Affinage

OCA2

P protein · UniProt Q04671

Length
838 aa
Mass
92.8 kDa
Annotated
2026-06-10
100 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OCA2 is a melanosomal membrane protein that operates at the first step of melanin synthesis and is directly required for melanin biosynthesis in melanocytes (PMID:8980282, PMID:24282555). It localizes to the melanosome membrane and regulates melanosomal ion homeostasis and pH: loss of OCA2 yields non-acidic melanosomes, impairs tyrosinase processing, and disrupts pigment production (PMID:11310796, PMID:25656818). Functionally, OCA2 acts as a Cl- channel whose loss lowers melanosomal Cl-, thereby de-repressing the TPC2 (TPCN2) channel, acidifying the melanosome lumen, and reducing pigmentation; OCA2 and TPCN2 variant knockin mice show synergistic hypopigmentation (PMID:41443368), and variant-effect assays confirm that pathogenic OCA2 mutations disrupt measurable channel/transporter activity (PMID:39636647). OCA2 traffics from the ER to melanosomes via N-terminal dileucine-based sorting signals recognized differentially by adaptor complexes AP-1 and AP-3, with delivery requiring BLOC-1 in cooperation with either adaptor (PMID:19116314, PMID:22718909, PMID:21392365). Its transcription is controlled by a long-range HERC2 intron 86 enhancer (rs12913832) that forms an allele-dependent chromatin loop to the OCA2 promoter engaging HLTF, LEF1, and MITF, and is repressed by the transcription factor TBX2 (PMID:18172690, PMID:22234890, PMID:26971330); common splicing variants such as the synonymous rs1800404 further modulate expression via exon skipping linked to lighter pigmentation (PMID:40996958). Beyond pigmentation, OCA2 has pleiotropic roles, genetically controlling sleep loss in cavefish (PMID:34293332) and contributing to melanosome-dependent chemoresistance (PMID:30977151).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1997 High

    Established that OCA2 is itself required for melanin biosynthesis rather than merely correlated with pigment, resolving whether the gene acts cell-autonomously in melanocytes.

    Evidence Complementation of p-null mouse melanocytes with wild-type and mutant human P cDNA, with melanin content as readout

    PMID:8980282

    Open questions at the time
    • Did not define the molecular activity of OCA2
    • No localization or mechanism by which it supports melanin synthesis
  2. 2001 Medium

    Linked OCA2 to melanosomal physiology by showing it sets melanosomal pH, framing it as an ion-transport regulator at the melanosome membrane.

    Evidence pH measurements in p-deficient vs wild-type mouse melanocytes plus melanosome-membrane localization

    PMID:11310796

    Open questions at the time
    • Direct ion-transport activity not demonstrated
    • Identity of transported anion inferred, not measured
  3. 2008 High

    Defined where OCA2 must act and how it gets there, showing melanosomal (not ER) localization is required for function and is encoded by a dileucine sorting motif.

    Evidence Live-cell imaging, fractionation, ER-retention rescue, dileucine mutagenesis, and adaptor co-IP in OCA2-deficient melanocytes; plus reporter/EMSA showing HERC2 rs12913832 reduces OCA2 promoter activity allele-specifically

    PMID:18172690 PMID:19116314

    Open questions at the time
    • Which adaptors bind each signal not fully resolved in 2008
    • Identity of allele-specific nuclear factors at rs12913832 unknown
  4. 2012 High

    Mapped the trafficking and transcriptional machinery for OCA2 — that AP-1/AP-3 read its dileucine signal by sequence context and BLOC-1 is universally required, and that a long-range chromatin loop drives allele-dependent expression.

    Evidence Sorting-signal mutagenesis with epistasis in AP-1/AP-3/BLOC-1 mutant lines and EM; ChIP, 3C, and qRT-PCR in darkly vs lightly pigmented human melanocytes

    PMID:22234890 PMID:22718909

    Open questions at the time
    • Structural basis of differential adaptor recognition unresolved
    • How HLTF/LEF1/MITF cooperate at the enhancer not detailed
  5. 2013 Medium

    Placed OCA2 at the first enzymatic step of melanin synthesis and revealed downstream consequences of its loss, including substrate diversion and altered ER-stress signaling.

    Evidence Morpholino knockdown in Astyanax embryos with HPLC metabolite profiling; thapsigargin ER-stress assays in Oca2-null melanocytes with eIF2alpha/UPR readouts; minigene splicing assays for two pathogenic variants

    PMID:23962237 PMID:24282555 PMID:24361966

    Open questions at the time
    • Mechanism linking OCA2 loss to Gadd34-PP1alpha-mediated eIF2alpha dephosphorylation incompletely defined
    • Substrate diversion to catecholamines not shown to be physiologically significant
  6. 2014 Medium

    Cross-species and ultrastructural studies tied OCA2 to melanosome maturation and pH-dependent chromatophore differentiation, while a localization study raised an endosomal/lysosomal alternative.

    Evidence Zebrafish oca2 mutant characterization with EM and bafilomycin rescue; siRNA knockdown with melanosome ultrastructure (2015); antibody-based confocal colocalization with LAMP2/BLOC-1

    PMID:24330346 PMID:25530116 PMID:25656818

    Open questions at the time
    • Localization study (#10) partially conflicts with melanosomal localization reported elsewhere
    • Cell-type-specific roles in iridophores vs melanophores mechanistically unexplained
  7. 2016 Medium

    Identified TBX2 as a direct transcriptional repressor of OCA2, integrating OCA2 expression into hormone-responsive (alpha-MSH/forskolin) melanogenic control.

    Evidence TBX2 siRNA knockdown with double-knockdown epistasis, ChIP, and luciferase reporter assays in mouse melanocytes

    PMID:26971330

    Open questions at the time
    • Interplay between TBX2 repression and HERC2 enhancer activation not integrated
    • Single lab, single model system
  8. 2018 High

    Demonstrated that OCA2 is the sole genetic determinant of albinism in independently evolved cavefish, establishing strict causal specificity.

    Evidence CRISPR/Cas9 mutagenesis and genetic complementation crosses in Astyanax mexicanus

    PMID:29555241

    Open questions at the time
    • Molecular activity of OCA2 still not directly measured
    • Does not address pleiotropic roles
  9. 2021 High

    Revealed OCA2 pleiotropy by genetically separating its role in sleep regulation from pigmentation, broadening its biological function beyond melanin.

    Evidence CRISPR mutagenesis, sleep quantification, non-complementation across cave populations, and QTL co-segregation in Astyanax

    PMID:34293332

    Open questions at the time
    • Mechanism by which OCA2 affects sleep unknown
    • Whether sleep role depends on melanosomal function untested
  10. 2024 Medium

    Established OCA2 channel/transporter activity as a directly measurable function disrupted by disease variants, providing a functional readout for variant classification.

    Evidence Multiplex variant-effect assays of localization and channel activity on 30 VUS, benchmarked against ClinVar classifications; computational structural modeling (2023) predicting an SLC13-like transporter fold and GOLD domain

    PMID:37431738 PMID:39636647

    Open questions at the time
    • Structural model (#14) is computational with no experimental validation of transport
    • Substrate identity (Na+/dicarboxylate vs Cl-) not resolved by these studies
  11. 2025 High

    Defined the direct molecular activity of OCA2 as a melanosomal Cl- channel and the mechanism by which it controls melanosomal pH, via Cl--dependent regulation of the TPC2 channel.

    Evidence Patch-clamp of TPC2, CRISPR/Cas9 OCA2 KO cells, and OCA2/TPCN2 knockin mice with pH and melanin readouts; plus minigene/association analysis of exon-10 skipping and rs1800404

    PMID:40996958 PMID:41443368

    Open questions at the time
    • Whether OCA2 transports additional ions or substrates beyond Cl- not excluded
    • Structural basis of OCA2 Cl- conduction not yet resolved experimentally

Open questions

Synthesis pass · forward-looking unresolved questions
  • How OCA2's melanosomal Cl- channel function mechanistically connects to its pleiotropic roles in sleep and chemoresistance remains unresolved.
  • No mechanism linking ion transport to sleep regulation
  • Drug-sequestration model for chemoresistance not directly tested
  • No experimental high-resolution structure of OCA2

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3
Localization
GO:0031410 cytoplasmic vesicle 3 GO:0005764 lysosome 2 GO:0005783 endoplasmic reticulum 2
Partners
AP-1AP-3BLOC-1TPCN2

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 The OCA2/P protein localizes to the melanosome membrane and is required for normal melanosomal pH; melanosomes from p-deficient mouse melanocytes have non-acidic (rather than normal acidic) pH, suggesting OCA2 regulates melanosomal pH in conjunction with the ATP-driven proton pump, likely by transporting anions to compensate for proton charge. pH measurements in cultured melanocytes from p-deficient vs wild-type mice; subcellular fractionation and localization to melanosome membrane Pigment cell research Medium 11310796
1997 Normal human P/OCA2 cDNA complements hypopigmentation in p-null mouse melanocytes, restoring melanin biosynthesis; OCA2 missense mutations (A481T, V443I) show minimal or partial complementation, establishing that OCA2 is directly required for melanin biosynthesis in melanocytes. Transfection of p-null melanocytes with wild-type and mutant human P cDNA; melanin content assay as functional readout The Journal of investigative dermatology High 8980282
2008 Endogenous OCA2 rapidly exits the ER and localizes to melanosomes in melanocytic cells (and to lysosomes in non-pigment cells). Melanosomal localization — not ER retention — is required for OCA2 function in melanin synthesis. A conserved N-terminal acidic dileucine motif is required for steady-state melanosomal localization; a second dileucine signal confers lysosomal localization. The two dileucine signals interact differentially with cytoplasmic adaptor proteins involved in melanosome trafficking. Live-cell imaging, subcellular fractionation, ER-retention mutagenesis rescue assays in OCA2-deficient melanocytes, mutagenesis of dileucine motifs, co-immunoprecipitation with adaptor proteins Molecular biology of the cell High 19116314
2012 Delivery of OCA2 to melanosomes requires both AP-3 and BLOC-1. AP-1 and AP-3 recognize the dileucine-based sorting signal of OCA2 based on primary sequence context, not position. AP-3 binding is necessary for steady-state melanosomal localization. Unlike tyrosinase (which uses AP-3 alone), both AP-1- and AP-3-favoring OCA2 variants require BLOC-1 for melanosomal transport, indicating BLOC-1 can cooperate with either adaptor during cargo sorting. Targeted mutagenesis of OCA2 dileucine sorting signal; functional complementation assays in OCA2-deficient cells; epistasis with AP-1, AP-3, BLOC-1 mutant cell lines; electron microscopy Molecular biology of the cell High 22718909
2010 Genetic epistasis experiments in mice show that BLOC-1 (pallid allele) is epistatic to OCA2 (pink-eyed dilution), and OCA2 deficiency acts as a semi-dominant enhancer of BLOC-2 (cocoa) and AP-3 (pearl) mutant phenotypes, establishing functional links between OCA2 and these three protein complexes in melanosome biogenesis. Double-mutant coat color epistasis analysis in C57BL/6J mice using pink-eyed dilution (Oca2), pallid (BLOC-1), cocoa (BLOC-2), and pearl (AP-3) alleles Pigment cell & melanoma research Medium 21392365
2008 The HERC2 intron 86 SNP rs12913832 region acts as a regulatory element that significantly reduces OCA2 promoter activity; the two alleles bind different subsets of nuclear extracts, providing a cis-regulatory mechanism for allele-specific OCA2 expression. Luciferase reporter assay in cell cultures; electrophoretic mobility shift assay (EMSA) Human genetics Medium 18172690
2012 The HERC2 rs12913832 region functions as a long-range enhancer regulating OCA2 transcription. In darkly pigmented melanocytes (T allele), transcription factors HLTF, LEF1, and MITF bind this enhancer and a chromatin loop forms between the enhancer and the OCA2 promoter, leading to elevated OCA2 expression. In lightly pigmented melanocytes (C allele), chromatin-loop formation, TF recruitment, and OCA2 expression are all reduced. Chromatin immunoprecipitation (ChIP) for TF binding; chromosome conformation capture (3C) for chromatin looping; quantitative RT-PCR for OCA2 expression in darkly vs lightly pigmented human melanocytes Genome research High 22234890
2013 Loss of Oca2 in melanocytes leads to accumulation of tyrosinase in the ER, arrest of the unfolded protein response (UPR), and increased resistance to ER stress. In Oca2-null melanocytes, thapsigargin-induced ER stress triggers rapid eIF2α dephosphorylation (rather than phosphorylation) mediated by the Gadd34-PP1α phosphatase complex, suppressing pro-apoptotic PERK signaling and promoting cell survival. Thapsigargin treatment of Oca2-null vs wild-type melanocytes; immunoblotting for eIF2α phosphorylation, UPR markers; pharmacological inhibition of Gadd34-PP1α complex; cell viability assays Pigment cell & melanoma research Medium 23962237
2015 siRNA-mediated knockdown of OCA2/P-protein in melan-a melanocytes significantly alters melanosomal morphology (size, shape, type, number) and reduces melanin content and tyrosinase-related protein levels, directly demonstrating OCA2's role in melanosome biogenesis. siRNA transfection of melan-a melanocytes, B16F10 and melan-p1 cells; transmission electron microscopy of melanosomes; melanin content and tyrosinase activity assays Molecular and cellular biochemistry Medium 25656818
2016 TBX2 transcription factor represses OCA2 expression in melanocytes. α-MSH and forskolin reduce TBX2 expression while stimulating melanogenesis. TBX2 knockdown increases OCA2 expression and melanin production; combined knockdown of TBX2 and OCA2 blocks this effect. ChIP and reporter assays show TBX2 directly binds and represses the OCA2 promoter. siRNA knockdown of TBX2 in primary and immortalized mouse melanocytes; chromatin immunoprecipitation (ChIP); luciferase reporter assay; melanin content measurement Molecular and cellular biochemistry Medium 26971330
2014 OCA2 colocalized with LAMP2 (a lysosomal/late endosomal marker) and significantly with BLOC-1, but not with ER, Golgi, or melanosome markers, when examined with newly generated specific antibodies in human melanocytes and RPE cells. Immunohistochemistry and confocal microscopy with newly generated anti-P antibodies; co-localization with subcellular organelle markers Journal of dermatological science Low 25530116
2018 CRISPR/Cas9-generated oca2 loss-of-function mutations in surface Astyanax mexicanus produce albinism due to disruption of the first step in melanin synthesis. Hybrid offspring from crosses of oca2-mutant surface fish with albino cavefish are albino, demonstrating that oca2 is solely responsible for albinism in multiple independently evolved cavefish populations. CRISPR/Cas9 mutagenesis in Astyanax mexicanus; genetic complementation test (cross between engineered surface mutants and cavefish) Developmental biology High 29555241
2013 Downregulation of oca2 expression in Astyanax surface fish embryos delays development of pigmented melanophores and simultaneously increases L-tyrosine and dopamine levels, demonstrating that OCA2 operates at the first step of the melanin synthesis pathway and that its loss diverts substrate (L-tyrosine) to catecholamine synthesis. Morpholino knockdown of oca2 in Astyanax surface fish embryos; HPLC measurement of L-tyrosine, dopamine, and norepinephrine; melanophore counting PloS one Medium 24282555
2021 oca2 has a pleiotropic role regulating both pigmentation and sleep. Surface Astyanax fish with engineered oca2 mutations show both albinism and reduced sleep. The oca2 mutation fails to complement sleep loss when oca2-mutant surface fish are crossed to independently evolved albino cavefish, establishing that oca2 is genetically responsible for sleep loss as well as albinism in cavefish. CRISPR/Cas9 oca2 mutagenesis; sleep quantification in F2 hybrid fish and oca2 surface mutants; genetic non-complementation test across cave populations; QTL co-segregation analysis Current biology : CB High 34293332
2023 Computational structural modeling (AlphaFold2) suggests OCA2 adopts a transporter fold similar to SLC13 family members (scaffold and transport domains with pseudo-inverted repeat topology including re-entrant loops), an elevator-type transport mechanism, and contains a cryptic GOLD domain likely responsible for ER-to-Golgi trafficking. Conserved asparagine residues in the putative ligand-binding site suggest OCA2 may function as a Na+/dicarboxylate symporter. Known pathogenic mutations map to the transport domain. AlphaFold2 structural modeling; sequence analysis; homology modeling; mapping of known mutations onto structural models Bioscience reports Low 37431738
2025 OCA2 functions as a Cl- channel on melanosomes; its loss-of-function reduces melanosomal Cl- and thereby enhances TPC2 (TPCN2) channel activity, lowering melanosomal pH and reducing pigment production. Cytosolic high Cl- inhibits TPC2 while luminal high Cl- enhances TPC2 activity. CRISPR/Cas9 OCA2 KO cell models and OCA2 p.Val443Ile knockin mice with TPCN2 p.Arg210Cys knockin show synergistic hypopigmentation in fur and retina. Patch-clamp analysis of TPC2 channel activity; CRISPR/Cas9 KO cell models; knockin mouse models; melanin content and pH measurements The Journal of investigative dermatology High 41443368
2019 Zebrafish oca2 loss-of-function mutations increase melanocyte sensitivity to cisplatin compared to wild-type, but do not increase cisplatin sensitivity in hair cells of the lateral line, suggesting that Oca2-dependent melanosome maturation contributes to cisplatin resistance specifically in melanocytes, potentially via drug sequestration. Zebrafish oca2 loss-of-function mutant larvae; cisplatin treatment; quantification of melanocyte and hair cell survival Experimental dermatology Medium 30977151
2014 In zebrafish, oca2 loss-of-function results in reduced number of differentiated melanophores (with immature melanosomes) but increased number of differentiated iridophores, indicating cell-type-specific roles for oca2 in chromatophore differentiation. Treatment with bafilomycin A1 (vacuolar ATPase inhibitor/cytoplasmic pH modifier) partially rescues melanosome maturation, consistent with OCA2's role in melanosomal pH regulation. Positional cloning; zebrafish oca2 mutant characterization; melanoblast and melanophore quantification; transmission electron microscopy; bafilomycin A1 pharmacological rescue Pigment cell & melanoma research Medium 24330346
2013 Two novel OCA2 splicing mutations (IVS14+5G>A and c.2139G>A) were shown by in vitro minigene assay to cause aberrant splicing (exon skipping or altered splice site usage), confirming their causal role in OCA2. In vitro hybrid-minigene splicing assay; in silico splice site prediction Gene Medium 24361966
2025 OCA2 exon 10 skipping is modulated by both exonic and intronic sequence context. Missense variants in exon 10 significantly influence skipping ratio. The common synonymous variant rs1800404-T (c.1065G>A/p.Ala355=) promotes exon 10 skipping and is associated with lighter skin and hair pigmentation. The exon-10-skipped protein isoform is predicted by structural modeling to exert a dominant-negative effect, explaining a dose-dependent hypopigmentation response. Minigene functional assay; hybrid human-murine exon/intron combination assays; association analysis in European population; computational structural modeling of skipped-transcript protein PLoS genetics Medium 40996958
2024 Subcellular localization and channel (transporter) activity assays on 30 OCA2 variants of uncertain significance show that pathogenic/likely pathogenic variants exhibit abnormal localization or abnormal channel activity, while benign/likely benign variants show normal function, establishing that OCA2 has measurable channel/transporter activity that is disrupted by disease-causing mutations. Multiplex assays of variant effect (MAVEs): subcellular localization assay and channel activity assay in cell-based systems; trio whole-exome sequencing for clinical cohort Pigment cell & melanoma research Medium 39636647

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Blue 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. Human genetics 227 18172690
2012 HERC2 rs12913832 modulates human pigmentation by attenuating chromatin-loop formation between a long-range enhancer and the OCA2 promoter. Genome research 209 22234890
2004 Interactive effects of MC1R and OCA2 on melanoma risk phenotypes. Human molecular genetics 205 14709592
2006 A three-single-nucleotide polymorphism haplotype in intron 1 of OCA2 explains most human eye-color variation. American journal of human genetics 162 17236130
2001 The mouse p (pink-eyed dilution) and human P genes, oculocutaneous albinism type 2 (OCA2), and melanosomal pH. Pigment cell research 139 11310796
1997 Complementation of hypopigmentation in p-mutant (pink-eyed dilution) mouse melanocytes by normal human P cDNA, and defective complementation by OCA2 mutant sequences. The Journal of investigative dermatology 107 8980282
2011 A global view of the OCA2-HERC2 region and pigmentation. Human genetics 99 22065085
2010 Association of the OCA2 polymorphism His615Arg with melanin content in east Asian populations: further evidence of convergent evolution of skin pigmentation. PLoS genetics 94 20221248
2009 Interactions between HERC2, OCA2 and MC1R may influence human pigmentation phenotype. Annals of human genetics 92 19208107
2008 Analysis of cultured human melanocytes based on polymorphisms within the SLC45A2/MATP, SLC24A5/NCKX5, and OCA2/P loci. The Journal of investigative dermatology 91 18650849
2018 CRISPR mutagenesis confirms the role of oca2 in melanin pigmentation in Astyanax mexicanus. Developmental biology 82 29555241
2013 A potential benefit of albinism in Astyanax cavefish: downregulation of the oca2 gene increases tyrosine and catecholamine levels as an alternative to melanin synthesis. PloS one 82 24282555
2005 Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma. European journal of human genetics : EJHG 74 15889046
2008 Localization to mature melanosomes by virtue of cytoplasmic dileucine motifs is required for human OCA2 function. Molecular biology of the cell 64 19116314
2003 MC1R mutations modify the classic phenotype of oculocutaneous albinism type 2 (OCA2). American journal of human genetics 62 12876664
2012 Differential recognition of a dileucine-based sorting signal by AP-1 and AP-3 reveals a requirement for both BLOC-1 and AP-3 in delivery of OCA2 to melanosomes. Molecular biology of the cell 58 22718909
2014 Computational screening of disease-associated mutations in OCA2 gene. Cell biochemistry and biophysics 57 23824587
2010 Human eye colour and HERC2, OCA2 and MATP. Forensic science international. Genetics 53 20457063
1994 Diverse mutations of the P gene among African-Americans with type II (tyrosinase-positive) oculocutaneous albinism (OCA2). Human molecular genetics 53 7874125
1997 Oculocutaneous albinism (OCA2) in sub-Saharan Africa: distribution of the common 2.7-kb P gene deletion mutation. Human genetics 49 9099845
2005 P gene mutations associated with oculocutaneous albinism type II (OCA2). Human mutation 45 15712365
2021 Pleiotropic function of the oca2 gene underlies the evolution of sleep loss and albinism in cavefish. Current biology : CB 44 34293332
1995 Frequent intragenic deletion of the P gene in Tanzanian patients with type II oculocutaneous albinism (OCA2). American journal of human genetics 44 7762554
2010 Association between a germline OCA2 polymorphism at chromosome 15q13.1 and estrogen receptor-negative breast cancer survival. Journal of the National Cancer Institute 43 20308648
2007 Multilocus OCA2 genotypes specify human iris colors. Human genetics 43 17619204
2011 Screening of TYR, OCA2, GPR143, and MC1R in patients with congenital nystagmus, macular hypoplasia, and fundus hypopigmentation indicating albinism. Molecular vision 42 21541274
1996 Assignment of genes coding for brown eye colour (BEY2) and brown hair colour (HCL3) on chromosome 15q. European journal of human genetics : EJHG 40 8875191
2014 oca2 Regulation of chromatophore differentiation and number is cell type specific in zebrafish. Pigment cell & melanoma research 37 24330346
2015 Amelanism in the corn snake is associated with the insertion of an LTR-retrotransposon in the OCA2 gene. Scientific reports 35 26597053
2010 Genetic analysis of three important genes in pigmentation and melanoma susceptibility: CDKN2A, MC1R and HERC2/OCA2. Experimental dermatology 34 20629734
2013 Albinism in phylogenetically and geographically distinct populations of Astyanax cavefish arises through the same loss-of-function Oca2 allele. Heredity 31 23572122
2013 Gender is a major factor explaining discrepancies in eye colour prediction based on HERC2/OCA2 genotype and the IrisPlex model. Forensic science international. Genetics 30 23601698
2015 Association study confirms the role of two OCA2 polymorphisms in normal skin pigmentation variation in East Asian populations. American journal of human biology : the official journal of the Human Biology Council 29 25809079
1997 Type 2 oculocutaneous albinism (OCA2) in Zimbabwe and Cameroon: distribution of the 2.7-kb deletion allele of the P gene. Human genetics 29 9341887
2007 Association of polymorphic sites in the OCA2 gene with eye colour using the tree scanning method. Annals of human genetics 28 18093281
2014 Interactions between ultraviolet light and MC1R and OCA2 variants are determinants of childhood nevus and freckle phenotypes. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 27 25410285
2012 Report of a novel OCA2 gene mutation and an investigation of OCA2 variants on melanoma risk in a familial melanoma pedigree. Journal of dermatological science 27 23103111
2015 Unrevealing the role of P-protein on melanosome biology and structure, using siRNA-mediated down regulation of OCA2. Molecular and cellular biochemistry 26 25656818
2014 Genetic variation in regulatory DNA elements: the case of OCA2 transcriptional regulation. Pigment cell & melanoma research 26 24387780
2013 High-resolution array-CGH in patients with oculocutaneous albinism identifies new deletions of the TYR, OCA2, and SLC45A2 genes and a complex rearrangement of the OCA2 gene. Pigment cell & melanoma research 26 24118800
2007 OCA2 481Thr, a hypofunctional allele in pigmentation, is characteristic of northeastern Asian populations. Journal of human genetics 24 17568986
2007 Distribution of two Asian-related coding SNPs in the MC1R and OCA2 genes. Biochemical genetics 24 17570052
2016 Importance of nonsynonymous OCA2 variants in human eye color prediction. Molecular genetics & genomic medicine 22 27468418
1994 The mouse pink-eyed dilution gene: association with hypopigmentation in Prader-Willi and Angelman syndromes and with human OCA2. Pigment cell research 22 7761348
2020 Germline and somatic albinism variants in amelanotic/hypomelanotic melanoma: Increased carriage of TYR and OCA2 variants. PloS one 20 32966289
2001 In Southern Africa, brown oculocutaneous albinism (BOCA) maps to the OCA2 locus on chromosome 15q: P-gene mutations identified. American journal of human genetics 20 11179026
2011 Distribution of OCA2∗481Thr and OCA2∗615Arg, associated with hypopigmentation, in several additional populations. Legal medicine (Tokyo, Japan) 19 21565543
2008 Linkage and association analysis of spectrophotometrically quantified hair color in Australian adolescents: the effect of OCA2 and HERC2. The Journal of investigative dermatology 18 18528436
2010 Functional interactions between OCA2 and the protein complexes BLOC-1, BLOC-2, and AP-3 inferred from epistatic analyses of mouse coat pigmentation. Pigment cell & melanoma research 16 21392365
2022 Oca2 targeting using CRISPR/Cas9 in the Malawi cichlid Astatotilapia calliptera. Royal Society open science 15 35601449
2019 Genome of the Malawi golden cichlid fish (Melanochromis auratus) reveals exon loss of oca2 in an amelanistic morph. Pigment cell & melanoma research 15 31131985
2017 OCA2 splice site variant in German Spitz dogs with oculocutaneous albinism. PloS one 15 28973042
2015 Mutational Analysis of the TYR and OCA2 Genes in Four Chinese Families with Oculocutaneous Albinism. PloS one 15 25919014
2013 Functional characterization of two novel splicing mutations in the OCA2 gene associated with oculocutaneous albinism type II. Gene 15 24361966
2007 Oculocutaneous albinism type 2 (OCA2) with homozygous 2.7-kb deletion of the P gene and sickle cell disease in a Cameroonian family. Identification of a common TAG haplotype in the mutated P gene. Journal of human genetics 15 17767372
2020 The distinctive geographic patterns of common pigmentation variants at the OCA2 gene. Scientific reports 14 32963319
2010 High resolution mapping of OCA2 intragenic rearrangements and identification of a founder effect associated with a deletion in Polish albino patients. Human genetics 14 21085994
1998 Mutations of the human P gene associated with Type II oculocutaneous albinism (OCA2). Mutations in brief no. 205. Online. Human mutation 14 10671067
2020 Nonhuman Primate Model of Oculocutaneous Albinism with TYR and OCA2 Mutations. Research (Washington, D.C.) 13 32259106
2013 Loss of Oca2 disrupts the unfolded protein response and increases resistance to endoplasmic reticulum stress in melanocytes. Pigment cell & melanoma research 13 23962237
2009 Genotyping of five single nucleotide polymorphisms in the OCA2 and HERC2 genes associated with blue-brown eye color in the Japanese population. Cell biochemistry and function 13 19472299
2009 Inheritance of a novel mutated allele of the OCA2 gene associated with high incidence of oculocutaneous albinism in a Polynesian community. Journal of human genetics 12 20019752
2003 A novel P gene missense mutation in a Japanese patient with oculocutaneous albinism type II (OCA2). Journal of dermatological science 12 12727022
2005 Albinism (OCA2) in Amerindians. American journal of physical anthropology 11 16369963
2023 Structural insights into pink-eyed dilution protein (Oca2). Bioscience reports 10 37431738
2021 A custom capture sequence approach for oculocutaneous albinism identifies structural variant alleles at the OCA2 locus. Human mutation 10 34246199
2019 Mutational Analysis of TYR, OCA2, and SLC45A2 Genes in Chinese Families with Oculocutaneous Albinism. Molecular genetics & genomic medicine 10 31199599
2017 Variants at the OCA2/HERC2 locus affect time to first cutaneous squamous cell carcinoma in solid organ transplant recipients collected using two different study designs. The British journal of dermatology 10 28456133
2021 Identification of OCA2 as a novel locus for the co-morbidity of asthma-plus-eczema. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 9 34155719
2025 Mutations in the albinism gene oca2 alter vision-dependent prey capture behavior in the Mexican tetra. The Journal of experimental biology 8 40094260
2016 The transcription factor TBX2 regulates melanogenesis in melanocytes by repressing Oca2. Molecular and cellular biochemistry 8 26971330
2011 Hexasomy of the Prader-Willi/Angelman critical region, including the OCA2 gene, in a patient with pigmentary dysplasia: case report. European journal of medical genetics 8 21621018
2006 Characterization of OCA2 cDNA in different porcine breeds and analysis of its potential effect on skin pigmentation in a red Iberian strain. Animal genetics 8 16573532
2024 The co-occurrence of genetic variants in the TYR and OCA2 genes confers susceptibility to albinism. Nature communications 7 39349469
2023 Unsuspected consequences of synonymous and missense variants in OCA2 can be detected in blood cell RNA samples of patients with albinism. Pigment cell & melanoma research 7 37650133
2015 A nonsense nucleotide substitution in the oculocutaneous albinism II gene underlies the original pink-eyed dilution allele (Oca2(p)) in mice. Experimental animals 7 25736709
2015 Commentary on: "Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study." Tombal B, Borre M, Rathenborg P, Werbrouck P, Van Poppel H, Heidenreich A, Iversen P, Braeckman J, Heracek J, Baskin-Bey E, Ouatas T, Perabo F, Phung D, Hirmand M, Smith MR. Institut de Recherche Clinique, Université Catholique de Louvain, Brussels, Belgium. Electronic address: bertrand.tombal@uclouvain.be. Aarhus University Hospital, Aarhus, Denmark. Herlev Hospital, Herlev, Denmark. AZ Groeninge Kortrijk, Kortrijk, Belgium. UZ Leuven, Leuven, Belgium. Klinik und Poliklinik für Urologie, RWTH University Aachen, Aachen, Germany. Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. UZ Brussel, Brussels, Belgium. Univerzita Karlova v Praze, Prague, Czech Republic. Astellas Pharma Global Development, Leiden, Netherlands. Astellas Pharma Global Development, Northbrook, IL, USA. Medivation Inc, San Francisco, CA, USA. Massachusetts General Hospital Cancer Center, Boston, MA, USA: Lancet Oncol. 2014 May;15(6):592-600; doi: 10.1016/S1470-2045(14)70129-9. [Epub 2014 Apr 14]. Urologic oncology 7 25937426
2010 Transcriptional activation of the general amino acid permease gene per1 by the histone deacetylase Clr6 Is regulated by Oca2 kinase. Molecular and cellular biology 7 20404084
2019 Melanosome maturation proteins Oca2, Mitfa and Vps11 are differentially required for cisplatin resistance in zebrafish melanocytes. Experimental dermatology 6 30977151
2019 Novel compound heterozygous mutations in OCA2 gene associated with non-syndromic oculocutaneous albinism in a Chinese Han patient: a case report. BMC medical genetics 6 31345173
2018 OCA2 rs4778137 polymorphism predicts survival of breast cancer patients receiving neoadjuvant chemotherapy. Gene 6 29409738
2024 Curation of OCA2 Variants of Uncertain Significance From Chinese Oculocutaneous Albinism Patients Based on Multiplex Assays. Pigment cell & melanoma research 5 39636647
2023 Association between Variants in the OCA2-HERC2 Region and Blue Eye Colour in HERC2 rs12913832 AA and AG Individuals. Genes 5 36980970
2022 Delineating Novel and Known Pathogenic Variants in TYR, OCA2 and HPS-1 Genes in Eight Oculocutaneous Albinism (OCA) Pakistani Families. Genes 5 35328057
2017 Retrospective analysis in oculocutaneous albinism patients for the 2.7 kb deletion in the OCA2 gene revealed a co-segregation of the controversial variant, p.R305W. Cell & bioscience 5 28451379
2014 Oculocutaneous albinism: developing novel antibodies targeting the proteins associated with OCA2 and OCA4. Journal of dermatological science 5 25530116
2012 Albinism and disease causing pathogens in Tanzania: are alleles that are associated with OCA2 being maintained by balancing selection? Medical hypotheses 5 23063908
2024 Genetic analysis of albinism caused by compound heterozygous mutations of the OCA2 gene in a Chinese family. Hereditas 4 38317267
2023 Redescription of Periplanetaarabica (Bey-Bienko, 1938) (Blattodea, Blattidae), with a comparative analysis of three species of Periplaneta Burmeister, 1838 (sensu stricto). ZooKeys 4 37234286
2023 Identification of Polymorphisms in the HERC2-OCA2 Gene Locus and their Association with Feather Color in Quail. The journal of poultry science 4 37234755
2023 Unveiling genetics of non-syndromic albinism using whole exome sequencing: A comprehensive study of TYR, TYRP1, OCA2 and MC1R genes in 17 families. Gene 4 37956964
2020 A new type of oculocutaneous albinism with a novel OCA2 mutation. Yeungnam University journal of medicine 4 32741191
2024 Modulating OCA2 Expression as a Promising Approach to Enhance Skin Brightness and Reduce Dark Spots. Biomolecules 3 39456217
2022 Resistance to Beta-cypermethrin, Azadirachtin, and Matrine, and Biochemical Characterization of Field Populations of Oedaleus asiaticus (Bey-Bienko) in Inner Mongolia, Northern China. Journal of insect science (Online) 3 36374481
2019 [Correlation between single nucleotide polymorphisms of rs4778137 located in OCA2 gene and clinical response of breast cancer patients receiving neoadjuvant chemotherapy]. Zhonghua yi xue za zhi 2 31216817
2025 From paleness to albinism: Contribution of OCA2 exon 10 skipping to hypopigmentation. PLoS genetics 1 40996958
2025 OCA2 deficiency enhances TPC2 channel activity to reduce melanosomal pH and pigment production. The Journal of investigative dermatology 1 41443368
2024 Functional analysis of two mutation sites in the OCA2 gene. Scientific reports 1 38926510
2024 Ancestral origins of TYR and OCA2 gene mutations in oculocutaneous albinism from two admixed populations in Colombia. PloS one 1 39556609
2023 Mutational Analysis of TYR, OCA2, SLC45A2, and TYRP1 Genes Identifies Novel and Reported Mutations in Chinese Families with Oculocutaneous Albinism. Alternative therapies in health and medicine 1 37471664

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