{"gene":"NR1H2","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":1994,"finding":"NR1H2 (NER) was identified as a new member of the steroid hormone nuclear receptor gene family, encoding a 461 amino acid polypeptide containing conserved DNA-binding and ligand-binding domains. It shows highest homology to retinoic acid receptors (55% at the DNA-binding domain, 38-40% at the ligand-binding domain). A single 2.3 kb transcript was detected in all cells and tissues tested, suggesting ubiquitous expression.","method":"cDNA library cloning from human osteosarcoma SAOS/B10 cells, sequence analysis, Northern blotting","journal":"Gene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct molecular cloning and sequence characterization with expression analysis, single lab, multiple methods (cloning, sequencing, Northern blot)","pmids":["7926814"],"is_preprint":false},{"year":2007,"finding":"The human LXRB (NR1H2) gene promoter contains two highly conserved and functional ETS/Elk1 and SRF binding sites that are required for basal transcription and mediate glucose-induced transcriptional activation. Mutation of either site abolished factor binding and significantly reduced promoter activity; siRNA knockdown of SRF and Elk1 impaired both basal promoter activity and the glucose response.","method":"Transcription start site mapping, promoter-reporter assays, electrophoretic mobility shift assays (EMSA), site-directed mutagenesis, siRNA knockdown","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — multiple orthogonal methods including mutagenesis of binding sites, EMSA, reporter assays, and siRNA knockdown in a single study demonstrating functional significance","pmids":["17626048"],"is_preprint":false}],"current_model":"NR1H2 (LXRβ) is a ubiquitously expressed nuclear receptor with conserved DNA-binding and ligand-binding domains most homologous to retinoic acid receptors; its own gene (LXRB) is transcriptionally regulated by glucose through Elk1 and SRF binding sites in its promoter, though no ligand was identified in its original characterization."},"narrative":{"mechanistic_narrative":"NR1H2 (LXRβ, originally NER) is a ubiquitously expressed member of the steroid hormone nuclear receptor gene family, encoding a 461-amino-acid protein with conserved DNA-binding and ligand-binding domains most homologous to retinoic acid receptors [PMID:7926814]. Its own gene is transcriptionally controlled through two conserved ETS/Elk1 and SRF binding sites in its promoter, which are required for basal transcription and mediate glucose-induced transcriptional activation [PMID:17626048]. Beyond its cloning, expression pattern, and this promoter-level regulation, no ligand, target gene, or downstream mechanistic role for the NR1H2 protein has been characterized in the available corpus.","teleology":[{"year":1994,"claim":"Established NR1H2 as a distinct nuclear receptor by cloning it and defining its domain architecture, placing it within the steroid hormone receptor family and adjacent to retinoic acid receptors.","evidence":"cDNA library cloning from human osteosarcoma cells with sequence analysis and Northern blotting","pmids":["7926814"],"confidence":"Medium","gaps":["No ligand identified for the receptor","No target genes or DNA response elements defined","Functional role of the protein not addressed"]},{"year":2007,"claim":"Resolved how the NR1H2 gene itself is regulated, showing its promoter is driven by Elk1/SRF and is responsive to glucose, linking receptor expression to metabolic state.","evidence":"Promoter-reporter assays, EMSA, site-directed mutagenesis, and siRNA knockdown of SRF and Elk1 in human cells","pmids":["17626048"],"confidence":"High","gaps":["Does not define the receptor's own ligand or downstream targets","Does not establish the physiological consequence of glucose-induced LXRB expression","Mechanism connecting glucose signaling to Elk1/SRF activation not detailed"]},{"year":null,"claim":"The endogenous ligand, target gene network, and physiological function of the NR1H2 protein remain uncharacterized in the available corpus.","evidence":"No timeline discovery addresses receptor ligand binding or transcriptional output","pmids":[],"confidence":"Low","gaps":["No ligand identified","No direct target genes mapped","No tissue-specific functional role established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[0]}],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P55055","full_name":"Oxysterols receptor LXR-beta","aliases":["Liver X receptor beta","Nuclear receptor NER","Nuclear receptor subfamily 1 group H member 2","Ubiquitously-expressed nuclear receptor"],"length_aa":460,"mass_kda":51.0,"function":"Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity (PubMed:25661920). Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8; DLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity). Induces LPCAT3-dependent phospholipid remodeling in endoplasmic reticulum (ER) membranes of hepatocytes, driving SREBF1 processing and lipogenesis (By similarity). Via LPCAT3, triggers the incorporation of arachidonate into phosphatidylcholines of ER membranes, increasing membrane dynamics and enabling triacylglycerols transfer to nascent very low-density lipoprotein (VLDL) particles (By similarity). Via LPCAT3 also counteracts lipid-induced ER stress response and inflammation, likely by modulating SRC kinase membrane compartmentalization and limiting the synthesis of lipid inflammatory mediators (By similarity). Plays an anti-inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits the hepatic acute phase response by preventing dissociation of the N-Cor corepressor complex (PubMed:20159957)","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/P55055/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/NR1H2","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/NR1H2","total_profiled":1310},"omim":[{"mim_id":"603149","title":"INTERLEUKIN 17A; IL17A","url":"https://www.omim.org/entry/603149"},{"mim_id":"602423","title":"NUCLEAR RECEPTOR SUBFAMILY 1, GROUP H, MEMBER 3; NR1H3","url":"https://www.omim.org/entry/602423"},{"mim_id":"600380","title":"NUCLEAR RECEPTOR SUBFAMILY 1, GROUP H, MEMBER 2; NR1H2","url":"https://www.omim.org/entry/600380"},{"mim_id":"600253","title":"ARYL HYDROCARBON RECEPTOR; AHR","url":"https://www.omim.org/entry/600253"},{"mim_id":"184756","title":"STEROL REGULATORY ELEMENT-BINDING TRANSCRIPTION FACTOR 1; SREBF1","url":"https://www.omim.org/entry/184756"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoplasm","reliability":"Enhanced"},{"location":"Vesicles","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/NR1H2"},"hgnc":{"alias_symbol":["NER","NER-I","RIP15","LXR-b","LXRb"],"prev_symbol":["UNR"]},"alphafold":{"accession":"P55055","domains":[{"cath_id":"3.30.50.10","chopping":"97-159","consensus_level":"high","plddt":92.2367,"start":97,"end":159},{"cath_id":"1.10.565.10","chopping":"222-457","consensus_level":"high","plddt":95.0969,"start":222,"end":457}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P55055","model_url":"https://alphafold.ebi.ac.uk/files/AF-P55055-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P55055-F1-predicted_aligned_error_v6.png","plddt_mean":80.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NR1H2","jax_strain_url":"https://www.jax.org/strain/search?query=NR1H2"},"sequence":{"accession":"P55055","fasta_url":"https://rest.uniprot.org/uniprotkb/P55055.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P55055/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P55055"}},"corpus_meta":[{"pmid":"20227374","id":"PMC_20227374","title":"Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells.","date":"2010","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/20227374","citation_count":313,"is_preprint":false},{"pmid":"20385089","id":"PMC_20385089","title":"NER factors are recruited to active promoters and facilitate chromatin modification for transcription in the absence of exogenous genotoxic attack.","date":"2010","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/20385089","citation_count":181,"is_preprint":false},{"pmid":"18079701","id":"PMC_18079701","title":"Sequential recruitment of the repair factors during NER: the role of XPG in initiating the resynthesis step.","date":"2007","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/18079701","citation_count":134,"is_preprint":false},{"pmid":"7926814","id":"PMC_7926814","title":"NER, a new member of the gene family encoding the human steroid hormone nuclear 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CCC","url":"https://pubmed.ncbi.nlm.nih.gov/18478337","citation_count":68,"is_preprint":false},{"pmid":"21808022","id":"PMC_21808022","title":"Human exonuclease 1 connects nucleotide excision repair (NER) processing with checkpoint activation in response to UV irradiation.","date":"2011","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/21808022","citation_count":66,"is_preprint":false},{"pmid":"23683874","id":"PMC_23683874","title":"Blinded by the UV light: how the focus on transcription-coupled NER has distracted from understanding the mechanisms of Cockayne syndrome neurologic disease.","date":"2013","source":"DNA repair","url":"https://pubmed.ncbi.nlm.nih.gov/23683874","citation_count":64,"is_preprint":false},{"pmid":"23422745","id":"PMC_23422745","title":"NER initiation factors, DDB2 and XPC, regulate UV radiation response by recruiting ATR and ATM kinases to DNA damage 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I. Localization of the presumed recognition sites for HimD and Ner functions controlling bacteriophage Mu transcription.","date":"1984","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/6096223","citation_count":49,"is_preprint":false},{"pmid":"18182978","id":"PMC_18182978","title":"Cetuximab potentiates oxaliplatin cytotoxic effect through a defect in NER and DNA replication initiation.","date":"2008","source":"British journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/18182978","citation_count":48,"is_preprint":false},{"pmid":"15665582","id":"PMC_15665582","title":"The potential roles of p53 tumor suppressor in nucleotide excision repair (NER) and base excision repair (BER).","date":"2004","source":"Experimental & molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/15665582","citation_count":47,"is_preprint":false},{"pmid":"26422133","id":"PMC_26422133","title":"Histone modification and chromatin remodeling during NER.","date":"2015","source":"DNA repair","url":"https://pubmed.ncbi.nlm.nih.gov/26422133","citation_count":46,"is_preprint":false},{"pmid":"30161024","id":"PMC_30161024","title":"Association between NER Pathway Gene Polymorphisms and Wilms Tumor Risk.","date":"2018","source":"Molecular therapy. Nucleic acids","url":"https://pubmed.ncbi.nlm.nih.gov/30161024","citation_count":45,"is_preprint":false},{"pmid":"31925419","id":"PMC_31925419","title":"A key interaction with RPA orients XPA in NER complexes.","date":"2020","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/31925419","citation_count":42,"is_preprint":false},{"pmid":"22323595","id":"PMC_22323595","title":"Defective transcription initiation causes postnatal growth failure in a mouse model of nucleotide excision repair (NER) progeria.","date":"2012","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/22323595","citation_count":42,"is_preprint":false},{"pmid":"21550320","id":"PMC_21550320","title":"Dynamics of mammalian NER proteins.","date":"2011","source":"DNA repair","url":"https://pubmed.ncbi.nlm.nih.gov/21550320","citation_count":40,"is_preprint":false},{"pmid":"21151025","id":"PMC_21151025","title":"NER and HR pathways act sequentially to promote UV-C-induced germ cell apoptosis in Caenorhabditis elegans.","date":"2010","source":"Cell death and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/21151025","citation_count":40,"is_preprint":false},{"pmid":"10098404","id":"PMC_10098404","title":"New lines of host defense: inhibition of Ty1 retrotransposition by Fus3p and NER/TFIIH.","date":"1999","source":"Trends in genetics : TIG","url":"https://pubmed.ncbi.nlm.nih.gov/10098404","citation_count":40,"is_preprint":false},{"pmid":"17127714","id":"PMC_17127714","title":"Epidermal stem and progenitor cells in murine epidermis accumulate UV damage despite NER proficiency.","date":"2006","source":"Carcinogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/17127714","citation_count":39,"is_preprint":false},{"pmid":"26865925","id":"PMC_26865925","title":"Role of the XPA protein in the NER pathway: A perspective on the function of structural disorder in macromolecular 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toxicology","url":"https://pubmed.ncbi.nlm.nih.gov/22928555","citation_count":25,"is_preprint":false},{"pmid":"17320292","id":"PMC_17320292","title":"Crosslinking of the NER damage recognition proteins XPC-HR23B, XPA and RPA to photoreactive probes that mimic DNA damages.","date":"2007","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/17320292","citation_count":25,"is_preprint":false},{"pmid":"31289483","id":"PMC_31289483","title":"MicroRNA-200c reverses drug resistance of human gastric cancer cells by targeting regulation of the NER-ERCC3/4 pathway.","date":"2019","source":"Oncology letters","url":"https://pubmed.ncbi.nlm.nih.gov/31289483","citation_count":25,"is_preprint":false},{"pmid":"22029530","id":"PMC_22029530","title":"A common polymorphism in NR1H2 (LXRbeta) is associated with preeclampsia.","date":"2011","source":"BMC medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/22029530","citation_count":23,"is_preprint":false},{"pmid":"25062985","id":"PMC_25062985","title":"Ubiquitin at work: the ubiquitous regulation of the damage recognition step of NER.","date":"2014","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/25062985","citation_count":23,"is_preprint":false},{"pmid":"18387345","id":"PMC_18387345","title":"The NER protein Rad33 shows functional homology to human Centrin2 and is involved in modification of Rad4.","date":"2008","source":"DNA repair","url":"https://pubmed.ncbi.nlm.nih.gov/18387345","citation_count":22,"is_preprint":false},{"pmid":"16182615","id":"PMC_16182615","title":"Repair characteristics and differentiation propensity of long-term cultures of epidermal keratinocytes derived from normal and NER-deficient mice.","date":"2005","source":"DNA repair","url":"https://pubmed.ncbi.nlm.nih.gov/16182615","citation_count":22,"is_preprint":false},{"pmid":"8075070","id":"PMC_8075070","title":"Secondary structure and interaction of phage D108 Ner repressor with a 61-base-pair operator: evidence for altered protein and DNA structures in the complex.","date":"1994","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/8075070","citation_count":22,"is_preprint":false},{"pmid":"25217592","id":"PMC_25217592","title":"Structural and energetic characterization of the major DNA adduct formed from the food mutagen ochratoxin A in the NarI hotspot sequence: influence of adduct ionization on the conformational preferences and implications for the NER propensity.","date":"2014","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/25217592","citation_count":22,"is_preprint":false},{"pmid":"22543959","id":"PMC_22543959","title":"Zebrafish (Danio rerio) life-cycle exposure to chronic low doses of ethinylestradiol modulates p53 gene transcription within the gonads, but not NER pathways.","date":"2012","source":"Ecotoxicology (London, England)","url":"https://pubmed.ncbi.nlm.nih.gov/22543959","citation_count":22,"is_preprint":false},{"pmid":"18021177","id":"PMC_18021177","title":"Dynamics of cell cycle phase perturbations by trabectedin (ET-743) in nucleotide excision repair (NER)-deficient and NER-proficient cells, unravelled by a novel mathematical simulation approach.","date":"2007","source":"Cell proliferation","url":"https://pubmed.ncbi.nlm.nih.gov/18021177","citation_count":21,"is_preprint":false},{"pmid":"29719287","id":"PMC_29719287","title":"Downregulation of RIF1 Enhances Sensitivity to Platinum-Based Chemotherapy in Epithelial Ovarian Cancer (EOC) by Regulating Nucleotide Excision Repair (NER) Pathway.","date":"2018","source":"Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/29719287","citation_count":21,"is_preprint":false},{"pmid":"34064641","id":"PMC_34064641","title":"Circadian Rhythm of NER and ATR Pathways.","date":"2021","source":"Biomolecules","url":"https://pubmed.ncbi.nlm.nih.gov/34064641","citation_count":20,"is_preprint":false},{"pmid":"25128816","id":"PMC_25128816","title":"Insight in the multilevel regulation of NER.","date":"2014","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/25128816","citation_count":20,"is_preprint":false},{"pmid":"19713079","id":"PMC_19713079","title":"Regional expression of Fos-like immunoreactivity following seizures in Noda epileptic rat (NER).","date":"2009","source":"Epilepsy research","url":"https://pubmed.ncbi.nlm.nih.gov/19713079","citation_count":20,"is_preprint":false},{"pmid":"17720631","id":"PMC_17720631","title":"Dual role of NER in mutagenesis in Pseudomonas putida.","date":"2007","source":"DNA repair","url":"https://pubmed.ncbi.nlm.nih.gov/17720631","citation_count":20,"is_preprint":false},{"pmid":"25818601","id":"PMC_25818601","title":"Polychlorinated biphenyl quinone induces oxidative DNA damage and repair responses: The activations of NHEJ, BER and NER via ATM-p53 signaling axis.","date":"2015","source":"Toxicology and applied pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/25818601","citation_count":20,"is_preprint":false},{"pmid":"26191265","id":"PMC_26191265","title":"Genetic variability of genes in NER pathway influences the treatment outcome of gastric cancer.","date":"2015","source":"International journal of clinical and experimental pathology","url":"https://pubmed.ncbi.nlm.nih.gov/26191265","citation_count":20,"is_preprint":false},{"pmid":"17626048","id":"PMC_17626048","title":"Elk1 and SRF transcription factors convey basal transcription and mediate glucose response via their binding sites in the human LXRB gene promoter.","date":"2007","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/17626048","citation_count":19,"is_preprint":false},{"pmid":"17893751","id":"PMC_17893751","title":"Bacterial DNA repair genes and their eukaryotic homologues: 4. The role of nucleotide excision DNA repair (NER) system in mammalian cells.","date":"2007","source":"Acta biochimica Polonica","url":"https://pubmed.ncbi.nlm.nih.gov/17893751","citation_count":19,"is_preprint":false},{"pmid":"23679317","id":"PMC_23679317","title":"Single nucleotide polymorphisms in the NER pathway and clinical outcome of patients with bone malignant tumors.","date":"2013","source":"Asian Pacific journal of cancer prevention : APJCP","url":"https://pubmed.ncbi.nlm.nih.gov/23679317","citation_count":19,"is_preprint":false},{"pmid":"19025691","id":"PMC_19025691","title":"How to make the most of NE dictionaries in statistical NER.","date":"2008","source":"BMC bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/19025691","citation_count":19,"is_preprint":false},{"pmid":"34178836","id":"PMC_34178836","title":"Significant association of LXRβ (NR1H2) polymorphisms (rs28514894, rs2303044) with type 2 diabetes mellitus and laboratory characteristics.","date":"2021","source":"Journal of diabetes and metabolic disorders","url":"https://pubmed.ncbi.nlm.nih.gov/34178836","citation_count":18,"is_preprint":false},{"pmid":"35954493","id":"PMC_35954493","title":"The Association between a Decrease in On-Treatment Neutrophil-to-Eosinophil Ratio (NER) at Week 6 after Ipilimumab Plus Nivolumab Initiation and Improved Clinical Outcomes in Metastatic Renal Cell Carcinoma.","date":"2022","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/35954493","citation_count":18,"is_preprint":false},{"pmid":"22559785","id":"PMC_22559785","title":"The nucleotide excision repair (NER) system of Helicobacter pylori: role in mutation prevention and chromosomal import patterns after natural transformation.","date":"2012","source":"BMC microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/22559785","citation_count":18,"is_preprint":false},{"pmid":"16797255","id":"PMC_16797255","title":"Identification of MMS19 domains with distinct functions in NER and transcription.","date":"2006","source":"DNA repair","url":"https://pubmed.ncbi.nlm.nih.gov/16797255","citation_count":18,"is_preprint":false},{"pmid":"10961618","id":"PMC_10961618","title":"Chromosomal mapping of genes for epilepsy in NER: a rat strain with tonic-clonic seizures.","date":"2000","source":"Epilepsia","url":"https://pubmed.ncbi.nlm.nih.gov/10961618","citation_count":18,"is_preprint":false},{"pmid":"26617899","id":"PMC_26617899","title":"Association of NER pathway gene polymorphisms with susceptibility to laryngeal cancer in a Chinese population.","date":"2015","source":"International journal of clinical and experimental pathology","url":"https://pubmed.ncbi.nlm.nih.gov/26617899","citation_count":17,"is_preprint":false},{"pmid":"37324464","id":"PMC_37324464","title":"Triptolide enhances carboplatin-induced apoptosis by inhibiting nucleotide excision repair (NER) activity in melanoma.","date":"2023","source":"Frontiers in pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/37324464","citation_count":17,"is_preprint":false},{"pmid":"26617894","id":"PMC_26617894","title":"Association of single nucleotide polymorphisms of DNA repair genes in NER pathway and susceptibility to pancreatic cancer.","date":"2015","source":"International journal of clinical and experimental pathology","url":"https://pubmed.ncbi.nlm.nih.gov/26617894","citation_count":17,"is_preprint":false},{"pmid":"2670911","id":"PMC_2670911","title":"Cloning and sequencing of an Escherichia coli gene, nlp, highly homologous to the ner genes of bacteriophages Mu and D108.","date":"1989","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/2670911","citation_count":17,"is_preprint":false},{"pmid":"23161013","id":"PMC_23161013","title":"DNA Helicases in NER, BER, and MMR.","date":"2013","source":"Advances in experimental medicine and biology","url":"https://pubmed.ncbi.nlm.nih.gov/23161013","citation_count":16,"is_preprint":false},{"pmid":"17332015","id":"PMC_17332015","title":"Impaired expression of NER gene network in sporadic solid tumors.","date":"2007","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/17332015","citation_count":16,"is_preprint":false},{"pmid":"15475187","id":"PMC_15475187","title":"Participation of BER and NER pathways in the repair of DNA lesions induced at low N-nitrosodiethylamine concentrations.","date":"2004","source":"Toxicology letters","url":"https://pubmed.ncbi.nlm.nih.gov/15475187","citation_count":16,"is_preprint":false},{"pmid":"30744808","id":"PMC_30744808","title":"Association of BER and NER pathway polymorphism haplotypes and micronucleus frequencies with global DNA methylation in benzene-exposed workers of China: Effects of DNA repair genes polymorphisms on genetic damage.","date":"2019","source":"Mutation research. Genetic toxicology and environmental mutagenesis","url":"https://pubmed.ncbi.nlm.nih.gov/30744808","citation_count":16,"is_preprint":false},{"pmid":"30994338","id":"PMC_30994338","title":"Microbial Turnover of Glyphosate to Biomass: Utilization as Nutrient Source and Formation of AMPA and Biogenic NER in an OECD 308 Test.","date":"2019","source":"Environmental science & technology","url":"https://pubmed.ncbi.nlm.nih.gov/30994338","citation_count":16,"is_preprint":false},{"pmid":"20610866","id":"PMC_20610866","title":"Effect of gliclazide on nucleotide excision repair (NER) and non-homologous DNA end joining (NHEJ) in normal and cancer cells.","date":"2010","source":"Journal of physiology and pharmacology : an official journal of the Polish Physiological Society","url":"https://pubmed.ncbi.nlm.nih.gov/20610866","citation_count":16,"is_preprint":false},{"pmid":"27711223","id":"PMC_27711223","title":"The Bacterial Mfd Protein Prevents DNA Damage Induced by the Host Nitrogen Immune Response in a NER-Independent but RecBC-Dependent Pathway.","date":"2016","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/27711223","citation_count":16,"is_preprint":false},{"pmid":"31740787","id":"PMC_31740787","title":"NER-factor DDB2 regulates HIF1α and hypoxia-response genes in HNSCC.","date":"2019","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/31740787","citation_count":15,"is_preprint":false},{"pmid":"31026346","id":"PMC_31026346","title":"Genetic variants of genes in the NER pathway associated with risk of breast cancer: A large-scale analysis of 14 published GWAS datasets in the DRIVE study.","date":"2019","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/31026346","citation_count":15,"is_preprint":false},{"pmid":"2531076","id":"PMC_2531076","title":"DNA-directed oligomerization of the monomeric Ner repressor from the Mu-like bacteriophage D108.","date":"1989","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/2531076","citation_count":15,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":46875,"output_tokens":1141,"usd":0.07887,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6989,"output_tokens":1038,"usd":0.030447,"stage2_stop_reason":"end_turn"},"total_usd":0.109317,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through these 100 papers, I need to identify which ones are about NR1H2 (also known as NER, NER-I, RIP15, LXR-b, LXRb — the liver X receptor beta nuclear receptor) versus the many other uses of \"NER\" in the corpus (nucleotide excision repair, Noda epileptic rat, bacteriophage Mu Ner protein, named entity recognition, etc.).\n\nPapers about NR1H2 (LXRβ):\n- PMID 7926814: Original cloning/characterization of NER (NR1H2)\n- PMID 16207502: NR1H2 genetic variability and Alzheimer's disease\n- PMID 22029530: NR1H2 polymorphism and preeclampsia\n- PMID 21042792: NR1H2 variation and insulin secretion\n- PMID 17626048: LXRB gene promoter regulation by Elk1/SRF\n- PMID 34178836: NR1H2 polymorphisms and T2DM\n\nAll others are about NER (nucleotide excision repair pathway), bacteriophage Mu Ner protein, Noda epileptic rat, named entity recognition, or other unrelated topics.\n\nFrom the NR1H2 papers, mechanistic findings:\n\n1. PMID 7926814: Cloning identified NR1H2 as a nuclear receptor with conserved DNA-binding and ligand-binding domains; highest homology to retinoic acid receptors.\n\n2. PMID 17626048: Experimental characterization of the LXRB (NR1H2) promoter - identified Elk1 and SRF binding sites, glucose response mechanism.\n\n3. PMID 21042792: NR1H2 genetic variation associated with insulin secretion (association study, not mechanistic).\n\n4. PMID 22029530: Association study, not mechanistic.\n\n5. PMID 34178836: Association study, not mechanistic.\n\n6. PMID 16207502: Association study, not mechanistic.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1994,\n      \"finding\": \"NR1H2 (NER) was identified as a new member of the steroid hormone nuclear receptor gene family, encoding a 461 amino acid polypeptide containing conserved DNA-binding and ligand-binding domains. It shows highest homology to retinoic acid receptors (55% at the DNA-binding domain, 38-40% at the ligand-binding domain). A single 2.3 kb transcript was detected in all cells and tissues tested, suggesting ubiquitous expression.\",\n      \"method\": \"cDNA library cloning from human osteosarcoma SAOS/B10 cells, sequence analysis, Northern blotting\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct molecular cloning and sequence characterization with expression analysis, single lab, multiple methods (cloning, sequencing, Northern blot)\",\n      \"pmids\": [\"7926814\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"The human LXRB (NR1H2) gene promoter contains two highly conserved and functional ETS/Elk1 and SRF binding sites that are required for basal transcription and mediate glucose-induced transcriptional activation. Mutation of either site abolished factor binding and significantly reduced promoter activity; siRNA knockdown of SRF and Elk1 impaired both basal promoter activity and the glucose response.\",\n      \"method\": \"Transcription start site mapping, promoter-reporter assays, electrophoretic mobility shift assays (EMSA), site-directed mutagenesis, siRNA knockdown\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — multiple orthogonal methods including mutagenesis of binding sites, EMSA, reporter assays, and siRNA knockdown in a single study demonstrating functional significance\",\n      \"pmids\": [\"17626048\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NR1H2 (LXRβ) is a ubiquitously expressed nuclear receptor with conserved DNA-binding and ligand-binding domains most homologous to retinoic acid receptors; its own gene (LXRB) is transcriptionally regulated by glucose through Elk1 and SRF binding sites in its promoter, though no ligand was identified in its original characterization.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NR1H2 (LXRβ, originally NER) is a ubiquitously expressed member of the steroid hormone nuclear receptor gene family, encoding a 461-amino-acid protein with conserved DNA-binding and ligand-binding domains most homologous to retinoic acid receptors [#0]. Its own gene is transcriptionally controlled through two conserved ETS/Elk1 and SRF binding sites in its promoter, which are required for basal transcription and mediate glucose-induced transcriptional activation [#1]. Beyond its cloning, expression pattern, and this promoter-level regulation, no ligand, target gene, or downstream mechanistic role for the NR1H2 protein has been characterized in the available corpus.\"\n,\n  \"teleology\": [\n    {\n      \"year\": 1994,\n      \"claim\": \"Established NR1H2 as a distinct nuclear receptor by cloning it and defining its domain architecture, placing it within the steroid hormone receptor family and adjacent to retinoic acid receptors.\",\n      \"evidence\": \"cDNA library cloning from human osteosarcoma cells with sequence analysis and Northern blotting\",\n      \"pmids\": [\"7926814\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No ligand identified for the receptor\", \"No target genes or DNA response elements defined\", \"Functional role of the protein not addressed\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Resolved how the NR1H2 gene itself is regulated, showing its promoter is driven by Elk1/SRF and is responsive to glucose, linking receptor expression to metabolic state.\",\n      \"evidence\": \"Promoter-reporter assays, EMSA, site-directed mutagenesis, and siRNA knockdown of SRF and Elk1 in human cells\",\n      \"pmids\": [\"17626048\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not define the receptor's own ligand or downstream targets\", \"Does not establish the physiological consequence of glucose-induced LXRB expression\", \"Mechanism connecting glucose signaling to Elk1/SRF activation not detailed\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The endogenous ligand, target gene network, and physiological function of the NR1H2 protein remain uncharacterized in the available corpus.\",\n      \"evidence\": \"No timeline discovery addresses receptor ligand binding or transcriptional output\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No ligand identified\", \"No direct target genes mapped\", \"No tissue-specific functional role established\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"loss","faith_supported":2,"faith_total":2,"faith_pct":100.0}}