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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

TSHR Gene

protein-coding GIFtS: 65
GCID: GC14P081421

thyroid stimulating hormone receptor

Explore 81 diseases affiliated with
TSHR via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Thyroid Stimulating Hormone Receptor¹ ²		Thyrotropin Receptor²
LGR3¹ ² ³		Thyrotropin Receptor-I, HTSHR-I²
CHNG1² ⁵		TSH-R³
HTSHR-I¹		Thyroid-Stimulating Hormone Receptor³
Seven Transmembrane Helix Receptor²

External Ids:	HGNC: 12373¹	Entrez Gene: 7253²	Ensembl: ENSG00000165409⁷	OMIM: 603372⁵	UniProtKB: P16473³

Export aliases for TSHR gene to outside databases

Previous GC identifers: GC14P078927 GC14P075238 GC14P079411 GC14P080491 GC14P061589

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for TSHR:

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. (provided by RefSeq, Dec 2008)

UniProtKB/Swiss-Prot: TSHR_HUMAN, P16473

Function: Receptor for thyrothropin. Plays a central role in controlling thyroid cell metabolism. The activity of this

receptor is mediated by G proteins which activate adenylate cyclase. Also acts as a receptor for thyrostimulin

(GPA2+GPB5)

Gene Wiki entry for TSHR (Thyrotropin receptor)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000014.8 NC_018925.1 NT_026437.12

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the TSHR gene promoter:
CREB AP-1 ATF-2 deltaCREB c-Jun
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: TSHR promoter sequence

Search SABiosciences Chromatin IP Primers for TSHR

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat TSHR

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 14q31 Ensembl cytogenetic band: 14q31.1 HGNC cytogenetic band: 14q24-q31

TSHR Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TSHR gene location

GeneLoc information about chromosome 14 GeneLoc Exon Structure

GeneLoc location for GC14P081421: view genomic region (about GC identifiers)

Start:	81,421,333 bp from pter	End:	81,612,646 bp from pter
Size:	191,314 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: TSHR_HUMAN, P16473 (See protein sequence)

Recommended Name: Thyrotropin receptor precursor

Size: 764 amino acids; 86830 Da

Subunit: Interacts (via the PDZ-binding motif) with SCRIB; regulates TSHR trafficking and function

Subcellular location: Cell membrane; Multi-pass membrane protein

Sequence caution: Sequence=AAA70232.1; Type=Frameshift; Positions=130, 135, 612;

3 PDB 3D structures from and Proteopedia for TSHR:

1XUM (3D)

2XWT (3D)

3G04 (3D)

Secondary accessions: A0PJU7 G3V2A9 Q16503 Q8TB90 Q96GT6 Q9P1V4 Q9ULA3 Q9UPH3

Alternative splicing: 3 isoforms: P16473-1 P16473-2 P16473-3 (No experimental confirmation available. Ref.9 (AAI27629) sequence is in conflict in position: 269:R->S)

Explore the universe of human proteins at neXtProt for TSHR: NX_P16473

Post-translational modifications:

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P16473

TSHR Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (3 alternative transcripts):

NP_000360.2 NP_001018046.1 NP_001136098.1

ENSEMBL proteins:

ENSP00000441235 ENSP00000340113 ENSP00000451092 ENSP00000451202 ENSP00000450549

ENSP00000298171

Reactome Protein details: P16473
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	Uscn Proteins for TSHR

Gene Ontology (GO): 3 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005886	plasma membrane	TAS	--
GO:0005887	integral to plasma membrane	TAS	8552586
GO:0016021	integral to membrane	--	--

TSHR for ontologies About GeneDecksing

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	Uscn ELISAs and CLIAs for TSHR

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

TSHR for domains About GeneDecksing

5 InterPro domains/families:

IPR017452 GPCR_Rhodpsn_7TM

IPR002131 Gphrmn_rcpt

IPR026906 LRR_5

IPR002274 TSH_rcpt

IPR000276 GPCR_Rhodpsn

Graphical View of Domain Structure for InterPro Entry P16473

ProtoNet protein and cluster: P16473

3 Blocks protein families:

IPB001611 Leucine-rich repeat signature

IPB002131 Glycoprotein hormone receptor signature

IPB002274 Thyrotropin receptor precursor signature

UniProtKB/Swiss-Prot: TSHR_HUMAN, P16473

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

Similarity: Contains 7 LRR (leucine-rich) repeats

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: TSHR_HUMAN, P16473

Function: Receptor for thyrothropin. Plays a central role in controlling thyroid cell metabolism. The activity of this

receptor is mediated by G proteins which activate adenylate cyclase. Also acts as a receptor for thyrostimulin

(GPA2+GPB5)

Genatlas biochemistry entry for TSHR:

thyroid stimulating hormone,receptor,G protein coupled receptor superfamily,thyroid hormone synthesis and metabolism

pathway

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		hsa-miR-3673 hsa-miR-3611 hsa-miR-196a* hsa-miR-3065-5p hsa-miR-143 hsa-miR-645 hsa-miR-205* hsa-miR-590-3p

		SwitchGear 3'UTR luciferase reporter plasmid: TSHR 3' UTR sequence

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Gene Editing
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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TSHR

Gene Ontology (GO): 3 molecular function terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004996	thyroid-stimulating hormone receptor activity	TAS	8552586
GO:0005515	protein binding	IPI	15775968
GO:0016500	protein-hormone receptor activity	--	--

TSHR for ontologies About GeneDecksing

Animal Models:
11 MGI mutant phenotypes (inferred from 2 alleles) (MGI details for Tshr):

behavior/neurological	cellular	endocrine/exocrine gland	growth/size	hearing/vestibular/ear
hematopoietic system	homeostasis/metabolism	immune system	mortality/aging	nervous system
reproductive system

TSHR for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/8 super-pathways (see all 8) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Class A/1 (Rhodopsin-like receptors)

	Class A/1 (Rhodopsin-like receptors)	1.00			Neuroactive ligand-receptor interaction	0.38
	GPCR ligand binding	0.75

Signaling by GPCR

	Signaling by GPCR	1.00			Signal Transduction	0.56
	GPCR downstream signaling	0.89

Arf6 signaling events

Arf6 signaling events

1.00

Arf6 trafficking events

Arf6 trafficking events

1.00

Allograft rejection

Autoimmune thyroid disease

0.60

Pathway sources
See GeneCards unified pathways
Show all pathways

3 BioSystems Pathways for TSHR

	Peptide GPCRs
	Arf6 trafficking events
	Arf6 signaling events

5/7 Reactome Pathways for TSHR (see all 7)

	GPCR downstream signaling
	Hormone ligand-binding receptors
	Signal Transduction
	Signaling by GPCR
	GPCR ligand binding

2 Kegg Pathways (Kegg details for TSHR):

	Neuroactive ligand-receptor interaction
	Autoimmune thyroid disease

TSHR for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for TSHR

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/92 Interacting proteins for TSHR (P16473³ ENSP00000298171⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 92)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
FLNB	O75369³, ENSP00000295956⁴	I2D: score=2 STRING: ENSP00000295956
FN1	P02751³, ENSP00000346839⁴	I2D: score=2 STRING: ENSP00000346839
HSPA5	P11021³, ENSP00000324173⁴	I2D: score=2 STRING: ENSP00000324173
PIK3R1	P27986³, ENSP00000274335⁴	I2D: score=2 STRING: ENSP00000274335
CALR	P27797³, ENSP00000320866⁴	I2D: score=1 STRING: ENSP00000320866

About this table

Gene Ontology (GO): 5/9 biological process terms (GO ID links to tree view) (see all 9): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0007186	G-protein coupled receptor signaling pathway	TAS	8552586
GO:0007187	G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	TAS	8552586
GO:0007189	adenylate cyclase-activating G-protein coupled receptor signaling pathway	--	--
GO:0007267	cell-cell signaling	TAS	7920658
GO:0008284	positive regulation of cell proliferation	TAS	7920658

TSHR for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

TSHR for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for TSHR

1 HMDB Compound for TSHR About this table

Compound	Synonyms	CAS #	PubMed Ids
Cyclic AMP	Cyclic AMP (see all 19)	60-92-4	--

1 DrugBank Compound for TSHR About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Thyrotropin Alfa	Follicle-stimulating hormone beta subunit (see all 4)	9002-71-5	target	agonist	11752352 15571461 9039330

10/74 Novoseek chemical compound relationships for TSHR gene (see all 74) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
methimazole	73.9	5	18964302 (1), 16571093 (1)
mc 1-2	73.6	10	10411114 (2), 10487700 (2), 9528975 (2), 10958310 (1) (see all 5)
thyroxine	72.5	15	10633214 (1), 17084554 (1), 10840997 (1), 7744989 (1) (see all 15)
sodium iodide	70.3	19	10090312 (1), 12966202 (1), 17199440 (1), 12485453 (1) (see all 14)
carbimazole	69.9	3	19141763 (1), 17042691 (1), 10646656 (1)
iodine	68.9	29	16990652 (6), 19550078 (2), 15911145 (2), 11041453 (1) (see all 17)
iodide	66.9	31	8981006 (2), 15691889 (2), 9398703 (1), 9413803 (1) (see all 20)
propylthiouracil	59.9	4	8051490 (1), 12790806 (1), 15163329 (1)
triiodothyronine	58.5	13	17287406 (1), 10840997 (1), 12790806 (1), 12899792 (1) (see all 9)
adenylate	46.5	23	8147896 (2), 8137933 (2), 7702564 (2), 16335676 (2) (see all 17)

Search CenterWatch for drugs/clinical trials and news about TSHR

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for TSHR gene (3 alternative transcripts):

NM_000369.2 NM_001018036.2 NM_001142626.2

Unigene Cluster for TSHR:

Thyroid stimulating hormone receptor

Hs.160411 [show with all ESTs]

Unigene Representative Sequence: NM_000369

9 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000557096 ENST00000541158 ENST00000342443(uc001xvb.1 uc001xvc.3 uc010tvs.2)

ENST00000553763 ENST00000555326 ENST00000554263 ENST00000554435 ENST00000556031

ENST00000298171(uc001xvd.1)

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		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat TSHR
		8 QIAGEN miScript miRNA Assays for microRNAs that regulate TSHR:
		hsa-miR-3673 hsa-miR-3611 hsa-miR-196a* hsa-miR-3065-5p hsa-miR-143 hsa-miR-645 hsa-miR-205* hsa-miR-590-3p

		SwitchGear 3'UTR luciferase reporter plasmid: TSHR 3' UTR sequence

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Additional cDNA sequence:

AB209207.1 AF035261.1 AK095769.1 AK303378.1 AY429111.1 BC009237.2 BC024205.2 BC063613.1

BC108653.1 BC120972.2 BC120973.2 BC127628.1 BC127629.1 BC141970.1 M31774.1 M32215.1

M73747.1 S45272.1 S49816.1 S82807.1

9 DOTS entries:

DT.453667 DT.87046423 DT.91762220 DT.95161141 DT.120771538 DT.75184241 DT.99936172 DT.95368852

DT.99995997

24/46 AceView cDNA sequences (see all 46):

BC024205 AI870633 BE045816 AI142049 BC063613 AY429111 BF036966 AK095769

T29862 BE207611 BF510960 BF034165 BF034029 M32215 BE272336 BX484832

S82807 AA384557 BG207816 NM_000369 BE206608 M31774 BE740743 AF035261

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

TSHR expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: --

About this image

TSHR expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

2 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Adipose

Body Subcutaneous White Adipose

Adipose

Visceral White Adipose

Adipose

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 1 LifeMap Cell

Name

Category

Thyroid Progenitors (Efficient derivation...)

Thyroid

See TSHR Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for TSHR

SOURCE GeneReport for Unigene cluster: Hs.160411

UniProtKB/Swiss-Prot: TSHR_HUMAN, P16473

Tissue specificity: Expressed in the thyroid

SABiosciences Expression via Pathway-Focused PCR Arrays including TSHR:

G-Protein-Coupled Receptor Signaling PathwayFinder in human mouse rat

G Protein Coupled Receptors 384HT in human mouse rat

Tumor Metastasis in human mouse rat

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In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TSHR

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for TSHR gene from 4/18 species (see all 18) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	TSHR¹	thyroid stimulating hormone receptor	71.62(n) 73.87(a)		428900 NM_001193588.1 NP_001180517.1
lizard (Anolis carolinensis)	Reptilia	TSHR⁶	--	71(a)	1 ↔ 1	1(17924371-17953600)
zebrafish (Danio rerio)	Actinopterygii	tshr¹	thyroid stimulating hormone receptor	63.15(n) 61.46(a)		560609 NM_001145763.1 NP_001139235.1
fruit fly (Drosophila melanogaster)	Insecta	Fsh³	G-protein coupled receptor protein signaling pathway more	37(a) (best of 2)		3 90C2 --

ENSEMBL Gene Tree for TSHR (if available)
TreeFam Gene Tree for TSHR (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for TSHR gene

LHCGR² LGR5² FSHR² RXFP1² LGR6² RXFP2² LGR4²

2 SIMAP similar genes for TSHR using alignment to 5 protein entries: TSHR_HUMAN (see all proteins):

LHCGR FSHR

TSHR for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

UniProtKB/Swiss-Prot: TSHR_HUMAN, P16473

Polymorphism: The Asp727Glu polymorphism is associated with Graves disease in a Russian population. The Glu727 allele

and the heterozygous Asp727Glu genotype are related to higher risk of the disease. The Asp727Glu polymorphism

significantly ameliorates G(s)alpha protein activation in the presence of the gain-of-function mutation Ala593Asn

although it is functionally inert in the context of the wild-type TSHR

SNP ID	Valid	Clinical significance	Chr 14 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs61747482^1,2	C,F,	non-pathogenic	90227237(+)	`AGGAGG/CACTTC`	6	/H /D	mis¹		3		NS NA EU	5937
rs28937584^1,2	C	pathogenic	90039177(+)	`TCACCG/CACTTC`	2	/H /D	mis¹ ese³		2		NA	4
rs121908866^1,2	C,F	pathogenic	90039437(+)	`GGGCTG/AGGTTT`	2	/* /W	stg¹		1		NA	4550
rs121908863^1,2	C,	pathogenic	90090511(+)	`ACAACC/GCTTAC`	6	P A	mis¹		0	--	--	--	--
rs121908869^1,2	C	pathogenic	90227221(+)	`CACCTG/CCAAGG`	6	/S /C	mis¹		1		NA	4552
rs201417739^1,2	C	other	90039753(+)	`TCCTCA/CCCAGC`	2	T P	mis¹		0	--	--	--	--
rs121908873^1,2	C	other	90043303(+)	`CCCAAA/G/TCCACT`	3	N S I	mis¹		0	--	--	--	--
rs111538471^1,2	F	--	61587636(+)	`GAGACC/TCCGTC`	3	--	us2k¹		2		CSA	4
rs113647920^1,2		--	61587706(+)	`AATTCA/GAGGTG`	3	--	us2k¹		3		CSA WA	121
rs111992078^1,2	C,	--	61588429(+)	`AGTTTG/ATTTAT`	3	--	us2k¹		1		WA	2

HapMap Linkage Disequilibrium report for TSHR (81421333 - 81612646 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 10 variations for TSHR
4 CNVs: 87283 101995 101996 0178
6 Indels: 61402 45302 42399 61403 33588 45301
Human Gene Mutation Database (HGMD): TSHR

Locus Specific Mutation Databases (LSDB): TSHR

5/15 SABiosciences Cancer Mutation PCR Assays for TSHR (see all 15):

Cosmic Id	AA Change
26419	p.D633Y
26451	p.I568T
26420	p.D633H
26418	p.T632I
26415	p.D619G

3 SABiosciences Cancer Mutation PCR Arrays containing TSHR:

Thyroid Cancer

Cancer Comprehensive Panel 384HT

Tumor Suppressor Panel 384HT

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing TSHR

DNA2.0 Custom Variant and Variant Library Synthesis for TSHR

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

TSHR for disorders           About GeneDecksing

OMIM gene information: 603372
OMIM disorders: 275200  609152  603373
UniProtKB/Swiss-Prot: TSHR_HUMAN, P16473

Note=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)

Note=Autoantibodies against TSHR are directly responsible for the pathogenesis and hyperthyroidism of Graves

disease. Antibody interaction with TSHR results in an uncontrolled receptor stimulation

Defects in TSHR are the cause of congenital hypothyroidism non-goitrous type 1 (CHNG1) [MIM:275200]; also

known as congenital hypothyroidism due to TSH resistance. CHNG1 is 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. CHNG1 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

Defects in TSHR are the cause of familial gestational hyperthyroidism (HTFG) [MIM:603373]. HTFG is a condition

characterized by abnormally high levels of serum thyroid hormones occurring during early pregnancy

Defects in TSHR are the cause of hyperthyroidism non-autoimmune (HTNA) [MIM:609152]. It is 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

20/81 diseases for TSHR (see all 81): About MalaCards

thyroiditis hyperthyroidism struma ovarii mitral valve prolapse

thyroid adenoma, hyperfunctioning, somatic hyperthyroidism, familial gestational multinodular goiter nontoxic goiter

thyrotoxic periodic paralysis goiter endemic goiter toxic diffuse goiter

hypersensitivity reaction type ii disease neonatal thyrotoxicosis thyrotoxicosis dry eye syndrome

myxedema hypothyroidism precocious puberty hyperthyroxinemia

9 diseases from the University of Copenhagen DISEASES database for TSHR:

Hyperthyroidism Hypersensitivity reaction type II disease Hypothyroidism Goiter

Thyroiditis Thyrotoxicosis Thyroid cancer Adenoma

Thyroid adenoma

10/91 Novoseek disease relationships for TSHR gene (see all 91) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
graves disease	96.4	483	10365678 (6), 16235153 (4), 8636291 (4), 9920067 (4) (see all 99)
hyperthyroidism	91.9	239	15284197 (4), 12240901 (4), 17129985 (3), 9589634 (3) (see all 99)
autoimmune thyroid disease	89.9	58	10659563 (2), 9546816 (2), 7921224 (2), 19328414 (2) (see all 44)
toxic adenoma	89.4	34	8626855 (4), 9525885 (1), 8549796 (1), 14514342 (1) (see all 25)
thyroid-associated ophthalmopathy	86.1	20	14724083 (2), 16643732 (2), 9001189 (1), 12568121 (1) (see all 13)
myxedema	86	23	1981364 (1), 9398703 (1), 10852437 (1), 12242030 (1) (see all 17)
hashimotos thyroiditis	84.3	24	19850692 (2), 18942492 (2), 9183516 (2), 2226281 (1) (see all 19)
tsh resistance	83.4	8	16135555 (2), 11379397 (1), 16060907 (1), 17237844 (1) (see all 6)
thyroid diseases	82.5	54	12457447 (2), 18777457 (2), 10584424 (1), 16042141 (1) (see all 43)
neonatal hyperthyroidism	82.1	6	10855389 (1), 19803950 (1), 12707626 (1), 8964822 (1) (see all 6)

Genatlas disease: TSHR

hypothyroidism,congenital,with high TSH,TSH unresponsiveness (TSHR defect in few cases),including thyroid hypoplasia

Genetic Association Database (GAD): TSHR
Human Genome Epidemiology (HuGE) Navigator: TSHR (53 documents)

Export disorders for TSHR gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for TSHR gene, integrated from 9 sources (see all 983):
(articles sorted by number of sources associating them with TSHR)

Utopia: connect your pdf to the dynamic
world of online information

Association of Graves' disease with intragenic polymorphism of the thyrotropin receptor gene in a cohort of Singapore patients of multi- ethnic origins. (PubMed id 12930595)^{1, 2, 4, 9} Ho S.-C.... Khoo D.H. (2003)
Polymorphisms in thyroid hormone pathway genes are associated with plasma TSH and iodothyronine levels in healthy subjects. (PubMed id 12788902)^{1, 2, 4} Peeters R.P.... Visser T.J. (2003)
A germline single nucleotide polymorphism at the intracellular domain of the human thyrotropin receptor does not have a major effect on the development of Graves' disease. (PubMed id 12593721)^{1, 2, 4} Ban Y.... Tomer Y. (2002)
Cloning, sequencing and expression of the human thyrotropin (TSH) receptor: evidence for binding of autoantibodies. (PubMed id 2610690)^{1, 2, 3} Libert F.... Vassart G. (1989)
Molecular cloning, sequence and functional expression of the cDNA for the human thyrotropin receptor. (PubMed id 2558651)^{1, 2, 3} Nagayama Y.... Rapoport B. (1989)
A novel activating mutation in the thyrotropin receptor gene in an autonomously functioning thyroid nodule developed by a Japanese patient. (PubMed id 11022192)^{1, 2, 9} Kosugi S.... Mori T. (2000)
The polymorphisms of codon 727 and 52 of thyroid-stimulating hormone receptor gene are not associated with mitral valve prolapse syndrome in Taiwan Chinese. (PubMed id 12558129)^{1, 4, 9} Chou H.T....Tsai F.J. (2002)
Functional significance of the thyrotropin receptor germline polymorphism D727E. (PubMed id 12589819)^{1, 2, 9} Sykiotis G.P.... Papavassiliou A.G. (2003)
Premature birth and low birth weight associated with nonautoimmune hyperthyroidism due to an activating thyrotropin receptor gene mutation. (PubMed id 15163335)^{1, 2, 9} Vaidya B....Ellard S. (2004)
Oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in the Japanese population. (PubMed id 12213664)^{1, 2, 9} Vanvooren V.... Noguchi S. (2002)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 7253	HGNC: 12373	AceView: TSHR	Ensembl:ENSG00000165409	euGenes: HUgn7253
ECgene: TSHR	Kegg: 7253	H-InvDB: TSHR

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for TSHR	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for TSHR	Genetics and Cytogenetics in Oncology and Haematology
TSH receptor database	http://endokrinologie.uniklinikum-leipzig.de/tsh/
GRIS	http://gris.ulb.ac.be/
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/TSHR
SHMPD	http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=TSHR
Wikipedia	http://en.wikipedia.org/wiki/TSH_receptor
Sequence-structure-function-analysis of glycoprotein hormone receptors	http://www.ssfa-gphr.de/

Intellectual Property for TSHR gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

About This Section

Patent Information for TSHR gene:
Search GeneIP for patents involving TSHR

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Uscn, Thermo Fisher Scientific, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences),
In Situ Hybridization Assays from
Advanced Cell Diagnostics
About This Section


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TSHR Gene

thyroid stimulating hormone receptor

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Down Syndrome
preterm delivery
Toxic diffuse goiter
Genetic Susceptibility
HYPERTHYROIDISM, FAMILIAL GESTATIONAL
THYROID CARCINOMA ANAPLASTIC
THYROID FOLLICULAR CARCINOMA
Thyroid Nodule
aggressiveness
lung metastases
Thyroid-Associated Ophthalmopathy
THYROID ECTOPIC
Hyperthyroidism
primary tumor
Edema
HYPOTHYROIDISM PRIMARY
Cancer
Diabetes Mellitus Insulin-Dependent
multinodular goiter
Eye Diseases
somatic mutations
bone loss
follicular thyroid cancer
Neonatal thyrotoxicosis
toxic adenoma
Congenital hypothyroidism
Inflammation
recurrent thyroid cancer
Germ-Line Mutation
Thyroid Neoplasms
Hypertrophy
Toxic multinodular goiter
DRUG WITHDRAWAL
cancer recurrence
Iodine deficiency
Mental Retardation
Tumors
Metastasis
Autoimmunity
mimicry
Necrosis
Hyperthyroxinemia
SMOKING HABIT
Viral hepatitis
TSH RESISTANCE
neoplastic transformation
Thyroiditis
Lymphadenopathy
Melanoma
Autoimmune Diseases
Endemic goiter
Adenoma Follicular
Hyperplasia
Goiter Nodular
Carcinoma
Hypothyroidism
Leukemia
Thyroid Cancer
Hydatidiform Mole
Osteosarcoma
Sjogrens Syndrome
Carcinoma Papillary
THYROID PAPILLARY CARCINOMA
Carcinoma Anaplastic
Proptosis
Neonatal hyperthyroidism
Goiter
Nontoxic goiter
Thyroiditis Subacute
THYROID ADENOMA
Hypoplasia
TOXIC GOITER
Adenoma
Mitral Valve Prolapse
Carcinoma Medullary
hyperfunction
autoimmune thyroid disease
Thyroid Diseases
Struma Ovarii
Puberty Precocious
papillary thyroid cancer
Hepatitis C Chronic
Autoimmune Response
Graves Disease
DYSFUNCTION THYROID
Strabismus
Hashimotos Thyroiditis
Cholera
THYROID CARCINOMA
Myxedema
Lupus Erythematosus Systemic

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TSHR Gene

thyroid stimulating hormone receptor

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