Affinage

THRB

Thyroid hormone receptor beta · UniProt P10828

Length
461 aa
Mass
52.8 kDa
Annotated
2026-06-10
100 papers in source corpus 26 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

THRB encodes thyroid hormone receptor beta (TRβ), a ligand-dependent nuclear transcription factor in which a C-terminal ligand-binding domain captures the thyroid hormone T3 with high affinity while a structurally separable domain binds thyroid hormone response elements (TREs) in target gene promoters (PMID:1653889, PMID:2203342). The receptor was first established as a functional thyroid hormone receptor in vivo through tight genetic linkage of the c-erbA beta locus to generalized thyroid hormone resistance (GTHR) (PMID:2905763), and subsequent mutational analysis defined the architecture of its ligand-binding domain: missense substitutions and small deletions in two 'hot spot' regions (the distal L2 subdomain and the tau1/dimerization junction in exons 9-10), and even the hinge region, selectively reduce T3 binding while sparing DNA binding (PMID:2153155, PMID:2169728, PMID:1661299, PMID:1324420). These ligand-binding mutants act as dominant-negative inhibitors of thyroid hormone signaling, and this property is genetically separable from both T3 binding and homodimer DNA-binding affinity, depending on residues such as Arg311 (PMID:1653889, PMID:8381821, PMID:9100577). TRβ both activates and represses transcription in a T3-dependent manner, silencing AP-1/TPA-inducible promoters such as collagenase and, at the chromatin level, occupying enhancers (e.g., CYP3A4) to control super-enhancer landscapes that drive hepatocyte maturation (PMID:8247013, PMID:35452598). Through this transcriptional output TRβ governs diverse physiological programs—hearing and thyroid axis regulation, where excess TRα1 can substitute for its loss (PMID:11726557); isoform-specific TRβ2-dependent cone opsin specification and retinal layering (PMID:40072114); time-of-day-dependent hepatic lipid metabolism and protection against steatosis (PMID:40603776); direct transcriptional activation of SIRT3 and suppression of MAPK/ERK and PI3K/AKT/STAT3 signaling (PMID:34401962, PMID:34936295); and erythroid and osteoblast-mediated bone differentiation (PMID:27734462, PMID:37992217). THRB is itself suppressed post-transcriptionally by miRNAs targeting its 3'-UTR in thyroid cancer (PMID:21159845). Beyond causing dominant-negative GTHR through ligand-binding-domain mutations (PMID:2905763, PMID:2153155, PMID:2169728), TRβ1-specific splicing variants that spare TRβ2 cause autosomal dominant macular dystrophy without thyroid hormone resistance, establishing distinct isoform functions (PMID:37547476, PMID:40295579).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1988 High

    Establishing whether THRB encodes a physiologically active thyroid hormone receptor, genetic linkage tied the c-erbA beta locus to generalized thyroid hormone resistance, defining THRB as a functional receptor gene in humans.

    Evidence RFLP linkage analysis in a GTHR kindred

    PMID:2905763

    Open questions at the time
    • Linkage alone did not identify the causal mutation
    • No molecular mechanism for resistance established at this stage
  2. 1990 High

    To define the molecular lesion behind resistance and prove receptor function, mutation analysis and in vitro assays showed a ligand-binding-domain missense mutation reduces T3 binding while preserving DNA binding and acting dominant-negatively, and yeast expression confirmed THRB is intrinsically sufficient for both T3 and TRE binding.

    Evidence cDNA/genomic sequencing, in vitro T3- and DNA-binding assays in GTHR kindred; heterologous yeast expression with binding assays

    PMID:2153155 PMID:2169728 PMID:2203342

    Open questions at the time
    • Did not yet establish full set of structural determinants of T3 binding
    • Mechanism of dominant-negative interference not resolved
  3. 1991 High

    To map the functional architecture of the receptor, deletion and clustering analyses demonstrated that T3 binding and DNA binding are physically separable domains and that ligand-binding mutations cluster in two 'hot spot' regions, with homozygosity producing more severe disease.

    Evidence In vitro translation, T3- and DNA-binding assays on a Thr332 deletion mutant; PCR sequencing of seven mutations across kindreds

    PMID:1653889 PMID:1661299

    Open questions at the time
    • Structural basis of hot-spot clustering inferred from sequence, not crystallography
    • How dominant-negative interference operates at the promoter not defined
  4. 1992 Medium

    To extend the ligand-binding map, a hinge-domain mutation was shown to reduce T3 affinity while retaining TRE binding, implicating cooperative interactions between the hinge and ligand-binding subdomains.

    Evidence PCR sequencing, in vitro expression, T3- and DNA-binding assays

    PMID:1324420

    Open questions at the time
    • Single kindred, single lab
    • Cooperativity inferred rather than structurally demonstrated
  5. 1993 High

    To separate ligand binding from the disease-causing dominant-negative property, the Arg311His mutant was found to be T3-binding-defective yet lacking dominant-negative activity, identifying Arg311 as required for the structural integrity underlying transcriptional interference rather than for ligand binding per se; in parallel, mutants were shown to fail at T3-dependent repression of the AP-1-driven collagenase promoter.

    Evidence In vitro synthesis, T3-binding and transfection dominant-negative assays; cotransfection collagenase-CAT reporter assays in COS-7 cells

    PMID:8247013 PMID:8381821

    Open questions at the time
    • Cofactor basis of dominant-negative vs non-dominant-negative behavior not identified
    • AP-1 repression mechanism (tethering vs DNA binding) not resolved
  6. 1997 High

    To dissect how mutant receptors silence transcription, a C-terminally truncated TRβ1 was shown to bind TREs as homodimers and RXRβ heterodimers and repress basal promoter activity T3-insensitively, with DNA-binding affinity uncorrelated to dominant-negative strength.

    Evidence In vitro transcription/translation, gel retardation and reporter assays across DR4, F2 and palindromic TREs

    PMID:9100577

    Open questions at the time
    • Corepressor identity not defined
    • Single lab
  7. 2001 High

    To define in vivo physiological roles and isoform relationships, mouse epistasis showed THRB is required for hearing and thyroid axis function and that elevated TRα1 can substitute for THRB loss, revealing overlapping and divergent isoform functions.

    Evidence Thrb-null x Thra double-mutant epistasis with auditory and hormonal readouts

    PMID:11726557

    Open questions at the time
    • Target genes mediating hearing function not identified
    • Cell-type-specific requirements not resolved
  8. 2016 High

    To establish post-transcriptional and lineage roles, miRNA studies showed THRB is directly targeted by miR-21/miR-146a (suppressing DIO1/APP) in thyroid cancer and by miR-200a-3p, with THRB acting as a positive regulator of erythroid differentiation.

    Evidence 3'-UTR luciferase assays, qRT-PCR/Western, TRE promoter assays, gain/loss-of-function and zebrafish overexpression

    PMID:21159845 PMID:27734462

    Open questions at the time
    • Direct THRB target genes in erythropoiesis not mapped
    • Causal contribution of THRB loss to thyroid carcinogenesis not established
  9. 2022 High

    To define THRB's genome-scale transcriptional mechanism, ChIP-seq/ATAC-seq showed T3-dependent THRB occupancy at the CYP3A4 enhancer restores super-enhancer activity and NFIC expression to drive hepatocyte maturation.

    Evidence ChIP-seq, ATAC-seq, H3K27Ac ChIP-seq and RNA-seq in hPSC-derived hepatocytes

    PMID:35452598

    Open questions at the time
    • Full enhancer repertoire and coactivator complexes not enumerated
    • In vivo relevance to human liver development not tested
  10. 2023 Medium

    To uncover isoform-specific tissue functions, a TRβ1-disrupting splicing variant was linked to autosomal dominant macular dystrophy without thyroid hormone resistance, and bone-cell studies established THRB as the mediator of T3-induced osteoblast maturation and indirect osteoclast stimulation.

    Evidence WGS/Sanger segregation and isoform analysis; Thrb-/- osteoblast assays with osteoclast co-culture

    PMID:37547476 PMID:37992217

    Open questions at the time
    • Retinal mechanism not directly assayed in 2023 work
    • Osteoblast-derived signal to osteoclasts beyond RANKL/OPG not fully defined
  11. 2024 Medium

    To define metabolic and signaling outputs, THRB was shown to direct time-of-day-dependent hepatic lipid metabolism and an anti-steatotic program, to transcriptionally activate SIRT3 to rescue metabolic dysfunction, and to mediate T3-induced suppression of MAPK/ERK and PI3K/AKT/STAT3 signaling.

    Evidence THRBKO temporal liver omics and hepatocyte agonist assays; dual luciferase/ChIP for SIRT3; siRNA knockdown with phospho-signaling readouts in glioma cells

    PMID:34401962 PMID:34936295 PMID:40603776

    Open questions at the time
    • Direct vs indirect targets in lipid rhythm not fully separated
    • Mechanism of MAPK/PI3K suppression (direct vs transcriptional) not resolved
  12. 2025 Medium

    To confirm the molecular basis of the retinal phenotype, functional splicing assays showed TRβ1-specific variants cause exon skipping/aberrant proteins supporting a gain-of-function mechanism for macular dystrophy, and CRISPR knockout of thrb2 in medaka established TRβ2's requirement for cone opsin specification and retinal layering.

    Evidence Minigene splicing assays in three families; CRISPR/Cas9 thrb2 knockout with retinal histology and opsin/phototransduction gene expression

    PMID:40072114 PMID:40295579

    Open questions at the time
    • Gain-of-function mechanism not reconstituted biochemically
    • Retinal opsin study performed in fish ortholog

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TRβ selects context-specific enhancers and assembles distinct coactivator/corepressor complexes to switch between activation, AP-1 repression, and dominant-negative silencing across hepatic, retinal, neuronal, bone, and erythroid programs remains unresolved.
  • Coregulator complexes recruited by ligand-bound vs mutant TRβ not defined
  • Determinants of isoform-specific (TRβ1 vs TRβ2) target selection unknown
  • Structural basis distinguishing dominant-negative from non-dominant-negative mutants not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 4 GO:0008289 lipid binding 3 GO:0060089 molecular transducer activity 3
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 1
Pathway
R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1430728 Metabolism 2 R-HSA-162582 Signal Transduction 1 R-HSA-4839726 Chromatin organization 1
Partners
RXRB

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 THRB (c-erbA beta) was genetically linked to generalized thyroid hormone resistance (GTHR) syndrome in humans, establishing THRB as a functional thyroid hormone receptor gene in vivo. Tight linkage (LOD score at recombination fraction 0) was demonstrated between the GTHR phenotype and the c-erbA beta locus on chromosome 3. Restriction enzyme RFLP linkage analysis in a GTHR kindred Molecular endocrinology (Baltimore, Md.) High 2905763
1990 A missense mutation in the T3-binding domain of c-erbA beta (Pro448His, caused by a C-to-A substitution at cDNA position 1643) was identified in GTHR kindred A. The mutant receptor showed decreased T3-binding affinity (~2-fold reduction) compared to wild-type but retained normal DNA-binding activity to thyroid hormone response elements, and functioned as a dominant negative inhibitor of thyroid hormone action in vivo. Direct cDNA/genomic DNA sequencing, allelic-specific hybridization, in vitro T3-binding assay, avidin-biotin DNA-binding assay with TRE-containing fragments The Journal of clinical investigation / Biochemical and biophysical research communications High 2153155 2169728
1991 A 3-bp deletion in the T3-binding domain of c-erbA beta (loss of Thr332) was identified in GTHR kindred S. The homozygous mutant receptor synthesized in vitro failed to bind T3 but retained wild-type-level binding affinity to thyroid hormone response elements (TSH beta and GH gene TREs), demonstrating that T3-binding and DNA-binding functions are separable domains. Homozygous expression produced a more severe phenotype than heterozygous expression, establishing a dominant-negative mechanism. In vitro translation of cloned full-length mutant cDNA, T3-binding assay, DNA-binding assay with TRE-containing promoter fragments Molecular endocrinology (Baltimore, Md.) High 1653889
1991 Seven novel point mutations in c-erbA beta were identified in unrelated GTHR kindreds and clustered in two regions of the ligand-binding domain: the distal ligand-binding subdomain L2, and the junction of the tau1 and dimerization subdomains (exons 9-10). Four of these mutations tested showed reduced T3-binding affinity, delineating two 'hot spot' regions of the ligand-binding domain critical for receptor function. PCR-direct sequencing of exons, in vitro T3-binding assay for 4 mutants The Journal of clinical investigation High 1661299
1992 A point mutation in the hinge domain of c-erbA beta (Ala229Thr, in exon 7) caused GTHR. The in vitro expressed mutant receptor retained high-affinity binding to thyroid hormone response elements but showed 3-fold reduced T3-binding affinity, demonstrating that the hinge domain (carboxy-terminal part) contributes to optimal ligand-binding activity, and suggesting cooperative interactions between the hinge and ligand-binding subdomains. PCR-direct sequencing, in vitro expression, T3-binding assay, DNA-binding assay to TREs Molecular endocrinology (Baltimore, Md.) Medium 1324420
1993 A missense mutation at codon 311 of c-erbA beta (Arg311His) produced a receptor with significantly defective T3-binding activity (Ka ~5 x 10^8 M-1 vs wild-type) but no detectable dominant negative activity in a transfection assay, in contrast to many other beta-receptor mutants causing generalized resistance. This identified Arg311 as critical for the structural integrity required for dominant-negative function, not merely for T3 binding. Reticulocyte lysate in vitro synthesis, T3-binding assay, RNA phenotyping in leukocytes/fibroblasts, transfection dominant-negative activity assay The Journal of clinical investigation High 8381821
1993 Dominant-negative and non-dominant-negative c-erbA beta mutant receptors (S, CL, and G-H) all augmented TPA/12-O-tetradecanoyl-phorbol-13-acetate induction of the collagenase promoter and showed defective T3-mediated repression, demonstrating that THRB normally represses TPA-inducible (AP-1-driven) gene expression in a T3-dependent manner and that this function is impaired by T3-binding domain mutations. Transient cotransfection of mutant receptor constructs with collagenase promoter-CAT reporter in COS-7 cells, +/- T3 and TPA treatment Molecular endocrinology (Baltimore, Md.) Medium 8247013
1997 A truncated c-erbA beta1 receptor (TR beta-EZ, 28-amino acid carboxy-terminal deletion due to premature stop codon) abolished T3 binding. The truncated receptor bound DNA as a homodimer to DR4, F2, and palindromic TREs (with altered affinity patterns vs wild-type), formed heterodimers with RXR beta, and repressed basal promoter activity (silencing) through these TREs in a T3-insensitive manner. The degree of homodimer DNA-binding affinity did not correlate with degree of dominant-negative transcriptional activity, indicating these are functionally separable. In vitro transcription/translation, gel retardation DNA-binding assays, transient transfection reporter assays (TK-promoter with TREs), +/- T3 The Journal of clinical endocrinology and metabolism High 9100577
1990 Full-length rat liver TR beta was expressed in yeast (Saccharomyces cerevisiae) using a copper-responsive metallothionein promoter and ubiquitin-fusion system. The partially purified yeast-expressed THRB protein had high T3-binding affinity (Kd = 0.34 nM) and could bind thyroid hormone response elements in gel retardation analysis, establishing that THRB is sufficient for both T3 binding and TRE binding in a heterologous eukaryotic system. Yeast expression system, [125I]T3 binding assay, gel retardation (EMSA) with TRE-containing DNA Biochemical and biophysical research communications Medium 2203342
1994 A Rana catesbeiana TR beta cDNA was cloned and shown to encode a 48 kDa protein that binds T3 with high affinity (mean Kd: 0.032 nM) after in vitro transcription and translation, confirming conservation of T3-binding function of the TR beta across vertebrate species. PCR cloning, in vitro transcription/translation, T3-binding assay Developmental genetics Medium 7923937
2001 Deletion of THRB (Thrb-null mice) causes deafness and thyroid hyperactivity. A targeted mutation in the related Thra gene (Thra tm2) that deletes TR alpha2 and causes overexpression of TR alpha1 suppresses both the auditory and thyroid phenotypes in Thrb-null mice. This genetic epistasis established that (1) THRB is required for hearing and normal thyroid axis function, and (2) increased TR alpha1 expression can substitute for THRB in these roles, revealing functional overlap and divergence between TR isoforms. Mouse genetics — double-mutant (Thrb-null x Thra tm2) epistasis analysis, auditory threshold measurement, thyroid hormone level measurement Human molecular genetics High 11726557
2010 miR-21 and miR-146a directly inhibit THRB expression by binding to its 3'-UTR. Four miRNAs (miR-21, -146a, -181a, -221) that are upregulated in papillary thyroid carcinoma suppress THRB protein (to 10-28% of control) and reduce expression of THRB target genes DIO1 and APP. These miRNAs also reduced thyroid hormone response element (TRE) activity in promoter assays, establishing a post-transcriptional regulatory mechanism for THRB suppression in thyroid cancer. Luciferase 3'-UTR reporter assay (direct miR-THRB interaction), cell transfection with pre-miRs, qRT-PCR and Western blot for THRB and target genes, TRE promoter assay The Journal of clinical endocrinology and metabolism High 21159845
2016 THRB is a direct target of miR-200a-3p. Gain- and loss-of-function studies showed THRB promotes erythroid gene expression. MiR-200a overexpression inhibits erythroid differentiation in K562 and TF-1 cells, and this is partly mediated through suppression of THRB, establishing THRB as a positive regulator of erythroid differentiation. Bioinformatics target prediction, luciferase 3'-UTR reporter assay, miR-200a overexpression in cell lines, THRB gain/loss-of-function with erythroid gene expression readout, zebrafish in vivo overexpression British journal of haematology Medium 27734462
2022 THRB functions as a nuclear receptor to regulate hepatocyte maturation. Addition of thyroid hormone T3 increased THRB binding to the CYP3A4 proximal enhancer and restored super-enhancer status and expression of NFIC, and reduced AFP expression in hPSC-derived hepatocytes. This established that the T3/THRB axis directly regulates chromatin accessibility and super-enhancer activity to promote hepatocyte maturation. ChIP-seq (THRB binding to CYP3A4 enhancer), ATAC-seq, H3K27Ac ChIP-seq, RNA-seq, T3 treatment of hPSC-hepatocytes in 2D and 3D culture systems Cell stem cell High 35452598
2021 THRB acts as a transcription factor for SIRT3. Dual luciferase reporter gene and ChIP assays verified that THRB binds the promoter of SIRT3 mRNA. Overexpression of THRB rescued Aβ42-induced metabolic dysfunction (improved NAD+/NADH ratio, ATP levels, SIRT3 activity), while THRB silencing aggravated it, establishing THRB as a direct transcriptional activator of SIRT3 in neurons. Dual luciferase reporter assay, ChIP assay, THRB overexpression/silencing, metabolic assays (NAD+/NADH, ATP, SIRT3 deacetylation activity) Neurochemical research Medium 34401962
2021 T3 promotes glioma cell senescence and apoptosis through THRA and THRB. Knockdown of THRB reversed T3-induced G1 and G2 phase cell cycle arrest, increased cyclin D1 expression, and markedly increased phosphorylated ERK, AKT, and STAT3 proteins, indicating that THRB mediates T3-induced suppression of MAPK/ERK and PI3K/AKT/STAT3 signaling pathways in glioma cells. siRNA knockdown of THRB in glioma cell lines (HS683, A172), flow cytometry for apoptosis and cell cycle, Western blot for p-ERK, p-AKT, p-STAT3, cyclin D1 Journal of environmental pathology, toxicology and oncology Medium 34936295
2023 A splicing variant in THRB (c.283+1G>A) that disrupts the 5' region encoding the N-terminal domain of the TRβ1 isoform (leaving TRβ2 intact) causes autosomal dominant macular dystrophy without thyroid hormone resistance syndrome, demonstrating isoform-specific function of TRβ1 in the retina distinct from TRβ2's role in the hypothalamic-pituitary-thyroid axis. WGS, Sanger sequencing segregation analysis in multiple pedigrees, genotype-phenotype correlation across RTHβ and macular dystrophy patients; isoform structure analysis Frontiers in cell and developmental biology Medium 37547476
2025 Functional splicing assays confirmed that THRB variants c.283+1G>A and c.283G>A cause complete exon 5 skipping or a 6 bp deletion, generating aberrant TRβ1 proteins. These results support a gain-of-function mechanism for TRβ1 isoform in autosomal dominant macular dystrophy. In vitro minigene splicing assay, next-generation sequencing, Sanger sequencing in three families Scientific reports Medium 40295579
1999 The human THRB and NR1D2 genes are physically linked on chromosome 3 (~1 Mb apart) and also linked to RARB, paralleling the THRA/NR1D1/RARA cluster, establishing that these receptor gene clusters arose from a single large-scale genomic duplication. Physical mapping, genomic linkage analysis Genomics Medium 10198169
2023 THRB knockout (Thrb-/-) osteoblasts showed mitigated responsiveness to thyroid hormone (both short 48h and long-term 10d T3 treatment), reduced mineralization, altered osteoblast marker gene expression, and a low RANKL/OPG ratio. Supernatants from Thrb-/- osteoblasts reduced osteoclast numbers, while supernatants from T3-treated wild-type (but not Thrb-/-) osteoblasts increased osteoclast TRAP and CTSK expression, establishing that THRB mediates T3-induced indirect stimulation of osteoclasts via osteoblasts. Primary osteoblasts from Thrb-/- mice, T3 treatment, mineralization assays, qPCR for bone marker genes, indirect osteoclast co-culture experiments with conditioned media Journal of cellular biochemistry Medium 37992217
2023 KMT2D epigenetically regulates THRB expression in papillary thyroid cancer cells. ChIP assay demonstrated that KMT2D associates with the NCOA6 promoter, and KMT2D knockdown decreased H3K4me2 and H3K9me2 marks and reduced NCOA6 and THRB expression, resulting in decreased PTC cell migration and invasion. ChIP assay (KMT2D at NCOA6 promoter), KMT2D knockdown (siRNA), Western blot (H3K4me2, H3K9me2, NCOA6, THRB), migration/invasion assays Frontiers in bioscience (Landmark edition) Low 36722273
2020 Two novel THRB mutations (N331H and L346R) in the ligand-binding domain showed impaired gene transactivation in dual-luciferase reporter assays. Molecular modeling revealed that N331H reduces T3-stabilizing hydrogen bonds in the ligand-binding cavity, while L346R causes more severe changes via altered hydrophobicity and molecular volume in the ligand-binding cavity, correlating with greater thyrotrophic resistance for L346R. Dual-luciferase reporter transactivation assay, molecular modeling based on crystallography data, clinical TSH/FT4 measurements Endocrine Medium 31902113
2024 THRB activation by its ligand T3 ameliorates ER stress. In neuronal cells, T3 treatment reduced MPP+-induced mitochondrial membrane potential dissipation and ROS generation. In the MPTP mouse model of Parkinson's disease, simultaneous treatment with the THRB ligand T3 (and Nr1h4 ligand GW4064) protected against ER stress gene expression, dopaminergic cell death, and functional motor deficits. In vitro ER stress induction (tunicamycin), T3 treatment of neuronal cells, mitochondrial membrane potential assay, ROS measurement, MPTP mouse model with behavioral/histological readouts Life science alliance Low 38609183
2024 THRB-deficient (THRBKO) mice showed altered diurnal metabolic rhythms in the liver with elevated cholesterol, tri- and diacylglycerides, and fatty acids indicating a pro-steatotic state, establishing that THRB specifically regulates the time-of-day-dependent lipid metabolism in liver. THRB agonization in hepatocytes under steatosis-promoting conditions in vitro confirmed the anti-steatotic role. Liver transcriptome analysis of THRBKO mice, temporal transcriptome and lipidome profiling, in vitro THRB agonist treatment of hepatocytes under steatosis-inducing conditions npj metabolic health and disease Medium 40603776
2025 Knockout of thrb2 (THRB isoform 2) in medaka fish using CRISPR/Cas9 resulted in increased UV opsin (sws1) expression while decreasing other cone opsins, increased lens thickness, decreased thickness of ganglion cell layer, outer plexiform layer, and outer nuclear layer, and reduced expression of phototransduction genes (grk7a, grk7b, pde6c), establishing that TRβ2 is required for normal cone opsin specification and retinal layering. CRISPR/Cas9 knockout of thrb2 in medaka, retinal histology, cone opsin gene expression analysis, phototransduction gene expression, behavioral swimming speed analysis Cells Medium 40072114

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Characterization of seven novel mutations of the c-erbA beta gene in unrelated kindreds with generalized thyroid hormone resistance. Evidence for two "hot spot" regions of the ligand binding domain. The Journal of clinical investigation 234 1661299
1990 A base mutation of the C-erbA beta thyroid hormone receptor in a kindred with generalized thyroid hormone resistance. Molecular heterogeneity in two other kindreds. The Journal of clinical investigation 178 2153155
1988 Tight linkage between the syndrome of generalized thyroid hormone resistance and the human c-erbA beta gene. Molecular endocrinology (Baltimore, Md.) 161 2905763
1989 Presence of two members of c-erbA receptor gene family (c-erbA beta and c-erbA2) in smallest region of somatic homozygosity on chromosome 3p21-p25 in human breast carcinoma. Journal of the National Cancer Institute 126 2573734
1991 A homozygous deletion in the c-erbA beta thyroid hormone receptor gene in a patient with generalized thyroid hormone resistance: isolation and characterization of the mutant receptor. Molecular endocrinology (Baltimore, Md.) 121 1653889
1996 Cloning and characterization of a melanin biosynthetic THR1 reductase gene essential for appressorial penetration of Colletotrichum lagenarium. Molecular plant-microbe interactions : MPMI 111 8672814
2010 Thyroid hormone receptor beta (THRB) is a major target gene for microRNAs deregulated in papillary thyroid carcinoma (PTC). The Journal of clinical endocrinology and metabolism 76 21159845
1991 A new point mutation in the 3,5,3'-triiodothyronine-binding domain of the c-erbA beta thyroid hormone receptor is tightly linked to generalized thyroid hormone resistance. The Journal of clinical endocrinology and metabolism 67 1846005
1993 An arginine to histidine mutation in codon 311 of the C-erbA beta gene results in a mutant thyroid hormone receptor that does not mediate a dominant negative phenotype. The Journal of clinical investigation 66 8381821
1988 Nucleotide sequence and fine structural analysis of the Corynebacterium glutamicum hom-thrB operon. Molecular microbiology 64 2835591
1992 A point mutation (Ala229 to Thr) in the hinge domain of the c-erbA beta thyroid hormone receptor gene in a family with generalized thyroid hormone resistance. Molecular endocrinology (Baltimore, Md.) 57 1324420
1988 Organization and regulation of the Corynebacterium glutamicum hom-thrB and thrC loci. Molecular microbiology 54 2835590
1994 Stable Expression of hom-1-thrB in Corynebacterium glutamicum and Its Effect on the Carbon Flux to Threonine and Related Amino Acids. Applied and environmental microbiology 50 16349146
1989 Expression of the ErbA-beta class of thyroid hormone receptors is selectively lost in human colon carcinoma. The Journal of clinical investigation 50 2553781
1991 The region of common allelic losses in sporadic renal cell carcinoma is bordered by the loci D3S2 and THRB. Genomics 49 1685475
2018 Deficiency of the melanin biosynthesis genes SCD1 and THR1 affects sclerotial development and vegetative growth, but not pathogenicity, in Sclerotinia sclerotiorum. Molecular plant pathology 43 29024255
2001 Suppression of the deafness and thyroid dysfunction in Thrb-null mice by an independent mutation in the Thra thyroid hormone receptor alpha gene. Human molecular genetics 40 11726557
1990 Chromatin superstructure-dependent crosslinking with DNA of the histone H5 residues Thr1, His25 and His62. Journal of molecular biology 37 2106584
1990 Thyroid hormone and DNA binding properties of a mutant c-erbA beta receptor associated with generalized thyroid hormone resistance. Biochemical and biophysical research communications 37 2169728
1981 Nucleotide sequence of the thrB gene of E. coli, and its two adjacent regions; the thrAB and thrBC junctions. Nucleic acids research 37 6259626
2010 Aberrant methylation of the THRB gene in tissue and plasma of breast cancer patients. Cancer genetics and cytogenetics 34 20082849
1988 A frequent HindIII RFLP on chromosome 3p21-25 detected by a genomic erbA beta sequence. Nucleic acids research 34 2894009
1992 An arginine to histidine mutation in codon 315 of the c-erbA beta thyroid hormone receptor in a kindred with generalized resistance to thyroid hormones results in a receptor with significant 3,5,3'-triiodothyronine binding activity. The Journal of clinical endocrinology and metabolism 31 1314846
1995 Effect of inducible thrB expression on amino acid production in Corynebacterium lactofermentum ATCC 21799. Applied and environmental microbiology 30 7887627
2021 Curcumin Alleviates Aβ42-Induced Neuronal Metabolic Dysfunction via the Thrb/SIRT3 Axis and Improves Cognition in APPTG Mice. Neurochemical research 27 34401962
1997 Deoxyribonucleic acid binding and transcriptional silencing by a truncated c-erbA beta 1 thyroid hormone receptor identified in a severely retarded patient with resistance to thyroid hormone. The Journal of clinical endocrinology and metabolism 26 9100577
1995 A novel point mutation (R243Q) in exon 7 of the c-erbA beta thyroid hormone receptor gene in a family with resistance to thyroid hormone. Thyroid : official journal of the American Thyroid Association 25 8563471
2004 Expression of THR1, a 1,3,8-trihydroxynaphthalene reductase gene involved in melanin biosynthesis in the phytopathogenic fungus Bipolaris oryzae, is enhanced by near-ultraviolet radiation. Pigment cell research 24 14717841
1994 Cloning of a thyroid hormone-responsive Rana catesbeiana c-erbA-beta gene. Developmental genetics 24 7923937
1994 Transcriptional analysis and regulatory signals of the hom-thrB cluster of Brevibacterium lactofermentum. Journal of bacteriology 23 7961509
2022 The nuclear receptor THRB facilitates differentiation of human PSCs into more mature hepatocytes. Cell stem cell 21 35452598
1979 Construction and expression of a hybrid plasmid containing the Escherichia coli thrA and thrB genes. Molecular & general genetics : MGG 21 390305
2021 Single-Cell Transcriptome Profiling of Thyroid Hormone Effectors in the Human Fetal Neocortex: Expression of SLCO1C1, DIO2, and THRB in Specific Cell Types. Thyroid : official journal of the American Thyroid Association 20 34114484
2018 Reduction of Feedback Inhibition in Homoserine Kinase (ThrB) of Corynebacterium glutamicum Enhances l-Threonine Biosynthesis. ACS omega 20 30023797
1996 New point mutation (R243W) in the hormone binding domain of the c-erbA beta 1 gene in a family with generalized resistance to thyroid hormone. Human mutation 18 8664910
1997 Lack of loss of heterozygosity at the c-erbA beta locus in gastrointestinal tumors. Oncology 17 9143402
2017 Structure of the adenylation domain Thr1 involved in the biosynthesis of 4-chlorothreonine in Streptomyces sp. OH-5093-protein flexibility and molecular bases of substrate specificity. The FEBS journal 16 28704585
1996 Expression of c-erbA alpha, c-erbA beta and Rev-erbA alpha mRNA during the conversion of brown adipose tissue into white adipose tissue. Molecular and cellular endocrinology 15 8822265
1994 Generalized thyroid hormone resistance due to a deletion of the carboxy terminus of the c-erbA beta receptor. Molecular and cellular endocrinology 15 8187964
1987 Cloning and expression in Escherichia coli of the homoserine kinase (thrB) gene from Brevibacterium lactofermentum. Molecular & general genetics : MGG 15 3035340
2013 Thyroid hormone resistance: a novel mutation in thyroid hormone receptor beta (THRB) gene - case report. The Turkish journal of pediatrics 14 24217081
1996 Construction of L-lysine-overproducing strains of Brevibacterium lactofermentum by targeted disruption of the hom and thrB genes. Applied microbiology and biotechnology 14 9008889
1991 Tight linkage of the human c-erbA beta gene with the syndrome of generalized thyroid hormone resistance is present in multiple kindreds. Journal of endocrinological investigation 14 1677017
1991 Dinucleotide repeat polymorphism in the human thyroid hormone receptor beta gene (THRB) on chromosome 3. Nucleic acids research 14 1754415
2023 Effect of the Fetal THRB Genotype on the Placenta. The Journal of clinical endocrinology and metabolism 13 37149816
2019 Role of THRB, ARG1, and ADRB2 Genetic Variants on Bronchodilators Response in Asthmatic Children. Journal of aerosol medicine and pulmonary drug delivery 13 30855197
2018 THR1 mediates GCN4 and CDC4 to link morphogenesis with nutrient sensing and the stress response in Candida albicans. International journal of molecular medicine 13 30320368
2016 Successful every-other-day liothyronine therapy for severe resistance to thyroid hormone beta with a novel THRB mutation; case report. BMC endocrine disorders 13 26754848
1993 Competitive polymerase chain reaction quantitation of c-erbA beta 1, c-erbA alpha 1, and c-erbA alpha 2 messenger ribonucleic acid levels in normal, heterozygous, and homozygous fibroblasts of kindred S with thyroid hormone resistance. The Journal of clinical endocrinology and metabolism 13 8408473
1990 In vivo expression of rat liver c-erbA beta thyroid hormone receptor in yeast (Saccharomyces cerevisiae). Biochemical and biophysical research communications 13 2203342
2023 Expanding the phenotype of THRB: a range of macular dystrophies as the major clinical manifestations in patients with a dominant splicing variant. Frontiers in cell and developmental biology 12 37547476
2016 MicroRNA 200a inhibits erythroid differentiation by targeting PDCD4 and THRB. British journal of haematology 12 27734462
2013 Incidental identification of a thyroid hormone receptor beta (THRB) gene variant in a family with autoimmune thyroid disease. Thyroid : official journal of the American Thyroid Association 12 23806029
1993 Dominant and nondominant negative C-erbA beta 1 receptors associated with thyroid hormone resistance syndromes augment 12-O-tetradecanoyl-phorbol-13-acetate induction of the collagenase promoter and exhibit defective 3,5,3'-triiodothyronine-mediated repression. Molecular endocrinology (Baltimore, Md.) 12 8247013
1990 Yeast homoserine kinase. Characteristics of the corresponding gene, THR1, and the purified enzyme, and evolutionary relationships with other enzymes of threonine metabolism. European journal of biochemistry 12 2165904
2014 Resistance to thyroid hormone due to mutations in the THRB gene impairs bone mass and affects calcium and phosphorus homeostasis. Bone 11 25063548
1997 Mutations in the c-erbA beta 1 gene: do they underlie euthyroid fibromyalgia? Medical hypotheses 11 9076694
1987 Cloning and nucleotide sequence of the thrB gene from the cyanobacterium Calothrix PCC 7601. Molecular microbiology 11 2838727
1999 Linkage of the nuclear hormone receptor genes NR1D2, THRB, and RARB: evidence for an ancient, large-scale duplication. Genomics 10 10198169
2018 Novel THRB mutation analysis in congenital hypothyroidism with thyroid dysgenesis. Journal of cellular biochemistry 9 30074255
2023 Changes in brain structure in subjects with resistance to thyroid hormone due to THRB mutations. Thyroid research 8 37592301
2018 Variable Clinical Characteristics and Molecular Spectrum of Patients with Syndromes of Reduced Sensitivity to Thyroid Hormone: Genetic Defects in the THRB and SLC16A2 Genes. Hormone research in paediatrics 8 30497070
1992 Increased messenger RNA levels of the antagonist thyroid hormone receptor erbA-alpha 2 and decreased levels of erbA-alpha 1 and erbA-beta 1 receptor messenger RNAs in neoplastic rodent cells. Cancer research 8 1559222
2019 Very Severe Resistance to Thyroid Hormone β in One of Three Affected Members of a Family with a Novel Mutation in the THRB Gene. Thyroid : official journal of the American Thyroid Association 7 31432759
2010 One Novel and Two Recurrent THRB Mutations Associated with Resistance to Thyroid Hormone: Structure-based Computational Mutation Prediction. Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology 7 23926384
2005 DNA-based diagnosis of thyroid hormone resistance syndrome: a novel THRB mutation associated with mild resistance to thyroid hormone. Clinica chimica acta; international journal of clinical chemistry 7 15913586
2020 Enhancement of S-adenosylmethionine production by deleting thrB gene and overexpressing SAM2 gene in Bacillus amyloliquefaciens. Biotechnology letters 6 32577851
2013 The first case of association between postpartum thyroiditis and thyroid hormone resistance in an Italian patient showing a novel p.V283A THRB mutation. Thyroid : official journal of the American Thyroid Association 6 23134553
2002 Characterization of the hom-thrC-thrB cluster in aminoethoxyvinylglycine-producing Streptomyces sp. NRRL 5331. Microbiology (Reading, England) 6 11988515
2024 Valencene as a novel potential downregulator of THRB in NSCLC: network pharmacology, molecular docking, molecular dynamics simulation, ADMET analysis, and in vitro analysis. Molecular diversity 5 39425858
2023 Thyroid hormone receptor Thra and Thrb knockout differentially affects osteoblast biology and thyroid hormone responsiveness in vitro. Journal of cellular biochemistry 5 37992217
2023 Generation of THRB-GS(E125G_G126S) and THRB-KO human iPSC lines to study noncanonical thyroid hormone signalling. Stem cell research 5 38100912
2022 Clinically Symptomatic Resistance to Thyroid Hormone β Syndrome Because of THRB Gene Mosaicism. The Journal of clinical endocrinology and metabolism 5 35689814
2021 Low THRB (thyroid hormone receptor beta) Promoter Methylation Levels in Peripheral Blood Leukocytes Induced By Systematic Inflammation Are Involved in Low Thyroid Hormone Function in Metabolic Syndrome. Hypertension (Dallas, Tex. : 1979) 5 34397273
1995 Molecular cloning of the hom-thrC-thrB cluster from Bacillus sp. ULM1: expression of the thrC gene in Escherichia coli and corynebacteria, and evolutionary relationships of the threonine genes. Folia microbiologica 5 8768250
1991 Polymerase chain reaction (PCR) for detection of BamHI polymorphism at the THRB gene. Nucleic acids research 5 1649459
2023 KMT2D Regulates the NCOA6/THRB Signal Axis through Epigenetic Modification to Promote the Migration and Invasion of Papillary Thyroid Cancer. Frontiers in bioscience (Landmark edition) 4 36722273
2021 T3 Promotes Glioma Cell Senescence and Apoptosis via THRA and THRB. Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer 4 34936295
2019 Phenotype variability and different genotype of four patients with thyroid hormone resistance syndrome due to variants in the THRB gene. Hippokratia 4 32581500
2013 Coexistence of THRB and TBG gene mutations in a Turkish family. The Journal of clinical endocrinology and metabolism 4 23633200
1994 The c-erbA beta thyroid hormone receptor. Expression and cDNA sequence analysis of the hormone-binding domain in human cancer cell lines. Acta oncologica (Stockholm, Sweden) 4 7917362
1991 Polymerase chain reaction (PCR) for detection of MspI and DraI polymorphism at the THRB gene. Nucleic acids research 4 1712945
2025 Identification of new families and variants in autosomal dominant macular dystrophy associated with THRB. Scientific reports 3 40295579
2023 Thyroid hormone resistance resulting from a novel mutation in the THRB gene in a Chinese child: A case report. Medicine 3 37115071
2022 Thyroid hormone resistance syndrome caused by a novel mutation in the thyroid hormone receptor-beta gene (THRB, GLU457LYS) treated with methimazole. Clinical case reports 3 36381023
2021 Clinical Consequences of Variable Results in the Measurement of Free Thyroid Hormones: Unusual Presentation of a Family with a Novel Variant in the THRB Gene Causing Resistance to Thyroid Hormone Syndrome. European thyroid journal 3 34956926
2020 Structural insights revealed by two novel THRB mutations. Endocrine 3 31902113
2018 A Novel Thyroid Hormone Receptor Beta Mutation (G357R) in a Family with Resistance to Thyroid Hormone Beta: Extending the Borders of the "Hot" Region in the THRB Gene. Thyroid : official journal of the American Thyroid Association 3 30458118
1994 Generalized resistance to thyroid hormone: identification of a novel c-erbA beta thyroid hormone receptor variant (Leu450) in a Japanese family and analysis of its secondary structure by the Chou and Fasman method. The Japanese journal of human genetics 3 7873749
1993 Close proximity of c-erbA2 and c-erbA-beta genes on the short arm of chromosome 3. Oncogene 3 8393165
1991 PCR detection of the HindIII polymorphism at the thyroid hormone receptor, beta, gene (THRB). Nucleic acids research 3 1649461
2025 The Beneficial Role of the Thyroid Hormone Receptor Beta 2 (thrb2) in Facilitating the First Feeding and Subsequent Growth in Medaka as Fish Larval Model. Cells 2 40072114
2025 Mutation of the Thyroid Hormone Receptor Beta Gene (THRB) Causes Vitelliform Macular Dystrophy with High Intrafamilial Variability. Genes 2 41153457
2024 Nr1h4 and Thrb ameliorate ER stress and provide protection in the MPTP mouse model of Parkinson's. Life science alliance 2 38609183
2024 Transcription factor STAT4 counteracts radiotherapy resistance in breast carcinoma cells by activating the MALAT1/miR-21-5p/THRB regulatory network. American journal of cancer research 2 38726265
2024 Thyroid hormone receptor beta (THRB) dependent regulation of diurnal hepatic lipid metabolism in adult male mice. npj metabolic health and disease 2 40603776
2022 Reduced pituitary size in subjects with mutations in the THRB gene and thyroid hormone resistance. Endocrine connections 2 34860176
2020 Resistance to thyroid hormone due to a novel THRB p.Val349Ala mutation in a Taiwanese boy. Journal of the Formosan Medical Association = Taiwan yi zhi 2 32505587
2020 Hypercholesterolemia in Two Siblings with Resistance to Thyroid Hormones Due to Disease-Causing Variant in Thyroid Hormone Receptor (THRB) Gene. Medicina (Kaunas, Lithuania) 2 33333891
2012 THRB genetic polymorphisms can predict severe myelotoxicity after definitive chemoradiotherapy in patients with esophageal squamous cell carcinoma. International journal of medical sciences 2 23136537

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