Affinage

NR2E3

Photoreceptor-specific nuclear receptor · UniProt Q9Y5X4

Length
410 aa
Mass
44.7 kDa
Annotated
2026-04-29
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NR2E3 is a photoreceptor-specific orphan nuclear receptor that acts as a master transcriptional switch during retinal development, suppressing cone-specific gene expression while activating rod-specific genes including rhodopsin. It functions within a multi-protein complex containing CRX, NRL, and NR1D1, co-occupying promoter and enhancer regions of photoreceptor genes; its ligand-binding domain adopts a dimeric auto-repressed conformation that can be modulated by the endogenous ligand biliverdin (PMID:24069298, PMID:35508617, PMID:15190009). Mutations in NR2E3 cause enhanced S-cone syndrome (recessive) and retinitis pigmentosa (dominant via the G56R dominant-negative allele), with loss of function leading to hybrid rod-cone photoreceptors prone to degeneration (PMID:10655056, PMID:17564971, PMID:38485095). Outside the retina, NR2E3 activates p53 by promoting p300-dependent p53 acetylation, maintains epigenetic accessibility of the DINO lncRNA locus during liver injury, and suppresses Wnt/β-catenin signaling to restrain hepatocellular carcinogenesis (PMID:22025681, PMID:30991008, PMID:38790135).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 High

    Identification of NR2E3 as the gene mutated in enhanced S-cone syndrome and its exclusive expression in the outer nuclear layer established it as a critical photoreceptor fate determinant, answering the question of what gene underlies this retinal dystrophy.

    Evidence Mutation analysis in ESCS families combined with retinal expression localization (human); independent identification of the rd7 mouse mutation in murine Nr2e3

    PMID:10655056 PMID:10805811

    Open questions at the time
    • Mechanism of photoreceptor fate control unknown
    • No direct transcriptional targets identified
    • Ligand identity unknown
  2. 2001 High

    Demonstration that Nr2e3 loss leads to excess cone cell proliferation in rd7 mice established that NR2E3 normally suppresses cone generation, shifting the question from 'what gene' to 'how does it control photoreceptor identity'.

    Evidence In situ hybridization, immunohistochemistry, and histological analysis of rd7 retinas showing ectopic cone proliferation

    PMID:11487564

    Open questions at the time
    • Whether NR2E3 acts in progenitors or post-mitotic cells unresolved
    • No interacting partners identified
  3. 2004 High

    Discovery that NR2E3 forms a multi-protein complex with NR1D1, NRL, and CRX on rod gene promoters revealed the cooperative transcriptional machinery through which NR2E3 activates rod phototransduction genes.

    Evidence Yeast two-hybrid, GST pulldown, co-immunoprecipitation from bovine retinal nuclear extract, and synergistic promoter activation assays

    PMID:15190009

    Open questions at the time
    • Genome-wide target repertoire unknown
    • Structural basis of complex assembly unresolved
  4. 2005 High

    Identification of NR2E3's dual transcriptional function — repressing cone-specific genes while activating rhodopsin through interaction with CRX on shared chromatin targets — answered how a single factor could enforce rod versus cone identity.

    Evidence SELEX binding site selection, ChIP on mouse retina showing co-occupancy with CRX, transcriptional assays demonstrating activation of rhodopsin and repression of cone opsins

    PMID:15634773 PMID:15689355

    Open questions at the time
    • Mechanism of context-dependent switching between activation and repression unclear
    • Cofactor recruitment basis unknown
  5. 2006 High

    Ectopic NR2E3 expression in the cone-only Nrl−/− retina completely suppressed cone differentiation and generated rod-like cells, establishing NR2E3 as sufficient to impose rod identity and placing it as the terminal effector of the NRL→NR2E3 transcriptional hierarchy.

    Evidence Transgenic NR2E3 expression in Nrl−/− retina with FACS-purified photoreceptor gene profiling; complementary BrdU/proliferation studies in rd7 mice

    PMID:16868010 PMID:17266784

    Open questions at the time
    • Whether NR2E3 acts cell-autonomously in all photoreceptor subtypes unclear
    • NRL-independent functions not fully delineated
  6. 2008 High

    Placing NR2E3 downstream of NRL and CRX in the rod transcriptional hierarchy, and identifying direct chromatin targets including Prph2, defined the regulatory cascade controlling rod gene expression programs.

    Evidence NRL/CRX synergistic activation of Nr2e3 promoter; ChIP demonstrating Prph2 as a direct NR2E3 target with reduced expression in rd7 retinas

    PMID:18294621 PMID:18763016

    Open questions at the time
    • Comprehensive genome-wide target map not yet available
    • Epigenetic mechanism of target regulation unclear
  7. 2009 High

    Systematic biochemical analysis of 25 disease-associated mutations revealed that DBD mutations impair DNA binding, nuclear localization, and partner interaction while the G56R adRP mutation acts as a dominant negative competing for CRX, explaining distinct disease mechanisms for ESCS versus adRP.

    Evidence BRET2 dimerization assays, EMSA, mutagenesis-based rhodopsin promoter assays, Co-IP mapping across multiple variants; ChIP identification of additional direct targets

    PMID:19006237 PMID:19379737 PMID:19823680 PMID:19898638

    Open questions at the time
    • Structural basis of dominant-negative mechanism at atomic resolution unknown
    • In vivo validation of variant-specific mechanisms incomplete
  8. 2011 High

    Discovery of NR2E3's extra-retinal functions — forming complexes with p53/p300 to drive p53 acetylation and activating ESR1 transcription via PIAS3 recruitment — expanded the gene's functional repertoire beyond photoreceptor biology.

    Evidence Co-IP of NR2E3-p53-p300 complexes with p53 stability and target gene assays; ChIP on ESR1 promoter with PIAS3 co-recruitment in breast cancer cells

    PMID:22025681 PMID:22174013

    Open questions at the time
    • Physiological relevance of p53 regulation in retinal cells unknown
    • Whether ESR1 regulation extends beyond cancer cell lines unresolved
  9. 2013 High

    The crystal structure of the NR2E3 LBD revealed a dimeric auto-repressed conformation with a filled ligand pocket and AF2 helix blocking cofactor recruitment, providing the first structural explanation for NR2E3's constitutive repressor activity.

    Evidence X-ray crystallography at 2.8 Å with structure-guided mutagenesis validating AF2 and dimer interface contributions to repression

    PMID:24069298

    Open questions at the time
    • Ligand identity unknown at this point
    • How ligand binding would relieve auto-repression structurally unresolved
  10. 2015 High

    Systematic BRET2 mapping of LBD heterodimerization selectivity — NR2E3 heterodimerizes with NRL and NR1D1 but not TLX or RXRα — and demonstration that ESCS-causing LBD variants selectively disrupt these interactions defined the molecular specificity of the NR2E3 interaction network.

    Evidence BRET2 interaction assays across multiple nuclear receptor partners and disease variants

    PMID:25703721

    Open questions at the time
    • Whether PPARγ/TRβ heterodimers identified later have retinal relevance unclear
    • Ternary complex stoichiometry unresolved
  11. 2019 Medium

    NR2E3 was shown to maintain chromatin accessibility at the DINO lncRNA locus, enabling p53 activation during liver injury, revealing an epigenetic gatekeeper role outside the retina.

    Evidence NR2E3 KO mice with ATAC-seq/ChIP-seq showing reduced chromatin accessibility at DINO, impaired p53 activation after APAP or CCl4 treatment

    PMID:30991008

    Open questions at the time
    • Mechanism by which NR2E3 maintains open chromatin not defined
    • Relevance to human liver injury not confirmed
  12. 2022 Medium

    Identification of biliverdin as an endogenous ligand for NR2E3 answered the longstanding question of whether this 'orphan' receptor has a natural ligand, connecting heme catabolism to photoreceptor gene regulation.

    Evidence Ligand-binding assays with retinal extracts, NR2E3-dependent reporter activation by biliverdin, pharmacological inhibition of biliverdin synthesis reducing photoreceptor populations in zebrafish rescued by exogenous biliverdin

    PMID:35508617

    Open questions at the time
    • Structural basis of biliverdin-LBD interaction unresolved
    • Independent replication needed
    • Whether biliverdin modulates the auto-repressed conformation unknown
  13. 2024 Medium

    Single-cell transcriptomics of NR2E3-null human retinal organoids and mouse retinas revealed hybrid rod-cone photoreceptor populations and a disease-specific branch point in rod development, while loss of NR2E3 was shown to activate Wnt/β-catenin signaling and accelerate hepatocellular carcinoma.

    Evidence scRNA-seq of patient iPSC-derived organoids and isogenic controls; scRNA-seq of two Nr2e3 mutant mouse models; NR2E3 KO mice with ATAC-seq, Co-IP, ChIP, and cancer phenotyping

    PMID:38485095 PMID:38652563 PMID:38790135

    Open questions at the time
    • Whether hybrid photoreceptors represent a transitional state or stable population unclear
    • Mechanism linking NR2E3 loss to Sp1/β-catenin/p300 complex formation not fully defined
    • Therapeutic targetability of the Wnt axis in NR2E3-null context untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural mechanism by which biliverdin binding alters NR2E3's auto-repressed conformation, how NR2E3 switches between activator and repressor modes at different genomic loci, and whether its extra-retinal functions in p53 regulation and Wnt suppression are physiologically relevant in normal human tissues.
  • No co-crystal structure of NR2E3 LBD with biliverdin
  • Context-dependent activation vs. repression mechanism unresolved
  • In vivo relevance of NR2E3-p53 axis in human tissues beyond liver injury models unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-5357801 Programmed Cell Death 2 R-HSA-162582 Signal Transduction 1
Partners
CRXEP300NR1D1NRLPIAS3PPARGTP53
Complex memberships
NR2E3-CRX-NRL-NR1D1 rod transcriptional complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 NR2E3 is expressed exclusively in the outer nuclear layer of the human retina and mutations in NR2E3 cause enhanced S-cone syndrome, establishing NR2E3 as a ligand-dependent transcription factor with a role in determining photoreceptor phenotype during retinogenesis. Expression analysis (localization to outer nuclear layer), mutation analysis in ESCS cohort Nature genetics High 10655056
2000 A 380-nt deletion in the coding region of murine Nr2e3 (mPNR) that eliminates a portion of the DNA-binding domain causes the rd7 retinal degeneration phenotype, demonstrating that Nr2e3 expression is critical for normal development and function of photoreceptor cells. RT-PCR, sequencing of rd7 mouse retinal RNA; chromosomal mapping to rd7 locus PNAS High 10805811
2001 Nr2e3 mutation in rd7 mice results from a splicing error caused by a genomic deletion; Nr2e3 is expressed in late retinal progenitors and its loss leads to excess cone cell proliferation and retinal dysplasia. In situ hybridization, immunohistochemistry, histological analysis of rd7 retinas Human molecular genetics High 11487564
2004 NR2E3 interacts with NR1D1 (Rev-erbα) as identified by yeast two-hybrid and confirmed by GST pulldown and co-immunoprecipitation; NR2E3, NR1D1, NRL, and CRX form a multi-protein transcriptional regulatory complex in bovine retinal nuclear extract, synergistically activating rod phototransduction gene promoters. Yeast two-hybrid, GST pulldown, co-immunoprecipitation, transient transfection promoter activity assays Human molecular genetics High 15190009
2005 Nr2e3 is expressed exclusively in rods in the mature vertebrate retina; Nr2e3 functions as a repressor of multiple cone-specific genes in rod photoreceptors, as demonstrated by identification of an optimal Nr2e3 DNA-binding site, transcriptional activity assays of wild-type and disease-associated mutants, and gene expression analysis of rd7 mice. Immunolocalization, SELEX (binding site selection), transfection-based transcriptional assays, gene expression analysis of rd7 retinas The Journal of neuroscience High 15634773
2005 Nr2e3 physically interacts with CRX through their respective DNA-binding domains; Nr2e3 and CRX co-occupy promoter/enhancer regions of rod and cone genes in rod photoreceptors in a Crx-dependent manner; Nr2e3 enhances rhodopsin transcription but represses S- and M-cone opsin transcription when interacting with Crx, demonstrating dual transcriptional regulatory function. Yeast two-hybrid, co-immunoprecipitation, chromatin immunoprecipitation (ChIP) on mouse retina, transient transfection assays in HEK293 cells, quantitative RT-PCR of rd7 retina Human molecular genetics High 15689355
2006 Ectopic expression of NR2E3 in the Nrl-/- cone-only retina completely suppressed cone differentiation and generated rod-like photoreceptors; NR2E3 acts as a strong suppressor of cone genes and activator of a subset of rod genes (including rhodopsin) independent of NRL and CRX presence, establishing NR2E3 as a critical regulator of photoreceptor functional specificity. Transgenic mouse expression of NR2E3 in Nrl-/- retina, FACS-purified photoreceptor gene profiling Human molecular genetics High 16868010
2007 The G56R mutation in the first zinc finger of NR2E3 causes autosomal dominant retinitis pigmentosa through a different pathogenetic mechanism than recessive NR2E3 mutations, attributed to the dual role of NR2E3 in photoreceptor-specific gene regulation. Mutation identification in adRP families, clinical characterization American journal of human genetics Medium 17564971
2008 NRL binds to a sequence element in the Nr2e3 promoter and enhances its activity synergistically with CRX, establishing NRL as an upstream activator of Nr2e3 in the rod photoreceptor transcriptional hierarchy; NRL can only partially suppress cone development in the absence of NR2E3. Promoter activity assays, transgenic mouse studies, gene profiling Brain research High 18294621
2009 NR2E3 directly targets multiple genes in developing and mature retina including transcription factors (Ror1, Rorgamma, Nr1d1, Nr2c1) and phototransduction genes (Gnb1, blue opsin, Gnat2, Gnb3), as demonstrated by chromatin immunoprecipitation assays; GNB1 protein is diminished in Nr2e3rd7/rd7 adult retinas. Quantitative RT-PCR, subtractive hybridization, chromatin immunoprecipitation (ChIP), immunohistochemistry Experimental eye research High 19379737
2009 The adRP-linked G56R mutant NR2E3 protein acts as a dominant negative by competing for CRX interaction while abolishing DNA binding, repressing rod gene transactivation in trans; disease-causing mutations in the DNA-binding domain impair NR2E3 homodimerization and/or CRX interaction, revealing different disease mechanisms for adRP vs. ESCS. Bioluminescence Resonance Energy Transfer (BRET2) assays for protein-protein interaction, transfection-based transcriptional assays PloS one High 19823680
2009 The dominant negative activity of the G56R mutant NR2E3 protein is the molecular mechanism of adRP; impaired repression of cone-specific genes by corepressors atrophin-1 (DRPLA protein) and atrophin-2 (RERE) was identified as a molecular mechanism underlying modified phenotypes. Functional analysis of mutant proteins, co-expression studies Human mutation Medium 19006237
2009 Biochemical characterization of 25 NR2E3 disease-associated mutations showed that mutations in the DNA-binding domain (DBD) impair DNA binding, nuclear localization, and interaction with NRL and CRX; mutations in the ligand-binding domain (LBD) similarly affect these functions; two variants between DBD and LBD showed no functional defect. Site-directed mutagenesis, nuclear localization assay, gel-shift (EMSA), rhodopsin promoter activity assays, co-immunoprecipitation in mammalian cells Molecular vision High 19898638
2011 Early-born post-mitotic photoreceptor precursors in the rd7 retina express cone-specific genes in the absence of Nr2e3; Nr2e3 driven by the Nrl promoter (in rod-committed precursors) completely rescues the rd7 phenotype, supporting the transcriptional dominance model and showing Nr2e3 is required to suppress S-cone gene expression during normal rod differentiation. GFP birthdating of photoreceptor precursors, BrdU labeling, transgenic rescue in rd7 background Human molecular genetics High 21813656
2011 NR2E3 (PNR) forms complexes with p53 and the acetyltransferase p300, stimulates p53 acetylation, increases p53 protein stability, and induces expression of a subset of p53 target genes, thereby acting as a positive regulator of p53 transcriptional activity and apoptosis. High-throughput genetic screen, co-immunoprecipitation, p53-responsive promoter reporter assays, p53 stability assays Molecular and cellular biology High 22025681
2011 NR1D1 (Rev-erbα) is co-expressed with NR2E3 in the outer nuclear layer of developing and adult mouse retina; knockdown of Nr1d1 impairs retinal function; several genes are co-targeted by both NR2E3 and NR1D1 including Nr2c1, Recoverin, Rgr, Rarres2, Pde8a, and Nupr1, demonstrating a functional partnership in retinal transcriptional networks. Nr1d1 knockdown, electroretinogram, co-localization immunohistochemistry, gene expression analysis PloS one Medium 21408158
2011 NR2E3 regulates ESR1 (estrogen receptor alpha) expression in breast cancer cells via direct binding to the ESR1 promoter with concomitant recruitment of PIAS3, establishing NR2E3 as an upstream transcriptional activator of ESR1. ChIP assay on ESR1 promoter, reporter assays, co-immunoprecipitation with PIAS3, knockdown studies EMBO molecular medicine Medium 22174013
2013 Crystal structure of apo NR2E3 ligand-binding domain (LBD) at 2.8 Å reveals a dimeric auto-repressed conformation in which the putative ligand-binding pocket is filled with bulky hydrophobic residues and the AF2 helix occupies the canonical cofactor binding site; mutations disrupting either the AF2/cofactor-binding interface or dimer interface compromised transcriptional repressor activity. X-ray crystallography (2.8 Å), structure-guided mutagenesis, transcriptional repressor activity assays in cells PloS one High 24069298
2014 NR2E3 (PNR) activates transcription of IL-13Rα2 through direct recruitment to the IL-13Rα2 promoter in ERα-negative breast cancer cells; IL-13Rα2 upregulation leads to ERK1/2 phosphorylation upon IL-13 stimulation, promoting cancer cell migration and metastasis in vitro and in vivo. ChIP on IL-13Rα2 promoter, reporter assays, in vitro migration assays, in vivo metastasis models, signaling pathway analysis Oncogene Medium 24747967
2014 In vivo delivery of Nr1d1 (Rev-erbα) rescues Nr2e3-associated retinal degeneration in rd7 mice through re-regulation of key genes in the Nr2e3-directed transcriptional network, demonstrating that Nr1d1 functions as a genetic modifier that restores retinal homeostasis. In vivo gene delivery (AAV), electroretinogram, histology, immunohistochemistry, molecular gene expression analysis PloS one Medium 24498227
2015 NR2E3 LBD homodimerization is abrogated by specific ESCS-causing missense variants (L263P, L336P, L353V, R385P, M407K) but not others (A256V, R039G, R311Q, R334G); NR2E3 LBD heterodimerizes with NRL and NR1D1 but not TLX/NR2E1 or RXRα/NR2C1; LBD variants affect interaction with NRL and NR1D1 but not CRX. Bioluminescence Resonance Energy Transfer (BRET2) protein interaction assays, homology modeling Human mutation High 25703721
2017 PNR/NR2E3 LBD forms heterodimers with PPARγ/NR1C3 and TRβ/NR1A2 but not PPARα or PPARδ; PNR and PPARγ are co-expressed in human retinal tissue and can be co-immunoprecipitated as a native complex; disease-associated NR2E3 LBD sequence variants disrupt PNR/PPARγ complex formation; wild-type PNR but not a PNR309G mutant represses PPARγ-mediated transcription. LBD interaction assays, co-immunoprecipitation from native retinal extracts, reporter assays Cell death & disease Medium 28300834
2019 NR2E3 maintains active epigenetic status of the long noncoding RNA DINO promoter to enable DINO induction and subsequent p53 activation in response to acute liver injury; NR2E3 KO mice exhibit impaired DINO induction, reduced chromatin accessibility at the DINO locus, and impaired p53 activation following APAP or carbon tetrachloride treatment. NR2E3 knockout mice, ChIP-seq/ATAC-seq (chromatin accessibility), DINO/p53 functional assays in vivo and in vitro FASEB journal Medium 30991008
2019 Nr2e3 knockout zebrafish fail to differentiate rod photoreceptors (no rod-specific gene expression, no outer segment formation) without increase in S-cone or UV-cone numbers; Nr2e3 synergizes with Crx and Nrl to enhance rhodopsin gene expression in vitro; selective L-/M-cone degeneration occurs post-development in Nr2e3-null zebrafish. CRISPR knockout zebrafish, histology, gene expression analysis, in vitro rhodopsin reporter assays Biochimica et biophysica acta High 30684641
2022 Biliverdin, a conserved heme catabolism product, specifically binds to NR2E3's ligand-binding domain and induces NR2E3-dependent reporter gene expression; inhibition of biliverdin synthesis decreases photoreceptor cell populations in zebrafish larvae, rescued by exogenous biliverdin, establishing biliverdin as an endogenous small molecule ligand for NR2E3. Ligand-binding assay with retinal extracts, NR2E3-dependent reporter gene assay, zebrafish pharmacological inhibition + rescue Scientific reports Medium 35508617
2024 In human retinal organoids, NR2E3 is required for proper expression of phototransduction genes including rhodopsin; NR2E3-null rods misexpress cone-specific phototransduction genes; scRNA-seq reveals a branch point unique to the disease state in the rod developmental lineage. Retinal organoids from patient iPSCs and isogenic controls, single-cell RNA sequencing (scRNA-seq), joint multimodal single-cell sequencing Journal of clinical investigation High 38652563
2024 Loss of NR2E3 activates Wnt/β-catenin signaling through increased formation of a transcription complex of Sp1, β-catenin, and p300 on target gene promoters, with increased chromatin accessibility; NR2E3 KO mice show accelerated hepatocellular carcinoma with enhanced Wnt/β-catenin activation and p53 inactivation. NR2E3 KO mice, ATAC-seq, co-immunoprecipitation, ChIP on target promoters, cancer cell functional assays Advanced science Medium 38790135
2024 scRNA-seq of Nr2e3 mutant mouse retinas identifies a previously unreported hybrid cone subpopulation co-expressing rod and cone genes that is more abundant in mutant retinas; a subpopulation of rods transitions toward cone cell fate in Nr2e3 mutants; hybrid photoreceptors with high misexpression are prone to regulated necrosis. Single-cell RNA sequencing of wildtype and two Nr2e3 mutant mouse models Neurobiology of disease Medium 38485095
2008 Prph2 (peripherin/rds) is a direct transcriptional target of NR2E3 as demonstrated by chromatin immunoprecipitation; Prph2 mRNA and protein levels are reduced in Nr2e3rd7/rd7 retinas, and Prph2 mutant mice have similar photoreceptor degeneration to Nr2e3rd7/rd7 mice. Chromatin immunoprecipitation (ChIP), positional cloning, quantitative gene expression, comparative histology Mammalian genome Medium 18763016
2006 NR2E3 acts in late mitotic retinal progenitors to suppress cone generation; NR2E3 is expressed in late retinal progenitors and differentiating photoreceptors; ectopic mitotic progenitor cells in the outer nuclear layer of Nr2e3rd7/rd7 retinas give rise to excess cones. Immunohistochemistry, in situ hybridization, BrdU proliferation assays, TUNEL apoptosis assay in Nr2e3rd7/rd7 mice Visual neuroscience Medium 17266784

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate. Nature genetics 395 10655056
2005 The rod photoreceptor-specific nuclear receptor Nr2e3 represses transcription of multiple cone-specific genes. The Journal of neuroscience : the official journal of the Society for Neuroscience 239 15634773
2005 The photoreceptor-specific nuclear receptor Nr2e3 interacts with Crx and exerts opposing effects on the transcription of rod versus cone genes. Human molecular genetics 227 15689355
2004 Photoreceptor-specific nuclear receptor NR2E3 functions as a transcriptional activator in rod photoreceptors. Human molecular genetics 221 15190009
2002 The nuclear receptor NR2E3 plays a role in human retinal photoreceptor differentiation and degeneration. Proceedings of the National Academy of Sciences of the United States of America 200 11773633
2000 A deletion in a photoreceptor-specific nuclear receptor mRNA causes retinal degeneration in the rd7 mouse. Proceedings of the National Academy of Sciences of the United States of America 183 10805811
2001 Excess cone cell proliferation due to lack of a functional NR2E3 causes retinal dysplasia and degeneration in rd7/rd7 mice. Human molecular genetics 163 11487564
2003 Shared mutations in NR2E3 in enhanced S-cone syndrome, Goldmann-Favre syndrome, and many cases of clumped pigmentary retinal degeneration. Archives of ophthalmology (Chicago, Ill. : 1960) 142 12963616
1991 Expression of the pNR-2/pS2 protein in diverse human epithelial tumours. British journal of cancer 114 1911216
2008 Rod differentiation factor NRL activates the expression of nuclear receptor NR2E3 to suppress the development of cone photoreceptors. Brain research 108 18294621
2007 Recurrent mutation in the first zinc finger of the orphan nuclear receptor NR2E3 causes autosomal dominant retinitis pigmentosa. American journal of human genetics 101 17564971
2006 In vivo function of the orphan nuclear receptor NR2E3 in establishing photoreceptor identity during mammalian retinal development. Human molecular genetics 101 16868010
2004 Nuclear receptor NR2E3 gene mutations distort human retinal laminar architecture and cause an unusual degeneration. Human molecular genetics 92 15229190
2004 Mutation analysis of NR2E3 and NRL genes in Enhanced S Cone Syndrome. Human mutation 90 15459973
2009 NR2E3 mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP). Human mutation 83 19718767
1991 Antipeptide antibodies against the pNR-2 oestrogen-regulated protein of human breast cancer cells and detection of pNR-2 expression in normal tissues by immunohistochemistry. The Journal of pathology 82 1707960
1987 Effects of tamoxifen and 4-hydroxytamoxifen on the pNR-1 and pNR-2 estrogen-regulated RNAs in human breast cancer cells. The Journal of biological chemistry 76 2824472
2009 Nr2e3-directed transcriptional regulation of genes involved in photoreceptor development and cell-type specific phototransduction. Experimental eye research 74 19379737
2006 The transcription factor Nr2e3 functions in retinal progenitors to suppress cone cell generation. Visual neuroscience 72 17266784
2004 Expression of photoreceptor-specific nuclear receptor NR2E3 in rod photoreceptors of fetal human retina. Investigative ophthalmology & visual science 70 15277507
1997 Homodimerization and hetero-oligomerization of the single-domain trefoil protein pNR-2/pS2 through cysteine 58. The Biochemical journal 70 9355742
2000 The photoreceptor cell-specific nuclear receptor gene (PNR) accounts for retinitis pigmentosa in the Crypto-Jews from Portugal (Marranos), survivors from the Spanish Inquisition. Human genetics 68 11071390
2012 Urine podocin:nephrin mRNA ratio (PNR) as a podocyte stress biomarker. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 65 22863839
1990 Expression of the oestrogen regulated pNR-2 mRNA in human breast cancer: relation to oestrogen receptor mRNA levels and response to tamoxifen therapy. British journal of cancer 63 2153395
2009 Mutations in NR2E3 can cause dominant or recessive retinal degenerations in the same family. Human mutation 61 19006237
2012 Characterization of pupil responses to blue and red light stimuli in autosomal dominant retinitis pigmentosa due to NR2E3 mutation. Investigative ophthalmology & visual science 60 22807301
2011 Nuclear receptor Rev-erb alpha (Nr1d1) functions in concert with Nr2e3 to regulate transcriptional networks in the retina. PloS one 60 21408158
2009 Cellular origin of fundus autofluorescence in patients and mice with a defective NR2E3 gene. The British journal of ophthalmology 59 19429590
1997 High-resolution solution structure of human pNR-2/pS2: a single trefoil motif protein. Journal of molecular biology 56 9096235
2007 The Gly56Arg mutation in NR2E3 accounts for 1-2% of autosomal dominant retinitis pigmentosa. Molecular vision 53 17982421
2011 Excess cones in the retinal degeneration rd7 mouse, caused by the loss of function of orphan nuclear receptor Nr2e3, originate from early-born photoreceptor precursors. Human molecular genetics 50 21813656
2020 Nr2e3 is a genetic modifier that rescues retinal degeneration and promotes homeostasis in multiple models of retinitis pigmentosa. Gene therapy 48 32123325
2011 Reconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer. EMBO molecular medicine 42 22174013
2005 Novel NR2E3 mutations (R104Q, R334G) associated with a mild form of enhanced S-cone syndrome demonstrate compound heterozygosity. Ophthalmology 41 16225923
2009 Phenotypic features of patients with NR2E3 mutations. Archives of ophthalmology (Chicago, Ill. : 1960) 39 19139342
2014 Modifier genes as therapeutics: the nuclear hormone receptor Rev Erb alpha (Nr1d1) rescues Nr2e3 associated retinal disease. PloS one 38 24498227
2013 The crystal structure of the orphan nuclear receptor NR2E3/PNR ligand binding domain reveals a dimeric auto-repressed conformation. PloS one 37 24069298
2009 Mutations in the DNA-binding domain of NR2E3 affect in vivo dimerization and interaction with CRX. PloS one 37 19823680
2008 Dual role of Nr2e3 in photoreceptor development and maintenance. Experimental eye research 35 18547563
2019 Correction of NR2E3 Associated Enhanced S-cone Syndrome Patient-specific iPSCs using CRISPR-Cas9. Genes 34 30959774
2012 Mutations in TULP1, NR2E3, and MFRP genes in Indian families with autosomal recessive retinitis pigmentosa. Molecular vision 34 22605927
2008 Analysis of the involvement of the NR2E3 gene in autosomal recessive retinal dystrophies. Clinical genetics 34 18294254
2008 Mapping of genetic modifiers of Nr2e3 rd7/rd7 that suppress retinal degeneration and restore blue cone cells to normal quantity. Mammalian genome : official journal of the International Mammalian Genome Society 33 18286335
2007 Atypical mild enhanced S-cone syndrome with novel compound heterozygosity of the NR2E3 gene. American journal of ophthalmology 33 17601449
2014 IL-13Rα2 mediates PNR-induced migration and metastasis in ERα-negative breast cancer. Oncogene 32 24747967
1995 Production and comparison of mature single-domain 'trefoil' peptides pNR-2/pS2 Cys58 and pNR-2/pS2 Ser58. The Biochemical journal 32 8948462
2021 Allele-Specific Knockout by CRISPR/Cas to Treat Autosomal Dominant Retinitis Pigmentosa Caused by the G56R Mutation in NR2E3. International journal of molecular sciences 31 33807610
2007 Genetic ablation of cone photoreceptors eliminates retinal folds in the retinal degeneration 7 (rd7) mouse. Investigative ophthalmology & visual science 31 17525215
2007 An alcohol oxidase biosensor using PNR redox mediator at carbon film electrodes. Talanta 31 18371810
2009 The spectrum of retinal diseases caused by NR2E3 mutations in Israeli and Palestinian patients. Archives of ophthalmology (Chicago, Ill. : 1960) 30 19273793
2006 The zebrafish orphan nuclear receptor genes nr2e1 and nr2e3 are expressed in developing eye and forebrain. Gene expression patterns : GEP 30 17127102
2003 Cone deactivation kinetics and GRK1/GRK7 expression in enhanced S cone syndrome caused by mutations in NR2E3. Investigative ophthalmology & visual science 30 12601058
2009 A comprehensive analysis of sequence variants and putative disease-causing mutations in photoreceptor-specific nuclear receptor NR2E3. Molecular vision 29 19898638
2012 Double concentric autofluorescence ring in NR2E3-p.G56R-linked autosomal dominant retinitis pigmentosa. Investigative ophthalmology & visual science 27 22661467
2006 Identification of potent agonists of photoreceptor-specific nuclear receptor (NR2E3) and preparation of a radioligand. Bioorganic & medicinal chemistry letters 27 16879962
2019 Knockout of Nr2e3 prevents rod photoreceptor differentiation and leads to selective L-/M-cone photoreceptor degeneration in zebrafish. Biochimica et biophysica acta. Molecular basis of disease 26 30684641
2013 Disruption of the human cone photoreceptor mosaic from a defect in NR2E3 transcription factor function in young adults. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 24 23604511
2018 Cone Vision Changes in the Enhanced S-Cone Syndrome Caused by NR2E3 Gene Mutations. Investigative ophthalmology & visual science 23 29971438
2010 Dorsal eye selector pannier (pnr) suppresses the eye fate to define dorsal margin of the Drosophila eye. Developmental biology 23 20691679
2006 Apo[a] size and PNR explain African American-Caucasian differences in allele-specific apo[a] levels for small but not large apo[a]. Journal of lipid research 23 16495513
2004 Enhanced S-cone syndrome in a Japanese family with a nonsense NR2E3 mutation (Q350X). Acta ophthalmologica Scandinavica 23 15453866
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2005 "Point of no return (PNR)" in progressive IgA nephropathy: significance of blood pressure and proteinuria management up to PNR. Journal of nephrology 22 16358226
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2007 Nr2e3 and Nrl can reprogram retinal precursors to the rod fate in Xenopus retina. Developmental dynamics : an official publication of the American Association of Anatomists 18 17377979
1995 NMR-based structural studies of the pNR-2/pS2 single domain trefoil peptide. Similarities to porcine spasmolytic peptide and evidence for a monomeric structure. European journal of biochemistry 18 8521850
2019 NR2E3 is a key component in p53 activation by regulating a long noncoding RNA DINO in acute liver injuries. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17 30991008
1980 Electrophysiological analysis of taurine and glycine action on neurons of the mudpuppy retina. II. ERG, PNR and Müller cell recordings. Brain research 17 6249455
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2010 Helicoid subretinal fibrosis associated with a novel recessive NR2E3 mutation p.S44X. Archives of ophthalmology (Chicago, Ill. : 1960) 16 20212206
2009 Association of NR2E3 but not NRL mutations with retinitis pigmentosa in the Chinese population. Investigative ophthalmology & visual science 16 19933183
2024 NR2E3 loss disrupts photoreceptor cell maturation and fate in human organoid models of retinal development. The Journal of clinical investigation 15 38652563
2016 Inhibition of Bacillus cereus Growth and Toxin Production by Bacillus amyloliquefaciens RD7-7 in Fermented Soybean Products. Journal of microbiology and biotechnology 15 26528531
2016 Two-color pupillometry in enhanced S-cone syndrome caused by NR2E3 mutations. Documenta ophthalmologica. Advances in ophthalmology 15 27033713
2015 Differential dimerization of variants linked to enhanced S-cone sensitivity syndrome (ESCS) located in the NR2E3 ligand-binding domain. Human mutation 14 25703721
2011 Orphan nuclear receptor PNR/NR2E3 stimulates p53 functions by enhancing p53 acetylation. Molecular and cellular biology 14 22025681
2008 Drosophila C-terminal binding protein, dCtBP is required for sensory organ prepattern and sharpens proneural transcriptional activity of the GATA factor Pnr. Developmental biology 14 18773887
2012 Peculiar fundus abnormalities and pathognomonic electrophysiological findings in a 14-month-old boy with NR2E3 mutations. Ophthalmic genetics 13 23039133
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2015 Deregulation of NR2E3, an orphan nuclear receptor, by benzo(a)pyrene-induced oxidative stress is associated with histone modification status change of the estrogen receptor gene promoter. Toxicology letters 12 26149760
2013 Systematic analyses of the cytotoxic effects of compound 11a, a putative synthetic agonist of photoreceptor-specific nuclear receptor (PNR), in cancer cell lines. PloS one 12 24066170
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2014 A novel mutation in the NR2E3 gene associated with Goldmann-Favre syndrome and vasoproliferative tumor of the retina. Molecular vision 11 24891813
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2024 The Loss of an Orphan Nuclear Receptor NR2E3 Augments Wnt/β-catenin Signaling via Epigenetic Dysregulation that Enhances Sp1-β catenin-p300 Interactions in Hepatocellular Carcinoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 7 38790135
2022 Structural and functional characterization of a hypothetical protein in the RD7 region in clinical isolates of Mycobacterium tuberculosis - an in silico approach to candidate vaccines. Journal, genetic engineering & biotechnology 7 35394551
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