NR1H2 / LXR-beta - the paralogue arm of the menin-LXR contact, present in both species and absent from the paper's conclusion

{
  "accession": "Q13133",
  "symbol": "NR1H3",
  "length_aa": 447,
  "length_difference_aa": 13,
  "discriminator": "primary gene symbol only; length cannot separate them"
}

{
  "source_pmid": "25962847",
  "source_class": "focused mechanistic study, but this pair is a supplementary paralogue control",
  "n_intact_records": 2,
  "n_spoke_expanded": 0,
  "n_source_publications": 1,
  "intact_acs": [
    "EBI-11364863",
    "EBI-11364867"
  ],
  "species": [
    "Homo sapiens (HepG2)",
    "Mus musculus"
  ],
  "figures": {
    "SF4a": "human HepG2",
    "SF4b": "mouse"
  },
  "functional_arm_reported": false,
  "discussed_in_abstract": false,
  "brief_stated_record_count": 1,
  "rest_record_count": 2,
  "shared_pdb_entries": []
}

{
  "subcellular": "NUCLEUS - and in UniProt that is a SEQUENCE PREDICTION AND NOTHING ELSE. P55055 fetched 2026-09-21 carries exactly one SUBCELLULAR LOCATION value, 'Nucleus', on a single support: ECO:0000255 PROSITE-ProRule PRU00407, the nuclear-receptor DNA-binding-domain profile rule. There is NO ECO:0000269 experimental attribution, no ECO:0000250 orthologue inference, and no cytoplasmic value at all [E_q89_nr1h2_loc1]. The human experiment that does exist is not in UniProt: CFP-LXR-beta chimeras are nuclear and partially nucleolar by fluorescence microscopy [E_q89_nr1h2_loc2].",
  "subnuclear": "PARTIALLY NUCLEOLAR, AND THE NUCLEOLAR POOL IS GOVERNED BY AF-2. Lall, Kuruvilla and Prüfer expressed CFP-LXR-alpha and wild-type and mutant CFP-LXR-beta and marked the nucleolus with anti-fibrillarin: significantly more CFP-LXR-beta than CFP-LXR-alpha was present in nucleoli; mutations in the basic-rich sequences of the DNA-binding domain caused SOME exclusion of CFP-LXR-beta; and mutations in activation function-2 - the protein-protein interaction surface common to all nuclear receptors - RESULTED IN EXCLUSION from the nucleolus. The authors read this as protein-protein interactions regulating nucleolar sequestration of LXR-beta [E_q89_nr1h2_loc2].",
  "how_this_differs_from_the_paralogue_and_why": "Q87 wrote gene-nr1h3 in tranche 2 and recorded LXR-alpha's subnuclear compartment as UNPUBLISHED, correctly refusing to transfer this result to the paralogue, and raised nucleolar exclusion through the conserved AF-2 as a live hypothesis for LXR-alpha. THE TWO ENTRIES NOW LEGITIMATELY DIFFER, and the difference is measured rather than assumed: the same experiment imaged both receptors side by side and found LXR-beta significantly MORE nucleolar than LXR-alpha. So the honest statement is not 'beta is nucleolar, alpha is unknown' but 'beta is more nucleolar than alpha in the one experiment that compared them'. See the correction note in data.correction_owed_to_gene_nr1h3."
}

{
  "answer": "UBIQUITOUS, and that is the point of the paralogue pair. UniProt records NR1H2 tissue specificity as 'Ubiquitous' in one word [E_q89_nr1h2_loc1], against NR1H3/LXR-alpha's liver-, intestine- and macrophage-enriched distribution which gene-nr1h3 records from HPA. This entry's own prose already states the distinction; the field records it so the coverage reporter can see it.",
  "haematopoietic": "The bounded haematopoietic query returns a real literature - (NR1H2 OR \"LXR-beta\" OR LXRbeta)[tiab] with a macrophage/monocyte/lymphocyte/haematopoietic clause returns 98 records on 2026-09-21 - but this beat did not enumerate or title-check it, so no cell-type-specific claim is made from it beyond the ubiquity UniProt records. Recording the count and the non-enumeration rather than a number dressed as a finding.",
  "leukaemia": "ALMOST NOTHING. (NR1H2 OR LXRB OR \"LXR-beta\" OR LXRbeta)[tiab] AND (leukemia OR leukaemia)[tiab] returns THREE records on 2026-09-21, and all three are about LXR AGONIST PHARMACOLOGY in AML rather than about NR1H2 as a protein: an aptamer-targeted exosome/liposome LXR-agonist nanoparticle (41854184), dendrogenin A plus cytarabine (32610562), and a review of ligand-dependent lethal autophagy (29368971). Titles read; abstracts not read."
}

{
  "state": "STEROL/OXYSTEROL-LOADED, as for the paralogue - LXR-beta is ligand-activated by oxysterols, so its active state is a lipid state of the cell rather than a differentiation state. See cell-state-lipid-pufa-dependence for the adjacent metabolic state in this graph.",
  "bounded": "No NR1H2 cell-state measurement in any leukaemia or KMT2A-fusion system. The three leukaemia records are agonist-pharmacology papers that do not separate the two receptors.",
  "kept_consistent_with": "gene-nr1h3 records the same state for LXR-alpha; the two are deliberately identical here because the ligand is shared and nothing distinguishes them on this dimension."
}

{
  "entry": "gene-nr1h3 (data.subnuclear_localization, and the same sentence inside data.localization.subnuclear)",
  "current_text": "'UNPUBLISHED for LXR-alpha in any cell type. The one nucleolar result in this receptor family (PMID 19356704) is about LXR-BETA / NR1H2 and must not be attached here.'",
  "what_it_should_say": "The refusal to transfer the LXR-beta MUTANT result to LXR-alpha was right and should stand. But 'UNPUBLISHED for LXR-alpha in any cell type' overstates the gap: PMID 19356704 imaged CFP-LXR-alpha alongside CFP-LXR-beta in the same experiment with fibrillarin as the nucleolar marker, and reports that significantly more CFP-LXR-beta than CFP-LXR-alpha was in the nucleoli. That is a measurement of LXR-alpha's nucleolar content - a comparatively LOW one - not an absence of one. Suggested replacement: 'LXR-alpha was imaged in exactly one study, as the comparator arm of an LXR-beta experiment: CFP-LXR-alpha is nuclear with significantly LESS nucleolar signal than CFP-LXR-beta (PMID 19356704). No study has LXR-alpha as its subject, and the AF-2 exclusion result is LXR-beta's.'",
  "citation": "PMID 19356704, DOI 10.1016/j.cellbi.2009.01.015. ABSTRACT READ IN FULL, full text not read - the relevant sentence is in the abstract: 'Significantly more CFP-LXRbeta than CFP-LXRalpha in the nucleoli.'",
  "severity": "minor - it strengthens rather than overturns the paralogue entry, and the refusal it protects was correct. Reported and not edited, per the standing instruction not to edit files this beat does not own."
}

{
  "date": "2026-09-21",
  "tool": "NCBI esearch db=pubmed",
  "query": "(NR1H2[tiab] OR \"LXR-beta\"[tiab] OR LXRbeta[tiab] OR LXRB[tiab]) AND (nucleolus[tiab] OR nucleolar[tiab] OR subnuclear[tiab] OR \"nuclear speckles\"[tiab] OR \"nuclear bodies\"[tiab])",
  "querytranslation": "(\"NR1H2\"[Title/Abstract] OR \"LXR-beta\"[Title/Abstract] OR \"LXRbeta\"[Title/Abstract] OR \"LXRB\"[Title/Abstract]) AND (\"nucleolus\"[Title/Abstract] OR \"nucleolar\"[Title/Abstract] OR \"subnuclear\"[Title/Abstract] OR \"nuclear speckles\"[Title/Abstract] OR \"nuclear bodies\"[Title/Abstract])",
  "count": 2,
  "on_topic": 1,
  "the_one": "19356704 - the CFP chimera study recorded here. The other hit (39323333) was not on this topic at title level.",
  "name_list_searched": [
    "NR1H2",
    "LXR-beta",
    "LXRbeta",
    "LXRB"
  ],
  "not_searched": "The unhyphenated 'LXRbeta' and hyphenated 'LXR-beta' were both run because they are different strings; 'NER' and 'UNR', UniProt's other two synonyms, were NOT run - 'UNR' collides with the unrelated CSDE1/UNR and 'NER' is nucleotide excision repair, both recorded in data/symbol-collisions.json for this gene pair.",
  "absence_class": "never-measured"
}