Affinage

THRB

Thyroid hormone receptor beta · UniProt P10828

Length
461 aa
Mass
52.8 kDa
Annotated
2026-04-28
100 papers in source corpus 22 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

THRB encodes thyroid hormone receptor beta (TRβ), a ligand-dependent nuclear transcription factor that binds triiodothyronine (T3) and thyroid hormone response elements (TREs) to activate or repress target genes governing metabolism, bone remodeling, erythropoiesis, hepatocyte maturation, and neuronal function. The receptor's ligand-binding and DNA-binding activities are structurally separable: disease-causing mutations cluster in two hot-spot regions of the ligand-binding domain and reduce T3 affinity while preserving TRE binding, and dominant negative mutants heterodimerize with RXRβ on TREs to block wild-type receptor function, causing generalized resistance to thyroid hormone (PMID:2905763, PMID:1661299, PMID:9100577). THRB directly transactivates target promoters including SIRT3, CYP3A4, and Klf9 in a T3-dependent manner, regulates the RANKL/OPG axis in osteoblasts, and is required for circadian hepatic lipid metabolism (PMID:34401962, PMID:35452598, PMID:37992217, PMID:40603776). A splice-site variant selectively disrupting the TRβ1 isoform while sparing TRβ2 causes inherited retinal dystrophy without thyroid hormone resistance, establishing isoform-specific functions in the retina (PMID:37547476).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1988 High

    Before this work, the molecular basis of generalized thyroid hormone resistance (GTHR) was unknown; RFLP linkage analysis in an affected kindred established THRB as the causative locus, connecting a nuclear receptor gene to a clinical endocrine syndrome.

    Evidence RFLP genetic linkage in a GTHR kindred

    PMID:2905763

    Open questions at the time
    • No mutation identified at nucleotide level
    • Mechanism of dominant inheritance not addressed
  2. 1990 High

    To understand how THRB mutations cause hormone resistance, biochemical dissection showed that the receptor is sufficient for both high-affinity T3 binding (Kd ~0.34 nM) and TRE binding, and that specific point mutations (e.g., Pro448His) reduce T3 affinity while retaining DNA binding, establishing the dominant negative paradigm.

    Evidence Heterologous expression in yeast (T3 and TRE binding), in vitro mutant receptor synthesis with T3- and DNA-binding assays

    PMID:2153155 PMID:2169728 PMID:2203342

    Open questions at the time
    • Cofactor requirements for transcriptional activity not defined
    • Structural basis for separable ligand vs. DNA binding not resolved
  3. 1991 High

    Mapping of multiple patient mutations revealed two hot-spot regions in the ligand-binding domain and showed that hinge-domain residues also contribute to T3 affinity, defining the molecular topography of hormone resistance.

    Evidence Sequencing of exons 7–10 from multiple kindreds, in vitro T3-binding assays of mutant receptors

    PMID:1324420 PMID:1653889 PMID:1661299

    Open questions at the time
    • Crystal structure not available to explain hot-spot clustering
    • Contribution of corepressor/coactivator interactions to phenotype not tested
  4. 1993 High

    The question of whether reduced T3 binding alone is sufficient for dominant negative activity was resolved: an Arg311His mutant lost both T3 binding and dominant negative function, and wild-type THRB was shown to mediate T3-dependent repression of AP-1 target genes, separating ligand-binding deficiency from dominant negative interference.

    Evidence T3-binding assay, transfection reporter assays with mutant receptors in COS-7 cells

    PMID:8247013 PMID:8381821

    Open questions at the time
    • Structural basis for Arg311 requirement in dominant negativity unknown
    • Whether all non-dominant-negative mutations share the same structural defect untested
  5. 1997 High

    A truncated receptor lacking the C-terminal 28 amino acids formed homodimers and RXRβ heterodimers on TREs but showed TRE-element-specific dominant negative potency, establishing that dimerization competence is necessary but DNA-binding affinity does not predict transcriptional silencing strength.

    Evidence EMSA, reporter assays with multiple TRE configurations, RXR heterodimerization assay

    PMID:9100577

    Open questions at the time
    • Corepressor recruitment to different TRE configurations not examined
    • In vivo relevance of TRE-specific dominant negativity not tested
  6. 2001 High

    Genetic epistasis in mice showed that overexpression of TRα1 compensates for Thrb loss to rescue deafness and thyroid hyperactivity, demonstrating functional redundancy between TR isoforms and establishing that Thrb is required for normal auditory function.

    Evidence Thrb-null × Thra(tm2) double-mutant mice with auditory threshold and thyroid activity measurements

    PMID:11726557

    Open questions at the time
    • Cell-type-specific requirement in cochlea not delineated
    • Whether TRα1 overexpression fully recapitulates TRβ target gene programs unknown
  7. 2010 High

    Post-transcriptional regulation of THRB was established when miR-21 and miR-146a were shown to directly target the THRB 3′-UTR and suppress protein levels to 10–28% of control, reducing downstream TRE-mediated transcription.

    Evidence 3′-UTR luciferase reporter, pre-miR transfection, western blot, TRE-reporter assay

    PMID:21159845

    Open questions at the time
    • Physiological contexts in which miR-mediated THRB repression is rate-limiting not defined
    • Effect on specific T3-responsive tissues in vivo not tested
  8. 2016 Medium

    THRB was identified as a positive regulator of erythropoiesis: gain-of-function promoted erythroid differentiation in K562/TF-1 cells and zebrafish, while loss-of-function reduced erythroid gene expression, expanding THRB's functional repertoire beyond classical thyroid hormone target tissues.

    Evidence 3′-UTR reporter for miR-200a, gain/loss-of-function in K562 and TF-1 cells, zebrafish primitive erythropoiesis assay

    PMID:27734462

    Open questions at the time
    • Direct transcriptional targets in erythroid progenitors not identified
    • Relevance to definitive mammalian erythropoiesis not confirmed
  9. 2021 Medium

    ChIP demonstrated direct THRB binding to the SIRT3 promoter in hippocampal neurons, and THRB overexpression rescued Aβ42-induced metabolic dysfunction (NAD+/NADH, ATP, SIRT3 activity), establishing a THRB→SIRT3 transcriptional axis in neuronal metabolism.

    Evidence ChIP, dual luciferase reporter, THRB overexpression/knockdown in primary neurons, metabolic assays, APP-transgenic mouse cognition tests

    PMID:34401962

    Open questions at the time
    • Whether this axis operates in non-AD neuronal physiology unclear
    • THRB occupancy at SIRT3 promoter not assessed genome-wide
  10. 2022 High

    THRB was shown to drive hepatocyte maturation by binding the CYP3A4 proximal enhancer and restoring NFIC super-enhancer status in hPSC-derived hepatocytes, providing a mechanistic link between T3 signaling and chromatin remodeling during liver differentiation.

    Evidence RNA-seq, ATAC-seq, H3K27Ac ChIP-seq, T3 treatment, transplantation into mouse liver

    PMID:35452598

    Open questions at the time
    • Whether THRB directly recruits chromatin remodeling machinery or acts through intermediary factors unclear
    • Full set of THRB-bound enhancers during hepatocyte maturation not catalogued
  11. 2023 Medium

    A splice-site variant (c.283+1G>A) selectively disrupting TRβ1 while leaving TRβ2 intact caused retinal dystrophy without thyroid hormone resistance across three pedigrees, establishing that TRβ1 is specifically required for cone photoreceptor/retinal health independently of systemic thyroid hormone homeostasis.

    Evidence Whole genome sequencing and segregation analysis in three pedigrees

    PMID:37547476

    Open questions at the time
    • Functional rescue of retinal phenotype not performed
    • Mechanism by which TRβ1 loss damages cones not defined
  12. 2023 Medium

    Cell-type-specific expression of THRB in calretinin+ and somatostatin+ interneurons of human fetal cortex was mapped, and Thrb knockout in osteoblasts was shown to impair TH-driven mineralization and reduce RANKL/OPG ratio, extending THRB's required roles to brain interneuron identity and bone remodeling.

    Evidence Single-cell RNA-seq of human fetal cortex; primary osteoblast cultures from Thrb-/- mice with differentiation, qRT-PCR, and conditioned-medium osteoclast assays

    PMID:34114484 PMID:37992217

    Open questions at the time
    • Functional consequences of THRB loss in specific interneuron subtypes not tested
    • Osteoblast findings are in vitro and lack in vivo bone phenotyping
  13. 2024 Medium

    THRB activation by T3 was shown to mitigate ER stress and mitochondrial dysfunction in neuronal cells and protect dopaminergic neurons in a Parkinson's disease model, and THRB deficiency in mouse liver was found to disrupt diurnal lipid metabolic rhythms, broadening THRB's roles to neuroprotection and circadian metabolic regulation.

    Evidence ER stress gene expression, mitochondrial assays, MPTP mouse model; temporal RNA-seq and lipidomics of Thrb-KO mice

    PMID:38609183 PMID:40603776

    Open questions at the time
    • Neuroprotection study used ligand activation rather than THRB-specific genetic manipulation
    • Whether circadian lipid defects are direct transcriptional targets of THRB or indirect systemic effects not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the genome-wide map of direct THRB binding sites across tissues, the structural basis for isoform-specific (TRβ1 vs TRβ2) functions, the identity of coregulators that confer tissue-specific transcriptional outcomes, and the mechanism by which THRB modulates circadian metabolic programs in the liver.
  • No genome-wide ChIP-seq map of THRB across multiple tissues published
  • Structural basis for TRβ1-specific retinal function unknown
  • Coregulator complexes mediating tissue-specific THRB activity not systematically identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 2 R-HSA-1430728 Metabolism 1
Partners
CYP3A4KLF9NFICRXRBSIRT3

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 The THRB gene (c-erbA beta), encoding a thyroid hormone receptor, was genetically linked to the syndrome of generalized thyroid hormone resistance (GTHR) by restriction fragment length polymorphism analysis in a kindred, establishing THRB as the causative locus and demonstrating its role as a functional T3 receptor in the pituitary, liver, CNS, and other tissues. Genetic linkage analysis (RFLP), restriction enzyme analysis Molecular endocrinology (Baltimore, Md.) High 2905763
1990 A point mutation (Pro448His) in the T3-binding domain of THRB reduces T3-binding affinity in the mutant receptor while retaining normal DNA-binding activity, acting as a dominant negative inhibitor of thyroid hormone action in generalized thyroid hormone resistance. Direct sequencing of PCR-amplified genomic DNA, in vitro synthesis of mutant receptor, T3-binding assay, DNA-binding assay (avidin-biotin) The Journal of clinical investigation / Biochemical and biophysical research communications High 2153155 2169728
1990 The THRB receptor, expressed in yeast, binds T3 with high affinity (Kd = 0.34 nM) and binds thyroid hormone response elements (TREs), demonstrating that the receptor is sufficient for both ligand and DNA binding without other mammalian cofactors. Heterologous expression in Saccharomyces cerevisiae, [125I]T3 binding assay, gel retardation assay with TRE Biochemical and biophysical research communications Medium 2203342
1991 A homozygous 3-bp deletion in the THRB T3-binding domain (loss of Thr332) abolishes T3 binding but retains normal binding to thyroid hormone response elements of the TSH-beta and GH genes, demonstrating that T3 binding and DNA binding are separable functions of THRB; the homozygous mutant receptor acts as a potent dominant negative. cDNA cloning and sequencing, in vitro synthesis of mutant receptor, T3-binding assay, TRE-binding assay Molecular endocrinology (Baltimore, Md.) High 1653889
1991 Multiple point mutations in THRB cluster in two 'hot spot' regions of the ligand-binding domain (distal L2 subdomain and the junction of the tau1 and dimerization subdomains in exons 9-10), and four tested mutations reduce T3-binding affinity, supporting these as the molecular basis of generalized thyroid hormone resistance. PCR amplification and direct sequencing of exons, in vitro T3-binding assay The Journal of clinical investigation High 1661299
1991 A point mutation in the hinge domain of THRB (Ala229Thr, exon 7) reduces T3-binding affinity approximately 3-fold while retaining high-affinity binding to thyroid hormone response elements, indicating that the hinge domain contributes to full ligand-binding activity and that multiple subdomains cooperate for optimal T3 binding. Direct sequencing of PCR-amplified fibroblast THRB cDNA, in vitro expression and T3-binding assay, TRE-binding assay Molecular endocrinology (Baltimore, Md.) High 1324420
1993 An Arg311His mutation in THRB severely reduces T3-binding affinity but abolishes dominant negative activity in transfection assays, demonstrating that Arg311 is critical for the structural integrity required for dominant negative function and that impaired T3 binding alone is insufficient to confer dominant negativity. cDNA cloning, in vitro reticulocyte lysate synthesis, T3-binding assay, RNA phenotyping, transfection assay for dominant negative activity The Journal of clinical investigation High 8381821
1993 Dominant negative THRB mutants (S and CL) and the non-dominant negative mutant (G-H) augment TPA-induced collagenase promoter activity and show defective T3-mediated repression, demonstrating that THRB normally mediates T3-dependent repression of AP-1/TPA-responsive genes and that this function requires T3 binding. Transient transfection assay (COS-7 cells), collagenase promoter-CAT reporter, cotransfection with mutant receptors, +/- T3 and TPA treatment Molecular endocrinology (Baltimore, Md.) Medium 8247013
1997 A truncated THRB receptor (28 aa carboxy-terminal deletion, TR-beta-EZ) abolishes T3 binding, forms homodimers and heterodimers with RXRbeta on TREs, and represses basal transcription in a TRE-specific manner with stronger dominant negative activity on DR4 and F2 elements but weaker silencing via palindromic TRE compared to wild-type, demonstrating that homodimer-DNA binding affinity does not predict dominant negative transcriptional activity. In vitro expression, TRE electrophoretic mobility shift assay, transfection reporter (thymidine kinase promoter-luciferase with different TREs), RXR heterodimerization assay The Journal of clinical endocrinology and metabolism High 9100577
2001 In Thrb-null mice, deletion of the Thra gene's TR-alpha2 splice variant (which does not bind T3) with concomitant overexpression of TR-alpha1 suppresses the deafness and thyroid hyperactivity caused by Thrb loss, demonstrating that increased TR-alpha1 expression can substitute for TR-beta and that TR-alpha2 is dispensable for hearing. Genetic epistasis using Thrb-null × Thra(tm2) mouse crosses; auditory threshold measurement; thyroid activity assays Human molecular genetics High 11726557
2010 miR-21 and miR-146a directly bind the 3'-UTR of THRB and inhibit its expression; miR-21, miR-146a, and miR-221 reduce THRB transcript levels 37–48% and suppress THRB protein to 10–28% of control, with downstream effects on thyroid hormone response element activity and target genes DIO1 and APP. Luciferase reporter assay with cloned THRB 3'-UTR, pre-miR transfection in cell lines, RT-PCR, western blot, promoter assay with TRE-TK-Luc construct The Journal of clinical endocrinology and metabolism High 21159845
2016 miR-200a-3p targets THRB (and PDCD4); loss-of-function of THRB reduces erythroid gene expression, and gain-of-function of THRB promotes erythroid differentiation in K562 and TF-1 cells and in zebrafish, establishing THRB as a positive regulator of erythropoiesis downstream of miR-200a. Bioinformatics target prediction, luciferase 3'-UTR reporter assay, miR overexpression, gain- and loss-of-function studies in cell lines, in vivo zebrafish primitive erythropoiesis assay British journal of haematology Medium 27734462
2021 THRB directly binds the SIRT3 gene promoter and transcriptionally activates SIRT3 expression; THRB overexpression reverses Aβ42-induced metabolic dysfunction (reduced NAD+/NADH ratio, ATP, SIRT3 deacetylation activity) in hippocampal neurons, while THRB silencing aggravates it. Dual luciferase reporter gene assay, ChIP assay for THRB binding to SIRT3 promoter, THRB overexpression/knockdown in primary neurons, metabolic assays (NAD+/NADH, ATP, deacetylation activity), APPTG mouse cognitive testing Neurochemical research Medium 34401962
2022 THRB, activated by thyroid hormone T3, binds the CYP3A4 proximal enhancer and restores the super-enhancer status and gene expression of NFIC in hPSC-derived hepatocytes, promoting hepatocyte maturation; this was demonstrated by ATAC-seq, H3K27Ac ChIP-seq, and RNA-seq showing reduced THRB motif accessibility without reduced THRB transcription in immature hepatocytes. RNA-seq, ATAC-seq, H3K27Ac ChIP-seq, THRB motif analysis, T3 addition experiments, transplantation into mouse liver Cell stem cell High 35452598
2023 KMT2D histone methyltransferase epigenetically regulates THRB expression through NCOA6; ChIP assay demonstrated KMT2D association with NCOA6, and KMT2D knockdown reduces H3K4me2, H3K9me2, NCOA6, and THRB levels, decreasing PTC cell proliferation, migration and invasion. ChIP assay, CCK-8 proliferation assay, wound-healing assay, transwell invasion assay, qRT-PCR, western blot Frontiers in bioscience (Landmark edition) Low 36722273
2023 A dominant splicing variant (c.283+1G>A) in THRB disrupts a splice site in the 5'-region encoding the N-terminal domain of TRβ1 isoform while leaving the TRβ2 isoform intact, causing non-syndromic inherited retinal dystrophies (cone dystrophy, Stargardt disease, macular dystrophy) without thyroid hormone resistance, demonstrating isoform-specific function of TRβ1 in the retina. Whole genome sequencing, segregation analysis, genotype-phenotype correlation across three pedigrees Frontiers in cell and developmental biology Medium 37547476
2023 In human fetal neocortex, single-cell transcriptomics reveals that THRB is selectively expressed in two classes of interneurons (calretinin+ from caudal ganglionic eminence and somatostatin+ from medial ganglionic eminence), whereas THRA is broadly expressed, establishing cell-type-specific roles for the two TR isoforms in human brain development. Single-cell RNA-seq analysis of human fetal cerebral cortex, UMAP clustering, differential gene expression Thyroid : official journal of the American Thyroid Association Medium 34114484
2023 Thrb knockout in primary mouse osteoblasts mitigates thyroid hormone responsiveness (impaired induction of mineralization, osteoblast marker genes, and Klf9 target gene), and reduces the RANKL/OPG ratio such that supernatants from Thrb-/- osteoblasts reduce osteoclast numbers, demonstrating that THRB in osteoblasts is required for TH-driven bone remodeling signaling. Primary osteoblast cultures from Thrb-/- mice, differentiation assays, qRT-PCR, RANKL/OPG ratio measurement, conditioned medium transfer to primary osteoclasts, Trap/Ctsk expression Journal of cellular biochemistry Medium 37992217
2024 Activation of THRB by its ligand T3 ameliorates tunicamycin-induced ER stress gene expression in neuronal cells, reduces MPP+-induced mitochondrial membrane potential loss and ROS generation, and protects against dopaminergic cell death in the MPTP mouse model of Parkinson's disease. ER stress gene expression analysis, mitochondrial membrane potential assay, ROS measurement, in vitro MPP+ neuronal model, in vivo MPTP mouse model with behavioral and histological readouts Life science alliance Medium 38609183
2024 THRB deficiency in mouse liver alters diurnal metabolic rhythms, leading to elevated cholesterol, tri- and diacylglycerides, and fatty acids in a time-of-day-dependent manner, demonstrating that THRB is required for circadian regulation of hepatic lipid metabolism. Temporal transcriptome (RNA-seq) and lipidome profiling of THRB knockout (THRBKO) mice; THRB agonization in hepatocytes under steatosis-promoting conditions in vitro npj metabolic health and disease Medium 40603776
2025 High-fructose diet suppresses Thrb expression in bone marrow mesenchymal stem cells, leading to cholesterol accumulation and impaired osteogenic differentiation; activation of Thrb ameliorates bone loss, identifying the Thrb/Prkcz/cholesterol accumulation pathway as a mechanism linking fructose intake to osteoporosis. Murine high-fructose diet model, bone density measurement, osteogenic differentiation assay of BMSCs, Thrb expression analysis, cholesterol measurement, Thrb activation and Prkcz inhibition experiments Cell death discovery Low 40204733

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.) 160 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
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
2022 The nuclear receptor THRB facilitates differentiation of human PSCs into more mature hepatocytes. Cell stem cell 19 35452598
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 15 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
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 Effect of the Fetal THRB Genotype on the Placenta. The Journal of clinical endocrinology and metabolism 12 37149816
2016 MicroRNA 200a inhibits erythroid differentiation by targeting PDCD4 and THRB. British journal of haematology 12 27734462
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
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 11 23806029
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
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 10 37547476
2014 Resistance to thyroid hormone due to mutations in the THRB gene impairs bone mass and affects calcium and phosphorus homeostasis. Bone 10 25063548
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 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
2023 Thyroid hormone receptor Thra and Thrb knockout differentially affects osteoblast biology and thyroid hormone responsiveness in vitro. Journal of cellular biochemistry 3 37992217
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
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
2023 Thyroid hormone resistance resulting from a novel mutation in the THRB gene in a Chinese child: A case report. Medicine 2 37115071
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
2009 Multiple genomic aberrations in a patient with mental retardation and hypogonadism: 45,X/46,X,psu dic(Y) karyotype, thyroid hormone receptor beta (THRB) mutation and heterozygosity for Wilson disease. American journal of medical genetics. Part A 2 19725132
1991 BglI RFLP for the human erb-A beta locus on chromosome 3p22-3p24.1 (THRB). Nucleic acids research 2 1679539
2025 A high-fructose diet leads to osteoporosis by suppressing the expression of Thrb and facilitating the accumulation of cholesterol. Cell death discovery 1 40204733
2024 Nr1h4 and Thrb ameliorate ER stress and provide protection in the MPTP mouse model of Parkinson's. Life science alliance 1 38609183
2024 Thyroid hormone receptor beta (THRB) dependent regulation of diurnal hepatic lipid metabolism in adult male mice. npj metabolic health and disease 1 40603776