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THRB

gene
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Also known as THRB1THRB2NR1A2THR1ERBA-BETAGRTHTRbetaTRbc-erbA-betac-erbA-2THRbetaTRbeta1THRbeta1Thrbeta2

Summary

THRB (thyroid hormone receptor beta, HGNC:11799) is a protein-coding gene on chromosome 3p24.2, encoding Thyroid hormone receptor beta (P10828). Nuclear hormone receptor that can act as a repressor or activator of transcription.

The protein encoded by this gene is a nuclear hormone receptor for triiodothyronine. It is one of the several receptors for thyroid hormone, and has been shown to mediate the biological activities of thyroid hormone. Knockout studies in mice suggest that the different receptors, while having certain extent of redundancy, may mediate different functions of thyroid hormone. Mutations in this gene are known to be a cause of generalized thyroid hormone resistance (GTHR), a syndrome characterized by goiter and high levels of circulating thyroid hormone (T3-T4), with normal or slightly elevated thyroid stimulating hormone (TSH). Several alternatively spliced transcript variants encoding the same protein have been observed for this gene.

Source: NCBI Gene 7068 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): thyroid hormone resistance, generalized, autosomal dominant (Strong, GenCC) — +2 more curated relationships
  • GWAS associations: 80
  • Clinical variants (ClinVar): 745 total — 46 pathogenic, 31 likely-pathogenic
  • Phenotypes (HPO): 39
  • Druggable target: yes — 117 molecules with ChEMBL bioactivity
  • Transcription factor: yes — 66 downstream targets (CollecTRI)
  • MANE Select transcript: NM_001354712

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:11799
Approved symbolTHRB
Namethyroid hormone receptor beta
Location3p24.2
Locus typegene with protein product
StatusApproved
AliasesTHRB1, THRB2, NR1A2, THR1, ERBA-BETA, GRTH, TRbeta, TRb, c-erbA-beta, c-erbA-2, THRbeta, TRbeta1, THRbeta1, Thrbeta2
Ensembl geneENSG00000151090
Ensembl biotypeprotein_coding
OMIM190160
Entrez7068

Gene structure

Transcript identifiers

Ensembl transcripts: 54 — 52 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000280696, ENST00000356447, ENST00000396671, ENST00000413780, ENST00000416420, ENST00000418247, ENST00000428492, ENST00000431815, ENST00000447414, ENST00000447875, ENST00000453729, ENST00000642307, ENST00000643772, ENST00000644321, ENST00000645139, ENST00000646209, ENST00000646300, ENST00000646432, ENST00000646966, ENST00000851503, ENST00000851504, ENST00000851505, ENST00000851506, ENST00000851507, ENST00000851508, ENST00000851509, ENST00000851510, ENST00000851511, ENST00000851512, ENST00000851513, ENST00000851514, ENST00000851515, ENST00000851516, ENST00000851517, ENST00000851518, ENST00000851519, ENST00000851520, ENST00000851521, ENST00000851522, ENST00000851523, ENST00000851524, ENST00000965290, ENST00000965291, ENST00000965292, ENST00000965293, ENST00000965294, ENST00000965295, ENST00000965296, ENST00000965297, ENST00000965298, ENST00000965299, ENST00000965300, ENST00000965301, ENST00000965302

RefSeq mRNA: 18 — MANE Select: NM_001354712 NM_000461, NM_001128176, NM_001128177, NM_001252634, NM_001354708, NM_001354709, NM_001354710, NM_001354711, NM_001354712, NM_001354713, NM_001354714, NM_001354715, NM_001374822, NM_001374823, NM_001374824, NM_001374825, NM_001374826, NM_001374827

CCDS: CCDS2641

Canonical transcript exons

ENST00000646209 — 11 exons

ExonStartEnd
ENSE000010735172413331624133462
ENSE000010735182414667524146822
ENSE000010735192414350124143706
ENSE000013959062433730024337371
ENSE000013979132422893824229001
ENSE000016124622429722624297371
ENSE000016428672415239024152490
ENSE000017181322412749924127757
ENSE000035403572419007424190334
ENSE000038308172449465224494850
ENSE000039017672411715324123125

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 98.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.6473 / max 244.0114, expressed in 979 samples.

FANTOM5 promoters (20 alternative TSS)

Promoter IDTPM avgSamples expressed
414822.9023803
414830.7282358
414870.547997
414810.3878211
414850.3807191
414860.169475
414880.152285
414840.113651
414650.053411
414720.05077

Top tissues by expression

296 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
Brodmann (1909) area 23UBERON:001355498.54gold quality
middle temporal gyrusUBERON:000277197.50gold quality
tibiaUBERON:000097996.43gold quality
postcentral gyrusUBERON:000258195.94gold quality
parietal lobeUBERON:000187295.65gold quality
endothelial cellCL:000011595.60gold quality
superior frontal gyrusUBERON:000266195.46gold quality
entorhinal cortexUBERON:000272894.14gold quality
calcaneal tendonUBERON:000370193.58gold quality
mammary ductUBERON:000176592.09gold quality
tendonUBERON:000004391.19gold quality
parotid glandUBERON:000183190.59gold quality
skeletal muscle tissue of rectus abdominisUBERON:000451190.24gold quality
primary visual cortexUBERON:000243690.22gold quality
descending thoracic aortaUBERON:000234590.02gold quality
renal medullaUBERON:000036289.41gold quality
thoracic aortaUBERON:000151589.33gold quality
occipital lobeUBERON:000202189.32gold quality
ascending aortaUBERON:000149689.26gold quality
seminal vesicleUBERON:000099889.09gold quality
hindlimb stylopod muscleUBERON:000425288.69gold quality
synovial jointUBERON:000221788.42gold quality
epithelium of mammary glandUBERON:000324488.13gold quality
dorsolateral prefrontal cortexUBERON:000983487.89gold quality
prefrontal cortexUBERON:000045187.72gold quality
aortaUBERON:000094787.72gold quality
frontal cortexUBERON:000187087.47gold quality
muscle of legUBERON:000138386.86gold quality
mammary glandUBERON:000191186.77gold quality
thoracic mammary glandUBERON:000520086.75gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

ExperimentMarker?Max mean expression
E-MTAB-11121yes796.36
E-HCAD-25yes75.44
E-HCAD-35yes66.24
E-MTAB-7316yes24.02
E-CURD-119yes17.12
E-ANND-3yes12.30
E-GEOD-137537no3.19
E-GEOD-83139no3.05

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

66 targets.

TargetRegulation
ACACA
ADAM2
ANGPTL3
APOA2Repression
APOC2Activation
APOC3
CAT
CCND1Repression
CGARepression
CREB1Repression
CTNNB1Unknown
CYP27B1
DHCR24
E2F1Activation
FGF21
FN1Activation
GH1
GHRHR
GNAS
GPHA2
GTF2B
HCN4Repression
HIF1AActivation
ITGB3
KCND3
KCNMA1
LDLRUnknown
MLXIPLActivation
MMP12
MYH6

JASPAR motifs

MotifNameFamily
MA1574.1THRBThyroid hormone receptor-related factors (NR1)
MA1574.2THRBThyroid hormone receptor-related factors (NR1)
MA1575.1THRBThyroid hormone receptor-related factors (NR1)
MA1575.2THRBThyroid hormone receptor-related factors (NR1)
MA1576.1THRBThyroid hormone receptor-related factors (NR1)
MA1576.2THRBThyroid hormone receptor-related factors (NR1)

JASPAR matrix evidence (PMIDs): PMID:19741045

Upstream regulators (CollecTRI, top): NEUROD1, PAX1, POU1F1, POU2F1, THRA, THRB

miRNA regulators (miRDB)

391 targeting THRB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4262100.0073.263931
HSA-MIR-3163100.0077.238605
HSA-MIR-126-5P100.0072.713180
HSA-LET-7A-3P100.0074.033932
HSA-LET-7B-3P100.0074.083913
HSA-LET-7F-1-3P100.0074.023928
HSA-MIR-98-3P100.0074.083907
HSA-MIR-9-5P100.0072.282361
HSA-MIR-574-5P100.0066.01989
HSA-MIR-4795-3P100.0074.624024
HSA-MIR-200B-3P100.0073.312693
HSA-MIR-200C-3P100.0073.352685
HSA-MIR-429100.0073.442698
HSA-MIR-5692A100.0074.406850
HSA-MIR-4455100.0065.481587
HSA-MIR-428299.9975.366408
HSA-MIR-181A-5P99.9972.962995
HSA-MIR-181B-5P99.9972.972996
HSA-MIR-181C-5P99.9972.952996
HSA-MIR-181D-5P99.9973.042997
HSA-MIR-548AW99.9972.573559
HSA-MIR-453199.9969.703181
HSA-MIR-548C-3P99.9974.017587
HSA-MIR-3667-3P99.9967.171636
HSA-MIR-450099.9972.722367
HSA-MIR-318599.9968.121959
HSA-MIR-453499.9966.581907
HSA-MIR-186-5P99.9970.833707
HSA-MIR-27A-3P99.9872.132955
HSA-MIR-27B-3P99.9872.132955

Literature-anchored findings (GeneRIF, showing 40)

  • TR surfaces and conformations required to bind nuclear receptor corepressor (PMID:11818500)
  • neurodevelopmental functions of thyroid hormone signaling (PMID:11861164)
  • affected receptor amino acid sequences.lost their trans-activation function and exhibited dominant negative activity. (PMID:11889175)
  • genetic analysis revealed a novel heterozygous missense mutation at codon 334 of thyroid hormone receptor beta1 in a family with resistance to thyroid hormone (PMID:11929097)
  • a point mutation, not anticipated to occur in resistance to thyroid hormone, causes variable phenotypes. (PMID:12006711)
  • Thrb(PV)/Thrb(PV) mice have severe hearing impairment that is already present at 3 weeks of age. This hearing loss is associated with disruption of postnatal morphogenesis of the tectorial membrane and organ of Corti. (PMID:12382103)
  • x-ray crystal structures of two hTRbeta ligand-binding domains, Ala 317 Thr and Arg 316 His (PMID:12554782)
  • expression of functionally impaired mutants of THRB1 in papillary carcinomas is rare (PMID:12843201)
  • The crystal structure of human thyroid hormone receptor beta at 2.8-A resolution with GC-24 bound explains its agonist activity and unique isoform specificity. (PMID:14673100)
  • Except for cardiac hypertrophy, the presence of a germline TR-beta mutation had surprisingly little effect on cardiac function. (PMID:14684607)
  • thyroid hormone receptor-beta cell cycle-dependent expression regulates variable hormone sensitivity (PMID:14767065)
  • partial dissociation of TR/retinoid X receptor heterodimer complex from the TRE is involved in the suppression of transcription induced by polychlorinated biphenyls (PMID:14985366)
  • novel point mutation, a heterozygous transition c.1031G>C in exon 9 theoretically substituting Gly344Ala results in bone development retardation (PMID:15080770)
  • developmental and tissue-specific expression of human thyroid hormone receptor beta1 5’-UTR mRNAs may regulate T3-responsiveness in target tissues by modulating TRbeta protein translation (PMID:15105435)
  • Most patients with resistance to thyroid hormone carry a mutation in this gene. (PMID:15186611)
  • unliganded TRbeta1 suppresses promoter activity driven by LXRalpha and its ligand, whereas transactivation by T3-bound TRbeta1 is not affected by LXRalpha in the presence or absence of oxysterols (PMID:15319359)
  • two novel TRbeta mutations occurring in the same nucleotide (PMID:15598685)
  • results suggested that T3 upregulates cellular proliferation on LNCaP cells but not other prostatic carcinoma cells and PZ-HPV-7 and CA-HPV-10 cells express the novel TRbeta1, which locates at cell nuclear membrane (PMID:15867011)
  • a small subset of TRbeta mutations that arise in resistance to thyroid hormone syndrome inhibit both T3 binding and formation of TRbeta homodimers on thyroid hormone response elements (PMID:15886199)
  • Modulation of hepatic TRbeta1, a key regulator of gene expression involved in lipid metabolism by soy proteins may be a novel mechanism by which soy components lower blood lipid level and exert their hypocholesterolemic actions. (PMID:15987841)
  • Pituitary and peripheral tissue responses to graded doses of liothyronine in 5 affected members of a family with thyroid hormone resistance due to the common TRbeta mutation P453T are reported. (PMID:16099238)
  • Association of TRbeta1 expression with growth pattern and the presence of K-ras mutations suggest that abnormalities in thyroid hormone signalling involving TRbeta1 play a role in the development of some types of colorectal adenocarcinomas (PMID:16231318)
  • Thyroid hormone receptor (TR) D-domain has the potential to form functionally important extensions of the DNA-binding domain (DBD) and ligand-binding domain (LBD) or unfold to permit TRs to adapt to different DNA response elements. (PMID:16781732)
  • The E333D TRbeta mutation is responsible for the resistance to thyroid hormone syndrome in a case report. (PMID:17177139)
  • apo THRBs form tetramers in solution which dissociate into dimers upon thyroid hormone T3 binding (PMID:17260956)
  • Mediates Akt activation by T3 in pancreatic beta cells. (PMID:17293442)
  • These findings provide a molecular rationale for the role of hS14 in TR-dependent transcriptional activation of the expression of specific genes. (PMID:17418816)
  • the two systems, TRs and IGF1/IGF1R could also be functionally associated. (PMID:17560756)
  • an insertion mutation in thyroid hormone receptor-beta may have a role in thyroid hormone resistance (PMID:17596672)
  • Generalized resistance to thyroid hormone with chronic thyroiditis with a novel mutation, G347A, of the TR beta gene. (PMID:17827792)
  • hypermethylation of the TRbeta gene as an alternative gene silencing mechanism is highly prevalent in thyroid cancer (PMID:17911173)
  • Activation of the thyroid hormone receptor beta/retinoid X receptor alpha heterodimer by T(3) stimulated expression of the hepatic leukemia factor, which increases HIF-1alpha gene expression. (PMID:18239067)
  • We report the first case of a woman with resistance to thyroid hormone, which was found to be caused by a missense mutation (V349M) in the TR beta gene. (PMID:18363280)
  • Furin overexpression in some types of hepatocellular carcinomas is TR dependent. (PMID:18467449)
  • Mutational analysis of the TRRB gene allows definitive diagnosis of thyroid hormone resistance syndrome, potentially avoiding the need for protracted and expensive pituitary function testing. (PMID:18561095)
  • As TRbeta(H435Y) has been found in both resistance to thyroid hormone and pituitary carcinoma, these results serve perhaps as the first example of chemical rescue that targets a mutant protein involved in multiple disease states. (PMID:18683837)
  • In this work, a single surface mutation, D355R, was shown to be crucial for converting the modestly stable monomeric ligand binding domain of the human thyroid hormone receptor (TR LBD) into a stable dimer. (PMID:18798561)
  • Analysis of the T3 receptor genes revealed 15 SNPs, including 7 novel. Only THRB-in9-G/A was associated with higher serum TSH in a large population of Danish twins. (PMID:18844476)
  • Our findings suggest that flexibility plays an important role in interaction between the receptor & its coregulators, & point out important aspects of experimental design that should be addressed when using TRbeta ligand binding domain & its agonists. (PMID:19000767)
  • the Thyroid hormone beta1 receptor mediates the T3 upregulation of protein synthesis and cell size, together with the cell proliferation and survival, playing a crucial role in the T3 regulation of the PI3K/Akt pathway. (PMID:19160403)

Cross-species orthologs

184 orthologs

OrganismSymbolGene ID
danio_reriothrbENSDARG00000021163
mus_musculusThrbENSMUSG00000021779
rattus_norvegicusThrbENSRNOG00000006649
drosophila_melanogasterHr96FBGN0015240
caenorhabditis_elegansWBGENE00001062
caenorhabditis_elegansWBGENE00003608
caenorhabditis_elegansWBGENE00003611
caenorhabditis_elegansWBGENE00003614
caenorhabditis_elegansWBGENE00003615
caenorhabditis_elegansWBGENE00003617
caenorhabditis_elegansWBGENE00003618
caenorhabditis_elegansWBGENE00003620
caenorhabditis_elegansWBGENE00003624
caenorhabditis_elegansWBGENE00003632
caenorhabditis_elegansWBGENE00003634
caenorhabditis_elegansWBGENE00003638
caenorhabditis_elegansWBGENE00003640
caenorhabditis_elegansWBGENE00003641
caenorhabditis_elegansWBGENE00003642
caenorhabditis_elegansWBGENE00003643
caenorhabditis_elegansWBGENE00003644
caenorhabditis_elegansWBGENE00003645
caenorhabditis_elegansWBGENE00003646
caenorhabditis_elegansWBGENE00003648
caenorhabditis_elegansWBGENE00003649
caenorhabditis_elegansWBGENE00003651
caenorhabditis_elegansWBGENE00003653
caenorhabditis_elegansWBGENE00003655
caenorhabditis_elegansWBGENE00003658
caenorhabditis_elegansWBGENE00003660
caenorhabditis_elegansWBGENE00003662
caenorhabditis_elegansnhr-73WBGENE00003663
caenorhabditis_elegansnhr-77WBGENE00003667
caenorhabditis_elegansWBGENE00003669
caenorhabditis_elegansnhr-81WBGENE00003671
caenorhabditis_elegansnhr-82WBGENE00003672
caenorhabditis_elegansWBGENE00003676
caenorhabditis_elegansWBGENE00003677
caenorhabditis_elegansWBGENE00003680
caenorhabditis_elegansWBGENE00003682
caenorhabditis_elegansWBGENE00003684
caenorhabditis_elegansWBGENE00003685
caenorhabditis_elegansWBGENE00003686
caenorhabditis_elegansWBGENE00003688
caenorhabditis_elegansWBGENE00003689
caenorhabditis_elegansWBGENE00003692
caenorhabditis_elegansWBGENE00003693
caenorhabditis_elegansWBGENE00003694
caenorhabditis_elegansWBGENE00003696
caenorhabditis_elegansWBGENE00003698
caenorhabditis_elegansWBGENE00003699
caenorhabditis_elegansWBGENE00003700
caenorhabditis_elegansWBGENE00003702
caenorhabditis_elegansWBGENE00003704
caenorhabditis_elegansWBGENE00003705
caenorhabditis_elegansWBGENE00003707
caenorhabditis_elegansWBGENE00003708
caenorhabditis_elegansWBGENE00003712
caenorhabditis_elegansWBGENE00003713
caenorhabditis_elegansWBGENE00003714
caenorhabditis_elegansWBGENE00003715
caenorhabditis_elegansWBGENE00003716
caenorhabditis_elegansWBGENE00003717
caenorhabditis_elegansWBGENE00003718
caenorhabditis_elegansWBGENE00003720
caenorhabditis_elegansWBGENE00003721
caenorhabditis_elegansWBGENE00003722
caenorhabditis_elegansWBGENE00003723
caenorhabditis_elegansWBGENE00003724
caenorhabditis_elegansWBGENE00003725
caenorhabditis_elegansWBGENE00003728
caenorhabditis_elegansWBGENE00006471
caenorhabditis_elegansunc-55WBGENE00006790
caenorhabditis_elegansWBGENE00007367
caenorhabditis_elegansWBGENE00008056
caenorhabditis_elegansnhr-165WBGENE00008158
caenorhabditis_elegansWBGENE00008208
caenorhabditis_elegansnhr-169WBGENE00008289
caenorhabditis_elegansWBGENE00008309
caenorhabditis_elegansnhr-174WBGENE00008474
caenorhabditis_elegansWBGENE00008619
caenorhabditis_elegansWBGENE00008630
caenorhabditis_elegansWBGENE00008778
caenorhabditis_elegansWBGENE00008830
caenorhabditis_elegansWBGENE00008884
caenorhabditis_elegansWBGENE00008901
caenorhabditis_elegansnhr-265WBGENE00009608
caenorhabditis_elegansWBGENE00010017
caenorhabditis_elegansWBGENE00010180
caenorhabditis_elegansWBGENE00010186
caenorhabditis_elegansWBGENE00010215
caenorhabditis_elegansWBGENE00010410
caenorhabditis_elegansWBGENE00010600
caenorhabditis_elegansWBGENE00010601
caenorhabditis_elegansWBGENE00010602
caenorhabditis_elegansWBGENE00010603
caenorhabditis_elegansWBGENE00010604
caenorhabditis_elegansWBGENE00011002
caenorhabditis_elegansWBGENE00011150
caenorhabditis_elegansWBGENE00011396
caenorhabditis_elegansWBGENE00011520
caenorhabditis_elegansWBGENE00011565
caenorhabditis_elegansWBGENE00011566
caenorhabditis_elegansWBGENE00011568
caenorhabditis_elegansnhr-217WBGENE00011651
caenorhabditis_elegansWBGENE00011750
caenorhabditis_elegansWBGENE00012050
caenorhabditis_elegansWBGENE00012056
caenorhabditis_elegansWBGENE00012446
caenorhabditis_elegansWBGENE00012449
caenorhabditis_elegansWBGENE00012596
caenorhabditis_elegansWBGENE00012703
caenorhabditis_elegansWBGENE00013067
caenorhabditis_elegansWBGENE00013483
caenorhabditis_elegansnhr-276WBGENE00013512
caenorhabditis_elegansWBGENE00013584
caenorhabditis_elegansWBGENE00013940
caenorhabditis_elegansWBGENE00014068
caenorhabditis_elegansnhr-245WBGENE00014189
caenorhabditis_elegansWBGENE00014193
caenorhabditis_elegansWBGENE00015497
caenorhabditis_elegansWBGENE00015758
caenorhabditis_elegansWBGENE00015897
caenorhabditis_elegansWBGENE00015900
caenorhabditis_elegansWBGENE00015901
caenorhabditis_elegansWBGENE00015902
caenorhabditis_elegansWBGENE00016091
caenorhabditis_elegansWBGENE00016233
caenorhabditis_elegansWBGENE00016364
caenorhabditis_elegansWBGENE00016365
caenorhabditis_elegansWBGENE00016366
caenorhabditis_elegansWBGENE00016367
caenorhabditis_elegansWBGENE00016368
caenorhabditis_elegansWBGENE00016517
caenorhabditis_elegansWBGENE00016772
caenorhabditis_elegansWBGENE00016926
caenorhabditis_elegansWBGENE00016927
caenorhabditis_elegansWBGENE00017503
caenorhabditis_elegansWBGENE00017512
caenorhabditis_elegansWBGENE00017961
caenorhabditis_elegansWBGENE00018189
caenorhabditis_elegansWBGENE00018265
caenorhabditis_elegansWBGENE00018266
caenorhabditis_elegansWBGENE00018404
caenorhabditis_elegansWBGENE00018412
caenorhabditis_elegansWBGENE00018415
caenorhabditis_elegansWBGENE00018539
caenorhabditis_elegansWBGENE00018541
caenorhabditis_elegansWBGENE00018542
caenorhabditis_elegansWBGENE00018544
caenorhabditis_elegansWBGENE00018545
caenorhabditis_elegansWBGENE00018622
caenorhabditis_elegansWBGENE00019115
caenorhabditis_elegansWBGENE00019116
caenorhabditis_elegansWBGENE00019741
caenorhabditis_elegansWBGENE00019742
caenorhabditis_elegansWBGENE00019743
caenorhabditis_elegansWBGENE00020015
caenorhabditis_elegansWBGENE00020062
caenorhabditis_elegansWBGENE00020152
caenorhabditis_elegansWBGENE00020153
caenorhabditis_elegansWBGENE00020385
caenorhabditis_elegansWBGENE00020460
caenorhabditis_elegansWBGENE00020555
caenorhabditis_elegansWBGENE00020750
caenorhabditis_elegansWBGENE00020849
caenorhabditis_elegansWBGENE00020850
caenorhabditis_elegansWBGENE00020851
caenorhabditis_elegansWBGENE00020852
caenorhabditis_elegansWBGENE00021163
caenorhabditis_elegansWBGENE00021522
caenorhabditis_elegansWBGENE00021610
caenorhabditis_elegansWBGENE00021611
caenorhabditis_elegansWBGENE00021617
caenorhabditis_elegansWBGENE00022097
caenorhabditis_elegansWBGENE00022637
caenorhabditis_elegansWBGENE00022639
caenorhabditis_elegansWBGENE00022640
caenorhabditis_elegansWBGENE00022726
caenorhabditis_elegansWBGENE00022756
caenorhabditis_elegansWBGENE00022805
caenorhabditis_elegansWBGENE00044353
caenorhabditis_elegansWBGENE00044699
caenorhabditis_elegansWBGENE00045515

Paralogs (18): NR1H4 (ENSG00000012504), NR1H3 (ENSG00000025434), RORA (ENSG00000069667), RARB (ENSG00000077092), VDR (ENSG00000111424), PPARD (ENSG00000112033), THRA (ENSG00000126351), NR1D1 (ENSG00000126368), NR1H2 (ENSG00000131408), RARA (ENSG00000131759), PPARG (ENSG00000132170), NR1I3 (ENSG00000143257), RORC (ENSG00000143365), NR1I2 (ENSG00000144852), RARG (ENSG00000172819), NR1D2 (ENSG00000174738), PPARA (ENSG00000186951), RORB (ENSG00000198963)

Protein

Protein identifiers

Thyroid hormone receptor beta — P10828 (reviewed: P10828)

Alternative names: Nuclear receptor subfamily 1 group A member 2, c-erbA-2, c-erbA-beta

All UniProt accessions (10): P10828, A0A024R2I8, A0A0C4DG57, A0A2R8YF24, C9JHC2, C9JJM3, C9JNQ4, C9JTN1, C9JZS5, J3KR21

UniProt curated annotations — full annotation on UniProt →

Function. Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.

Subunit / interactions. Binds DNA as a dimer; homodimer and heterodimer with RXRA. Interacts with the coactivators NCOA1/SRC1, NCOA2/GRIP1, NCOA7 and MED1/TRAP220 in a ligand-inducible manner. Interacts with the corepressor NCOR1 in absence of ligand. Interacts with C1D. Interacts with NR2F6; the interaction impairs the binding of the THRB homodimer and THRB:RXRB heterodimer to T3 response elements. Interacts with PRMT2 and THRSP. Interacts with TACC1; this interaction is decreased in the presence of thyroid hormone T3.

Subcellular location. Nucleus.

Disease relevance. Thyroid hormone resistance, generalized, autosomal dominant (GRTHD) [MIM:188570] An autosomal dominant disease characterized by high levels of circulating thyroid hormones (T3-T4), goiter, abnormal mental functions, increased susceptibility to infections, abnormal growth and bone maturation, tachycardia and deafness. Affected individuals may also have attention deficit-hyperactivity disorders (ADHD) and language difficulties. Patients have normal or slightly elevated thyroid stimulating hormone (TSH). The disease is caused by variants affecting the gene represented in this entry. Thyroid hormone resistance, generalized, autosomal recessive (GRTHR) [MIM:274300] An autosomal recessive disorder characterized by goiter, clinical euthyroidism, end-organ unresponsiveness to thyroid hormone, abnormal growth and bone maturation, and deafness. Patients also have high levels of circulating thyroid hormones, with elevated thyroid stimulating hormone. The disease is caused by variants affecting the gene represented in this entry. Selective pituitary thyroid hormone resistance (PRTH) [MIM:145650] Variant form of thyroid hormone resistance and is characterized by clinical hyperthyroidism, with elevated free thyroid hormones, but inappropriately normal serum TSH. Unlike GRTH, where the syndrome usually segregates with a dominant allele, the mode of inheritance in PRTH has not been established. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.

Similarity. Belongs to the nuclear hormone receptor family. NR1 subfamily.

Isoforms (2)

UniProt IDNamesCanonical?
P10828-1Beta-1yes
P10828-2Beta-2

RefSeq proteins (18): NP_000452, NP_001121648, NP_001121649, NP_001239563, NP_001341637, NP_001341638, NP_001341639, NP_001341640, NP_001341641, NP_001341642, NP_001341643, NP_001341644, NP_001361751, NP_001361752, NP_001361753, NP_001361754, NP_001361755, NP_001361756 (=MANE)

Domains & families (InterPro)

IDNameType
IPR000536Nucl_hrmn_rcpt_lig-bdDomain
IPR001628Znf_hrmn_rcptDomain
IPR001723Nuclear_hrmn_rcptFamily
IPR001728ThyrH_rcptFamily
IPR013088Znf_NHR/GATAHomologous_superfamily
IPR035500NHR-like_dom_sfHomologous_superfamily
IPR050234Nuclear_hormone_rcpt_NR1Family

Pfam: PF00104, PF00105

UniProt features (99 total): sequence variant 36, helix 20, binding site 14, turn 7, strand 7, mutagenesis site 5, zinc finger region 2, region of interest 2, sequence conflict 2, chain 1, domain 1, DNA-binding region 1, splice variant 1

Structure

Experimental structures (PDB)

34 structures, top 30 by resolution.

PDBMethodResolution (Å)
6KKBX-RAY DIFFRACTION1.7
2NLLX-RAY DIFFRACTION1.9
7WMHX-RAY DIFFRACTION1.97
1N46X-RAY DIFFRACTION2.2
2J4AX-RAY DIFFRACTION2.2
3D57X-RAY DIFFRACTION2.2
3GWSX-RAY DIFFRACTION2.2
2PINX-RAY DIFFRACTION2.3
7WLXX-RAY DIFFRACTION2.39
1NQ0X-RAY DIFFRACTION2.4
1NQ2X-RAY DIFFRACTION2.4
1XZXX-RAY DIFFRACTION2.5
3JZCX-RAY DIFFRACTION2.5
3IMYX-RAY DIFFRACTION2.55
7WMOX-RAY DIFFRACTION2.56
7WMNX-RAY DIFFRACTION2.57
6KKEX-RAY DIFFRACTION2.58
9IX5X-RAY DIFFRACTION2.65
6KNWX-RAY DIFFRACTION2.67
7WMLX-RAY DIFFRACTION2.67
9J0KX-RAY DIFFRACTION2.7
1NAXX-RAY DIFFRACTION2.7
6KNUX-RAY DIFFRACTION2.7
1Q4XX-RAY DIFFRACTION2.8
6KNVX-RAY DIFFRACTION2.8
7WMJX-RAY DIFFRACTION2.81
8RQNX-RAY DIFFRACTION2.88
1NQ1X-RAY DIFFRACTION2.9
7WMGX-RAY DIFFRACTION2.93
1R6GX-RAY DIFFRACTION3

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P10828-F180.240.69

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (14): 127; 145; 151; 161; 164; 282; 282; 331; 331; 435; 435; 107 …

Mutagenesis-validated functional residues (5):

PositionPhenotype
207–208modestly inhibits homodimer formation on a minimal response element (in vitro).
207–208inhibits homodimer formation on a minimal response element (in vitro).
243impairs hormone binding and ligand-dependent conformational changes.
331no effect on thyroid hormone binding.
355stabilizes homodimer.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

IDPathway
R-HSA-383280Nuclear Receptor transcription pathway
R-HSA-4090294SUMOylation of intracellular receptors
R-HSA-212436Generic Transcription Pathway
R-HSA-2990846SUMOylation
R-HSA-3108232SUMO E3 ligases SUMOylate target proteins
R-HSA-392499Metabolism of proteins
R-HSA-597592Post-translational protein modification
R-HSA-73857RNA Polymerase II Transcription
R-HSA-74160Gene expression (Transcription)

MSigDB gene sets: 338 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, TAATAAT_MIR126, GOBP_LUNG_EPITHELIUM_DEVELOPMENT, GGTGTGT_MIR329, GOBP_BEHAVIOR, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_LUNG_CELL_DIFFERENTIATION, AAGCCAT_MIR135A_MIR135B, CACCAGC_MIR138, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, CHANG_IMMORTALIZED_BY_HPV31_DN, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS

GO Biological Process (21): negative regulation of transcription by RNA polymerase II (GO:0000122), thyroid hormone receptor signaling pathway (GO:0002154), positive regulation of thyroid hormone receptor signaling pathway (GO:0002157), DNA-templated transcription (GO:0006351), sensory perception of sound (GO:0007605), negative regulation of female receptivity (GO:0007621), regulation of heart contraction (GO:0008016), female courtship behavior (GO:0008050), cell differentiation (GO:0030154), mRNA transcription by RNA polymerase II (GO:0042789), positive regulation of transcription by RNA polymerase II (GO:0045944), retinal cone cell development (GO:0046549), retinoic acid receptor signaling pathway (GO:0048384), type I pneumocyte differentiation (GO:0060509), cellular response to thyroid hormone stimulus (GO:0097067), retinal cone cell apoptotic process (GO:0097474), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), animal organ morphogenesis (GO:0009887), intracellular receptor signaling pathway (GO:0030522), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (15): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), transcription coactivator binding (GO:0001223), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), nuclear receptor activity (GO:0004879), zinc ion binding (GO:0008270), enzyme binding (GO:0019899), chromatin DNA binding (GO:0031490), thyroid hormone binding (GO:0070324), sequence-specific double-stranded DNA binding (GO:1990837), chromatin binding (GO:0003682), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-7 pathways:

CategoryPathways
Generic Transcription Pathway1
SUMO E3 ligases SUMOylate target proteins1
RNA Polymerase II Transcription1
Post-translational protein modification1
SUMOylation1
Metabolism of proteins1
Gene expression (Transcription)1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
transcription by RNA polymerase II4
regulation of transcription by RNA polymerase II3
hormone-mediated signaling pathway2
nuclear receptor-mediated signaling pathway2
regulation of DNA-templated transcription2
RNA polymerase II transcription regulatory region sequence-specific DNA binding2
DNA binding2
binding2
cellular anatomical structure2
negative regulation of DNA-templated transcription1
thyroid hormone receptor signaling pathway1
regulation of thyroid hormone receptor signaling pathway1
positive regulation of intracellular signal transduction1
gene expression1
RNA biosynthetic process1
sensory perception of mechanical stimulus1
regulation of female receptivity1
heart contraction1
regulation of blood circulation1
courtship behavior1
female mating behavior1
cellular developmental process1
mRNA transcription1
positive regulation of DNA-templated transcription1
eye photoreceptor cell development1
retinal cone cell differentiation1
lung epithelial cell differentiation1
cellular response to hormone stimulus1
response to thyroid hormone1
neuron apoptotic process1
retinal cell apoptotic process1
DNA-templated transcription1
regulation of gene expression1
regulation of RNA biosynthetic process1
anatomical structure morphogenesis1
animal organ development1
intracellular signal transduction1
cis-regulatory region sequence-specific DNA binding1
chromatin1
DNA-binding transcription factor activity1

Protein interactions and networks

STRING

1878 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
THRBTXNRD2Q9NNW7959
THRBJMJD1CQ15652800
THRBDIO2Q92813774
THRBTRHP20396745
THRBNCOA1Q15788741
THRBHMGN3Q15651726
THRBSLC16A2P36021680
THRBNCOR1O75376669
THRBRXRGP48443665
THRBCOPS2P61201655
THRBDIO3P55073645
THRBTSHBP01222639
THRBTRIP13Q15645626
THRBDIO1P49895598
THRBTRIP4Q15650592
THRBSERPINA7P05543592

IntAct

42 interactions, top by confidence:

ABTypeScore
THRBACTBpsi-mi:“MI:0914”(association)0.530
THRBNcor1psi-mi:“MI:0915”(physical association)0.510
THRBPIK3R1psi-mi:“MI:0407”(direct interaction)0.440
RXRATHRBpsi-mi:“MI:0407”(direct interaction)0.440
THRBEIF5Bpsi-mi:“MI:0915”(physical association)0.400
THRBPRMT2psi-mi:“MI:0915”(physical association)0.400
THRBpsi-mi:“MI:0915”(physical association)0.370
THRBpsi-mi:“MI:0915”(physical association)0.370
CCL1THRBpsi-mi:“MI:0915”(physical association)0.370
CCL22THRBpsi-mi:“MI:0915”(physical association)0.370
IFNL1THRBpsi-mi:“MI:0915”(physical association)0.370

BioGRID (124): THRB (Reconstituted Complex), THRB (Biochemical Activity), NCOA1 (Reconstituted Complex), THRB (Two-hybrid), PSMC5 (Two-hybrid), PSMC5 (Two-hybrid), NCOA1 (Reconstituted Complex), NCOR1 (Far Western), NCOR1 (Affinity Capture-Western), ACTA2 (Affinity Capture-MS), ACTBL2 (Affinity Capture-MS), ACTB (Affinity Capture-MS), PDLIM7 (Affinity Capture-MS), DNM3 (Affinity Capture-MS), NRAS (Affinity Capture-MS)

ESM2 similar proteins: A3RGC1, F1QJF4, F1QLY4, O13124, O35507, O42295, O42392, O42450, O54915, O57606, O75469, P04625, P10828, P11473, P13053, P15204, P18113, P18115, P18119, P35398, P37233, P37242, P45446, P48281, P49701, P51448, Q02777, Q13133, Q1L673, Q28037, Q28570, Q28571, Q5E9B6, Q60644, Q62685, Q62755, Q8R1B8, Q8SQ01, Q90382, Q90415

Diamond homologs: A0JNE3, A2T928, A4IIG7, G5ECR9, G5EDJ0, O02151, O45666, O76202, O97716, P10276, P10588, P10826, P10827, P10828, P11416, P12813, P13056, P13631, P16376, P18117, P18514, P18515, P18516, P18911, P20153, P22448, P22449, P22605, P22736, P22829, P28699, P31396, P33242, P33244, P41828, P41830, P43354, P45447, P49116, P49117

SIGNOR signaling

13 interactions.

AEffectBMechanism
MAPK1“down-regulates activity”THRBphosphorylation
MAPK3“down-regulates activity”THRBphosphorylation
D-thyroxine“up-regulates activity”THRB“chemical activation”
ASXL3“down-regulates activity”THRBbinding
3,3’,5’-triiodothyronine“up-regulates activity”THRBbinding
THRB“down-regulates activity”GATA2binding
Gbeta“down-regulates activity”THRBphosphorylation
ERK1/2“down-regulates activity”THRBphosphorylation
TRIP11up-regulatesTHRBbinding
RXRAup-regulatesTHRBbinding
RXRBup-regulatesTHRBbinding
L-thyroxine“up-regulates activity”THRB“chemical activation”
3,3’,5’-triiodothyronine“up-regulates activity”THRB“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

745 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic46
Likely pathogenic31
Uncertain significance387
Likely benign124
Benign83

Top pathogenic / likely-pathogenic (30)

Variant IDHGVSClassification
12535NM_001354712.2(THRB):c.1033G>C (p.Gly345Arg)Pathogenic
12536NM_001354712.2(THRB):c.1020G>C (p.Gln340His)Pathogenic
12537NM_001354712.2(THRB):c.1358C>A (p.Pro453His)Pathogenic
12538NG_009159.1:g.(?270821)(382671_?)delPathogenic
12539NM_001354712.2(THRB):c.1010_1012del (p.Thr337del)Pathogenic
12541NM_001354712.2(THRB):c.964G>C (p.Asp322His)Pathogenic
12542NM_001354712.2(THRB):c.949G>A (p.Ala317Thr)Pathogenic
12544NM_001354712.2(THRB):c.1034G>A (p.Gly345Asp)Pathogenic
12546NM_001354712.2(THRB):c.1040G>A (p.Gly347Glu)Pathogenic
12548NM_001354712.2(THRB):c.1349T>A (p.Leu450His)Pathogenic
12549NM_001354712.2(THRB):c.1341dup (p.Thr448fs)Pathogenic
12550NM_001354712.2(THRB):c.1357C>A (p.Pro453Thr)Pathogenic
12551NM_001354712.2(THRB):c.1327A>G (p.Lys443Glu)Pathogenic
12552NM_001354712.2(THRB):c.1033G>A (p.Gly345Ser)Pathogenic
12555NM_001354712.2(THRB):c.947G>A (p.Arg316His)Pathogenic
12556L325FPathogenic
12557NM_001354712.2(THRB):c.958C>T (p.Arg320Cys)Pathogenic
12558NM_001354712.2(THRB):c.1012C>T (p.Arg338Trp)Pathogenic
12559NM_001354712.2(THRB):c.1313G>A (p.Arg438His)Pathogenic
12560NM_001354712.2(THRB):c.1361_1362insC (p.Leu454fs)Pathogenic
12561NM_001354712.2(THRB):c.1376T>G (p.Phe459Cys)Pathogenic
12562NM_001354712.2(THRB):c.959G>T (p.Arg320Leu)Pathogenic
12563NM_001354712.2(THRB):c.1336T>C (p.Cys446Arg)Pathogenic
12565NM_001354712.2(THRB):c.1302C>A (p.Cys434Ter)Pathogenic
12567NM_001354712.2(THRB):c.727C>T (p.Arg243Trp)Pathogenic
12569NM_001354712.2(THRB):c.1009A>G (p.Thr337Ala)Pathogenic
12571NM_001354712.2(THRB):c.1305dup (p.Ala436fs)Pathogenic
1338370NM_001354712.2(THRB):c.830C>T (p.Thr277Ile)Pathogenic
1458636NC_000007.13:g.(?142457132)(142460438_?)dupPathogenic
2446361NM_001354712.2(THRB):c.283+1G>APathogenic

SpliceAI

4564 predictions. Top by Δscore:

VariantEffectΔscore
3:24127495:TCA:Tdonor_loss1.0000
3:24127496:CACCT:Cdonor_loss1.0000
3:24127497:ACC:Adonor_loss1.0000
3:24127548:CAGGT:Cacceptor_gain1.0000
3:24127552:T:TCacceptor_gain1.0000
3:24127758:C:CCacceptor_gain1.0000
3:24133459:CTGG:Cacceptor_gain1.0000
3:24133460:TGG:Tacceptor_gain1.0000
3:24133460:TGGCT:Tacceptor_loss1.0000
3:24133463:C:CCacceptor_gain1.0000
3:24143495:CCTTA:Cdonor_loss1.0000
3:24143496:CTTAC:Cdonor_loss1.0000
3:24143497:TTA:Tdonor_loss1.0000
3:24143498:TA:Tdonor_loss1.0000
3:24143499:A:ACdonor_gain1.0000
3:24143499:A:AGdonor_loss1.0000
3:24143500:C:CAdonor_loss1.0000
3:24143500:C:CCdonor_gain1.0000
3:24143521:T:TAdonor_gain1.0000
3:24143702:CACCA:Cacceptor_gain1.0000
3:24143703:ACCA:Aacceptor_gain1.0000
3:24143704:CCA:Cacceptor_gain1.0000
3:24143704:CCAC:Cacceptor_gain1.0000
3:24143705:CA:Cacceptor_gain1.0000
3:24143705:CAC:Cacceptor_gain1.0000
3:24143706:ACTG:Aacceptor_loss1.0000
3:24143707:C:CCacceptor_gain1.0000
3:24143707:CTGGG:Cacceptor_loss1.0000
3:24152489:CC:Cacceptor_gain1.0000
3:24152490:CC:Cacceptor_gain1.0000

AlphaMissense

3073 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
3:24122893:G:CF459L1.000
3:24122893:G:TF459L1.000
3:24122895:A:GF459L1.000
3:24122984:C:GR429P1.000
3:24122987:A:GL428P1.000
3:24123005:A:GL422P1.000
3:24123008:A:GL421P1.000
3:24123018:A:GW418R1.000
3:24123018:A:TW418R1.000
3:24123071:A:GL400P1.000
3:24123123:G:TR383S1.000
3:24127510:A:GL378P1.000
3:24127519:G:TA375D1.000
3:24127520:C:GA375P1.000
3:24127525:A:GL373P1.000
3:24127528:A:GL372P1.000
3:24127531:G:TA371D1.000
3:24127564:A:GL360P1.000
3:24127573:C:TG357D1.000
3:24127574:C:GG357R1.000
3:24127576:A:GL356P1.000
3:24127581:A:CF354L1.000
3:24127581:A:TF354L1.000
3:24127582:A:GF354S1.000
3:24127583:A:GF354L1.000
3:24127585:A:TI353N1.000
3:24127621:A:GL341P1.000
3:24127654:A:GL330S1.000
3:24127660:A:GL328S1.000
3:24127682:A:CY321D1.000

dbSNP variants (sampled 300 via entrez): RS1000000779 (3:24478598 G>A), RS1000004734 (3:24326096 T>A,C), RS1000005343 (3:24135240 G>T), RS1000010244 (3:24184800 G>A), RS1000038434 (3:24259763 A>G), RS1000042640 (3:24221313 G>C), RS1000046575 (3:24219358 G>C), RS1000047917 (3:24394234 A>G), RS1000048922 (3:24439789 C>T), RS1000057061 (3:24275938 T>A,C), RS1000077088 (3:24463216 C>T), RS1000098399 (3:24136850 G>A), RS1000100592 (3:24471754 T>A,C), RS1000103382 (3:24344882 T>C), RS1000105434 (3:24215606 A>G)

Disease associations

OMIM: gene MIM:190160 | disease phenotypes: MIM:167800, MIM:188570, MIM:274300, MIM:145650, MIM:148300, MIM:614044

GenCC curated gene-disease

DiseaseClassificationInheritance
thyroid hormone resistance, generalized, autosomal dominantStrongAutosomal dominant
resistance to thyroid hormone due to a mutation in thyroid hormone receptor betaSupportiveAutosomal recessive
thyroid hormone resistance, generalized, autosomal recessiveLimitedAutosomal recessive

Mondo (12): hereditary chronic pancreatitis (MONDO:0008185), thyroid hormone resistance, generalized, autosomal dominant (MONDO:0008569), thyroid hormone resistance, generalized, autosomal recessive (MONDO:0010131), generalized resistance to thyroid hormone (MONDO:0009043), thyroid hormone resistance syndrome (MONDO:0001328), hyperthyroidism (MONDO:0004425), selective pituitary resistance to thyroid hormone (MONDO:0007784), keratoconus (MONDO:0015486), trypsinogen deficiency (MONDO:0013543), neurodevelopmental disorder (MONDO:0700092), resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta (MONDO:0700478), (MONDO:0034217)

Orphanet (7): Autosomal dominant hereditary chronic pancreatitis (Orphanet:676), Syndrome of reduced sensitivity to thyroid hormone (Orphanet:596426), Resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta (Orphanet:566243), Generalized resistance to thyroid hormone (Orphanet:3221), Pituitary resistance to thyroid hormone (Orphanet:165994), OBSOLETE: Keratoconus (Orphanet:156071), NON RARE IN EUROPE: Isolated keratoconus (Orphanet:2335)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPOTerm
HP:0000006Autosomal dominant inheritance
HP:0000007Autosomal recessive inheritance
HP:0000365Hearing impairment
HP:0000403Recurrent otitis media
HP:0000407Sensorineural hearing impairment
HP:0000520Proptosis
HP:0000739Anxiety
HP:0000750Delayed speech and language development
HP:0000752Hyperactivity
HP:0000819Diabetes mellitus
HP:0000836Hyperthyroidism
HP:0000853Goiter
HP:0001328Specific learning disability
HP:0001518Small for gestational age
HP:0001530Mild postnatal growth retardation
HP:0001649Tachycardia
HP:0001962Palpitations
HP:0002750Delayed skeletal maturation
HP:0002925Elevated circulating thyroid-stimulating hormone concentration
HP:0002930Impaired sensitivity to thyroid hormone
HP:0003621Juvenile onset
HP:0004324Increased body weight
HP:0005978Type II diabetes mellitus
HP:0007018Attention deficit hyperactivity disorder
HP:0008223Compensated hypothyroidism
HP:0010655Epiphyseal stippling
HP:0011463Childhood onset
HP:0011788Increased circulating free T3
HP:0012378Fatigue
HP:0012758Neurodevelopmental delay

GWAS associations

80 associations (top):

StudyTraitp-value
GCST000585_10Mean corpuscular volume3.000000e-08
GCST000587_10Mean corpuscular hemoglobin4.000000e-10
GCST001765_40Red blood cell traits6.000000e-16
GCST002187_4Systolic blood pressure in sickle cell anemia7.000000e-06
GCST002260_4Narcolepsy4.000000e-08
GCST002337_117Amyotrophic lateral sclerosis (sporadic)6.000000e-07
GCST002481_10Acne (severe)1.000000e-06
GCST002541_46Menarche (age at onset)2.000000e-12
GCST003341_4antipsychotic drug dosage in schizophrenia or schizoaffective disorder2.000000e-06
GCST003449_2Erythrocyte cadmium concentration7.000000e-06
GCST003997_13Myopia2.000000e-12
GCST004004_13Mean corpuscular volume1.000000e-08
GCST004006_5Mean corpuscular hemoglobin9.000000e-11
GCST004601_40Red blood cell count2.000000e-30
GCST004602_102Mean corpuscular volume6.000000e-75
GCST004605_64Mean corpuscular hemoglobin concentration1.000000e-09
GCST004611_23High light scatter reticulocyte count4.000000e-12
GCST004612_57High light scatter reticulocyte percentage of red cells6.000000e-18
GCST004619_212Reticulocyte fraction of red cells1.000000e-17
GCST004621_56Red cell distribution width4.000000e-14
GCST004622_158Reticulocyte count4.000000e-09
GCST004625_63Monocyte count3.000000e-10
GCST004630_115Mean corpuscular hemoglobin7.000000e-77
GCST005212_16Asthma9.000000e-06
GCST005993_68Mean corpuscular hemoglobin5.000000e-23
GCST005996_56Red blood cell count2.000000e-11
GCST006011_99Mean corpuscular volume8.000000e-31
GCST006061_56Atrial fibrillation4.000000e-08
GCST006088_37Familial squamous cell lung carcinoma4.000000e-07
GCST006088_45Familial squamous cell lung carcinoma4.000000e-06

EFO canonical traits (31, from GWAS)

EFO IDTrait name
EFO:0004509hemoglobin measurement
EFO:0004527mean corpuscular hemoglobin
EFO:0006335systolic blood pressure
EFO:0004703age at menarche
EFO:0007792antipsychotic drug use measurement
EFO:0004305erythrocyte count
EFO:0004528mean corpuscular hemoglobin concentration
EFO:0007986reticulocyte count
EFO:0009188Red cell distribution width
EFO:0005091monocyte count
EFO:0006953family history of lung cancer
EFO:0004847age at onset
EFO:0004612high density lipoprotein cholesterol measurement
EFO:0004747protein measurement
EFO:0005188CCL11 measurement
EFO:0005939parental genotype effect measurement
EFO:0007964gestational serum measurement
EFO:0009270heel bone mineral density
EFO:0004337intelligence
EFO:0008328chronotype measurement
EFO:0005405response to antihypertensive drug
EFO:0006527smoking status measurement
EFO:0004530triglyceride measurement
EFO:0004462PR interval
EFO:0007874gut microbiome measurement
EFO:0004327electrocardiography
EFO:0004980appendicular lean mass
EFO:0004587lymphocyte count
EFO:0007989monocyte percentage of leukocytes
EFO:0010701mean reticulocyte volume

MeSH disease descriptors (8)

DescriptorNameTree numbers
D006980HyperthyroidismC19.874.397
D007640KeratoconusC11.204.627
D065886Neurodevelopmental DisordersF03.625
D018382Thyroid Hormone Resistance SyndromeC19.874.410.500
C537262Hereditary pancreatitis (supp.)
C567934Thyroid Hormone Resistance, Generalized, Autosomal Dominant (supp.)
C567936Thyroid Hormone Resistance, Generalized, Autosomal Recessive (supp.)
C564154Thyroid Hormone Resistance, Selective Pituitary (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1947 (SINGLE PROTEIN), CHEMBL2111462 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

117 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 603,105 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL1046AMINOCAPROIC ACID495,343
CHEMBL1091250INDIGOTINDISULFONATE4340
CHEMBL110691CHLORMADINONE ACETATE49,747
CHEMBL1113AMOXAPINE420,128
CHEMBL1117IDARUBICIN4136,065
CHEMBL1200478DYCLONINE HYDROCHLORIDE42,469
CHEMBL1200660ISOSORBIDE435,343
CHEMBL1200710CLOMIPRAMINE HYDROCHLORIDE45,044
CHEMBL1200714CHLORMEZANONE42,121
CHEMBL1200787PHENOXYBENZAMINE HYDROCHLORIDE42,483
CHEMBL1200938METHYSERGIDE MALEATE44
CHEMBL1201119LIOTHYRONINE SODIUM43,058
CHEMBL1201217DYCLONINE47,785
CHEMBL1208422ROSE BENGAL FREE ACID4476
CHEMBL12856INAMRINONE49,690
CHEMBL1329455MOLSIDOMINE417,116
CHEMBL137METRONIDAZOLE4141,757
CHEMBL1398126AMILORIDE HYDROCHLORIDE42,101
CHEMBL1455ALTRETAMINE4102,000
CHEMBL1472989BISOPROLOL FUMARATE410,035
CHEMBL1487ATORVASTATIN4
CHEMBL1517OXYTETRACYCLINE4
CHEMBL1544LIOTHYRONINE4
CHEMBL1562610MECLOFENAMATE SODIUM4
CHEMBL1563DAUNORUBICIN HYDROCHLORIDE4
CHEMBL1569AMANTADINE HYDROCHLORIDE4
CHEMBL1589ACETOHEXAMIDE4
CHEMBL1593558DEBRISOQUIN SULFATE4
CHEMBL1611PHENYTOIN SODIUM4
CHEMBL1624LEVOTHYROXINE4

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs892940THRB0.000

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: nhr — 1A. Thyroid hormone receptors

Most potent curated ligand interactions (10 total), top 10:

LigandActionAffinityParameter
tiratricolAgonist10.7pKd
sobetiromeAgonist10.17pKd
triiodothyronineAgonist10.1pKd
KB-141Agonist8.96pIC50
VK2809Agonist8.53pKi
T4Agonist8.52pIC50
compound 16g [PMID: 35507418]Agonist7.68pEC50
rT3Agonist7.34pKd
NH-3Antagonist7.03pKd
resmetiromAgonist6.68pEC50

Binding affinities (BindingDB)

232 measured of 274 human assays (276 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
5-[2,6-Dichloro-4-(3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-phenoxy]-N-(6,6-dimethyl-bicyclo[3.1.1]hept-2-yl)-2-hydroxy-benzamideKI0.04 nM
3-{3,5-dibromo-4-[4-hydroxy-3-(propan-2-yl)phenoxy]phenyl}propanoic acidIC500.1 nM
(2R)-2-amino-3-{4-[4-hydroxy-3-(propan-2-yl)phenoxy]-3,5-diiodophenyl}propanoic acidIC500.14 nM
3-{3,5-dichloro-4-[4-hydroxy-3-(propan-2-yl)phenoxy]phenyl}propanoic acidEC500.3 nM
2-{3,5-dichloro-4-[4-hydroxy-3-spiro[8-azabicyclo[3.2.1]octane-3,2’-(dihydro[1,3]dioxolane)]-8-ylsulfonylphenoxy]phenyl}-2,3,4,5-tetrahydro-1,2,4-triazine-3,5-dioneKI0.31 nM
dibromo phenylacetic acid, 11aEC500.38 nM
2-[3,5-dibromo-4-(cyclohexylmethoxy)phenyl]acetic acidEC500.42 nM
3,5-dimethyl-4-(4’-hydroxy-3’-isopropylbenzyl)phenoxyacetic acidKD0.44 nM
JMC496635 Compound 9EC500.53 nM
3-[3,5-dibromo-4-(hexyloxy)phenyl]propanoic acidEC500.6 nM
2-[3,5-dibromo-4-(hexyloxy)phenyl]acetic acidEC500.7 nM
2-[3,5-dibromo-4-(2-ethylbutoxy)phenyl]acetic acidEC500.82 nM
CHEMBL237529IC501.02 nM
(2S)-2-(1-{3,5-dibromo-4-[4-hydroxy-3-(propan-2-yl)phenoxy]phenyl}acetamido)-3-methylbutanoic acidEC501.4 nM
(2R)-2-(1-{3,5-dibromo-4-[4-hydroxy-3-(propan-2-yl)phenoxy]phenyl}acetamido)-2-phenylacetic acidEC501.5 nM
2-{3,5-dichloro-4-[4-hydroxy-3-(propan-2-yl)phenoxy]phenyl}acetic acidEC501.7 nM
(2R)-2-(1-{3,5-dibromo-4-[4-hydroxy-3-(propan-2-yl)phenoxy]phenyl}acetamido)-3-methylbutanoic acidEC502.3 nM
(2S)-2-(1-{3,5-dibromo-4-[4-hydroxy-3-(propan-2-yl)phenoxy]phenyl}acetamido)propanoic acidEC507.2 nM
(2S)-2-(1-{3,5-dibromo-4-[4-hydroxy-3-(propan-2-yl)phenoxy]phenyl}acetamido)-2-phenylacetic acidIC507.5 nM
3,5-dibromo-4-[4-hydroxy-3-(propan-2-yl)phenoxy]benzoic acidIC509.7 nM
2-Amino-3-[4-(4-hydroxy-3-isopropyl-phenoxy)-3,5-dimethyl-phenyl]-propionic acidKD9.7 nM
CO23EC5011 nM
2-{3,5-dichloro-4-[3-(3-ethylphenyl)-4-hydroxyphenoxy]phenyl}acetic acidIC5013 nM
(2R)-2-(1-{3,5-dibromo-4-[4-hydroxy-3-(propan-2-yl)phenoxy]phenyl}acetamido)propanoic acidEC5015 nM
2-(3,5-dibromo-4-{4-hydroxy-3-[(2-phenylethyl)carbamoyl]phenoxy}phenyl)acetic acidIC5015 nM
(2S)-2-(1-{3,5-dibromo-4-[3-fluoro-4-hydroxy-5-(propan-2-yl)phenoxy]phenyl}acetamido)-3-methylbutanoic acidEC5017 nM
2-(3,5-dichloro-4-{4-hydroxy-3-[2-(trifluoromethyl)phenyl]phenoxy}phenyl)acetic acidIC5018 nM
2-(3,5-dibromo-4-{3-[(2,2-diphenylethyl)carbamoyl]-4-hydroxyphenoxy}phenyl)acetic acidIC5018 nM
3-(3,5-dibromo-4-{[3-(ethylamino)phenyl]methoxy}phenyl)propanoic acidEC5023 nM
2-(1-{3,5-dibromo-4-[4-hydroxy-3-(propan-2-yl)phenoxy]phenyl}acetamido)acetic acidIC5026 nM
2-(3,5-dichloro-4-{3-[3-(difluoromethoxy)phenyl]-4-hydroxyphenoxy}phenyl)acetic acidIC5030 nM
3-{3,5-dibromo-4-[4-hydroxy-3-(propan-2-yl)-5-[(E)-2-(pyridin-4-yl)ethenyl]phenoxy]phenyl}propanoic acidEC5032 nM
2-(3,5-dichloro-4-{4-hydroxy-3-[3-(trifluoromethyl)phenyl]phenoxy}phenyl)acetic acidIC5040 nM
N-[3,5-dichloro-4-[(6-oxo-5-propanoyl-1H-pyridazin-3-yl)oxy]phenyl]-5-oxo-1,2,4-oxadiazolidine-3-carboxamideEC5043.3 nMUS-10800767: Thyroid hormone receptor beta agonist compounds
2-(3,5-dibromo-4-{4-hydroxy-3-[3-(trifluoromethyl)phenoxy]phenoxy}phenyl)acetic acidIC5050 nM
2-[4-(3-{8-azaspiro[bicyclo[3.2.1]octane-3,2’-oxolane]-8-ylsulfonyl}-4-hydroxyphenoxy)-3,5-dichlorophenyl]-2,3,4,5-tetrahydro-1,2,4-triazine-3,5-dioneEC5062 nM
(2S)-2-(1-{3,5-dibromo-4-[3-chloro-4-hydroxy-5-(propan-2-yl)phenoxy]phenyl}acetamido)-3-methylbutanoic acidEC5065 nM
(2S)-2-(1-{3,5-dibromo-4-[4-hydroxy-3-(propan-2-yl)phenoxy]phenyl}acetamido)-4-hydroxybutanoic acidEC5066 nM
USRE46024, 16EC5066 nMUS-RE46024
2-{4-[3-(benzylcarbamoyl)-4-hydroxyphenoxy]-3,5-dibromophenyl}acetic acidIC5084 nM
N-(3,5-dichloro-4-((5-(1-hydroxypropyl)-6-oxo-1,6-dihydropyridazin-3-yl)oxy)phenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazole-3-carboxamideEC5086.4 nMUS-10800767: Thyroid hormone receptor beta agonist compounds
N-[4-[(5-acetyl-6-oxo-1H-pyridazin-3-yl)oxy]-3,5-dichlorophenyl]-5-oxo-1,2,4-oxadiazolidine-3-carboxamideEC5091.3 nMUS-10800767: Thyroid hormone receptor beta agonist compounds
USRE46024, 13EC5092 nMUS-RE46024
JMC496635 Compound 5IC5093 nM
2-[3,5-dibromo-4-(4-hydroxy-3-{[2-(3-methoxyphenyl)ethyl]carbamoyl}phenoxy)phenyl]acetic acidIC5093 nM
2-[3,5-dibromo-4-(4-hydroxy-3-{[2-(2-methoxyphenyl)ethyl]carbamoyl}phenoxy)phenyl]acetic acidIC5096 nM
3-{3,5-dibromo-4-[(3-bromophenyl)methoxy]phenyl}propanoic acidIC5099 nM
2-(3,5-dichloro-4-{4-hydroxy-3-[3-(trifluoromethoxy)phenyl]phenoxy}phenyl)acetic acidIC50100 nM
USRE46024, 9EC50115 nMUS-RE46024
USRE46024, 7EC50117 nMUS-RE46024

ChEMBL bioactivities

2838 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
10.72IC500.019nMTHYROPROPIC ACID
10.72IC500.01905nMTHYROPROPIC ACID
10.70Ki0.02nMCHEMBL124126
10.60IC500.025nMCHEMBL289343
10.60IC500.02512nMCHEMBL289343
10.52Ki0.03nMCHEMBL125381
10.40Ki0.04nMCHEMBL124205
10.40Ki0.04nMCHEMBL3397339
10.39IC500.04074nMTIRATRICOL
10.32IC500.048nMTIRATRICOL
10.32IC500.04786nMTIRATRICOL
10.25IC500.05623nMCHEMBL124126
10.22Ki0.06nMCHEMBL124205
10.22Ki0.06nMCHEMBL203777
10.22IC500.06nMCHEMBL203777
10.22EC500.06nMCHEMBL392666
10.22IC500.06026nMCHEMBL203777
10.15Ki0.07nMCHEMBL413699
10.15Ki0.07nMCHEMBL3397337
10.10Ki0.08nMLIOTHYRONINE
10.10EC500.08nMCHEMBL248111
10.09Kd0.081nMLIOTHYRONINE
10.06Kd0.087nMLIOTHYRONINE
10.05Ki0.09nMCHEMBL3397341
10.05IC500.09nMCHEMBL4114879
10.02IC500.095nMCHEMBL39174
10.02IC500.0955nMCHEMBL39174
10.00Ki0.1nMCHEMBL126693
10.00Kd0.1nMSOBETIROME
10.00Kd0.1nMLIOTHYRONINE
9.99IC500.103nMRATHYRONINE
9.96IC500.11nMCHEMBL41314
9.96IC500.1096nMCHEMBL235173
9.96IC500.1096nMCHEMBL41314
9.95IC500.1122nMCHEMBL124205
9.89Ki0.13nMCHEMBL125728
9.85Ki0.14nMCHEMBL3397338
9.85Kd0.14nMLIOTHYRONINE
9.82IC500.15nMCHEMBL418432
9.82IC500.1514nMCHEMBL418432
9.80Ki0.16nMCHEMBL338602
9.78IC500.166nMCHEMBL124205
9.74Ki0.18nMCHEMBL3397340
9.71IC500.195nMCHEMBL413699
9.70EC500.2nMCHEMBL39174
9.70Kd0.2nMSOBETIROME
9.70EC500.2nMCHEMBL182339
9.70IC500.1995nMCHEMBL251456
9.66Kd0.22nMCHEMBL322361
9.64Ki0.23nMCHEMBL123920

PubChem BioAssay actives

945 with measured affinity, of 1600 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
3-[3,5-dibromo-4-(4-hydroxy-3-propan-2-ylphenoxy)phenyl]propanoic acid1797784: TRbeta-Binding Assay from Article 10.1021/jm021080f: “Thyroid receptor ligands. 1. Agonist ligands selective for the thyroid receptor beta1.”ic50<0.0001uM
2-[7-chloro-1-[(4-hydroxy-3-propan-2-ylphenyl)methyl]-2-methylindol-5-yl]oxyacetic acid1192347: Displacement of [125I]-L-3,5,3’-triiodothyronine from human TRbeta expressed in human Hela cell lysate measured after overnight incubation by competition binding assayski<0.0001uM
5-[2,6-dichloro-4-(3,5-dioxo-1,2,4-triazin-2-yl)phenoxy]-N-(6,6-dimethyl-2-bicyclo[3.1.1]heptanyl)-2-hydroxybenzamide213186: Inhibitory activity against [125I]T3 binding to human TRbeta1 receptorki<0.0001uM
2-[3,5-dichloro-4-(4-hydroxy-3-piperidin-1-ylsulfonylphenoxy)phenyl]-1,2,4-triazine-3,5-dione213186: Inhibitory activity against [125I]T3 binding to human TRbeta1 receptorki<0.0001uM
2-[4-(4-hydroxy-3-propan-2-ylphenoxy)-3,5-dimethylphenyl]-1,2,4-triazine-3,5-dione213186: Inhibitory activity against [125I]T3 binding to human TRbeta1 receptorki<0.0001uM
2-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]acetic acid1797784: TRbeta-Binding Assay from Article 10.1021/jm021080f: “Thyroid receptor ligands. 1. Agonist ligands selective for the thyroid receptor beta1.”ic50<0.0001uM
3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoic acid1797784: TRbeta-Binding Assay from Article 10.1021/jm021080f: “Thyroid receptor ligands. 1. Agonist ligands selective for the thyroid receptor beta1.”ic50<0.0001uM
5-[[4-(4-hydroxy-3-propan-2-ylphenoxy)-3,5-dimethylphenyl]methyl]-1,3-thiazolidine-2,4-dione307878: Agonist activity at THR in HepG2 cells by whole cell assayec500.0001uM
N-cyclohexyl-5-[2,6-dichloro-4-(3,5-dioxo-1,2,4-triazin-2-yl)phenoxy]-2-hydroxybenzamide213186: Inhibitory activity against [125I]T3 binding to human TRbeta1 receptorki0.0001uM
3-[3,5-dichloro-4-(4-hydroxy-3-propan-2-ylphenoxy)phenyl]propanoic acid1797785: TRbeta-Binding Assay and Thyroid Response Element (TRAFbeta1) Reporter Assay. from Article 10.1021/jm021080f: “Thyroid receptor ligands. 1. Agonist ligands selective for the thyroid receptor beta1.”ic500.0001uM
2-[7-chloro-1-[(4-hydroxy-3-propan-2-ylphenyl)methyl]indol-5-yl]oxyacetic acid1192347: Displacement of [125I]-L-3,5,3’-triiodothyronine from human TRbeta expressed in human Hela cell lysate measured after overnight incubation by competition binding assayski0.0001uM
2-[1-[(4-hydroxy-3-propan-2-ylphenyl)methyl]-2,7-dimethylindol-5-yl]oxyacetic acid1192347: Displacement of [125I]-L-3,5,3’-triiodothyronine from human TRbeta expressed in human Hela cell lysate measured after overnight incubation by competition binding assayski0.0001uM
2-[7-chloro-1-[(4-hydroxy-3-propan-2-ylphenyl)methyl]-3-methylindol-5-yl]oxyacetic acid1192347: Displacement of [125I]-L-3,5,3’-triiodothyronine from human TRbeta expressed in human Hela cell lysate measured after overnight incubation by competition binding assayski0.0001uM
[2-[[(1S)-1-(3-chlorophenyl)-2-fluoroethyl]amino]-7-methoxy-1,3-benzoxazol-5-yl]-[(5R)-2-(2-hydroxyethyl)-2,5-dimethylmorpholin-4-yl]methanone1678253: Inhibition of purified human plasma thrombin using Boc-Asp(OBzl)-Pro-Arg-AMC substrate incubated for 30 mins by fluorescence based assayic500.0001uM
5-[2,6-dichloro-4-(3,5-dioxo-1,2,4-triazin-2-yl)phenoxy]-2-hydroxy-N-phenylbenzenesulfonamide213186: Inhibitory activity against [125I]T3 binding to human TRbeta1 receptorki0.0001uM
2-[3-chloro-4-(4-hydroxy-3-piperidin-1-ylsulfonylphenoxy)-5-methylphenyl]-1,2,4-triazine-3,5-dione213186: Inhibitory activity against [125I]T3 binding to human TRbeta1 receptorki0.0001uM
(2R)-2-amino-3-[4-(4-hydroxy-3-propan-2-ylphenoxy)-3,5-diiodophenyl]propanoic acid1797784: TRbeta-Binding Assay from Article 10.1021/jm021080f: “Thyroid receptor ligands. 1. Agonist ligands selective for the thyroid receptor beta1.”ic500.0001uM
6-[[3-(4-hydroxy-3-propan-2-ylphenoxy)-2,4-dimethylphenyl]methyl]-1,3-thiazinane-2,4-dione307878: Agonist activity at THR in HepG2 cells by whole cell assayec500.0001uM
Liothyronine1799413: Competition Binding Assay from Article 10.1021/cb600311v: “Design and characterization of a thyroid hormone receptor alpha (TRalpha)-specific agonist.”kd0.0001uM
2-amino-3-[4-(4-hydroxy-3-propan-2-ylphenoxy)-3,5-diiodophenyl]propanoic acid299948: Inhibition of human thyroid hormone receptor beta 1ic500.0001uM
2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoic acid1417059: Agonist activity at GAL4 DNA-binding domain fused TRbeta receptor (unknown origin) ligand binding domain expressed in UAS-bla HEK 293T cells assessed as beta-lactamase transcriptional activation by FRET-based GeneBLAzer assayic500.0001uM
2-[4-[(4-hydroxy-3-propan-2-ylphenyl)methyl]-3,5-dimethylphenoxy]acetic acid1799448: TR Receptor Ligand Binding Assay from Article 10.1016/s1074-5521(98)90168-5: “A high-affinity subtype-selective agonist ligand for the thyroid hormone receptor.”kd0.0001uM
2-[3,5-dibromo-4-(4-hydroxy-3-propan-2-ylphenoxy)phenyl]acetic acid1797785: TRbeta-Binding Assay and Thyroid Response Element (TRAFbeta1) Reporter Assay. from Article 10.1021/jm021080f: “Thyroid receptor ligands. 1. Agonist ligands selective for the thyroid receptor beta1.”ic500.0001uM
4,6-dichloro-5-(4-hydroxy-3-propan-2-ylphenoxy)-1H-indole-2-carboxylic acid261713: Inhibition of human TR-beta-1 by radioligand binding assayic500.0001uM
3-[4-[(4-hydroxy-3-propan-2-ylphenyl)methyl]-3,5-dimethylphenyl]propanoic acid213184: Binding affinity of compound was determined against thyroid hormone receptor beta 1kd0.0002uM
2-[1-[(4-hydroxy-3-propan-2-ylphenyl)methyl]-3,7-dimethylindol-5-yl]oxyacetic acid1192347: Displacement of [125I]-L-3,5,3’-triiodothyronine from human TRbeta expressed in human Hela cell lysate measured after overnight incubation by competition binding assayski0.0002uM
2-[3,5-dichloro-4-[3-(3-ethylphenyl)-4-hydroxyphenoxy]phenyl]acetic acid1797796: TRbeta-Binding Assay from Article 10.1016/j.bmcl.2005.11.002: “Thyroid receptor ligands. Part 4: 4’-amido bioisosteric ligands selective for the thyroid hormone receptor beta.”ic500.0002uM
2-[4-[3-(2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-hydroxyphenoxy]-3,5-dichlorophenyl]-1,2,4-triazine-3,5-dione213186: Inhibitory activity against [125I]T3 binding to human TRbeta1 receptorki0.0002uM
2-[3,5-dichloro-4-(4-hydroxy-3-indol-1-ylsulfonylphenoxy)phenyl]-1,2,4-triazine-3,5-dione213186: Inhibitory activity against [125I]T3 binding to human TRbeta1 receptorki0.0002uM
(2S)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3-iodo-5-methylphenyl]propanoic acid240275: Agonist activity towards thyroid hormone receptor expressed in human HepG2 cellsec500.0002uM
2-[3,5-dichloro-4-(4-hydroxy-3-propan-2-ylphenoxy)phenyl]acetic acid345696: Displacement of [125I]3,5,3’-triiodo-L-thyronine His-tagged human recombinant TRbeta1 by scintillation proximity assayki0.0002uM
2-[4-(5-bromo-6-hydroxynaphthalen-1-yl)-3,5-dichloroanilino]-2-oxoacetic acid254845: Inhibitory concentration against cloned human thyroid hormone receptor beta 1ic500.0003uM
3-[4-(5-bromo-6-hydroxynaphthalen-1-yl)-3,5-dichloroanilino]-3-oxopropanoic acid254845: Inhibitory concentration against cloned human thyroid hormone receptor beta 1ic500.0003uM
4,6-dibromo-5-(4-hydroxy-3-propan-2-ylphenoxy)-1H-indole-2-carboxylic acid261713: Inhibition of human TR-beta-1 by radioligand binding assayic500.0003uM
2-[1-[(4-hydroxy-3-propan-2-ylphenyl)methyl]-7-methylindol-5-yl]oxyacetic acid1192347: Displacement of [125I]-L-3,5,3’-triiodothyronine from human TRbeta expressed in human Hela cell lysate measured after overnight incubation by competition binding assayski0.0003uM
2-[1-[(3-tert-butyl-4-hydroxyphenyl)methyl]-3-methylindol-5-yl]oxyacetic acid1192347: Displacement of [125I]-L-3,5,3’-triiodothyronine from human TRbeta expressed in human Hela cell lysate measured after overnight incubation by competition binding assayski0.0003uM
[2-[[(1S)-1-(3-chlorophenyl)-2-fluoroethyl]amino]-7-methoxy-1,3-benzoxazol-5-yl]-[5-(3-hydroxycyclobutyl)-2-methylmorpholin-4-yl]methanone1678253: Inhibition of purified human plasma thrombin using Boc-Asp(OBzl)-Pro-Arg-AMC substrate incubated for 30 mins by fluorescence based assayic500.0003uM
[2-[(3-chlorophenyl)methylamino]-7-methoxy-1,3-benzoxazol-5-yl]-[4-hydroxy-2-(2-hydroxyethyl)-5-methylpiperidin-1-yl]methanone1678253: Inhibition of purified human plasma thrombin using Boc-Asp(OBzl)-Pro-Arg-AMC substrate incubated for 30 mins by fluorescence based assayic500.0003uM
2-[6-(4-hydroxy-3-propan-2-ylphenoxy)-5,7-dimethyl-1-benzofuran-3-yl]acetic acid307878: Agonist activity at THR in HepG2 cells by whole cell assayec500.0003uM
(2S)-2-[[2-[3,5-dibromo-4-(4-hydroxy-3-propan-2-ylphenoxy)phenyl]acetyl]amino]-3-methylbutanoic acid1797787: TRbeta-Binding Assay and Thyroid Response Element (TRAFbeta1) Reporter Assay. from Article 10.1016/j.bmcl.2007.05.049: “Thyroid receptor ligands. Part 8: Thyromimetics derived from N-acylated-alpha-amino acid derivatives displaying modulated pharmacological selectivity compared with KB-141.”ic500.0003uM
2-[3,5-dichloro-4-(4-hydroxy-3-spiro[8-azabicyclo[3.2.1]octane-3,2’-oxolane]-8-ylsulfonylphenoxy)phenyl]-1,2,4-triazine-3,5-dione213186: Inhibitory activity against [125I]T3 binding to human TRbeta1 receptorki0.0003uM
2-[3,5-dichloro-4-(4-hydroxy-3-spiro[1,3-dioxolane-2,3’-8-azabicyclo[3.2.1]octane]-8’-ylsulfonylphenoxy)phenyl]-1,2,4-triazine-3,5-dione213186: Inhibitory activity against [125I]T3 binding to human TRbeta1 receptorki0.0003uM
3-[3,5-dichloro-4-(6-methoxy-5-propan-2-ylnaphthalen-1-yl)anilino]-3-oxopropanoic acid254845: Inhibitory concentration against cloned human thyroid hormone receptor beta 1ic500.0003uM
(2R)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoic acid213175: Concentration required to inhibit 50% of I-T3 binding to hTR1 (Thyroid hormone receptor beta) was determinedic500.0003uM
2-[4-(4-hydroxy-3-propan-2-ylphenoxy)-3,5-dimethylphenoxy]acetic acid213185: Binding affinity of compound was determined against thyroid hormone receptor beta 1kd0.0004uM
2-[4-[3-[(4-fluorophenyl)methyl]-4-hydroxyphenoxy]-3,5-dimethylphenyl]-1,2,4-triazine-3,5-dione454513: Binding affinity to thyroid receptor betaki0.0004uM
3-[3,5-dibromo-4-(4-hydroxy-3-propan-2-ylphenoxy)anilino]-3-oxopropanoic acid664440: Displacement of [125I]T3 from human recombinant thyroid harmone receptor beta after 16 to 48 hrs by gamma-ray detectionki0.0004uM
2-[1-[(4-hydroxy-3-propan-2-ylphenyl)methyl]-3-methylindol-5-yl]oxyacetic acid1192347: Displacement of [125I]-L-3,5,3’-triiodothyronine from human TRbeta expressed in human Hela cell lysate measured after overnight incubation by competition binding assayski0.0004uM
[2-[[(1R)-1-(3-chlorophenyl)ethyl]amino]-7-methoxy-1,3-benzoxazol-5-yl]-[(2S,5R)-5-ethyl-2-(2-hydroxyethyl)-2-methylmorpholin-4-yl]methanone1678253: Inhibition of purified human plasma thrombin using Boc-Asp(OBzl)-Pro-Arg-AMC substrate incubated for 30 mins by fluorescence based assayic500.0004uM
N-cyclobutyl-5-[2,6-dichloro-4-(3,5-dioxo-1,2,4-triazin-2-yl)phenoxy]-2-hydroxybenzenesulfonamide213186: Inhibitory activity against [125I]T3 binding to human TRbeta1 receptorki0.0004uM

CTD chemical–gene interactions

193 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Triiodothyroninedecreases reaction, increases expression, increases activity, affects cotreatment, affects binding (+3 more)31
bisphenol Aaffects methylation, decreases reaction, affects binding, affects cotreatment, increases methylation (+4 more)10
tetrabromobisphenol Adecreases reaction, increases activity, affects binding8
Thyroxineincreases reaction, increases activity, increases expression, affects binding, decreases reaction (+1 more)8
Valproic Acidincreases expression, affects expression, decreases methylation, affects cotreatment8
Benzo(a)pyrenedecreases methylation, affects methylation, decreases expression5
tetraiodothyroacetic aciddecreases reaction, increases reaction, affects binding, increases activity4
tetrachlorodianaffects binding, decreases reaction, increases activity4
3,3’,5-triiodothyroacetic acidincreases activity, increases reaction, affects binding3
trichostatin Aaffects cotreatment, increases expression3
2,2’,4,4’-tetrabromodiphenyl etherincreases expression, affects binding, affects reaction, decreases reaction3
bisphenol Sincreases activity, increases reaction, affects binding, decreases reaction3
Amiodaroneincreases expression, affects binding, decreases reaction, increases activity3
Diethylhexyl Phthalatedecreases activity, increases activity, decreases expression, affects expression, affects binding3
Tretinoinaffects binding, decreases reaction, increases activity, increases expression3
deoxynivalenolaffects cotreatment, decreases activity, decreases reaction, increases activity2
2,5,2’,5’-tetrachlorobiphenylincreases expression, decreases expression, increases abundance2
methoxyacetic acidincreases activity, increases reaction2
procymidoneaffects binding, increases activity2
acetochloraffects binding, decreases activity2
2,4,6-triiodophenolaffects binding, increases activity, decreases reaction2
entinostataffects cotreatment, increases expression2
belinostatincreases expression, affects cotreatment2
pyrachlostrobinincreases activity, affects binding2
bisphenol AFaffects activity, affects binding, decreases reaction2
Panobinostataffects cotreatment, increases expression2
Air Pollutantsincreases oxidation, affects cotreatment, decreases expression, increases abundance2
Doxorubicinaffects binding, decreases activity, decreases expression2
Phenylmercuric Acetateaffects cotreatment, increases expression2
Carbarylaffects binding, decreases activity2

ChEMBL screening assays

169 unique, capped per target: 129 binding, 40 functional

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1034533BindingInhibition of SRC2 binding to human TRbeta receptor ligand binding domain expressed in Escherichia coli BL21 (DE3) by fluorescence polarization assayImprovement of pharmacological properties of irreversible thyroid receptor coactivator binding inhibitors. — J Med Chem
CHEMBL1613771FunctionalPUBCHEM_BIOASSAY: Total Fluorescence Confirmation Counterscreen for Inhibitors of the Interaction of Thyroid Hormone Receptor and Steroid Receptor Coregulator 2, Fluorescein Fluoroprobe. (Class of assay: confirmatory) [Related pubchem assayPubChem BioAssay data set

Cellosaurus cell lines

33 cell lines: 15 induced pluripotent stem cell, 11 cancer cell line, 3 embryonic stem cell, 3 transformed cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_A7M6SEES3-1V human THRB, clone1Embryonic stem cellMale
CVCL_A7M7SEES3-1V human THRB, clone2Embryonic stem cellMale
CVCL_A7M8SEES3-1V human THRB, clone3Embryonic stem cellMale
CVCL_C0U8HT22-BLRP-hTRb/pSV40-BirAV5Transformed cell line
CVCL_C3GCHep-G2-THRBCancer cell lineMale
CVCL_C3GDHep-G2-THRB MUT p.K113N;T329PCancer cell lineMale
CVCL_C3GEHep-G2-THRB MUT p.K155E;K411ECancer cell lineMale
CVCL_C9SDHPS1673Induced pluripotent stem cellFemale
CVCL_C9SEHPS1674Induced pluripotent stem cellFemale
CVCL_C9SFHPS1675Induced pluripotent stem cellFemale

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

TrialPhaseStatusTitle
NCT00946296PHASE4COMPLETEDImpact of SSKI Pre-Treatment on Blood Loss in Thyroidectomy for Graves Disease
NCT03379181PHASE4COMPLETEDThermogenesis in Hyperthyroidism and Effect of Anti-Adrenergic Therapy
NCT03393728PHASE4COMPLETEDHeart Rate Variability and Hyperthyroidism: Evaluation of the Short-term Effects of Propanolol
NCT05512715PHASE4COMPLETEDLIthium as Bridging thErapy Prior to Radioactiveiodine in hyperThYroidism
NCT01485211PHASE4COMPLETEDCorneal Thickness Changes During Corneal Collagen Cross-linking With Ultraviolet-A Irradiation and Riboflavin
NCT02119039PHASE4COMPLETEDEffect of CACICOL20 on Corneal Epithelial Healing After Cross-linking in Patients With Keratoconus
NCT03245853PHASE4COMPLETEDEpi-On Corneal Crosslinking for Keratoconus
NCT03429569PHASE4UNKNOWNCross-Linking ACcéléré Iontophorèse Confocal kératocONE
NCT04427956PHASE4COMPLETEDCorneal Crosslinking Treatment Study
NCT07474870PHASE4NOT_YET_RECRUITINGOutcomes of CTAK Surgery
NCT03303053PHASE3UNKNOWNEfficacy and Safety of Cholestyramine and Prednisolone as Adjunctive Therapy in Treatment of Overt Hyperthyroidism
NCT04856488PHASE3RECRUITINGPreoperative Lugol’s Solution in Graves’ Disease and Toxic Nodular Goiter
NCT05118542PHASE3COMPLETEDEffect of Hyperthyroidism and Its Treatment in Graves’ Disease to Early Marker of Atherosclerosis
NCT00371202PHASE3UNKNOWNComparison of Penetrating Keratoplasty and Deep Lamellar Keratoplasty With the Big Bubble Technique for Keratoconus
NCT00647699PHASE3COMPLETEDCorneal Collagen Cross-linking for Progressive Keratoconus
NCT00815256PHASE3UNKNOWNSafety and Effectiveness of Collagen Cross Linking in Progressive Mild and Moderate Keratoconus
NCT00887900PHASE3COMPLETEDDeep Anterior Lamellar Keratoplasty (DALK)
NCT01112072PHASE3UNKNOWNCorneal Collagen Crosslinking and Intacs for Keratoconus and Ectasia
NCT01152541PHASE3UNKNOWNCorneal Collagen Crosslinking for Progressive Keratoconus and Ectasia Using Riboflavin/Dextran and Hypotonic Riboflavin
NCT01190306PHASE3TERMINATEDSafety Study of the VEGA UV-A System to Treat Keratoconus
NCT01344187PHASE3COMPLETEDSafety and Efficacy Study of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT01459679PHASE3TERMINATEDSafety & Efficacy of Corneal Collagen Cross-Linking in Eyes With Keratoconus or Corneal Ectasia After Refractive Surgery
NCT01464268PHASE3UNKNOWNTransepithelial Corneal Collagen Crosslinking for Keratoconus and Corneal Ectasia
NCT01604135PHASE3ACTIVE_NOT_RECRUITINGCollagen Crosslinking for Keratoconus - a Randomized Controlled Clinical Trial
NCT01643226PHASE3COMPLETEDSafety and Efficacy Study of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT01672814PHASE3COMPLETEDMicrowave Treatment and Corneal Collagen Crosslinking for Keratoconus
NCT01682993PHASE3TERMINATEDCorneal Cross Linking and Topography Guided Excimer Laser Treatment
NCT01972854PHASE3TERMINATEDSafety and Efficacy of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT02613780PHASE3UNKNOWNRefractive Treatment of Early Keratoconus
NCT02638376PHASE3UNKNOWNEvaluating the Safety and Efficacy of the KXL System for Corneal Collagen Cross-Linking in Eyes Having Keratoconus
NCT03080077PHASE3UNKNOWNSafety and Effectiveness of Corneal Crosslinking (CXL): Keratoconus and Post-Refractive Ectasia
NCT03187912PHASE3COMPLETEDAccelerated Corneal Cross-linking With Different Riboflavin Solutions
NCT03442751PHASE3COMPLETEDStudy to Evaluate the Safety and Efficacy of Epi-on Corneal Cross-linking in Eyes With Progressive Keratoconus
NCT03858036PHASE3UNKNOWNCorneal Collagen Cross-Linking (CXL) Performed With Epi-ON Versus Epi-OFF in Eyes With Keratoconus and Other Corneal Ectatic Disorders
NCT04897503PHASE3UNKNOWNCorneal Collagen Crosslinking for Keratoconus and Ectasia Using Riboflavin/Dextran or Riboflavin/Methylcellulose
NCT04905108PHASE3UNKNOWNTransepithelial (Epi-on) Corneal Collagen Crosslinking to Treat Keratoconus and Corneal Ectasia
NCT05027295PHASE3UNKNOWNAccelerated Corneal Collagen Crosslinking for Keratoconus and Ectasia Using Pulse or Continuous UV-A Light
NCT06100939PHASE3ACTIVE_NOT_RECRUITINGEpithelium-On Corneal Cross-linking in Subjects 8 to 45 Years of Age With Keratoconus
NCT06100952PHASE3ACTIVE_NOT_RECRUITINGEpithelium-On Corneal Cross-linking in Subjects 8 to 45 Years of Age with Keratoconus
NCT06450470PHASE3RECRUITINGUse of a Freeze-dried Amniotic Membrane Post Crosslinking in Subjects With Progressive Keratoconus

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 81

This page pulls from 81 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot