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): 523 total — 38 pathogenic, 34 likely-pathogenic (top 6% of genes corpus-wide)
• GTEx eGene: eQTL in 13 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 79
• Drug target: yes — 2 curated mechanism-of-action drugs; 354 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 2 — Thyrotropin, Thyrotropin Alfa
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types (inferred from mutation patterns)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.01 (unconstrained)
• 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: 13 — 7 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000298171

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 1, TSL 3: 1, TSL 4: 2, TSL 5: 3

ENST00000298171, ENST00000342443, ENST00000541158, ENST00000553763, ENST00000554263, ENST00000554435, ENST00000555326, ENST00000556031, ENST00000557096, ENST00000636454, ENST00000637447, ENST00000642209, ENST00001131363

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
ENSE00004782524	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.

Highest expression (Bgee): lobe of thyroid gland, thyroid gland, male germ line stem cell (sensu Vertebrata) in testis, thymus, bone marrow cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TSHR is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 13 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

14 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	sqtl	8.2e-123	-1.05	14:81105315:C:T
Brain Caudate basal ganglia	eqtl	1.9e-14	-0.42	14:80959081:C:G
Brain Putamen basal ganglia	eqtl	1.6e-13	-0.57	14:80968545:C:G
Adipose Subcutaneous	eqtl	8.4e-10	-0.30	14:80984708:C:T
Adipose Visceral Omentum	eqtl	5.7e-07	-0.33	14:80984708:C:T
Thyroid	eqtl	1.7e-05	+0.12	14:80978777:C:T
Skin Sun Exposed Lower leg	eqtl	3.1e-04	+0.22	14:80970996:C:T
Breast Mammary Tissue	eqtl	4.0e-04	+0.58	14:80534143:TTC:T
Brain Nucleus accumbens basal ganglia	eqtl	1.1e-03	+0.32	14:80971258:G:A
Skin Not Sun Exposed Suprapubic	eqtl	2.1e-03	+0.38	14:80980444:C:T
Adrenal Gland	eqtl	5.0e-03	+0.55	14:80967331:G:A
Colon Transverse	eqtl	1.8e-02	-0.86	14:80448645:A:G
Nerve Tibial	eqtl	2.6e-02	-0.21	14:80968545:C:G
Brain Spinal cord cervical c-1	eqtl	3.5e-02	+0.40	14:80961208:T:C

FANTOM5 promoters

showing 10 of 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

showing 100 of 295 tissues 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
caecum	UBERON:0001153	58.48	gold quality
left uterine tube	UBERON:0001303	58.07	gold quality
embryo	UBERON:0000922	57.96	gold quality
corpus callosum	UBERON:0002336	57.90	gold quality
gall bladder	UBERON:0002110	57.85	gold quality
oviduct epithelium	UBERON:0004804	57.56	silver quality
mucosa of transverse colon	UBERON:0004991	57.02	gold quality
sperm	CL:0000019	57.00	silver quality
minor salivary gland	UBERON:0001830	56.83	gold quality
apex of heart	UBERON:0002098	56.83	gold quality
fallopian tube	UBERON:0003889	56.74	gold quality
lower esophagus mucosa	UBERON:0035834	56.74	gold quality
male germ cell	CL:0000015	56.67	silver quality
omental fat pad	UBERON:0010414	56.58	gold quality
decidua	UBERON:0002450	56.55	gold quality
peritoneum	UBERON:0002358	56.54	gold quality
adipose tissue of abdominal region	UBERON:0007808	55.96	gold quality
monocyte	CL:0000576	55.68	gold quality
leukocyte	CL:0000738	55.68	gold quality
mononuclear cell	CL:0000842	55.63	gold quality
skin of leg	UBERON:0001511	55.47	gold quality
bone marrow	UBERON:0002371	55.41	gold quality
calcaneal tendon	UBERON:0003701	55.34	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	55.22	gold quality
islet of Langerhans	UBERON:0000006	54.87	gold quality
mouth mucosa	UBERON:0003729	54.83	gold quality
saliva-secreting gland	UBERON:0001044	54.56	gold quality
nucleus accumbens	UBERON:0001882	54.41	gold quality
spinal cord	UBERON:0002240	53.98	gold quality
hair follicle	UBERON:0002073	53.58	gold quality
skin of abdomen	UBERON:0001416	53.48	gold quality
muscle of leg	UBERON:0001383	53.40	gold quality
body of uterus	UBERON:0009853	53.36	gold quality
small intestine Peyer’s patch	UBERON:0003454	53.35	gold quality
blood	UBERON:0000178	53.26	gold quality
lower lobe of lung	UBERON:0008949	53.04	silver quality
zone of skin	UBERON:0000014	52.98	gold quality
small intestine	UBERON:0002108	52.94	gold quality
transverse colon	UBERON:0001157	52.86	gold quality
pancreas	UBERON:0001264	52.74	gold quality
muscle organ	UBERON:0001630	52.50	gold quality
skeletal muscle organ	UBERON:0014892	52.50	gold quality
cerebellar vermis	UBERON:0004720	52.15	gold quality
gastrocnemius	UBERON:0001388	52.07	gold quality
heart left ventricle	UBERON:0002084	51.80	gold quality
prefrontal cortex	UBERON:0000451	51.77	gold quality
anatomical system	UBERON:0000467	51.57	gold quality
material anatomical entity	UBERON:0000465	51.50	gold quality
multicellular organism	UBERON:0000468	51.50	gold quality
cardiac ventricle	UBERON:0002082	51.41	gold quality
body of pancreas	UBERON:0001150	51.40	gold quality
stomach	UBERON:0000945	51.30	gold quality
muscle tissue	UBERON:0002385	51.28	gold quality
hypothalamus	UBERON:0001898	51.13	gold quality
Brodmann (1909) area 10	UBERON:0013541	51.10	gold quality
tendon	UBERON:0000043	51.03	silver quality
endocervix	UBERON:0000458	51.00	gold quality
body of stomach	UBERON:0001161	50.92	gold quality
cortex of kidney	UBERON:0001225	50.88	gold quality
mucosa of stomach	UBERON:0001199	50.84	gold quality
adenohypophysis	UBERON:0002196	50.78	gold quality
uterine cervix	UBERON:0000002	50.76	gold quality
skeletal muscle tissue	UBERON:0001134	50.75	gold quality
ectocervix	UBERON:0012249	50.75	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	50.75	gold quality
adipose tissue	UBERON:0001013	50.59	gold quality
smooth muscle tissue	UBERON:0001135	50.54	gold quality
left ovary	UBERON:0002119	50.52	gold quality
pituitary gland	UBERON:0000007	50.43	gold quality
vagina	UBERON:0000996	50.42	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

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 64 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thyroid gland	tissue	257.0	high
Postcentral gyrus	tissue	20.9
Nucleus accumbens	tissue	20.2
Thymus	tissue	19.4
Hippocampus	tissue	18.0	not detected
Choroid plexus	tissue	16.6
Locus coeruleus	tissue	15.7
Retina	tissue	2.0
Lymph node	tissue	1.8	not detected
Hypothalamus	tissue	1.8
Skin 1	tissue	1.0	not detected
Bone marrow	tissue	1.0	not detected
Tonsil	tissue	0.8	not detected
Caudate putamen	tissue	0.8
Breast	tissue	0.7	not detected
Skeletal muscle	tissue	0.7	not detected
Spleen	tissue	0.7	not detected
Appendix	tissue	0.7	not detected
Testis	tissue	0.6	medium
Pons	tissue	0.6
Endometrium 1	tissue	0.6	not detected
Frontal cortex	tissue	0.6
Adrenal gland	tissue	0.6	not detected
Stomach 1	tissue	0.5	not detected
Adipose tissue	tissue	0.5	not detected
Salivary gland	tissue	0.5	not detected
Colon	tissue	0.4	not detected
Pancreas	tissue	0.4	not detected
Epididymis	tissue	0.4	not detected
Gallbladder	tissue	0.4	not detected
Prostate	tissue	0.4	not detected
Fallopian tube	tissue	0.4	not detected
Heart muscle	tissue	0.3	not detected
Rectum	tissue	0.3	not detected
Parathyroid gland	tissue	0.3	not detected
Urinary bladder	tissue	0.3	not detected
Placenta	tissue	0.3	not detected
Liver	tissue	0.3	not detected
Small intestine	tissue	0.3	not detected
Kidney	tissue	0.3	not detected
Duodenum	tissue	0.3	not detected
Ventral forebrain	tissue	0.3
Septum	tissue	0.3
Cervix	tissue	0.2	not detected
Pituitary gland	tissue	0.2
Seminal vesicle	tissue	0.2	not detected
Esophagus	tissue	0.2	not detected
Tongue	tissue	0.2
Amygdala	tissue	0.2
Lung	tissue	0.2	not detected
Prefrontal cortex	tissue	0.1
Cerebral cortex	tissue	0.1	not detected
Ovary	tissue	0.1	not detected
Vagina	tissue	0.1	not detected
Smooth muscle	tissue	0.1	not detected
Motor cortex	tissue	0.1
Basal ganglia	tissue	0.1	not detected
Midbrain	tissue	0.1
Medulla oblongata	tissue	0.1
Spinal cord	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 186; highest nTPM — Vermis (26.1), Flocculonodular lobe (25.7), Cerebellar cortex (23.1), Parietal operculum (22.3), Posterior insular cortex (22.2).

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

Targeting TSHR by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 105 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 7.35e-14, LOEUF 1.01, missense Z 1.32 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000298171 — one region, missense o/e 0.93.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:98849) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 67 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal thyroid follicle morphology	4
increased or absent threshold for auditory brainstem response	4
decreased body weight	3
decreased activity of thyroid gland	3
decreased circulating thyroxine level	3
decreased body size	2
small thyroid gland	2
increased circulating thyroid-stimulating hormone level	2
abnormal organ of Corti morphology	1
delayed bone ossification	1
decreased compact bone thickness	1
short limbs	1
decreased body length	1
circling	1
unidirectional circling	1
increased stereotypic behavior	1
anemia	1
postnatal growth retardation	1
reduced fertility	1
reduced male fertility	1
reduced female fertility	1
male infertility	1
female infertility	1
deafness	1
premature death	1

+42 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	P35376	97.6%	Diamond
Ovis aries	P35379	97.6%	Diamond
Macaca fascicularis	P32212	97.3%	Diamond
Equus caballus	P47799	95.8%	Diamond
Equus asinus	Q95179	95.8%	Diamond
Canis lupus familiaris	P14763	94.9%	Diamond
Felis catus	Q9BGN4	94.9%	Diamond
Sus scrofa	P49059	93.7%	Diamond
Cavia porcellus	Q8R428	90.8%	Diamond
Gallus gallus	P79763	90.3%	Diamond
Mesocricetus auratus	Q6R6L8	90.3%	Diamond
Cairina moschata	Q7ZTV5	90.3%	Diamond
Callithrix jacchus	O02721	87.2%	Diamond
Notamacropus eugenii	Q6YNB6	82.3%	Diamond
Xenopus tropicalis	B0BLW3	74.6%	Diamond
Ictalurus punctatus	Q6QMG1	60.3%	Diamond
Anthopleura elegantissima	P35409	50.2%	Diamond
Lymnaea stagnalis	P46023	38.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
DIO2-AS1	ncRNA	100628307
TSHR-AS1	ncRNA	101928462
CEP128	protein-coding	145508
DIO2	protein-coding	1734
GTF2A1-AS1	ncRNA	101928504
GTF2A1	protein-coding	2957
SNORA79	snoRNA	677845

Protein

Protein identifiers

Thyrotropin receptor — P16473 (reviewed: P16473)

Alternative names: Thyroid-stimulating hormone receptor

All UniProt accessions (5): P16473, A0A1B0GUJ5, A0A2R8Y709, 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 (189 total): sequence variant 70, strand 23, helix 23, sequence conflict 15, turn 9, 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 by resolution:

PDB	Title	Method	Resolution (Å)
2XWT	CRYSTAL STRUCTURE OF THE TSH RECEPTOR IN COMPLEX WITH A BLOCKING TYPE TSHR AUTOANTIBODY	X-RAY DIFFRACTION	1.9
7UTZ	Human thyrotropin analog TR1402 bound to human Thyrotropin receptor in complex with …	ELECTRON MICROSCOPY	2.4
3G04	Crystal structure of the TSH receptor in complex with a thyroid-stimulating autoantibody	X-RAY DIFFRACTION	2.55
7XW6	TSHR-Gs-M22 antibody-ML109 complex	ELECTRON MICROSCOPY	2.78
7T9I	Native human TSH bound to human Thyrotropin receptor in complex with miniGs399 (composite …	ELECTRON MICROSCOPY	2.9
7T9N	M22 Agonist Autoantibody bound to Human Thyrotropin receptor in complex with miniGs399 …	ELECTRON MICROSCOPY	2.9
7XW5	TSHR-thyroid stimulating hormone-Gs-ML109 complex	ELECTRON MICROSCOPY	2.96
7T9M	Human Thyrotropin receptor bound by CS-17 Inverse Agonist Fab/Org 274179-0 Antagonist	ELECTRON MICROSCOPY	3.1
7XW7	TSHR-K1-70 complex	ELECTRON MICROSCOPY	5.5

Predicted structure (AlphaFold)

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

Antibody-complex structures (SAbDab)

9 antibodies co-crystallized with this protein: 2XWT, 3G04, 7T9I, 7T9M, 7T9N, 7UTZ, 7XW5, 7XW6, 7XW7

Human Protein Atlas

Protein class: G-protein coupled receptors, GPCRs excl olfactory receptors, Predicted membrane proteins, GPCRHMM predicted membrane proteins, Predicted intracellular proteins, Cancer-related genes, Disease related genes, FDA approved drug targets, Biotech drugs, Human disease related genes

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH approved

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)

Type	Positions
Sulfotyrosine	385

Disulfide bonds (6)

Type	Positions
Disulfide bond	24–31, 29–41, 283–398, 284–408, 301–390, 494–569

Glycosylation sites (6)

Type	Positions
N-linked (glcnac…) asparagine	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 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-418555	G alpha (s) signalling events	curated
R-HSA-375281	Hormone ligand-binding receptors	curated
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-500792	GPCR ligand binding	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—

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

5 top-level categories:

Category	Pathways
Signaling by GPCR	2
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1
Signal Transduction	1
GPCR ligand binding	1

GO top-level categories

36 GO namespaces:

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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 12 of 25 annotations. The rest are phylogenetic / computational / electronic (IEA).

12 experimentally-supported GO terms:

GO term	NS	Evidence
adenylate cyclase-activating G protein-coupled receptor signaling pathway	BP	mutant phenotype
cell surface receptor signaling pathway	BP	mutant phenotype
cellular response to glycoprotein	BP	mutant phenotype
cellular response to thyrotropin-releasing hormone	BP	mutant phenotype
thyroid-stimulating hormone signaling pathway	BP	mutant phenotype
basolateral plasma membrane	CC	direct assay
plasma membrane	CC	direct assay
signaling receptor complex	CC	direct assay
G protein-coupled receptor activity	MF	direct assay
protein-containing complex binding	MF	direct assay
signaling receptor activity	MF	mutant phenotype
thyroid-stimulating hormone receptor activity	MF	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 1,284 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSHR	TPO	P07202	972
TSHR	TG	P01266	970
TSHR	SLC5A5	Q92911	937
TSHR	PAX8	Q06710	915
TSHR	FOXE1	O00358	883
TSHR	NKX2-1	P43699	879
TSHR	TSHB	P01222	832
TSHR	SLC26A4	O43511	807
TSHR	TRH	P20396	777
TSHR	DIO2	Q92813	773
TSHR	IYD	Q6PHW0	710
TSHR	THRB	P10828	697
TSHR	GNAS	Q5JWF2	677
TSHR	TPCN1	Q9ULQ1	674
TSHR	THRA	P10827	666

IntAct

Human interaction partners of TSHR in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

27 partners by confidence:

Partner	Interaction type	MIscore	Records
SCRIB	physical association	0.580	4
SMAD4	physical association	0.550	6
ADORA1	physical association	0.510	2
MID1IP1	physical association	0.510	2
SYT1	physical association	0.510	2
ACTB	physical association	0.370	1
ASPHD1	physical association	0.370	1
BNIP1	physical association	0.370	1
CD81	physical association	0.370	1
CRADD	physical association	0.370	1
HNRNPA1	physical association	0.370	1
JPH3	physical association	0.370	1
MOG	physical association	0.370	1
PTDSS1	physical association	0.370	1
RUNDC3A	physical association	0.370	1
TMCO3	physical association	0.370	1
TMEM119	physical association	0.370	1
PLXNB2	association	0.350	1
POTEF	association	0.350	1
SPOP	proximity	0.270	4
FBXW7	proximity	0.270	3
AKT1	proximity	0.270	1
BRAF	proximity	0.270	1
EGFR	proximity	0.270	1
PTEN	proximity	0.270	1
PTPN11	proximity	0.270	1
TP53	proximity	0.270	1

BioGRID (110 interactions; top human partners by supporting records): RNF144A (Reconstituted Complex; 4 records), BORA (Affinity Capture-MS; 3 records), ITPA (Affinity Capture-MS; 3 records), LAMA3 (Affinity Capture-MS; 3 records), MOCOS (Affinity Capture-MS; 3 records), POTEF (Affinity Capture-MS; 3 records), ADORA1 (Affinity Capture-Western; 2 records), ADRB2 (PCA; 2 records), CBWD1 (Affinity Capture-MS; 2 records), FBXO7 (Affinity Capture-MS; 2 records), HSPA5 (Affinity Capture-Western; 2 records), MID1IP1 (Affinity Capture-Western; 2 records), MLF1 (Affinity Capture-MS; 2 records), PC (Affinity Capture-MS; 2 records), PTK7 (Affinity Capture-MS; 2 records)

SIGNOR signaling

6 signaling 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

Protein complexes (CORUM) (4)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

4 complexes by size:

Complex	Subunits	Members
★ LHCGR-TSHR complex	2	LHCGR, TSHR
★ SCRIB-TSHR complex	2	TSHR, SCRIB
★ ATP1A1-TSHR complex	2	ATP1A1, TSHR
★ Thyrotropin receptor	1	TSHR

Ligand–receptor pairs (CellPhoneDB) (3)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

3 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
CGA;TSHB	receptor	Signaling by Choriogonadotropin
GPHB5;GPHA2	receptor
TSHB	receptor

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.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for TSHR: 523 ClinVar records (72 pathogenic / likely pathogenic); 18 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	38
Likely pathogenic	34
Uncertain significance	133
Likely benign	231
Benign	19

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 72 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
2736138	NM_000369.5(TSHR):c.1957C>G (p.Leu653Val)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
2736136	NM_000369.5(TSHR):c.1555C>T (p.Arg519Cys)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
314693	NM_000369.5(TSHR):c.394G>C (p.Gly132Arg)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	6
420145	NM_000369.5(TSHR):c.267_270delinsTCCT (p.Gln90Pro)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1050267	NM_000369.5(TSHR):c.1462T>C (p.Trp488Arg)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
189249	NM_000369.5(TSHR):c.545+2_545+3del	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2969580	NM_000369.5(TSHR):c.305_306del (p.Lys102fs)	Pathogenic	criteria provided, single submitter	2
3233814	NM_000369.5(TSHR):c.1348del (p.Arg450fs)	Pathogenic	criteria provided, single submitter	2
2444338	NM_000369.5(TSHR):c.1515C>A (p.Ser505Arg)	Pathogenic	criteria provided, single submitter	1
2664771	NM_000369.5(TSHR):c.1839C>A (p.Tyr613Ter)	Pathogenic	criteria provided, single submitter	1
2696500	NM_000369.5(TSHR):c.699_700del (p.Gln235fs)	Pathogenic	criteria provided, single submitter	1
2699268	NM_000369.5(TSHR):c.1543del (p.Ile515fs)	Pathogenic	criteria provided, single submitter	1
2701523	NM_000369.5(TSHR):c.1560G>A (p.Trp520Ter)	Pathogenic	criteria provided, single submitter	1
2750461	NM_000369.5(TSHR):c.1742dup (p.Tyr582fs)	Pathogenic	criteria provided, single submitter	1
2757754	NM_000369.5(TSHR):c.268C>T (p.Gln90Ter)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore TSHR’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 1,496):

Position(s)	Effect	Δscore	Sites
14:80971536	donor_gain	1.0000
14:80971559	donor_gain	1.0000
14:81068238	acceptor_gain	1.0000
14:81068244	acceptor_gain	1.0000
14:81092529–81092530	acceptor_loss	1.0000	6
14:81108373–81108374	acceptor_loss	1.0000	6
14:80955851–80955852	donor_loss	0.9900	6
14:80955855	donor_loss	0.9900
14:81068249	acceptor_gain	0.9900
14:81087903	acceptor_gain	0.9900

AlphaMissense

1,626 missense substitutions predicted likely pathogenic (of 5,074 scored), across 412 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M626	9	0.901	0.979
D474	8	0.989	0.996
D460	8	0.978	0.993
N210	8	0.976	0.996
N432	8	0.964	0.996
F197	8	0.957	0.993
F594	8	0.953	0.994
D410	8	0.948	0.990
N670	8	0.947	0.997
F72	8	0.945	0.992
S567	8	0.938	0.998
H282	8	0.931	0.982
D688	8	0.929	0.970
F221	8	0.922	0.977
F503	8	0.919	0.975
F685	8	0.917	0.991
D232	8	0.909	0.973
N187	8	0.904	0.994
F634	8	0.900	0.971
F97	8	0.895	0.982

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Thyroid Carcinoma)

Disease associations

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

GenCC curated gene-disease

5 curated gene-disease records:

Disease	Classification	Inheritance	Records
hypothyroidism due to TSH receptor mutations	Definitive	Autosomal recessive	4
familial gestational hyperthyroidism	Definitive	Autosomal dominant	3
familial hyperthyroidism due to mutations in TSH receptor	Strong	Autosomal dominant	3
athyreosis	Supportive	Autosomal dominant
thyroid hypoplasia	Supportive	Autosomal dominant

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (4 panels, 4 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

4 panels:

Panel	Rating
Congenital hypothyroidism	green
DDG2P	green
Hyperthyroidism	green
Paediatric disorders	green

Mondo (9): hypothyroidism due to TSH receptor mutations (MONDO:0010142), familial gestational hyperthyroidism (MONDO:0011309), familial hyperthyroidism due to mutations in TSH receptor (MONDO:0012203), ovarian cancer (MONDO:0008170), congenital hypothyroidism (MONDO:0018612), Smith-Lemli-Opitz syndrome (MONDO:0010035), hyperthyroidism (MONDO:0004425), athyreosis (MONDO:0019855), thyroid hypoplasia (MONDO:0019861)

Orphanet (6): Hypothyroidism due to TSH receptor mutations (Orphanet:90673), Familial hyperthyroidism due to mutations in TSH receptor (Orphanet:424), Familial gestational hyperthyroidism (Orphanet:99819), Rare ovarian cancer (Orphanet:213500), Congenital hypothyroidism (Orphanet:442), Smith-Lemli-Opitz syndrome (Orphanet:818)

HPO phenotypes

showing 60 of 79 phenotypes (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
HP:0001649	Tachycardia
HP:0001662	Bradycardia
HP:0001824	Weight loss
HP:0002014	Diarrhea
HP:0002019	Constipation
HP:0002045	Hypothermia
HP:0002360	Sleep disturbance
HP:0002378	Hand tremor
HP:0002925	Elevated circulating thyroid-stimulating hormone concentration
HP:0003265	Neonatal hyperbilirubinemia
HP:0003270	Abdominal distention
HP:0003577	Congenital onset
HP:0003623	Neonatal onset
HP:0003745	Sporadic
HP:0004322	Short stature
HP:0004491	Large posterior fontanelle
HP:0005616	Accelerated skeletal maturation
HP:0005930	Abnormal epiphysis morphology
HP:0005990	Thyroid hypoplasia
HP:0006579	Prolonged neonatal jaundice
HP:0008191	Thyroid agenesis
HP:0008223	Compensated hypothyroidism
HP:0008249	Thyroid hyperplasia
HP:0008282	Unconjugated hyperbilirubinemia
HP:0008828	Delayed proximal femoral epiphyseal ossification
HP:0008872	Feeding difficulties in infancy
HP:0010864	Severe intellectual disability
HP:0011437	Maternal autoimmune disease
HP:0011784	Thyrotoxicosis with diffuse goiter
HP:0011788	Increased circulating free T3

GWAS associations

18 associations:

Study	Trait	p-value
GCST010653_56	Thyroid stimulating hormone levels	4e-40
GCST005526_12	Graves’ disease	1e-38
GCST010653_55	Thyroid stimulating hormone levels	2e-31
GCST010653_54	Thyroid stimulating hormone levels	2e-27
GCST001200_11	Graves’ disease	7e-24
GCST010653_57	Thyroid stimulating hormone levels	7e-22
GCST010653_53	Thyroid stimulating hormone levels	3e-17
GCST006899_1	Thyroid stimulating hormone levels	2e-15
GCST010307_12	Urinary albumin excretion	4e-10
GCST004227_1	Obstetric antiphospholipid syndrome	8e-8
GCST002664_1	Maximal oxygen uptake response	9e-8
GCST005247_2	Male sexual orientation	5e-7
GCST001525_12	Visceral fat	8e-7
GCST000963_11	Uric acid levels	1e-6
GCST002361_25	Smooth-surface caries	1e-6
GCST000658_3	Optic nerve measurement (rim area)	4e-6
GCST007277_19	Tourette syndrome	4e-6
GCST000519_14	Hair morphology	6e-6

EFO canonical traits (from GWAS)

4 canonical traits:

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

6 disease descriptors:

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
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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the TSHR protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

2 curated-mechanism drugs:

Drug	Modality	Max phase
THYROTROPIN	Unknown	4
THYROTROPIN ALFA	Protein	4

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 6,277,948 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 354 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL112	ACETAMINOPHEN	4	159,007
CHEMBL1589	ACETOHEXAMIDE	4	18,443
CHEMBL184	ACYCLOVIR	4	98,123
CHEMBL545	ALCOHOL	4	4,651,986
CHEMBL1467	ALLOPURINOL	4	85,872
CHEMBL660	AMANTADINE	4	70,248
CHEMBL945	AMILORIDE	4	64,123
CHEMBL288470	AMINOPYRINE	4	8,309
CHEMBL633	AMIODARONE	4	30,023
CHEMBL243712	AMISULPRIDE	4	10,675
CHEMBL1113	AMOXAPINE	4	20,303
CHEMBL43	AMSACRINE	4	83,286
CHEMBL1305	ANTAZOLINE	4	9,229
CHEMBL647	APRACLONIDINE	4	13,857
CHEMBL25	ASPIRIN	4	696,632
CHEMBL641	ATOMOXETINE	4	13,258
CHEMBL1238	AZELAIC ACID	4	153,551
CHEMBL529	AZITHROMYCIN	4	75,962
CHEMBL1200	BENOXINATE	4	6,775
CHEMBL388590	BENZBROMARONE	4	8,286
CHEMBL1201039	BENZTHIAZIDE	4
CHEMBL720	BENZYL ALCOHOL	4
CHEMBL295124	BERBERINE	4
CHEMBL95889	BETAINE	4
CHEMBL942	BISACODYL	4
CHEMBL290106	BITHIONOL	4
CHEMBL1072	BUMETANIDE	4
CHEMBL820	BUSULFAN	4
CHEMBL127516	BUTAMBEN	4
CHEMBL108	CARBAMAZEPINE	4
CHEMBL965	CARBAMOYLCHOLINE	4
CHEMBL73234	CARBETAPENTANE	4
CHEMBL1256696	CARBETAPENTANE CITRATE	4
CHEMBL1233	CARISOPRODOL	4
CHEMBL513	CARMUSTINE	4
CHEMBL118	CELECOXIB	4
CHEMBL515	CHLORAMBUCIL	4
CHEMBL790	CHLORHEXIDINE	4
CHEMBL842	CHLOROTHIAZIDE	4
CHEMBL1200761	CHLOROTRIANISENE	4
CHEMBL498	CHLORPROPAMIDE	4
CHEMBL1371	CHLORZOXAZONE	4
CHEMBL799	CILOSTAZOL	4
CHEMBL30	CIMETIDINE	4
CHEMBL1208	CINOXACIN	4
CHEMBL1626	CLEMASTINE	4
CHEMBL565	CLOFIBRATE	4
CHEMBL415	CLOMIPRAMINE	4
CHEMBL104	CLOTRIMAZOLE	4
CHEMBL42	CLOZAPINE	4
CHEMBL107	COLCHICINE	4
CHEMBL669	CYCLOBENZAPRINE	4
CHEMBL771	CYCLOSERINE	4
CHEMBL516	CYPROHEPTADINE	4
CHEMBL602	CYSTEAMINE	4
CHEMBL476	DACARBAZINE	4
CHEMBL284348	DALFAMPRIDINE	4
CHEMBL53418	DANTHRON	4
CHEMBL1043	DAPSONE	4
CHEMBL1563	DAUNORUBICIN HYDROCHLORIDE	4

PharmGKB: 1 entry (CPIC guideline: no)

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)

17 measured of 38 human assays (49 total across all organisms); most potent 17 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
CHEMBL5281228	IC50	17 nM
(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
CHEMBL5285685	IC50	64 nM
1-acetyl-2,2,4-trimethyl-4-phenyl-3H-quinoline-6-carboxamide	IC50	88 nM	US-9174940: TSH receptor antagonizing tetrahydroquinoline compounds
CHEMBL5267043	IC50	156 nM
CHEMBL5270266	IC50	214 nM
CHEMBL5283477	IC50	270 nM
CHEMBL5275619	IC50	432 nM
CHEMBL5287707	IC50	449 nM
CHEMBL5279687	IC50	466 nM
CHEMBL5275140	IC50	606 nM
CHEMBL5267037	IC50	1440 nM
CHEMBL5270771	IC50	1750 nM
CHEMBL5286556	IC50	2050 nM
CHEMBL5285769	IC50	10000 nM
CHEMBL5268829	IC50	10000 nM

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	affects expression, affects reaction, increases expression, increases reaction, affects response to substance (+1 more)	4
Org 41841	affects binding, decreases activity, decreases reaction, increases activity	3
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases methylation	3
DDT	affects binding, decreases activity, decreases localization	3
bisphenol A	increases abundance, increases activity, affects cotreatment, increases methylation, decreases reaction	2
Cyclic AMP	decreases reaction, increases abundance, increases activity	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)	affects binding, decreases activity	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

17 cell lines: 7 transformed cell line, 5 cancer cell line, 5 spontaneously immortalized 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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00190697	Phase 4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00277160	Phase 4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00727961	Phase 4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT00740116	Phase 4	COMPLETED	Tranexamic Acid in Surgery of Advanced Ovarian Cancer
NCT00817479	Phase 4	COMPLETED	Tumor Gene Expression in Women With Ovarian Cancer
NCT01432015	Phase 4	COMPLETED	Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting
NCT01706120	Phase 4	UNKNOWN	Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
NCT01932125	Phase 4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT01953107	Phase 4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02035345	Phase 4	TERMINATED	Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment
NCT02243059	Phase 4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
NCT03164980	Phase 4	TERMINATED	QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer
NCT03384511	Phase 4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03543462	Phase 4	COMPLETED	Diaphragmatic Resection And Gynecological Ovarian Neoplasm
NCT03752216	Phase 4	COMPLETED	NIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib.
NCT03858166	Phase 4	TERMINATED	Efficacy and Safety of PEG-rhG-CSF Secondary Prophylaxis vs. Therapeutic Administration in Patients With Ovarian Cancer
NCT04024254	Phase 4	COMPLETED	A Study of Serum Folate Levels in Patients Treated With Olaparib
NCT04330040	Phase 4	COMPLETED	Prospective Multicentre Phase-IV Clinical Trial of Olaparib in Indian Patients With Ovarian and Metastatic Breast Cancer
NCT04352439	Phase 4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
NCT05187208	Phase 4	UNKNOWN	PARP Inhibitor Oral Maintenance in Low-Risk Ovarian Cancer
NCT05606692	Phase 4	RECRUITING	Influences of Propofol and Sevoflurane Anesthesia in Ovarian Cancer (Anesthetics)
NCT05926336	Phase 4	UNKNOWN	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06412120	Phase 4	RECRUITING	Study Evaluating Safety, Tolerability, and Metabolism of Niraparib
NCT06871787	Phase 4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT06887933	Phase 4	NOT_YET_RECRUITING	A Trial to Evaluate the Safety of Niraparib Tablets in Adult Female Participants With Advanced or Relapsed Epithelial Ovarian Cancer
NCT07469202	Phase 4	NOT_YET_RECRUITING	CYTALUX Dose Extension Study
NCT00001806	Phase 3	COMPLETED	Methods in Education for Breast Cancer Genetics
NCT00002477	Phase 3	UNKNOWN	Adjuvant Chemotherapy Compared With Observation in Treating Patients With Resected Early Stage Ovarian Epithelial Cancer
NCT00002568	Phase 3	COMPLETED	Combination Chemotherapy With or Without Surgery in Treating Patients With Stage III Ovarian Epithelial Cancer
NCT00002641	Phase 3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002717	Phase 3	COMPLETED	Paclitaxel and Cisplatin in Treating Patients With Stage III or Stage IV Ovarian Cancer or Primary Peritoneal Cancer
NCT00002764	Phase 3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00002819	Phase 3	TERMINATED	Chemotherapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Persistent Ovarian Epithelial Cancer
NCT00002894	Phase 3	COMPLETED	Platinum-based Chemotherapy With or Without Paclitaxel in Treating Patients With Relapsed Ovarian Cancer
NCT00002895	Phase 3	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	Phase 3	COMPLETED	S9701 Paclitaxel in Treating Patients With Advanced Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Remission
NCT00003214	Phase 3	COMPLETED	Chemosensitivity Testing to Assign Treatment for Patients With Stage III or Stage IV Ovarian Cancer
NCT00003322	Phase 3	COMPLETED	Combination Chemotherapy in Treating Patients With Primary Peritoneal or Stage III Epithelial Ovarian Cancer
NCT00003636	Phase 3	COMPLETED	Chemotherapy Plus Surgery in Treating Patients With Stage III or Stage IV Ovarian, Peritoneal, or Fallopian Tube Cancer
NCT00003644	Phase 3	COMPLETED	Carboplatin Plus Paclitaxel With or Without Continued Low-Dose Paclitaxel in Treating Patients With Early-Stage Ovarian Cancer
NCT00003695	Phase 3	COMPLETED	Chemotherapy With or Without Surgery in Treating Patients With Stage II or Stage III Ovarian Cancer
NCT00003998	Phase 3	COMPLETED	Carboplatin Plus Paclitaxel or Docetaxel in Treating Patients With Ovarian Epithelial Cancer
NCT00004115	Phase 3	UNKNOWN	Monoclonal Antibody Therapy in Treating Patients With Ovarian Cancer or Primary Peritoneal Cancer in Remission Following Surgery and Chemotherapy
NCT00004166	Phase 3	COMPLETED	Amifostine in Treating Patients With Ovarian Epithelial Cancer Who Are Receiving Chemotherapy
NCT00004921	Phase 3	COMPLETED	High-Dose Chemotherapy Compared With Standard Chemotherapy in Treating Patients With Stage III or Stage IV Ovarian Epithelial Cancer That Has Been Removed During Surgery
NCT00004934	Phase 3	COMPLETED	Paclitaxel and Carboplatin With or Without Epirubicin in Treating Patients With Stage IIB, Stage III, or Stage IV Invasive Ovarian Epithelial, Fallopian Tube, or Peritoneal Cancer
NCT00005590	Phase 3	COMPLETED	Levofloxacin to Prevent Infection Following Chemotherapy in Treating Patients With Solid Tumors or Lymphoma
NCT00006356	Phase 3	TERMINATED	Chemotherapy With or Without Surgery in Treating Patients With Recurrent Ovarian Cancer
NCT00006453	Phase 3	COMPLETED	Carboplatin With or Without Gemcitabine in Treating Patients With Advanced Ovarian Epithelial Cancer That Has Not Responded to Previous Chemotherapy
NCT00006454	Phase 3	COMPLETED	Paclitaxel Plus Carboplatin With or Without Topotecan in Treating Patients With Stage IIB, Stage III, or Stage IV Ovarian Epithelial Cancer
NCT00011986	Phase 3	COMPLETED	Combination Chemotherapy in Treating Patients With Stage III or Stage IV Ovarian Epithelial Cancer or Primary Peritoneal Cancer
NCT00028743	Phase 3	COMPLETED	Combination Chemotherapy Regimens in Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer
NCT00033605	Phase 3	COMPLETED	Octreotide in Preventing Diarrhea in Patients Who Are Undergoing Radiation Therapy to the Pelvis
NCT00043082	Phase 3	COMPLETED	S0200 Carboplatin With or Without Doxil in Patients With Recurrent Ovarian Cancer
NCT00050375	Phase 3	TERMINATED	Clinical Trial for Ovarian Cancer (OvaRex®)
NCT00052468	Phase 3	COMPLETED	Carboplatin/Paclitaxel +/-Gemcitabine in Treating Patients With Ovarian Epithelial or Fallopian Tube Cancer
NCT00057720	Phase 3	COMPLETED	TLK286 (Telcyta) vs. Doxil/Caelyx or Hycamtin in Platinum Refractory or Resistant Ovarian Cancer
NCT00098878	Phase 3	COMPLETED	Carboplatin in Treating Patients With Stage IC-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
NCT00102375	Phase 3	COMPLETED	Paclitaxel, Carboplatin, and Topotecan in Patients With Ovarian Cancer
NCT00102414	Phase 3	COMPLETED	Gemcitabine Plus Carboplatin Versus Carboplatin Monotherapy in Patients With Advanced Ovarian Cancer

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TSHR across ~30M SureChEMBL compounds — explore on Sugi Predict.