutation list and current outstanding issues in molecular diagnostics.VARIANTS OCA2 MET-404; TRP-419; ILE-633; CYS-679 AND CYS-684An intracellular anion channel critical for pigmentation.FUNCTIONCHANNEL ACTIVITYCHARACTERIZATION OF VARIANTS OCA2 ILE-443 AND GLU-614SUBCELLULAR LOCATIONContributes to a melanosome-specific anion (chloride) current that modulates melanosomal pH for optimal tyrosinase activity required for melanogenesis and the melanosome maturation (PubMed:25513726, PubMed:11310796, PubMed:15262401, PubMed:22234890). One of the components of the mammalian pigmentary system (PubMed:15262401, PubMed:18252222, PubMed:7601462). May serve as a key control point at which ethnic skin color variation is determined. Major determinant of brown and/or blue eye color (PubMed:15262401, PubMed:18252222, PubMed:7601462). Seems to regulate the post-translational processing of tyrosinase, which catalyzes the limiting reaction in melanin synthesis (By similarity).chloride(in) = chloride(out)Melanosome membraneMulti-pass membrane proteinQ04671-11Q04671-22Q04671-33Expressed in melanocytes and retinal pigment epithelium.Expressed at early stages of melanosome differentiation.Expression is under the control of an enhancer element that is encoded in an intron of the close-by HERC2 gene. The enhancer element containing the T-allele of the polymorphism rs12913832 mediates binding of the transcription factors HLTF, LEF1 and MITF and increases OCA2 expression. In contrast, transcription factor binding and OCA2 expression are reduced in carriers of the C-allele of polymorphism rs12913832. Thus, people homozygous for the C-allele have light-colored eyes, while people homozygous for the T-allele of polymorphism rs12913832 most often have brown eyes.Genetic variants in OCA2 define the skin/hair/eye pigmentation variation locus 1 (SHEP1) [MIM:227220]; also known as skin/hair/eye pigmentation type 1, blue/nonblue eyes or skin/hair/eye pigmentation type 1, blue/brown eyes or skin/hair/eye pigmentation type 1, blond/brown hair or eye color, brown/blue or eye color, blue/nonblue or eye color type 3 (EYCL3) or brown eye color type 2 (BEY2) or hair color type 3 (HCL3). Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair. OCA2 polymorphisms may act as a penetrance modifier of the risk of malignant melanoma.Albinism, oculocutaneous, 2
OCA2
An autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in skin, hair, and eyes. Although affected infants may appear at birth to have complete absence of melanin pigment, most patients acquire small amounts of pigment with age. Visual anomalies include decreased acuity and nystagmus. The phenotype is highly variable. The hair of affected individuals may turn darker with age, and pigmented nevi or freckles may be seen. African and African American individuals may have yellow hair and blue-gray or hazel irides. One phenotypic variant, 'brown OCA,' has been described in African and African American populations and is characterized by light brown hair and skin color and gray to tan irides.The disease is caused by variants affecting the gene represented in this entry.Belongs to the CitM (TC 2.A.11) transporter family.Retina International's Scientific NewsletterP mutationsQuestioning colour - Issue 54 of January 2005AlbinismAlternative splicingDisease variantGlycoproteinMembraneReference proteomeTransmembraneTransmembrane helixTransportWIAILGAIWLLILADIHGLGLVQAGRYYLSTPESRWGRSRCFPLPLPRADRWNWKVRGRWAVAVVMAVITFITMMIMLTMRQRWLFLHVIMVISNDATNDVAHQRHTIKEKNHRILVIWREKWCWRFCLFRCITAPSLPLATGRAVGRQHYHMHLEGRDGRRYPGAPAVELLQTSVPSGLAELVAGKRRLPRGAGGADPSHSCPRGAAGQSSWAPAGQEFASFLTKGRSHSSLPQMSSSRSKDSCFTENTPLLRNSLQEKGSRCIPVYHPEFITAEESWEDSSADWERRYLLSREVSGLSASASSEKGDLLDSPHIRLRLSKLRRCVQWLKVMGLFAFVVLCSILFSLYPDQGKLWQLLALSPLENYSVNLSSHVDSTLLQVDLAGALVASGPSRPGREEHIVVELTQADALGSRWRRPQQVTHNWTVYLNPRRSEHSVMSRTFEVLTRETVSISIRASLQQTQAVPLLMAHQYLRGSVETQVTIATAILAGVYALIIFEIVHRTLAAMLGSLAALAALAVIGDRPSLTHVVEWIDFETLALLFGMMILVAIFSETGFFDYCAVKAYRLSRGRVWAMIIMLCLIAAVLSAFLDNVTTMLLFTPVTIRLCEVLNLDPRQVLIAEVIFTNIGGAATAIGDPPNVIIVSNQELRKMGLDFAGFTAHMFIGICLVLLVCFPLLRLLYWNRKLYNKEPSEIVELKHEIHVWRLTAQRISPASREETAVRRLLLGKVLALEHLLARRLHTFHRQISQEDKNWETNIQELQKKHRISDGILLAKCLTVLGFVIFMFFLNSFVPGIHLDLGWIAILGAIWLLILADIHDFEIILHRVEWATLLFFAALFVLMEALAHLHLIEYVGEQTALLIKMVPEEQRLIAAIVLVVWVSALASSLIDNIPFTATMIPVLLNLSHDPEVGLPAPPLMYALAFGACLGGNGTLIGASANVVCAGIAEQHGYGFSFMEFFRLGFPMMVVSCTVGMCYLLVAHVVVGWN
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