TSHR

Summary

TSHR (thyroid stimulating hormone receptor, HGNC:12373) is a protein-coding gene on chromosome 14q24-q31, encoding Thyrotropin receptor (P16473). Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin.

The protein encoded by this gene is a membrane protein and a major controller of thyroid cell metabolism. The encoded protein is a receptor for thyrothropin and thyrostimulin, and its activity is mediated by adenylate cyclase. Defects in this gene are a cause of several types of hyperthyroidism. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 7253 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypothyroidism due to TSH receptor mutations (Definitive, GenCC) — +4 more curated relationships
• GWAS associations: 18
• Clinical variants (ClinVar): 498 total — 38 pathogenic, 29 likely-pathogenic
• Phenotypes (HPO): 79
• Druggable target: yes — 354 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types
• MANE Select transcript: NM_000369

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12373
Approved symbol	TSHR
Name	thyroid stimulating hormone receptor
Location	14q24-q31
Locus type	gene with protein product
Status	Approved
Aliases	LGR3
Ensembl gene	ENSG00000165409
Ensembl biotype	protein_coding
OMIM	603372
Entrez	7253

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000298171, ENST00000342443, ENST00000541158, ENST00000553763, ENST00000554263, ENST00000554435, ENST00000555326, ENST00000556031, ENST00000557096, ENST00000636454, ENST00000637447, ENST00000642209

RefSeq mRNA: 3 — MANE Select: NM_000369 NM_000369, NM_001018036, NM_001142626

CCDS: CCDS32131, CCDS55935, CCDS9872

Canonical transcript exons

ENST00000298171 — 10 exons

Exon	Start	End
ENSE00001092839	81068254	81068328
ENSE00001092852	81092531	81092608
ENSE00001135568	81108375	81108452
ENSE00001135605	81087954	81088028
ENSE00001311920	81096639	81096707
ENSE00001315993	81091069	81091143
ENSE00001318726	81139679	81139867
ENSE00003472977	81062148	81062219
ENSE00003906649	80955621	80955850
ENSE00003908527	81142940	81146306

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 99.28.

FANTOM5 (CAGE): breadth broad, TPM avg 1.8006 / max 710.5782, expressed in 215 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140862	1.0948	112
140854	0.2305	84
140855	0.1705	48
140864	0.1208	18
140860	0.0601	14
140863	0.0352	15
207320	0.0245	10
140853	0.0200	10
140858	0.0188	6
140856	0.0093	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	99.28	gold quality
left lobe of thyroid gland	UBERON:0001120	99.28	gold quality
thyroid gland	UBERON:0002046	99.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.80	gold quality
thymus	UBERON:0002370	76.24	gold quality
bone marrow cell	CL:0002092	72.59	gold quality
buccal mucosa cell	CL:0002336	68.93	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	67.97	gold quality
ventricular zone	UBERON:0003053	67.97	gold quality
lymph node	UBERON:0000029	66.67	gold quality
right lobe of liver	UBERON:0001114	65.75	gold quality
spleen	UBERON:0002106	64.55	gold quality
ganglionic eminence	UBERON:0004023	64.54	gold quality
tonsil	UBERON:0002372	63.36	gold quality
sural nerve	UBERON:0015488	62.60	gold quality
vermiform appendix	UBERON:0001154	61.75	gold quality
liver	UBERON:0002107	61.26	gold quality
right adrenal gland cortex	UBERON:0035827	61.04	gold quality
hindlimb stylopod muscle	UBERON:0004252	60.92	gold quality
left adrenal gland	UBERON:0001234	60.60	gold quality
right adrenal gland	UBERON:0001233	60.47	gold quality
left adrenal gland cortex	UBERON:0035825	60.11	gold quality
caudate nucleus	UBERON:0001873	60.08	gold quality
putamen	UBERON:0001874	59.65	gold quality
adrenal gland	UBERON:0002369	59.23	gold quality
right uterine tube	UBERON:0001302	59.01	gold quality
adrenal cortex	UBERON:0001235	58.90	gold quality
rectum	UBERON:0001052	58.89	gold quality
colonic epithelium	UBERON:0000397	58.78	silver quality
endometrium epithelium	UBERON:0004811	58.49	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.47
E-GEOD-99795	no	12.01

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AIRE, CREM, FOXE1, GABPA, NKX2-1, NR4A1, PAX8, PPARG, RUNX2, THRB, TTF1

miRNA regulators (miRDB)

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

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836

Literature-anchored findings (GeneRIF, showing 40)

• Interleukin-6 stimulates thyrotropin receptor expression in human orbital preadipocyte fibroblasts from patients with Graves’ ophthalmopathy (PMID:11716039)
• A familial case of congenital hypothyroidism caused by a homozygous mutation of the thyrotropin receptor gene. (PMID:11716047)
• These results indicated that Graves Disease patients have an expanded Th2 population responding to TSH-R and the dominance of the humoral immune system in such patients. (PMID:11814624)
• recent advances in the structure-function relationships of thyroid-stimulating hormone (TSH) and its receptor (PMID:11917095)
• structure-phenotype relationships of mutations at position 183 in determining specificity toward TSH and hCG (PMID:11923469)
• activation of the cAMP pathway by the TSH receptor involves switching of the ectodomain from a tethered inverse agonist to a true agonist. (PMID:11923470)
• TSH receptor is involved in cell-matrix interactions which modulate its functional properties (PMID:11981027)
• gain-of-function mutations of the TSH receptor, or Gs-alpha gene, may activate the cAMP pathway. (PMID:12039695)
• Thyrostimulin, a heterodimer of two new human glycoprotein hormone subunits, activates the thyroid-stimulating hormone receptor (thyrostimulin) (PMID:12045258)
• Germline mutations of TSH receptor gene as cause of nonautoimmune subclinical hypothyroidism. (PMID:12050212)
• At least three full-length TSHR mRNAs with distinct poly(A) sites and five alternatively spliced forms of TSHR mRNAs are expressed from the single hTSHR gene. (PMID:12081236)
• Data support the concept of a constitutively active TSHR dimer or monomer that is naturally inhibited by the formation of higher order complexes. (PMID:12223484)
• Similarities and differences in the phenotype of members of an Italian family with hereditary non-autoimmune hyperthyroidism associated with an activating TSH receptor germline mutation. (PMID:12240901)
• In a cell line transfected with hTSHR, TSH activates STAT3 phoshorylation via the TSHR and cAMP- and PKC-dependent pathways. (PMID:12242030)
• Knockout mice and transfected human TSHR were used to study the role of the TSHR signaling in thyroid development & differentiation. The major role of the TSH/TSHR pathway is controlling genes involved in iodide metabolism. (PMID:12432093)
• The TSHR mutants A593N and A593N/D727E constitutively activated the cAMP cascade, whereas the D727E mutant did not differ from the wild-type TSHR. (PMID:12589819)
• that the TSHR gene is not a major gene for Graves disease (PMID:12593721)
• Aberrant methylation of human TSHR is a likely molecular pathway responsible for the silencing of this gene in thyroid cancers. (PMID:12727856)
• The role of external factors (i.e. iodine deficiency) with respect to individual factors (i.e. genetic mutations) in the pathogenesis of toxic nodular goiter. (PMID:12762632)
• expression ex vivo indicates adipogenesis in progress in vivo and is associated with the autoimmune/inflammatory process in graves disease and thyroid eye disease but is not restricted to the orbit or influenced by thyroid hormone status (PMID:12790806)
• Genetic abnormality underlying the pathogenesis of a substantial subset of thyroid tumours has yet to be identified. Unresolved question of absence of genotype-phenotype correlation. Review. (PMID:12804102)
• shed A subunits induce or amplify the immune response leading to hyperthyroidism and provide new insight into the etiology of Graves disease (PMID:12813025)
• biological potency of TSHR mutants in thyroid cells does not correlate with their cAMP levels in transfected COS cells, highlighting the importance of cellular context and level of expression when assessing biological effects of oncogenic mutations (PMID:12933676)
• TSH does not alter the subunit structure of its cognate receptor (PMID:12960016)
• results indicate that the TSH receptor internalization might in part be responsible for TSH receptor desensitization on TSH binding (PMID:14576174)
• Results describe for the first time the successful affinity purification of human thyroid-stimulating hormone receptor autoantibodies. (PMID:14654252)
• natively conformed TSHR had a restricted set of epitopes recognized by TSHR-mAbs and the binding site for stimulating TSHR-Abs was highly conserved. (PMID:15297445)
• monomer formation from multimeric TSHRs might be an important requirement for TSHR cleavage and TSHR ectodomain shedding. (PMID:15319351)
• a novel epitope in the thyroid-stimulating hormone receptor ectodomain acts as intramolecular signaling interface (PMID:15345720)
• ICL(intracellular loop)2 interacts with ICL3 in close vicinity to F525 and T607, suggesting a conformational cooperation between ICL2 and ICL3 during Gq activation by TSHR. (PMID:15498884)
• we have demonstrated the presence of the autoantigenic target of Graves’ disease, the thyroid-stimulating hormone receptor, in normal human extraocular muscle (PMID:15779008)
• orbital fibroblasts subjected to adipocytic differentiation increase TSHr expression that responds specifically to bTSH and TSAb stimulation, and to TBAb inhibition. (PMID:15879364)
• Thyrotropin receptors form homo- and heterodimers, via interactions involving primarily their heptahelical domains. The large hormone-binding ectodomains were dispensable for dimerization but modulated protomer interaction. The dimers show allosterism. (PMID:15889138)
• TSHR is the first replicated GD-specific locus meriting further fine mapping and functional analysis to identify the aetiological variants. (PMID:16106256)
• Evidence that a hydrophobic cluster, comprising residues 652-656 of extracellular loop 3, strongly influences intramolecular signal transduction and G protein activation of the TSHR. (PMID:16150909)
• A novel homozygous missense mutation in codon 593 (A593 V) of the TSHR gene was identified in the affected individuals as the underlying molecular defect (PMID:16320156)
• TSH receptor is a member of the class A of G protein-coupled receptors, which have a higher affinity to beta-arrestin 2 than beta-arrestin 1 and do not colocalize with beta-arrestins in endosomes. (PMID:16513835)
• the R450H mutation is a commonly observed TSH receptor mutation in patients with TSH resistance in Japan (PMID:16756469)
• the combination of an activating mutation of the TSH receptor (T620I) and a mutation of the Ki-RAS (G12C) genes may play an important role in both the hyperfunction of follicular thyroid carcinoma and the carcinogenetic process (PMID:16756473)
• an activating mutation in transmembrane helix 6 of the thyrotropin receptor plays a key role in the development of hereditary hyperthyroidism (PMID:16756474)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tshr	ENSDARG00000037195
mus_musculus	Tshr	ENSMUSG00000020963
rattus_norvegicus	Tshr	ENSRNOG00000003972
drosophila_melanogaster	Lgr1	FBGN0016650
caenorhabditis_elegans		WBGENE00008239

Paralogs (2): LHCGR (ENSG00000138039), FSHR (ENSG00000170820)

Protein

Protein identifiers

Thyrotropin receptor — P16473 (reviewed: P16473)

Alternative names: Thyroid-stimulating hormone receptor

All UniProt accessions (5): A0A1B0GUJ5, A0A2R8Y709, P16473, G3V381, Q0VAP8

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin. Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin. TSHR is coupled to G(s) proteins and mediates the activation of adenylate cyclase. This leads to the generation of cyclic adenosine monophosphate (cAMP), which in turn activates protein kinase A (PKA). PKA subsequently phosphorylates downstream targets involved in thyroid hormone biosynthesis and secretion, including thyroid peroxidase (TPO) and the sodium/iodide symporter (NIS). Additionally, plays a central role in controlling thyroid cell metabolism.

Subunit / interactions. Interacts with heterodimer GPHA2:GPHB5; this interaction stimulates cAMP production. Interacts (via the PDZ-binding motif) with SCRIB; regulates TSHR trafficking and function. Interacts with GNAS.

Subcellular location. Cell membrane. Basolateral cell membrane.

Tissue specificity. Expressed in thyroide cells (at protein level). Expressed in the thyroid.

Post-translational modifications. Glycosylated. Sulfated. Sulfation on Tyr-385 plays a role in thyrotropin receptor binding and activation.

Disease relevance. Defects in TSHR are found in patients affected by hyperthyroidism with different etiologies. Somatic, constitutively activating TSHR mutations and/or constitutively activating G(s)alpha mutations have been identified in toxic thyroid nodules (TTNs) that are the predominant cause of hyperthyroidism in iodine deficient areas. These mutations lead to TSH independent activation of the cAMP cascade resulting in thyroid growth and hormone production. TSHR mutations are found in autonomously functioning thyroid nodules (AFTN), toxic multinodular goiter (TMNG) and hyperfunctioning thyroid adenomas (HTA). TMNG encompasses a spectrum of different clinical entities, ranging from a single hyperfunctioning nodule within an enlarged thyroid, to multiple hyperfunctioning areas scattered throughout the gland. HTA are discrete encapsulated neoplasms characterized by TSH-independent autonomous growth, hypersecretion of thyroid hormones, and TSH suppression. Defects in TSHR are also a cause of thyroid neoplasms (papillary and follicular cancers). Autoantibodies against TSHR are directly responsible for the pathogenesis and hyperthyroidism of Graves disease. Antibody interaction with TSHR results in an uncontrolled receptor stimulation. Hypothyroidism, congenital, non-goitrous, 1 (CHNG1) [MIM:275200] A non-autoimmune condition characterized by resistance to thyroid-stimulating hormone (TSH) leading to increased levels of plasma TSH and low levels of thyroid hormone. It presents variable severity depending on the completeness of the defect. Most patients are euthyroid and asymptomatic, with a normal sized thyroid gland. Only a subset of patients develop hypothyroidism and present a hypoplastic thyroid gland. The disease is caused by variants affecting the gene represented in this entry. Familial gestational hyperthyroidism (HTFG) [MIM:603373] A condition characterized by abnormally high levels of serum thyroid hormones occurring during early pregnancy. The disease is caused by variants affecting the gene represented in this entry. Hyperthyroidism, non-autoimmune (HTNA) [MIM:609152] A condition characterized by abnormally high levels of serum thyroid hormones, thyroid hyperplasia, goiter and lack of anti-thyroid antibodies. Typical features of Graves disease such as exophthalmia, myxedema, antibodies anti-TSH receptor and lymphocytic infiltration of the thyroid gland are absent. The disease is caused by variants affecting the gene represented in this entry.

Polymorphism. Polymorphism at position 727 could be associated with Graves disease.

Similarity. Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P16473-1	Long	yes
P16473-2	Short
P16473-3	3

RefSeq proteins (3): NP_000360, NP_001018046, NP_001136098 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR002131	Gphrmn_rcpt_fam	Family
IPR002274	TSH_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR026906	LRR_5	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily

Pfam: PF00001, PF13306

UniProt features (183 total): sequence variant 70, strand 23, helix 16, sequence conflict 15, turn 10, topological domain 8, transmembrane region 7, mutagenesis site 7, repeat 7, glycosylation site 6, disulfide bond 6, splice variant 4, signal peptide 1, chain 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
2XWT	X-RAY DIFFRACTION	1.9
7UTZ	ELECTRON MICROSCOPY	2.4
3G04	X-RAY DIFFRACTION	2.55
7XW6	ELECTRON MICROSCOPY	2.78
7T9I	ELECTRON MICROSCOPY	2.9
7T9N	ELECTRON MICROSCOPY	2.9
7XW5	ELECTRON MICROSCOPY	2.96
7T9M	ELECTRON MICROSCOPY	3.1
7XW7	ELECTRON MICROSCOPY	5.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16473-F1	73.67	0.39

Antibody-complex structures (SAbDab): 9 — 2XWT, 3G04, 7T9I, 7T9M, 7T9N, 7UTZ, 7XW5, 7XW6, 7XW7

Functional residue map

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

Post-translational modifications (1): 385

Disulfide bonds (6): 24–31, 29–41, 283–398, 284–408, 301–390, 494–569

Glycosylation sites (6): 77, 99, 113, 177, 198, 302

Mutagenesis-validated functional residues (7):

Position	Phenotype
283	abolishes cell surface expression.
385–387	inhibits intracellular camp accumulation.
385–387	abolishes sulfation. inhibits intracellular camp accumulation.
385	reduces binding with thyrotropin. inhibits intracellular camp accumulation.
385	reduces sulfation. reduces binding with thyrotropin. inhibits intracellular camp accumulation.
387	no change in intracellular camp accumulation.
387	reduces sulfation. no change in intracellular camp accumulation.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-375281	Hormone ligand-binding receptors
R-HSA-418555	G alpha (s) signalling events

MSigDB gene sets: 272 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOCC_CELL_SURFACE, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_CELL_SIGNALING, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, MARTINEZ_RB1_TARGETS_UP, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, MODULE_205, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, LOPES_METHYLATED_IN_COLON_CANCER_DN, REACTOME_HORMONE_LIGAND_BINDING_RECEPTORS, KEGG_AUTOIMMUNE_THYROID_DISEASE, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (13): cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), cell-cell signaling (GO:0007267), positive regulation of cell population proliferation (GO:0008284), hormone-mediated signaling pathway (GO:0009755), thyroid-stimulating hormone signaling pathway (GO:0038194), positive regulation of cold-induced thermogenesis (GO:0120162), cellular response to glycoprotein (GO:1904588), cellular response to thyrotropin-releasing hormone (GO:1905229), signal transduction (GO:0007165), response to hormone (GO:0009725)

GO Molecular Function (7): G protein-coupled receptor activity (GO:0004930), thyroid-stimulating hormone receptor activity (GO:0004996), G protein-coupled peptide receptor activity (GO:0008528), signaling receptor activity (GO:0038023), protein-containing complex binding (GO:0044877), protein binding (GO:0005515), protein-hormone receptor activity (GO:0016500)

GO Cellular Component (5): plasma membrane (GO:0005886), cell surface (GO:0009986), basolateral plasma membrane (GO:0016323), signaling receptor complex (GO:0043235), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	3
G protein-coupled receptor activity	3
G protein-coupled receptor signaling pathway	3
cell communication	2
signaling	2
binding	2
cellular anatomical structure	2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cellular response to hormone stimulus	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
cellular response to oxygen-containing compound	1
response to glycoprotein	1
cellular response to peptide hormone stimulus	1
response to thyrotropin-releasing hormone	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
response to endogenous stimulus	1
response to chemical	1
transmembrane signaling receptor activity	1
protein-hormone receptor activity	1
thyroid-stimulating hormone signaling pathway	1
peptide receptor activity	1
molecular transducer activity	1
signaling receptor activity	1
membrane	1
cell periphery	1
basal plasma membrane	1
plasma membrane region	1
protein-containing complex	1

Protein interactions and networks

STRING

1522 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSHR	TG	P01266	972
TSHR	TPO	P07202	969
TSHR	NKX2-1	P43699	954
TSHR	IGF1R	P08069	950
TSHR	SLC5A5	Q92911	947
TSHR	PAX8	Q06710	918
TSHR	FOXE1	O00358	889
TSHR	TSHB	P01222	886
TSHR	GNAS	Q5JWF2	810
TSHR	SLC26A4	O43511	790
TSHR	CTLA4	P16410	781
TSHR	DIO2	Q92813	781
TSHR	TRH	P20396	768
TSHR	TRHR	P34981	732
TSHR	IYD	Q6PHW0	708

IntAct

44 interactions, top by confidence:

A	B	Type	Score
TSHR	SCRIB	psi-mi:“MI:0915”(physical association)	0.580
SCRIB	TSHR	psi-mi:“MI:0915”(physical association)	0.580
TSHR	SMAD4	psi-mi:“MI:0915”(physical association)	0.550
SMAD4	TSHR	psi-mi:“MI:2364”(proximity)	0.550
SMAD4	TSHR	psi-mi:“MI:0915”(physical association)	0.550
TSHR	ADORA1	psi-mi:“MI:0915”(physical association)	0.510
TSHR	MID1IP1	psi-mi:“MI:0915”(physical association)	0.510
TSHR	SYT1	psi-mi:“MI:0915”(physical association)	0.510
ADORA1	TSHR	psi-mi:“MI:0915”(physical association)	0.510
MID1IP1	TSHR	psi-mi:“MI:0915”(physical association)	0.510
SYT1	TSHR	psi-mi:“MI:0915”(physical association)	0.510
ACTB	TSHR	psi-mi:“MI:0915”(physical association)	0.370
BNIP1	TSHR	psi-mi:“MI:0915”(physical association)	0.370
CRADD	TSHR	psi-mi:“MI:0915”(physical association)	0.370
CD81	TSHR	psi-mi:“MI:0915”(physical association)	0.370
RUNDC3A	TSHR	psi-mi:“MI:0915”(physical association)	0.370
PTDSS1	TSHR	psi-mi:“MI:0915”(physical association)	0.370
TMCO3	TSHR	psi-mi:“MI:0915”(physical association)	0.370
JPH3	TSHR	psi-mi:“MI:0915”(physical association)	0.370
HNRNPA1	TSHR	psi-mi:“MI:0915”(physical association)	0.370
ASPHD1	TSHR	psi-mi:“MI:0915”(physical association)	0.370
TMEM119	TSHR	psi-mi:“MI:0915”(physical association)	0.370
MOG	TSHR	psi-mi:“MI:0915”(physical association)	0.370
TSHR	POTEF	psi-mi:“MI:0914”(association)	0.350
TSHR	PLXNB2	psi-mi:“MI:0914”(association)	0.350
TSHR	SCRIB	psi-mi:“MI:0403”(colocalization)	0.270

BioGRID (106): IQGAP2 (Affinity Capture-MS), SALL2 (Affinity Capture-MS), CAMK2D (Affinity Capture-MS), POTEF (Affinity Capture-MS), PC (Affinity Capture-MS), PTK7 (Affinity Capture-MS), TUBA1A (Affinity Capture-MS), CBWD1 (Affinity Capture-MS), MOCOS (Affinity Capture-MS), ITPA (Affinity Capture-MS), STIL (Affinity Capture-MS), SAMD1 (Affinity Capture-MS), LAMA3 (Affinity Capture-MS), BORA (Affinity Capture-MS), FBXO7 (Affinity Capture-MS)

ESM2 similar proteins: A0N0X6, A4IIW9, B2LT61, B2LT62, B2LT64, B2LT65, B3Y613, B3Y614, B3Y615, B3Y618, B5T267, O60602, O60603, P14778, P16473, P22888, P58681, P58682, Q0GC71, Q0ZUL9, Q15399, Q2PZH4, Q2V897, Q32Q07, Q5M8M9, Q5R482, Q61809, Q62929, Q66HV9, Q689D1, Q6GV17, Q6T752, Q6UXK5, Q704V6, Q7L985, Q8CBC6, Q8N7C0, Q95LA9, Q95M53, Q9BXR5

Diamond homologs: A2ARI4, A8WHP9, B0BLW3, D4AC13, E5DHB5, E7FE13, F1MLX5, F1MT22, F7D3V9, O75473, P0DM44, P14763, P16473, P56495, Q27987, Q3UVD5, Q8SPP9, Q9BGN4, Q9BXB1, Q9HBX8, Q9Z1P4, Q9Z2H4, O02721, P16235, P16582, P20395, P21463, P22888, P23945, P30549, P30730, P32212, P35376, P35378, P35379, P35409, P46023, P47750, P47799, P49059

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
TSH	“up-regulates activity”	TSHR	binding
TSHR	“up-regulates activity”	GNAS	binding
TSHR	“up-regulates activity”	GNAQ	binding
CGA	up-regulates	TSHR	binding
GPHA2	up-regulates	TSHR	binding
TSHB	up-regulates	TSHR	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 27 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of apoptotic process	6	8.3×	6e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 2 cancer types — COAD, WDTC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	38
Likely pathogenic	29
Uncertain significance	123
Likely benign	229
Benign	21

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
2444338	NM_000369.5(TSHR):c.1515C>A (p.Ser505Arg)	Pathogenic
2664771	NM_000369.5(TSHR):c.1839C>A (p.Tyr613Ter)	Pathogenic
2696500	NM_000369.5(TSHR):c.699_700del (p.Gln235fs)	Pathogenic
2699268	NM_000369.5(TSHR):c.1543del (p.Ile515fs)	Pathogenic
2701523	NM_000369.5(TSHR):c.1560G>A (p.Trp520Ter)	Pathogenic
2736136	NM_000369.5(TSHR):c.1555C>T (p.Arg519Cys)	Pathogenic
2736138	NM_000369.5(TSHR):c.1957C>G (p.Leu653Val)	Pathogenic
2750461	NM_000369.5(TSHR):c.1742dup (p.Tyr582fs)	Pathogenic
2757754	NM_000369.5(TSHR):c.268C>T (p.Gln90Ter)	Pathogenic
2790024	NM_000369.5(TSHR):c.667G>T (p.Gly223Ter)	Pathogenic
2829696	NM_000369.5(TSHR):c.1937C>G (p.Ser646Ter)	Pathogenic
2839940	NM_000369.5(TSHR):c.1337_1341dup (p.Val448Ter)	Pathogenic
2842687	NM_000369.5(TSHR):c.1120C>T (p.Gln374Ter)	Pathogenic
2859908	NM_000369.5(TSHR):c.1689T>G (p.Tyr563Ter)	Pathogenic
2866057	NM_000369.5(TSHR):c.952_962del (p.Leu318fs)	Pathogenic
2969580	NM_000369.5(TSHR):c.305_306del (p.Lys102fs)	Pathogenic
2982319	NM_000369.5(TSHR):c.1864del (p.Ile622fs)	Pathogenic
2993739	NM_000369.5(TSHR):c.1463G>A (p.Trp488Ter)	Pathogenic
3012862	NM_000369.5(TSHR):c.888del (p.Glu297fs)	Pathogenic
3233814	NM_000369.5(TSHR):c.1348del (p.Arg450fs)	Pathogenic
3244057	NC_000014.8:g.(?81422025)(81610697_?)del	Pathogenic
3244058	NC_000014.8:g.(?81609264)(81610697_?)del	Pathogenic
3244059	NC_000014.8:g.(?81528472)(81574816_?)del	Pathogenic
3244060	NC_000014.8:g.(?81606003)(81610697_?)del	Pathogenic
3370841	NM_000369.5(TSHR):c.1868C>T (p.Ala623Val)	Pathogenic
3377496	NM_000369.5(TSHR):c.1552G>T (p.Glu518Ter)	Pathogenic
4812824	NM_000369.5(TSHR):c.497del (p.Thr165_Ser166insTer)	Pathogenic
6431	NM_000369.5(TSHR):c.1856A>G (p.Asp619Gly)	Pathogenic
6432	NM_000369.5(TSHR):c.1867_1868delinsAT (p.Ala623Ile)	Pathogenic
6434	NM_000369.5(TSHR):c.500T>A (p.Ile167Asn)	Pathogenic

SpliceAI

2789 predictions. Top by Δscore:

Variant	Effect	Δscore
14:80955201:GA:G	donor_gain	1.0000
14:80955206:GGA:G	donor_gain	1.0000
14:80955207:GAG:G	donor_gain	1.0000
14:80971536:C:G	donor_gain	1.0000
14:80971559:T:G	donor_gain	1.0000
14:80971559:T:TG	donor_gain	1.0000
14:81068238:T:G	acceptor_gain	1.0000
14:81068244:T:A	acceptor_gain	1.0000
14:81068248:A:AG	acceptor_gain	1.0000
14:81092527:GCAGT:G	acceptor_loss	1.0000
14:81092528:CAG:C	acceptor_loss	1.0000
14:81092529:A:AG	acceptor_gain	1.0000
14:81092530:G:GA	acceptor_gain	1.0000
14:81092530:GT:G	acceptor_gain	1.0000
14:81092530:GTGAA:G	acceptor_gain	1.0000
14:81092609:G:GG	donor_gain	1.0000
14:81096706:GT:G	donor_gain	1.0000
14:81096708:G:GG	donor_gain	1.0000
14:81108370:TCTA:T	acceptor_loss	1.0000
14:81108371:CTAGT:C	acceptor_loss	1.0000
14:81108373:A:AG	acceptor_gain	1.0000
14:81108373:A:AT	acceptor_loss	1.0000
14:81108374:G:GA	acceptor_gain	1.0000
14:81108374:GT:G	acceptor_gain	1.0000
14:81108374:GTT:G	acceptor_gain	1.0000
14:81108374:GTTA:G	acceptor_gain	1.0000
14:81108374:GTTAC:G	acceptor_gain	1.0000
14:81108450:GCT:G	donor_gain	1.0000
14:81108453:GTGA:G	donor_gain	1.0000
14:81108455:GA:G	donor_gain	1.0000

AlphaMissense

5074 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:81143522:G:C	W488C	1.000
14:81143522:G:T	W488C	1.000
14:81143520:T:A	W488R	0.999
14:81143520:T:C	W488R	0.999
14:81143538:T:A	C494S	0.999
14:81143539:G:A	C494Y	0.999
14:81143539:G:C	C494S	0.999
14:81143763:T:A	C569S	0.999
14:81143763:T:C	C569R	0.999
14:81143764:G:A	C569Y	0.999
14:81143764:G:C	C569S	0.999
14:81143765:C:G	C569W	0.999
14:81139741:T:C	L252P	0.998
14:81143250:T:A	C398S	0.998
14:81143250:T:C	C398R	0.998
14:81143251:G:C	C398S	0.998
14:81143458:T:C	L467P	0.998
14:81143500:A:G	Y481C	0.998
14:81143538:T:C	C494R	0.998
14:81143539:G:T	C494F	0.998
14:81143540:C:G	C494W	0.998
14:81143551:G:A	G498D	0.998
14:81143757:A:C	S567R	0.998
14:81143759:T:A	S567R	0.998
14:81143759:T:G	S567R	0.998
14:81144061:C:A	P668Q	0.998
14:81139836:T:A	C284S	0.997
14:81139837:G:C	C284S	0.997
14:81143281:G:A	C408Y	0.997
14:81143425:T:C	L456P	0.997

dbSNP variants (sampled 300 via entrez): RS1000020605 (14:81076573 A>G,T), RS1000073540 (14:80981542 G>A,T), RS1000083744 (14:80995545 G>A,C), RS1000088965 (14:81132129 C>G,T), RS1000125470 (14:81036636 T>C), RS1000129463 (14:81040942 G>A), RS1000136307 (14:81076274 A>G), RS1000178463 (14:81105596 T>C), RS1000192718 (14:81038132 A>G), RS1000218003 (14:81089328 G>A), RS1000227013 (14:81035381 T>C), RS1000234644 (14:81019669 CTTA>C), RS1000252799 (14:80997439 G>T), RS1000264090 (14:81040561 A>C,G), RS1000265583 (14:80971584 T>C)

Disease associations

OMIM: gene MIM:603372 | disease phenotypes: MIM:603373, MIM:275200, MIM:609152, MIM:167000, MIM:600057, MIM:270400

GenCC curated gene-disease

Disease	Classification	Inheritance
hypothyroidism due to TSH receptor mutations	Definitive	Autosomal recessive
familial gestational hyperthyroidism	Definitive	Autosomal dominant
familial hyperthyroidism due to mutations in TSH receptor	Strong	Autosomal dominant
athyreosis	Supportive	Autosomal dominant
thyroid hypoplasia	Supportive	Autosomal dominant

Mondo (13): familial gestational hyperthyroidism (MONDO:0011309), hypothyroidism due to TSH receptor mutations (MONDO:0010142), familial hyperthyroidism due to mutations in TSH receptor (MONDO:0012203), ovarian cancer (MONDO:0008170), hyperthyroidism (MONDO:0004425), bladder exstrophy-epispadias-cloacal exstrophy complex (MONDO:0700039), Smith-Lemli-Opitz syndrome (MONDO:0010035), breast cancer (MONDO:0007254), congenital hypothyroidism (MONDO:0018612), epilepsy (MONDO:0005027), hereditary breast ovarian cancer syndrome (MONDO:0003582), athyreosis (MONDO:0019855), thyroid hypoplasia (MONDO:0019861)

Orphanet (8): Familial gestational hyperthyroidism (Orphanet:99819), Hypothyroidism due to TSH receptor mutations (Orphanet:90673), Familial hyperthyroidism due to mutations in TSH receptor (Orphanet:424), Rare ovarian cancer (Orphanet:213500), Classic bladder exstrophy (Orphanet:93930), Smith-Lemli-Opitz syndrome (Orphanet:818), Congenital hypothyroidism (Orphanet:442), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

79 total (30 of 79 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000158	Macroglossia
HP:0000239	Large fontanelles
HP:0000271	Abnormality of the face
HP:0000280	Coarse facial features
HP:0000282	Facial edema
HP:0000520	Proptosis
HP:0000713	Agitation
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0000821	Hypothyroidism
HP:0000836	Hyperthyroidism
HP:0000851	Congenital hypothyroidism
HP:0000853	Goiter
HP:0000952	Jaundice
HP:0000969	Edema
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001262	Excessive daytime somnolence
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001324	Muscle weakness
HP:0001510	Growth delay
HP:0001518	Small for gestational age
HP:0001537	Umbilical hernia
HP:0001615	Hoarse cry
HP:0001622	Premature birth

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000519_14	Hair morphology	6.000000e-06
GCST000658_3	Optic nerve measurement (rim area)	4.000000e-06
GCST000963_11	Uric acid levels	1.000000e-06
GCST001200_11	Graves’ disease	7.000000e-24
GCST001525_12	Visceral fat	8.000000e-07
GCST002361_7	Smooth-surface caries	1.000000e-06
GCST002664_1	Maximal oxygen uptake response	9.000000e-08
GCST004227_1	Obstetric antiphospholipid syndrome	8.000000e-08
GCST005247_2	Male sexual orientation	5.000000e-07
GCST005526_12	Graves’ disease	1.000000e-38
GCST006899_9	Thyroid stimulating hormone levels	2.000000e-15
GCST007277_19	Tourette syndrome	4.000000e-06
GCST010307_12	Urinary albumin excretion	4.000000e-10
GCST010653_78	Thyroid stimulating hormone levels	3.000000e-17
GCST010653_79	Thyroid stimulating hormone levels	2.000000e-27
GCST010653_80	Thyroid stimulating hormone levels	2.000000e-31
GCST010653_81	Thyroid stimulating hormone levels	4.000000e-40
GCST010653_82	Thyroid stimulating hormone levels	7.000000e-22

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005038	hair morphology
EFO:0004761	uric acid measurement
EFO:0004887	maximal oxygen uptake measurement
EFO:0004285	albuminuria

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D003409	Congenital Hypothyroidism	C05.116.099.343.347; C05.116.132.256; C16.320.240.625; C19.297.155; C19.874.482.281
D004827	Epilepsy	C10.228.140.490
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D006980	Hyperthyroidism	C19.874.397
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D019082	Smith-Lemli-Opitz Syndrome	C16.131.077.860; C16.320.565.398.850; C16.320.565.925.875; C18.452.584.500.937; C18.452.584.563.850; C18.452.648.398.850; C18.452.648.925.875
C566384	Hyperthyroidism, Familial Gestational (supp.)
C563786	Hyperthyroidism, Nonautoimmune (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1963 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

354 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,004,085 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1002	LEVOSALBUTAMOL	4	27,028
CHEMBL103	PROGESTERONE	4	162,141
CHEMBL1034	DICLOFENAC SODIUM	4	45,460
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1043	DAPSONE	4	64,779
CHEMBL107	COLCHICINE	4	93,932
CHEMBL1071	OXAPROZIN	4	51,044
CHEMBL1072	BUMETANIDE	4	22,087
CHEMBL1073	GLIPIZIDE	4	42,268
CHEMBL108	CARBAMAZEPINE	4	53,528
CHEMBL108545	METHYL SALICYLATE	4	125,516
CHEMBL1089	PHENELZINE	4	18,793
CHEMBL1104	EDROPHONIUM	4	17,617
CHEMBL1109	SULFAPHENAZOLE	4	4,065
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1115	PYRIDOSTIGMINE	4	13,658
CHEMBL112	ACETAMINOPHEN	4	157,242
CHEMBL1123	DICYCLOMINE	4	8,691
CHEMBL1165268	IODIPAMIDE	4	2,164
CHEMBL1170	TESTOSTERONE PROPIONATE	4	17,619
CHEMBL117785	TETRABENAZINE	4
CHEMBL118	CELECOXIB	4
CHEMBL1180725	PROPANTHELINE	4
CHEMBL1200	BENOXINATE	4
CHEMBL1200326	NICARDIPINE HYDROCHLORIDE	4
CHEMBL1200471	PYRITHIONE ZINC	4
CHEMBL1200560	GUANABENZ ACETATE	4
CHEMBL1200627	PROPIOLACTONE	4
CHEMBL1200761	CHLOROTRIANISENE	4
CHEMBL1200787	PHENOXYBENZAMINE HYDROCHLORIDE	4

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Glycoprotein hormone receptors

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 8b [PMID: 22408719]	Agonist	7.74	pEC50

Binding affinities (BindingDB)

3 measured of 24 human assays (24 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
BDBM189328	IC50	12 nM	US-9174940: TSH receptor antagonizing tetrahydroquinoline compounds
(3-chloro-4-fluorophenyl)methyl N-(1-acetyl-4-methyl-4-phenyl-2,3-dihydroquinolin-6-yl)carbamate	IC50	47 nM	US-9174940: TSH receptor antagonizing tetrahydroquinoline compounds
1-acetyl-2,2,4-trimethyl-4-phenyl-3H-quinoline-6-carboxamide	IC50	88 nM	US-9174940: TSH receptor antagonizing tetrahydroquinoline compounds

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.89	Potency	1.3	nM	FORMOTEROL
8.80	Potency	1.6	nM	CHEMBL45591
8.70	Potency	2	nM	E-DOXEPIN
8.60	Potency	2.5	nM	CHEMBL1318789
8.40	Potency	4	nM	BETAINE
8.40	Potency	4	nM	TRICHLOROETHYLENE
8.40	Potency	4	nM	CHEMBL1597046
8.38	EC50	4.2	nM	CHEMBL5618835
8.30	Potency	5	nM	CHEMBL1552133
8.30	Potency	5	nM	CHEMBL1580259
8.30	Potency	5	nM	CHEMBL1428273
8.30	Potency	5	nM	CHEMBL1378396
8.30	Potency	5	nM	CHEMBL1302121
8.30	Potency	5	nM	CHEMBL1420813
8.30	Potency	5	nM	CHEMBL1355090
8.30	Potency	5	nM	CHEMBL1381609
8.30	Potency	5	nM	CHEMBL1353729
8.30	Potency	5	nM	CHEMBL87310
8.20	Potency	6.3	nM	CHEMBL1541641
8.20	Potency	6.3	nM	CHEMBL1336298
8.20	Potency	6.3	nM	CHEMBL1449867
8.20	Potency	6.3	nM	CHEMBL1560355
8.20	Potency	6.3	nM	CHEMBL1425970
8.20	Potency	6.3	nM	CHEMBL1583467
8.20	Potency	6.3	nM	CHEMBL1474468
8.20	Potency	6.3	nM	CHEMBL1377856
8.20	Potency	6.3	nM	CHEMBL1349706
8.20	Potency	6.3	nM	CHEMBL1544244
8.20	Potency	6.3	nM	AZEPEXOLE
8.20	Potency	6.3	nM	CHEMBL142592
8.20	Potency	6.3	nM	DEXTROMETHORPHAN
8.20	Potency	6.3	nM	ACETOHEXAMIDE
8.10	Potency	7.9	nM	CHEMBL1594750
8.10	Potency	7.9	nM	CHEMBL1337829
8.10	Potency	7.9	nM	CHEMBL223306
8.10	Potency	7.9	nM	CHEMBL1333081
8.10	Potency	7.9	nM	CHEMBL1353300
8.10	Potency	7.9	nM	CHEMBL1391326
8.08	EC50	8.3	nM	CHEMBL5618807
8.00	Potency	10	nM	CHEMBL3348824
8.00	Potency	10	nM	CHEMBL1447333
8.00	Potency	10	nM	DINOPROSTONE
8.00	Potency	10	nM	CHEMBL1451739
8.00	Potency	10	nM	DIMPYLATE
8.00	Potency	10	nM	CYCLOHEXANONE OXIME
8.00	Potency	10	nM	(S)-AMPA
8.00	Potency	10	nM	CHEMBL1569493
8.00	Potency	10	nM	CHEMBL142735
8.00	Potency	10	nM	CHEMBL1341329
8.00	Potency	10	nM	CHEMBL1312282

PubChem BioAssay actives

2 with measured affinity, of 6100 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-(4-propylphenyl)-N-(pyridin-4-ylmethyl)quinoline-4-carboxamide	2130681: Agonist activity at TSHR (unknown origin)	ec50	0.0083	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Vorinostat	increases reaction, affects response to substance, affects cotreatment, affects expression, affects reaction (+1 more)	4
Org 41841	decreases reaction, increases activity, affects binding, decreases activity	3
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases methylation	3
DDT	affects binding, decreases activity, decreases localization	3
bisphenol A	decreases reaction, increases abundance, increases activity, affects cotreatment, increases methylation	2
Cyclic AMP	increases activity, decreases reaction, increases abundance	2
Diethylhexyl Phthalate	decreases expression, affects reaction, increases expression, increases phosphorylation	2
Nickel	decreases expression	2
Tretinoin	affects expression, decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
Chlorodiphenyl (54% Chlorine)	decreases activity, affects binding	2
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	increases expression	1
triphenyl phosphate	increases abundance, increases expression	1
trichostatin A	increases expression	1
tris(2-butoxyethyl) phosphate	increases abundance, increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
perfluorooctanoic acid	decreases expression	1
aflatoxin B2	increases methylation	1
tris(chloroethyl)phosphate	increases abundance, increases expression	1
diallyl trisulfide	increases expression	1
pentabromodiphenyl ether	decreases expression	1
efavirenz	increases expression	1
N-(2-hydroxybenzyl)glycine	affects binding, affects localization, increases cleavage, increases response to substance	1
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	increases expression, increases reaction	1
dipyrido(3,2-a-2’,3’-c)phenazine	affects binding, affects localization, increases cleavage, increases response to substance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
NCGC 00229600	decreases reaction, increases abundance, decreases activity, decreases expression	1
ammonium 4,8-dioxa-3H-perfluorononanoate	increases expression	1

ChEMBL screening assays

33 unique, capped per target: 24 functional, 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1613852	Functional	PUBCHEM_BIOASSAY: Confirmation Concentration-Response Assay for Agonists of the Thyroid Stimulating Hormone Receptor: Activators of Intracellular cAMP Concentrations in Parental HEK 293. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL3227399	Binding	Agonist activity at TSHR (unknown origin)	The Synthesis and Evaluation of Dihydroquinazolin-4-ones and Quinazolin-4-ones as Thyroid Stimulating Hormone Receptor Agonists. — Medchemcomm

Cellosaurus cell lines

16 cell lines: 7 transformed cell line, 5 spontaneously immortalized cell line, 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_3883	SW1736	Cancer cell line	Female
CVCL_C0TU	ACTOne TSHR	Transformed cell line	Female
CVCL_E3EJ	CHO TSHR-0	Transformed cell line	Female
CVCL_E3EK	CHO TSHR-WT	Transformed cell line	Female
CVCL_E3EL	CHO TSHR-800	Transformed cell line	Female
CVCL_E3EM	CHO TSHR-10,000	Transformed cell line	Female
CVCL_E3EN	CHO TSHR-289	Transformed cell line	Female
CVCL_F0HP	CHO-JP14	Spontaneously immortalized cell line	Female
CVCL_F0HQ	CHO-JP26	Spontaneously immortalized cell line	Female
CVCL_F0HR	CHO-JP28	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00727961	PHASE4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT00740116	PHASE4	COMPLETED	Tranexamic Acid in Surgery of Advanced Ovarian Cancer
NCT00817479	PHASE4	COMPLETED	Tumor Gene Expression in Women With Ovarian Cancer
NCT01432015	PHASE4	COMPLETED	Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting
NCT01706120	PHASE4	UNKNOWN	Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
NCT01932125	PHASE4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT01953107	PHASE4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02035345	PHASE4	TERMINATED	Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment
NCT02243059	PHASE4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
NCT03164980	PHASE4	TERMINATED	QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03543462	PHASE4	COMPLETED	Diaphragmatic Resection And Gynecological Ovarian Neoplasm
NCT03752216	PHASE4	COMPLETED	NIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib.
NCT03858166	PHASE4	TERMINATED	Efficacy and Safety of PEG-rhG-CSF Secondary Prophylaxis vs. Therapeutic Administration in Patients With Ovarian Cancer
NCT04024254	PHASE4	COMPLETED	A Study of Serum Folate Levels in Patients Treated With Olaparib
NCT04330040	PHASE4	COMPLETED	Prospective Multicentre Phase-IV Clinical Trial of Olaparib in Indian Patients With Ovarian and Metastatic Breast Cancer
NCT04352439	PHASE4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
NCT05187208	PHASE4	UNKNOWN	PARP Inhibitor Oral Maintenance in Low-Risk Ovarian Cancer
NCT05606692	PHASE4	RECRUITING	Influences of Propofol and Sevoflurane Anesthesia in Ovarian Cancer (Anesthetics)
NCT05926336	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06412120	PHASE4	RECRUITING	Study Evaluating Safety, Tolerability, and Metabolism of Niraparib
NCT06871787	PHASE4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT06887933	PHASE4	NOT_YET_RECRUITING	A Trial to Evaluate the Safety of Niraparib Tablets in Adult Female Participants With Advanced or Relapsed Epithelial Ovarian Cancer
NCT07469202	PHASE4	NOT_YET_RECRUITING	CYTALUX Dose Extension Study
NCT00001806	PHASE3	COMPLETED	Methods in Education for Breast Cancer Genetics
NCT00002477	PHASE3	UNKNOWN	Adjuvant Chemotherapy Compared With Observation in Treating Patients With Resected Early Stage Ovarian Epithelial Cancer
NCT00002568	PHASE3	COMPLETED	Combination Chemotherapy With or Without Surgery in Treating Patients With Stage III Ovarian Epithelial Cancer
NCT00002641	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002717	PHASE3	COMPLETED	Paclitaxel and Cisplatin in Treating Patients With Stage III or Stage IV Ovarian Cancer or Primary Peritoneal Cancer
NCT00002764	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00002819	PHASE3	TERMINATED	Chemotherapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Persistent Ovarian Epithelial Cancer
NCT00002894	PHASE3	COMPLETED	Platinum-based Chemotherapy With or Without Paclitaxel in Treating Patients With Relapsed Ovarian Cancer
NCT00002895	PHASE3	COMPLETED	Early Chemotherapy Based on CA 125 Level Alone Compared With Delayed Chemotherapy in Treating Patients With Recurrent Ovarian Epithelial , Fallopian Tube, or Primary Peritoneal Cancer
NCT00003120	PHASE3	COMPLETED	S9701 Paclitaxel in Treating Patients With Advanced Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Remission
NCT00003214	PHASE3	COMPLETED	Chemosensitivity Testing to Assign Treatment for Patients With Stage III or Stage IV Ovarian Cancer
NCT00003322	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Primary Peritoneal or Stage III Epithelial Ovarian Cancer
NCT00003636	PHASE3	COMPLETED	Chemotherapy Plus Surgery in Treating Patients With Stage III or Stage IV Ovarian, Peritoneal, or Fallopian Tube Cancer
NCT00003644	PHASE3	COMPLETED	Carboplatin Plus Paclitaxel With or Without Continued Low-Dose Paclitaxel in Treating Patients With Early-Stage Ovarian Cancer