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TSHR thyroid stimulating hormone receptor [ Homo sapiens (human) ]

Gene ID: 7253, updated on 2-Nov-2024

Summary

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Official Symbol
TSHRprovided by HGNC
Official Full Name
thyroid stimulating hormone receptorprovided by HGNC
Primary source
HGNC:HGNC:12373
See related
Ensembl:ENSG00000165409 MIM:603372; AllianceGenome:HGNC:12373
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
LGR3; CHNG1; hTSHR-I
Summary
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]
Expression
Restricted expression toward thyroid (RPKM 104.1) See more
Orthologs
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Genomic context

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See TSHR in Genome Data Viewer
Location:
14q31.1
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (80955621..81146306)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (75167122..75358539)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (81421965..81612650)

Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene DIO2 antisense RNA 1 Neighboring gene iodothyronine deiodinase 2 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr14:80930624-80931315 Neighboring gene centrosomal protein 128 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_37660 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_37671 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_37742 Neighboring gene high mobility group nucleosomal binding domain 2 pseudogene 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8818 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8819 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8820 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8821 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8822 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:81439163-81439664 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:81439665-81440164 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5983 Neighboring gene uncharacterized LOC101928462 Neighboring gene GPRASP3 pseudogene 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr14:81507651-81507772 Neighboring gene ribosomal protein L17 pseudogene 3 Neighboring gene NMNAT1 pseudogene 1 Neighboring gene uncharacterized LOC105370594 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8823 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8824 Neighboring gene general transcription factor IIA subunit 1 Neighboring gene small nucleolar RNA, H/ACA box 79

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. The first activating TSH receptor mutation in transmembrane domain 1 identified in a family with nonautoimmune hyperthyroidism. Biebermann H, et al. J Clin Endocrinol Metab, 2001 Sep. PMID 11549687
  2. Lysine 183 and glutamic acid 157 of the TSH receptor: two interacting residues with a key role in determining specificity toward TSH and human CG. Smits G, et al. Mol Endocrinol, 2002 Apr. PMID 11923469
  3. [Transcription and promoter hypermethylation of thyroid stimulating hormone receptor gene in human papillary thyroid carcinoma]. Dai YL, et al. Nan Fang Yi Ke Da Xue Xue Bao, 2010 Jan. PMID 20117998
  4. Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships. Szkudlinski MW, et al. Physiol Rev, 2002 Apr. PMID 11917095
  5. Signaling-sensitive amino acids surround the allosteric ligand binding site of the thyrotropin receptor. Kleinau G, et al. FASEB J, 2010 Jul. PMID 20179143, Free PMC Article

See all (391) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Genetic and Functional Studies of Patients with Thyroid Dyshormonogenesis and Defects in the TSH Receptor (TSHR).
    Title: Genetic and Functional Studies of Patients with Thyroid Dyshormonogenesis and Defects in the TSH Receptor (TSHR).
  2. TSHR-IGF-IR complex drives orbital fibroblast misbehavior in thyroid eye disease.
    Title: TSHR-IGF-IR complex drives orbital fibroblast misbehavior in thyroid eye disease.
  3. A Novel TSHR Gene Mutation in a Family with Non-autoimmune Hyperthyroidism.
    Title: A Novel TSHR Gene Mutation in a Family with Non-autoimmune Hyperthyroidism.
  4. TSHR Variant Screening and Phenotype Analysis in 367 Chinese Patients With Congenital Hypothyroidism.
    Title: TSHR Variant Screening and Phenotype Analysis in 367 Chinese Patients With Congenital Hypothyroidism.
  5. Mechanisms of thyrotropin receptor-mediated phenotype variability deciphered by gene mutations and M453T-knockin model.
    Title: Mechanisms of thyrotropin receptor-mediated phenotype variability deciphered by gene mutations and M453T-knockin model.
  6. Somatostatin Receptor Type 2 and Thyroid-Stimulating Hormone Receptor Expression in Oncocytic Thyroid Neoplasms: Implications for Prognosis and Treatment.
    Title: Somatostatin Receptor Type 2 and Thyroid-Stimulating Hormone Receptor Expression in Oncocytic Thyroid Neoplasms: Implications for Prognosis and Treatment.
  7. Molecular investigation of TSHR gene in Bangladeshi congenital hypothyroid patients.
    Title: Molecular investigation of TSHR gene in Bangladeshi congenital hypothyroid patients.
  8. Eighteen-years follow-up of congenital hypothyroidism by TSHR gene p.Arg109Gln and p.Arg450His variants.
    Title: Eighteen-years follow-up of congenital hypothyroidism by TSHR gene p.Arg109Gln and p.Arg450His variants.
  9. Unraveling the significance of TSHR mutations in indeterminate thyroid cytology specimens.
    Title: Unraveling the significance of TSHR mutations in indeterminate thyroid cytology specimens.
  10. [Pathogenic TSHR variants in children with thyroid dysgenesis].
    Title: [Pathogenic TSHR variants in children with thyroid dysgenesis].
Submit: New GeneRIF Correction See all GeneRIFs (271)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Familial gestational hyperthyroidism
MedGen: C1863959 OMIM: 603373 GeneReviews: Not available
not available
Familial hyperthyroidism due to mutations in TSH receptor
MedGen: C1836706 OMIM: 609152 GeneReviews: Not available
not available
Hypothyroidism due to TSH receptor mutations
MedGen: C3493776 OMIM: 275200 GeneReviews: Not available
not available

EBI GWAS Catalog

Description
A genome-wide association study identifies two new risk loci for Graves' disease.
EBI GWAS Catalog
A genome-wide association study of serum uric acid in African Americans.
EBI GWAS Catalog
Common variants in the trichohyalin gene are associated with straight hair in Europeans.
EBI GWAS Catalog
Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.
EBI GWAS Catalog
Genome-wide association identifies ATOH7 as a major gene determining human optic disc size.
EBI GWAS Catalog
Genome-wide association study identifies three novel genetic markers associated with elite endurance performance.
EBI GWAS Catalog
Genome-wide association study of primary dentition pit-and-fissure and smooth surface caries.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC75129

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables G protein-coupled peptide receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein-containing complex binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables signaling receptor activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables thyroid-stimulating hormone receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables thyroid-stimulating hormone receptor activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Process Evidence Code Pubs
involved_in G protein-coupled receptor signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
involved_in G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger TAS
Traceable Author Statement
more info
 PubMed 
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cell surface receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cell-cell signaling TAS
Traceable Author Statement
more info
 PubMed 
involved_in cellular response to glycoprotein IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to thyrotropin-releasing hormone IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in hormone-mediated signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of cell population proliferation TAS
Traceable Author Statement
more info
 PubMed 
involved_in positive regulation of cold-induced thermogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
involved_in thyroid-stimulating hormone signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in basolateral plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cell surface ISS
Inferred from Sequence or Structural Similarity
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  
part_of receptor complex IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
thyrotropin receptor
Names
TSH receptor
seven transmembrane helix receptor
thyrotropin receptor-I, hTSHR-I

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_009206.1 RefSeqGene

    Range
    5001..195778
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_523

mRNA and Protein(s)

  1. NM_000369.5 → NP_000360.2  thyrotropin receptor isoform 1 precursor

    See identical proteins and their annotated locations for NP_000360.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and it encodes the longer protein (isoform 1).
    Source sequence(s)
    AC007262, AC010072, AL136040
    Consensus CDS
    CCDS9872.1
    UniProtKB/Swiss-Prot
    A0A0A0MTJ0, A0PJU7, F5GYU5, G3V2A9, P16473, Q16503, Q8TB90, Q96GT6, Q9P1V4, Q9ULA3, Q9UPH3
    UniProtKB/TrEMBL
    Q59GA2
    Related
    ENSP00000298171.2, ENST00000298171.7
    Conserved Domains (4) summary
    sd00033
    Location:54 → 77
    LRR_RI; leucine-rich repeat [structural motif]
    pfam00001
    Location:431 → 678
    7tm_1; 7 transmembrane receptor (rhodopsin family)
    pfam13306
    Location:66 → 221
    LRR_5; Leucine rich repeats (6 copies)
    cl21561
    Location:417 → 609
    7tm_4; Olfactory receptor

  2. NM_001018036.3 → NP_001018046.1  thyrotropin receptor isoform 2

    See identical proteins and their annotated locations for NP_001018046.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2), also called ST4, differs in the 3' UTR and coding sequence compared to variant 1. The resulting isoform (2) has a shorter and distinct C-terminus compared to isoform 1.
    Source sequence(s)
    BC024205, BC063613
    Consensus CDS
    CCDS32131.1
    UniProtKB/TrEMBL
    Q0VAP8
    Related
    ENSP00000340113.6, ENST00000342443.10
    Conserved Domains (2) summary
    sd00033
    Location:54 → 77
    LRR_RI; leucine-rich repeat [structural motif]
    pfam13306
    Location:66 → 221
    LRR_5; Leucine rich repeats (6 copies)

  3. NM_001142626.3 → NP_001136098.1  thyrotropin receptor isoform 3 precursor

    See identical proteins and their annotated locations for NP_001136098.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 3' UTR and coding sequence and uses an alternate in-frame splice junction compared to variant 1. The resulting isoform (3) has a shorter and distinct C-terminus and contains an alternate internal segment compared to isoform 1.
    Source sequence(s)
    BC024205, BC108653, BC127628
    Consensus CDS
    CCDS55935.1
    UniProtKB/TrEMBL
    Q0VAP8
    Related
    ENSP00000450549.1, ENST00000554435.1
    Conserved Domains (2) summary
    sd00033
    Location:54 → 77
    LRR_RI; leucine-rich repeat [structural motif]
    pfam13306
    Location:66 → 221
    LRR_5; Leucine rich repeats (6 copies)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000014.9 Reference GRCh38.p14 Primary Assembly

    Range
    80955621..81146306
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011537119.3 → XP_011535421.1  thyrotropin receptor isoform X1

    UniProtKB/TrEMBL
    Q59GA2
    Conserved Domains (3) summary
    sd00033
    Location:54 → 84
    LRR_RI; leucine-rich repeat [structural motif]
    pfam00001
    Location:338 → 585
    7tm_1; 7 transmembrane receptor (rhodopsin family)
    cl21561
    Location:324 → 516
    7tm_4; Olfactory receptor

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060938.1 Alternate T2T-CHM13v2.0

    Range
    75167122..75358539
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054376675.1 → XP_054232650.1  thyrotropin receptor isoform X2

  2. XM_054376677.1 → XP_054232652.1  thyrotropin receptor isoform X3

  3. XM_054376678.1 → XP_054232653.1  thyrotropin receptor isoform X4

  4. XM_054376676.1 → XP_054232651.1  thyrotropin receptor isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P16473.3 GenPept UniProtKB/Swiss-Prot:P16473

Gene LinkOut

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