Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Thyrotropin receptor

The TSHR gene encodes the membrane bound TSH receptor. Through this receptor secretion of thyroid hormone and thyroid growth is stimulated. Inactivating mutations cause congenital hypothyroidism while activating mutations cause hyperthyroidism. Also somatic mutations were observed in some thyroid cancers.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Research Method Multiplex Ligation-Dependent Probe Amplification
Turnaround 25 days
Specimen type genomic DNA
Research Method Genomic sequencing of the entire coding region
Turnaround 25 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

Familial gestational hyperthyroidism
TSHR
Non-autoimmune hyperthyroidism
TSHR
Congenital nongoitrous hypothyroidism 1
TSHR
Hyperfunctioning thyroid adenoma
TSHR
Thyroid carcinoma with thyrotoxicosis
TSHR

References:

1.

Wilkie TM et. al. (1993) Identification, chromosomal location, and genome organization of mammalian G-protein-coupled receptors.

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2.

Lazar V et. al. (1999) Expression of the Na+/I- symporter gene in human thyroid tumors: a comparison study with other thyroid-specific genes.

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3.

Hase H et. al. (2006) TNFalpha mediates the skeletal effects of thyroid-stimulating hormone.

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4.

Rubin CJ et. al. (2010) Whole-genome resequencing reveals loci under selection during chicken domestication.

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5.

Loosfelt H et. al. (1992) Two-subunit structure of the human thyrotropin receptor.

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6.

Akamizu T et. al. (1990) Cloning, chromosomal assignment, and regulation of the rat thyrotropin receptor: expression of the gene is regulated by thyrotropin, agents that increase cAMP levels, and thyroid autoantibodies.

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7.

Murakami M et. al. (1990) Identification of immunogenic regions in human thyrotropin receptor for immunoglobulin G of patients with Graves' disease.

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8.

Heldin NE et. al. (1991) A somatic point mutation in a putative ligand binding domain of the TSH receptor in a patient with autoimmune hyperthyroidism.

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9.

Wadsworth HL et. al. (1990) An insertion in the human thyrotropin receptor critical for high affinity hormone binding.

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10.

Libert F et. al. (1990) Localization of human thyrotropin receptor gene to chromosome region 14q3 by in situ hybridization.

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11.

Rousseau-Merck MF et. al. (1990) Assignment of the human thyroid stimulating hormone receptor (TSHR) gene to chromosome 14q31.

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12.

Misrahi M et. al. (1990) Cloning, sequencing and expression of human TSH receptor.

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13.

Nagayama Y et. al. (1989) Molecular cloning, sequence and functional expression of the cDNA for the human thyrotropin receptor.

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14.

Libert F et. al. (1989) Cloning, sequencing and expression of the human thyrotropin (TSH) receptor: evidence for binding of autoantibodies.

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15.

Chan JY et. al. (1989) Cloning and characterization of a cDNA that encodes a 70-kDa novel human thyroid autoantigen.

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16.

Thomas JS et. al. (1982) Familial hyperthyroidism without evidence of autoimmunity.

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17.

Bahn RS et. al. (1994) A genomic point mutation in the extracellular domain of the thyrotropin receptor in patients with Graves' ophthalmopathy.

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18.

Van Sande J et. al. (1995) Somatic and germline mutations of the TSH receptor gene in thyroid diseases.

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19.

Kopp P et. al. (1995) Brief report: congenital hyperthyroidism caused by a mutation in the thyrotropin-receptor gene.

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20.

Duprez L et. al. (1994) Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism.

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21.

Feliciello A et. al. (1993) Expression of thyrotropin-receptor mRNA in healthy and Graves' disease retro-orbital tissue.

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22.

Parma J et. al. (1993) Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas.

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23.

Ohmori M et. al. (1996) Cloning of the single strand DNA-binding protein important for maximal expression and thyrotropin (TSH)-induced negative regulation of the TSH receptor.

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24.

de Roux N et. al. (1996) Four families with loss of function mutations of the thyrotropin receptor.

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25.

de Roux N et. al. (1996) A neomutation of the thyroid-stimulating hormone receptor in a severe neonatal hyperthyroidism.

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26.

Russo D et. al. (1997) Detection of an activating mutation of the thyrotropin receptor in a case of an autonomously hyperfunctioning thyroid insular carcinoma.

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27.

Kotsa KD et. al. (1997) No association between a thyrotropin receptor gene polymorphism and Graves' disease in the female population.

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28.

Clifton-Bligh RJ et. al. (1997) Two novel mutations in the thyrotropin (TSH) receptor gene in a child with resistance to TSH.

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29.

Abramowicz MJ et. al. (1997) Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland.

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30.

Parma J et. al. (1997) Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas.

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31.

Kopp P et. al. (1997) Congenital hyperthyroidism caused by a solitary toxic adenoma harboring a novel somatic mutation (serine281-->isoleucine) in the extracellular domain of the thyrotropin receptor.

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32.

Biebermann H et. al. (1997) Mutations of the human thyrotropin receptor gene causing thyroid hypoplasia and persistent congenital hypothyroidism.

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33.

Holzapfel HP et. al. (1997) Sporadic congenital hyperthyroidism due to a spontaneous germline mutation in the thyrotropin receptor gene.

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34.

Führer D et. al. (1997) Somatic mutations in the thyrotropin receptor gene and not in the Gs alpha protein gene in 31 toxic thyroid nodules.

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35.

Paschke R et. al. (1997) The thyrotropin receptor in thyroid diseases.

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36.

Führer D et. al. (1997) Identification of a new thyrotropin receptor germline mutation (Leu629Phe) in a family with neonatal onset of autosomal dominant nonautoimmune hyperthyroidism.

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37.

Grüters A et. al. (1998) Severe congenital hyperthyroidism caused by a germ-line neo mutation in the extracellular portion of the thyrotropin receptor.

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38.

Gagné N et. al. (1998) Apparent congenital athyreosis contrasting with normal plasma thyroglobulin levels and associated with inactivating mutations in the thyrotropin receptor gene: are athyreosis and ectopic thyroid distinct entities?

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39.

Rodien P et. al. (1998) Familial gestational hyperthyroidism caused by a mutant thyrotropin receptor hypersensitive to human chorionic gonadotropin.

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40.

Simanainen J et. al. (1999) Analysis of mutations in exon 1 of the human thyrotropin receptor gene: high frequency of the D36H and P52T polymorphic variants.

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41.

Khoo DH et. al. (1999) A germline mutation of the thyrotropin receptor gene associated with thyrotoxicosis and mitral valve prolapse in a Chinese family.

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42.

Graves P et. al. (1999) Post-translational processing of the natural human thyrotropin receptor: demonstration of more than two cleavage sites.

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43.

Trülzsch B et. al. (1999) The thyrotropin receptor mutation database.

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44.

Gabriel EM et. al. (1999) Germline polymorphism of codon 727 of human thyroid-stimulating hormone receptor is associated with toxic multinodular goiter.

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45.

Tonacchera M et. al. (2000) Congenital hypothyroidism with impaired thyroid response to thyrotropin (TSH) and absent circulating thyroglobulin: evidence for a new inactivating mutation of the TSH receptor gene.

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46.

Tonacchera M et. al. (2000) Activating thyrotropin receptor mutations are present in nonadenomatous hyperfunctioning nodules of toxic or autonomous multinodular goiter.

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47.

Mühlberg T et. al. (2000) Lack of association of nonautoimmune hyperfunctioning thyroid disorders and a germline polymorphism of codon 727 of the human thyrotropin receptor in a European Caucasian population.

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48.

Russo D et. al. (2000) A novel mutation in the thyrotropin (TSH) receptor gene causing loss of TSH binding but constitutive receptor activation in a family with resistance to TSH.

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49.

Biebermann H et. al. (2001) The first activating TSH receptor mutation in transmembrane domain 1 identified in a family with nonautoimmune hyperthyroidism.

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50.

Alberti L et. al. (2002) Germline mutations of TSH receptor gene as cause of nonautoimmune subclinical hypothyroidism.

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51.

Kakinuma A et. al. (2002) Multiple messenger ribonucleic acid transcripts and revised gene organization of the human TSH receptor.

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52.

Jordan N et. al. (2003) The W546X mutation of the thyrotropin receptor gene: potential major contributor to thyroid dysfunction in a Caucasian population.

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53.

Chen CR et. al. (2003) The thyrotropin receptor autoantigen in Graves disease is the culprit as well as the victim.

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54.

Abe E et. al. (2003) TSH is a negative regulator of skeletal remodeling.

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55.

Hiratani H et. al. (2005) Multiple SNPs in intron 7 of thyrotropin receptor are associated with Graves' disease.

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56.

Dechairo BM et. al. (2005) Association of the TSHR gene with Graves' disease: the first disease specific locus.

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57.

Calebiro D et. al. (2005) Intracellular entrapment of wild-type TSH receptor by oligomerization with mutants linked to dominant TSH resistance.

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58.

Chia SY et. al. (2007) Thyroid-stimulating hormone receptor messenger ribonucleic acid measurement in blood as a marker for circulating thyroid cancer cells and its role in the preoperative diagnosis of thyroid cancer.

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Update: Sept. 26, 2018