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TSHR Gene

protein-coding   GIFtS: 68
GCID: GC14P081421

Thyroid Stimulating Hormone Receptor

  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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This gene clusters with an RNA gene
Subcategory (RNA class): lncRNA

Quality score for the ORGUL clustered with this gene is 3

Aliases
Thyroid Stimulating Hormone Receptor1 2     Thyrotropin Receptor2
LGR32 3     Thyrotropin Receptor-I, HTSHR-I2
CHNG12 5     TSH-R3
hTSHR-I2     Thyroid-Stimulating Hormone Receptor3
Seven Transmembrane Helix Receptor2     

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

Export aliases for TSHR gene to outside databases

Previous GC identifers: GC14P078927 GC14P075238 GC14P079411 GC14P080491 GC14P061589


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for TSHR Gene:
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)

GeneCards Summary for TSHR Gene:
TSHR (thyroid stimulating hormone receptor) is a protein-coding gene. Diseases associated with TSHR include hyperthyroidism, and familial hyperthyroidism due to mutations in tsh receptor. GO annotations related to this gene include thyroid-stimulating hormone receptor activity. An important paralog of this gene is LHCGR.

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) Gene


(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 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000014.9  NT_026437.13  NC_018925.2  
Regulatory elements:
   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 plasmidTSHR promoter sequence
   Search Chromatin IP Primers for TSHR

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing 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, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, 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 Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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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
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

Explore proteomics data for TSHR at MOPED

Post-translational modifications: 

  • Glycosylation2 at Asn77, Asn99, Asn113, Asn177, Asn198, Asn302
  • Modification sites at PhosphoSitePlus

  • See TSHR Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    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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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    GTSHR: GPCR / Class A : Gonadotropin and TSH receptors

    IUPHAR Guide to PHARMACOLOGY protein family classification: TSH receptor
    Glycoprotein hormone receptors

    5 InterPro protein domains:
     IPR017452 GPCR_Rhodpsn_7TM
     IPR002131 Gphrmn_rcpt_fam
     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 domains:
    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


    TSHR for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: 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

         Gene Ontology (GO): 3 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004930G-protein coupled receptor activity ----
    GO:0004996thyroid-stimulating hormone receptor activity IEA--
    GO:0005515protein binding IPI15775968
         
    TSHR for ontologies           About GeneDecksing


    Phenotypes:
         10 MGI mutant phenotypes (inferred from 2 alleles(MGI details for Tshr):
     behavior/neurological  endocrine/exocrine gland  growth/size/body  hearing/vestibular/ear  hematopoietic system 
     homeostasis/metabolism  immune system  mortality/aging  nervous system  reproductive system 

    TSHR for phenotypes           About GeneDecksing

    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for TSHR
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    Block miRNA regulation of human, mouse, rat TSHR using miScript Target Protectors
    8 qRT-PCR 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 plasmidTSHR 3' UTR sequence
    Inhib. RNA
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    GenScript: all cDNA clones in your preferred vector (see all 3): TSHR (NM_000369)
    Browse Sino Biological Human cDNA Clones
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TSHR


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    TSHR_HUMAN, P16473: Cell membrane; Multi-pass membrane protein
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane5
    extracellular2
    cytosol1
    nucleus1

    Gene Ontology (GO): 4 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005886plasma membrane TAS--
    GO:0005887integral component of plasma membrane TAS8552586
    GO:0016021integral component of membrane ----
    GO:0043235receptor complex IDA--

    TSHR for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, 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 Apr 2014 via Entrez Gene).
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    SuperPaths for TSHR About   (see all 10)  
    See pathways by source

    SuperPathContained pathways About
    1Peptide ligand-binding receptors
    Class A/1 (Rhodopsin-like receptors)0.71
    Neuroactive ligand-receptor interaction0.36
    GPCR ligand binding0.71
    2Signaling by GPCR
    Signaling by GPCR0.90
    Signal Transduction0.58
    GPCR downstream signaling0.90
    3Allograft rejection
    Autoimmune thyroid disease0.61
    4Neuropeptides signaling through G protein alpha i and G protein alpha q
    Peptide GPCRs0.46
    5Insulin secretion
    Thyroid hormone synthesis0.36

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    4 BioSystems Pathways for TSHR
        Thyroxine (Thyroid Hormone) Production
    Arf6 signaling events
    Arf6 trafficking events
    Peptide GPCRs

    2 Reactome Pathways for TSHR
        Hormone ligand-binding receptors
    G alpha (s) signalling events


    3 Kegg Pathways  (Kegg details for TSHR):
        Neuroactive ligand-receptor interaction
    Thyroid hormone synthesis
    Autoimmune thyroid disease


    TSHR for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler 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

    Interactions:

        GeneGlobe Interaction Network for TSHR

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

    Selected Interacting proteins for TSHR (P164733 ENSP000002981714) via UniProtKB, MINT, STRING, and/or I2D (see all 92)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    FLNBO753693, ENSP000002959564I2D: score=2 STRING: ENSP00000295956
    FN1P027513, ENSP000003468394I2D: score=2 STRING: ENSP00000346839
    HSPA5P110213, ENSP000003241734I2D: score=2 STRING: ENSP00000324173
    PIK3R1P279863, ENSP000002743354I2D: score=2 STRING: ENSP00000274335
    CALRP277973, ENSP000003208664I2D: score=1 STRING: ENSP00000320866
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    Gene Ontology (GO): Selected biological process terms (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0007186G-protein coupled receptor signaling pathway TAS8552586
    GO:0007187G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger TAS8552586
    GO:0007189adenylate cyclase-activating G-protein coupled receptor signaling pathway ----
    GO:0007267cell-cell signaling TAS7920658
    GO:0008284positive regulation of cell proliferation TAS7920658

    TSHR for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for TSHR

    1 HMDB Compound for TSHR    About this table
    CompoundSynonyms CAS #PubMed Ids
    Cyclic AMPCyclic AMP (see all 19)60-92-4--

    1 DrugBank Compound for TSHR    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Thyrotropin AlfaFollicle-stimulating hormone beta subunit (see all 4)9002-71-5targetagonist11752352 15571461 9039330

    2 IUPHAR Ligands for TSHR (TSH receptor)    About this table
    LigandTypeActionAffinityPubmed IDs
    [125I]TSH
    AgonistFull agonist--
    TSH
    AgonistFull agonist--

    Selected Novoseek inferred 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)



    TSHR for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 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,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    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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    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
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      QuantiFast Probe-based Assays in human, mouse, rat TSHR

    Additional mRNA 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 

    Selected AceView cDNA sequences (see all 46):

    BC024205 BC063613 BF036966 BE045816 AI870633 AY429111 AI142049 BF034165 
    M32215 BE272336 AA384557 BF510960 BG207816 NM_000369 BC009237 AK095769 
    AF035261 M31774 BE206608 BX484832 BF034029 S49816 BE207611 BE740743 

    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™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    TSHR expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    TSHR Expression
    About this image


    TSHR expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 5) fully expand
     
     Thyroid (Endocrine System)
             Thyroid Progenitors
     
     Adipose (Muscoskeletal System)    fully expand to see all 2 entries
             Body Subcutaneous White Adipose
     
     Thymus (Hematopoietic System)
             Double Negative 3 Thymocytes Thymus
     
     Gut Tube (Gastrointestinal Tract)
             Foregut
     
     Blood (Cardiovascular System)
             Double Negative 3 Thymocytes Thymus
    TSHR Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    TSHR Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.160411

    UniProtKB/Swiss-Prot: TSHR_HUMAN, P16473
    Tissue specificity: Expressed in the thyroid

        Pathway & Disease-focused RT2 Profiler 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

    Primer
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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)
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    This gene was present in the common ancestor of animals.

    Orthologs for TSHR gene from Selected species (see all 15)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Tshr1 , 5 thyroid stimulating hormone receptor1, 5 86.17(n)1
    86.78(a)1
      12 (44.51 cM)5
    220951  NM_011648.51  NP_035778.31 
     914009935 
    chicken
    (Gallus gallus)
    Aves TSHR1 thyroid stimulating hormone receptor 71.63(n)
    74.09(a)
      428900  NM_001193588.1  NP_001180517.1 
    lizard
    (Anolis carolinensis)
    Reptilia TSHR6
    thyroid stimulating hormone receptor
    71(a)
    1 ↔ 1
    1(17924371-17953600)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia tshr1 thyroid stimulating hormone receptor 67.61(n)
    69.08(a)
      100492843  XM_002938373.2  XP_002938419.2 
    zebrafish
    (Danio rerio)
    Actinopterygii tshr1 thyroid stimulating hormone receptor 63.86(n)
    62.55(a)
      560609  NM_001145763.2  NP_001139235.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Fsh3 G-protein coupled receptor protein
    signaling pathway more
    37(a)
    (best of 2)
      3 90C2   --
    worm
    (Caenorhabditis elegans)
    Secernentea C50H2.13 steroid hormone receptor 30(a)   V(9892549-9897216)   --


    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)
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    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):
    FSHR    LHCGR

    TSHR for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, 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), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Polymorphic Variants from UniProtKB/Swiss-Prot
    TSHR_HUMAN, P16473: 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


    Selected SNPs for TSHR (see all 4179)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 14 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1219088631,2,,4
    CHypothyroidism, congenital, non-goitrous, 1 (CHNG1)4 pathogenic162546446(+) ACAACC/GCTTAC 6 P A mis10--------
    VAR_0115264
    Hypothyroidism, congenital, non-goitrous, 1 (CHNG1)4--see VAR_0115262 D N mis40--------
    VAR_0035674
    Papillary cancer4--see VAR_0035672 F I mis40--------
    VAR_0115314
    Hyperthyroidism, non-autoimmune (HTNA)4--see VAR_0115312 I F mis40--------
    VAR_0115354
    Hyperthyroidism, non-autoimmune (HTNA)4--see VAR_0115352 V A mis40--------
    VAR_0115544
    Hyperthyroidism, non-autoimmune (HTNA)4--see VAR_0115542 N Y mis40--------
    VAR_0035684
    Papillary cancer4--see VAR_0035682 D E mis40--------
    VAR_0035664
    Familial gestational hyperthyroidism (HTFG)4--see VAR_0035662 K R mis40--------
    VAR_0172974
    Hypothyroidism, congenital, non-goitrous, 1 (CHNG1)4--see VAR_0172972 C R mis40--------
    VAR_0115384
    Hypothyroidism, congenital, non-goitrous, 1 (CHNG1)4--see VAR_0115382 A T mis40--------

    HapMap Linkage Disequilibrium report for TSHR (81421333 - 81612646 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for TSHR (see all 17):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2748928CNV Deletion23290073
    esv2661838CNV Deletion23128226
    esv2748927CNV Deletion23290073
    esv2265006CNV Deletion18987734
    esv2036394CNV Deletion18987734
    esv2585992CNV Deletion19546169
    esv4614CNV Deletion18987735
    esv2748926CNV Deletion23290073
    esv2495579CNV Deletion19546169
    nsv1374CNV Insertion18451855

    Human Gene Mutation Database (HGMD): TSHR
    Locus Specific Mutation Databases (LSDB): TSHR

    Selected Site Specific Mutation Identification with PCR Assays for TSHR (see all 15):
    Cosmic IdAA Change
    26419p.D633Y
    26451p.I568T
    26420p.D633H
    26418p.T632I
    26415p.D619G
    3 Site Specific Cancer Mutation PCR Panels containing TSHR:
    Thyroid Cancer
    Cancer Comprehensive Panel 384HT
    Tumor Suppressor Panel 384HT
    SeqTarget long-range PCR primers 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

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    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
  • 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. Note=The disease is caused by mutations 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. Note=The disease is caused by mutations
    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. Note=The disease is caused by mutations affecting the gene represented in this entry

  • Selected diseases for TSHR (see all 82):    
    About MalaCards
    hyperthyroidism    familial hyperthyroidism due to mutations in tsh receptor    hyperthyroidism, familial gestational    myxedema
    neonatal thyrotoxicosis    congenital hypothyroidism, nongoitrous 1    thyrotoxicosis    thyroid adenoma, hyperfunctioning, somatic
    multinodular goiter    thyroid carcinoma with thyrotoxicosis    toxic diffuse goiter    hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia
    endemic goiter    struma ovarii    neonatal hypothyroidism    nontoxic goiter
    transient congenital hypothyroidism    thyroiditis    thymic hyperplasia    goiter

    10 diseases from the University of Copenhagen DISEASES database for TSHR:
    Hyperthyroidism     Hypersensitivity reaction type II disease     Hypothyroidism     Goiter
    Thyroiditis     Thyrotoxicosis     Thyroid cancer     Adenoma
    Exophthalmos     Thyroid adenoma

    TSHR for disorders           About GeneDecksing

    Selected Novoseek inferred 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

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    PubMed articles for TSHR gene, integrated from 10 sources (see all 995):
    (articles sorted by number of sources associating them with TSHR)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. 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. (Thyroid 2003)
    2. 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. (J. Clin. Endocrinol. Metab. 2003)
    3. 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. (Thyroid 2002)
    4. 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. (Biochem. Biophys. Res. Commun. 1989)
    5. Molecular cloning, sequence and functional expression of the cDNA for the human thyrotropin receptor. (PubMed id 2558651)1, 2, 3 Nagayama Y.... Rapoport B. (Biochem. Biophys. Res. Commun. 1989)
    6. Thyrotropin receptor and thyroid transcription factor-1 genes variant in Chinese children with congenital hypothyroidism. (PubMed id 18379122)1, 4, 9 Yuan Z.F....Zhao Z.Y. (Endocr. J. 2008)
    7. 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. (Eur. J. Endocrinol. 2000)
    8. 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. (Jpn Heart J 2002)
    9. Prevalence of TSH receptor and Gsalpha mutations in 45 autonomously functioning thyroid nodules in Japan. (PubMed id 19550078)1, 4, 9 Nishihara E....Miyauchi A. (Endocr. J. 2009)
    10. Association of the thyroid stimulating hormone receptor gene (TSHR) with Graves' disease. (PubMed id 19244275)1, 4, 9 Brand O.J....Gough S.C. (Hum. Mol. Genet. 2009)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    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)
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    Entrez Gene: 7253 HGNC: 12373 AceView: TSHR Ensembl:ENSG00000165409 euGenes: HUgn7253
    ECgene: TSHR Kegg: 7253 H-InvDB: TSHR

    (According to HUGE)
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      --

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

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    NameDescription
    PharmGKB entry for TSHR Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for TSHR Genetics and Cytogenetics in Oncology and Haematology
    TSH receptor databasehttp://endokrinologie.uniklinikum-leipzig.de/tsh/
    GRIShttp://gris.ulb.ac.be/
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=TSHR[genesymbol]
    SHMPDhttp://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 receptorshttp://www.ssfa-gphr.de/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    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



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