NameThyrotropin receptor
Synonyms
  • LGR3
  • Thyroid-stimulating hormone receptor
  • TSH-R
Gene NameTSHR
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000978|Thyrotropin receptor
MRPADLLQLVLLLDLPRDLGGMGCSSPPCECHQEEDFRVTCKDIQRIPSLPPSTQTLKLI
ETHLRTIPSHAFSNLPNISRIYVSIDVTLQQLESHSFYNLSKVTHIEIRNTRNLTYIDPD
ALKELPLLKFLGIFNTGLKMFPDLTKVYSTDIFFILEITDNPYMTSIPVNAFQGLCNETL
TLKLYNNGFTSVQGYAFNGTKLDAVYLNKNKYLTVIDKDAFGGVYSGPSLLDVSQTSVTA
LPSKGLEHLKELIARNTWTLKKLPLSLSFLHLTRADLSYPSHCCAFKNQKKIRGILESLM
CNESSMQSLRQRKSVNALNSPLHQEYEENLGDSIVGYKEKSKFQDTHNNAHYYVFFEEQE
DEIIGFGQELKNPQEETLQAFDSHYDYTICGDSEDMVCTPKSDEFNPCEDIMGYKFLRIV
VWFVSLLALLGNVFVLLILLTSHYKLNVPRFLMCNLAFADFCMGMYLLLIASVDLYTHSE
YYNHAIDWQTGPGCNTAGFFTVFASELSVYTLTVITLERWYAITFAMRLDRKIRLRHACA
IMVGGWVCCFLLALLPLVGISSYAKVSICLPMDTETPLALAYIVFVLTLNIVAFVIVCCC
YVKIYITVRNPQYNPGDKDTKIAKRMAVLIFTDFICMAPISFYALSAILNKPLITVSNSK
ILLVLFYPLNSCANPFLYAIFTKAFQRDVFILLSKFGICKRQAQAYRGQRVPPKNSTDIQ
VQKVTHDMRQGLHNMEDVYELIENSHLTPKKQGQISEEYMQTVL
Number of residues764
Molecular Weight86828.965
Theoretical pI6.98
GO Classification
Functions
  • G-protein coupled peptide receptor activity
  • thyroid-stimulating hormone receptor activity
Processes
  • thyroid-stimulating hormone signaling pathway
  • cell-cell signaling
  • activation of adenylate cyclase activity
  • G-protein coupled receptor signaling pathway
  • positive regulation of cell proliferation
  • G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
  • adenylate cyclase-activating G-protein coupled receptor signaling pathway
  • hormone-mediated signaling pathway
Components
  • plasma membrane
  • receptor complex
  • integral component of plasma membrane
General FunctionThyroid-stimulating hormone receptor activity
Specific FunctionReceptor 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).
Pfam Domain Function
Transmembrane Regions414-441 451-473 495-517 538-560 581-602 626-649 661-682
GenBank Protein ID903760
UniProtKB IDP16473
UniProtKB Entry NameTSHR_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0010345|Thyrotropin receptor (TSHR)
ATGAGGCCGGCGGACTTGCTGCAGCTGGTGCTGCTGCTCGACCTGCCCAGGGACCTGGGC
GGAATGGGGTGTTCGTCTCCACCCTGCGAGTGCCATCAGGAGGAGGACTTCAGAGTCACC
TGCAAGGATATTCAACGCATCCCCAGCTTACCGCCCAGTACGCAGACTCTGAAGCTTATT
GAGACTCACCTGAGAACTATTCCAAGTCATGCATTTTCTAATCTGCCCAATATTTCCAGA
ATCTACGTATCTATAGATGTGACTCTGCAGCAGCTGGAATCACACTCCTTCTACAATTTG
AGTAAAGTGACTCACATAGAAATTCGGAATACCAGGAACTTAACTTACATAGACCCTGAT
GCCCTCAAAGAGCTCCCCCTCCTAAAGTTCCTTGGCATTTTCAACACTGGACTTAAAATG
TTCCCTGACCTGACCAAAGTTTATTCCACTGATATATTCTTTATACTTGAAATTACAGAC
AACCCTTACATGACGTCAATCCCTGTGAATGCTTTTCAGGGACTATGCAATGAAACCTTG
ACACTGAAGCTGTACAACAATGGCTTTACTTCAGTCCAAGGATATGCTTTCAATGGGACA
AAGCTGGATGCTGTTTACCTAAACAAGAATAAATACCTGACAGTTATTGACAAAGATGCA
TTTGGAGGAGTATACAGTGGACCAAGCTTGCTGGACGTGTCTCAAACCAGTGTCACTGCC
CTTCCATCCAAAGGCCTGGAGCACCTGAAGGAACTGATAGCAAGAAACACCTGGACTCTT
AAGAAACTTCCACTTTCCTTGAGTTTCCTTCACCTCACACGGGCTGACCTTTCTTACCCA
AGCCACTGCTGTGCTTTTAAGAATCAGAAGAAAATCAGAGGAATCCTTGAGTCCTTGATG
TGTAATGAGAGCAGTATGCAGAGCTTGCGCCAGAGAAAATCTGTGAATGCCTTGAATAGC
CCCCTCCACCAGGAATATGAAGAGAATCTGGGTGACAGCATTGTTGGGTACAAGGAAAAG
TCCAAGTTCCAGGATACTCATAACAACGCTCATTATTACGTCTTCTTTGAAGAACAAGAG
GATGAGATCATTGGTTTTGGCCAGGAGCTCAAAAACCCCCAGGAAGAGACTCTACAAGCT
TTTGACAGCCATTATGACTACACCATATGTGGGGACAGTGAAGACATGGTGTGTACCCCC
AAGTCCGATGAGTTCAACCCGTGTGAAGACATAATGGGCTACAAGTTCCTGAGAATTGTG
GTGTGGTTCGTTAGTCTGCTGGCTCTCCTGGGCAATGTCTTTGTCCTGCTTATTCTCCTC
ACCAGCCACTACAAACTGAACGTCCCCCGCTTTCTCATGTGCAACCTGGCCTTTGCGGAT
TTCTGCATGGGGATGTACCTGCTCCTCATCGCCTCTGTAGACCTCTACACTCACTCTGAG
TACTACAACCATGCCATCGACTGGCAGACAGGCCCTGGGTGCAACACGGCTGGTTTCTTC
ACTGTCTTTGCAAGCGAGTTATCGGTGTATACGCTGACGGTCATCACCCTGGAGCGCTGG
TATGCCATCACCTTCGCCATGCGCCTGGACCGGAAGATCCGCCTCAGGCACGCATGTGCC
ATCATGGTTGGGGGCTGGGTTTGCTGCTTCCTTCTCGCCCTGCTTCCTTTGGTGGGAATA
AGTAGCTATGCCAAAGTCAGTATCTGCCTGCCCATGGACACCGAGACCCCTCTTGCTCTG
GCATATATTGTTTTTGTTCTGACGCTCAACATAGTTGCCTTCGTCATCGTCTGCTGCTGT
TATGTGAAGATCTACATCACAGTCCGAAATCCGCAGTACAACCCAGGGGACAAAGATACC
AAAATTGCCAAGAGGATGGCTGTGTTGATCTTCACCGACTTCATATGCATGGCCCCAATC
TCATTCTATGCTCTGTCAGCAATTCTGAACAAGCCTCTCATCACTGTTAGCAACTCCAAA
ATCTTGCTGGTACTCTTCTATCCACTTAACTCCTGTGCCAATCCATTCCTCTATGCTATT
TTCACCAAGGCCTTCCAGAGGGATGTGTTCATCCTACTCAGCAAGTTTGGCATCTGTAAA
CGCCAGGCTCAGGCATACCGGGGGCAGAGGGTTCCTCCAAAGAACAGCACTGATATTCAG
GTTCAAAAGGTTACCCACGAGATGAGGCAGGGTCTCCACAACATGGAAGATGTCTATGAA
CTGATTGAAAACTCCCATCTAACCCCAAAGAAGCAAGGCCAAATCTCAGAAGAGTATATG
CAAACGGTTTTGTAA
GenBank Gene IDM73747
GeneCard IDNot Available
GenAtlas IDTSHR
HGNC IDHGNC:12373
Chromosome Location14
Locus14q31
References
  1. Nagayama Y, Kaufman KD, Seto P, Rapoport B: Molecular cloning, sequence and functional expression of the cDNA for the human thyrotropin receptor. Biochem Biophys Res Commun. 1989 Dec 29;165(3):1184-90. 2558651
  2. Libert F, Lefort A, Gerard C, Parmentier M, Perret J, Ludgate M, Dumont JE, Vassart G: Cloning, sequencing and expression of the human thyrotropin (TSH) receptor: evidence for binding of autoantibodies. Biochem Biophys Res Commun. 1989 Dec 29;165(3):1250-5. 2610690
  3. Misrahi M, Loosfelt H, Atger M, Sar S, Guiochon-Mantel A, Milgrom E: Cloning, sequencing and expression of human TSH receptor. Biochem Biophys Res Commun. 1990 Jan 15;166(1):394-403. 2302212
  4. Frazier AL, Robbins LS, Stork PJ, Sprengel R, Segaloff DL, Cone RD: Isolation of TSH and LH/CG receptor cDNAs from human thyroid: regulation by tissue specific splicing. Mol Endocrinol. 1990 Aug;4(8):1264-76. 2293030
  5. Graves PN, Tomer Y, Davies TF: Cloning and sequencing of a 1.3 KB variant of human thyrotropin receptor mRNA lacking the transmembrane domain. Biochem Biophys Res Commun. 1992 Sep 16;187(2):1135-43. 1530609
  6. Takeshita A, Nagayama Y, Fujiyama K, Yokoyama N, Namba H, Yamashita S, Izumi M, Nagataki S: Molecular cloning and sequencing of an alternatively spliced form of the human thyrotropin receptor transcript. Biochem Biophys Res Commun. 1992 Nov 16;188(3):1214-9. 1445355
  7. Heilig R, Eckenberg R, Petit JL, Fonknechten N, Da Silva C, Cattolico L, Levy M, Barbe V, de Berardinis V, Ureta-Vidal A, Pelletier E, Vico V, Anthouard V, Rowen L, Madan A, Qin S, Sun H, Du H, Pepin K, Artiguenave F, Robert C, Cruaud C, Bruls T, Jaillon O, Friedlander L, Samson G, Brottier P, Cure S, Segurens B, Aniere F, Samain S, Crespeau H, Abbasi N, Aiach N, Boscus D, Dickhoff R, Dors M, Dubois I, Friedman C, Gouyvenoux M, James R, Madan A, Mairey-Estrada B, Mangenot S, Martins N, Menard M, Oztas S, Ratcliffe A, Shaffer T, Trask B, Vacherie B, Bellemere C, Belser C, Besnard-Gonnet M, Bartol-Mavel D, Boutard M, Briez-Silla S, Combette S, Dufosse-Laurent V, Ferron C, Lechaplais C, Louesse C, Muselet D, Magdelenat G, Pateau E, Petit E, Sirvain-Trukniewicz P, Trybou A, Vega-Czarny N, Bataille E, Bluet E, Bordelais I, Dubois M, Dumont C, Guerin T, Haffray S, Hammadi R, Muanga J, Pellouin V, Robert D, Wunderle E, Gauguet G, Roy A, Sainte-Marthe L, Verdier J, Verdier-Discala C, Hillier L, Fulton L, McPherson J, Matsuda F, Wilson R, Scarpelli C, Gyapay G, Wincker P, Saurin W, Quetier F, Waterston R, Hood L, Weissenbach J: The DNA sequence and analysis of human chromosome 14. Nature. 2003 Feb 6;421(6923):601-7. Epub 2003 Jan 1. 12508121
  8. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  9. Cornelis S, Uttenweiler-Joseph S, Panneels V, Vassart G, Costagliola S: Purification and characterization of a soluble bioactive amino-terminal extracellular domain of the human thyrotropin receptor. Biochemistry. 2001 Aug 21;40(33):9860-9. 11502179
  10. Nakabayashi K, Matsumi H, Bhalla A, Bae J, Mosselman S, Hsu SY, Hsueh AJ: Thyrostimulin, a heterodimer of two new human glycoprotein hormone subunits, activates the thyroid-stimulating hormone receptor. J Clin Invest. 2002 Jun;109(11):1445-52. 12045258
  11. Lahuna O, Quellari M, Achard C, Nola S, Meduri G, Navarro C, Vitale N, Borg JP, Misrahi M: Thyrotropin receptor trafficking relies on the hScrib-betaPIX-GIT1-ARF6 pathway. EMBO J. 2005 Apr 6;24(7):1364-74. Epub 2005 Mar 17. 15775968
  12. Jiang X, Dreano M, Buckler DR, Cheng S, Ythier A, Wu H, Hendrickson WA, el Tayar N: Structural predictions for the ligand-binding region of glycoprotein hormone receptors and the nature of hormone-receptor interactions. Structure. 1995 Dec 15;3(12):1341-53. 8747461
  13. Sanders J, Chirgadze DY, Sanders P, Baker S, Sullivan A, Bhardwaja A, Bolton J, Reeve M, Nakatake N, Evans M, Richards T, Powell M, Miguel RN, Blundell TL, Furmaniak J, Smith BR: Crystal structure of the TSH receptor in complex with a thyroid-stimulating autoantibody. Thyroid. 2007 May;17(5):395-410. 17542669
  14. Chistiakov DA, Savost'anov KV, Turakulov RI, Petunina N, Balabolkin MI, Nosikov VV: Further studies of genetic susceptibility to Graves' disease in a Russian population. Med Sci Monit. 2002 Mar;8(3):CR180-4. 11887032
  15. Ban Y, Greenberg DA, Concepcion ES, Tomer Y: 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. Thyroid. 2002 Dec;12(12):1079-83. 12593721
  16. Ho SC, Goh SS, Khoo DH: Association of Graves' disease with intragenic polymorphism of the thyrotropin receptor gene in a cohort of Singapore patients of multi-ethnic origins. Thyroid. 2003 Jun;13(6):523-8. 12930595
  17. Farid NR, Kascur V, Balazs C: The human thyrotropin receptor is highly mutable: a review of gain-of-function mutations. Eur J Endocrinol. 2000 Jul;143(1):25-30. 10870027
  18. Heldin NE, Gustavsson B, Westermark K, Westermark B: A somatic point mutation in a putative ligand binding domain of the TSH receptor in a patient with autoimmune hyperthyroidism. J Clin Endocrinol Metab. 1991 Dec;73(6):1374-6. 1955520
  19. Parma J, Duprez L, Van Sande J, Cochaux P, Gervy C, Mockel J, Dumont J, Vassart G: Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature. 1993 Oct 14;365(6447):649-51. 8413627
  20. Bahn RS, Dutton CM, Heufelder AE, Sarkar G: A genomic point mutation in the extracellular domain of the thyrotropin receptor in patients with Graves' ophthalmopathy. J Clin Endocrinol Metab. 1994 Feb;78(2):256-60. 7508946
  21. Porcellini A, Ciullo I, Laviola L, Amabile G, Fenzi G, Avvedimento VE: Novel mutations of thyrotropin receptor gene in thyroid hyperfunctioning adenomas. Rapid identification by fine needle aspiration biopsy. J Clin Endocrinol Metab. 1994 Aug;79(2):657-61. 8045989
  22. Paschke R, Tonacchera M, Van Sande J, Parma J, Vassart G: Identification and functional characterization of two new somatic mutations causing constitutive activation of the thyrotropin receptor in hyperfunctioning autonomous adenomas of the thyroid. J Clin Endocrinol Metab. 1994 Dec;79(6):1785-9. 7989485
  23. Duprez L, Parma J, Van Sande J, Allgeier A, Leclere J, Schvartz C, Delisle MJ, Decoulx M, Orgiazzi J, Dumont J, et al.: Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism. Nat Genet. 1994 Jul;7(3):396-401. 7920658
  24. Gustavsson B, Eklof C, Westermark K, Westermark B, Heldin NE: Functional analysis of a variant of the thyrotropin receptor gene in a family with Graves' disease. Mol Cell Endocrinol. 1995 Jun;111(2):167-73. 7556878
  25. Kopp P, van Sande J, Parma J, Duprez L, Gerber H, Joss E, Jameson JL, Dumont JE, Vassart G: Brief report: congenital hyperthyroidism caused by a mutation in the thyrotropin-receptor gene. N Engl J Med. 1995 Jan 19;332(3):150-4. 7800007
  26. Sunthornthepvarakui T, Gottschalk ME, Hayashi Y, Refetoff S: Brief report: resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene. N Engl J Med. 1995 Jan 19;332(3):155-60. 7528344
  27. Ohno M, Endo T, Ohta K, Gunji K, Onaya T: Point mutations in the thyrotropin receptor in human thyroid tumors. Thyroid. 1995 Apr;5(2):97-100. 7647578
  28. Cuddihy RM, Bryant WP, Bahn RS: Normal function in vivo of a homozygotic polymorphism in the human thyrotropin receptor. Thyroid. 1995 Aug;5(4):255-7. 7488864
  29. Tonacchera M, Van Sande J, Cetani F, Swillens S, Schvartz C, Winiszewski P, Portmann L, Dumont JE, Vassart G, Parma J: Functional characteristics of three new germline mutations of the thyrotropin receptor gene causing autosomal dominant toxic thyroid hyperplasia. J Clin Endocrinol Metab. 1996 Feb;81(2):547-54. 8636266
  30. de Roux N, Polak M, Couet J, Leger J, Czernichow P, Milgrom E, Misrahi M: A neomutation of the thyroid-stimulating hormone receptor in a severe neonatal hyperthyroidism. J Clin Endocrinol Metab. 1996 Jun;81(6):2023-6. 8964822
  31. de Roux N, Misrahi M, Brauner R, Houang M, Carel JC, Granier M, Le Bouc Y, Ghinea N, Boumedienne A, Toublanc JE, Milgrom E: Four families with loss of function mutations of the thyrotropin receptor. J Clin Endocrinol Metab. 1996 Dec;81(12):4229-35. 8954020
  32. Russo D, Tumino S, Arturi F, Vigneri P, Grasso G, Pontecorvi A, Filetti S, Belfiore A: Detection of an activating mutation of the thyrotropin receptor in a case of an autonomously hyperfunctioning thyroid insular carcinoma. J Clin Endocrinol Metab. 1997 Mar;82(3):735-8. 9062474
  33. Clifton-Bligh RJ, Gregory JW, Ludgate M, John R, Persani L, Asteria C, Beck-Peccoz P, Chatterjee VK: Two novel mutations in the thyrotropin (TSH) receptor gene in a child with resistance to TSH. J Clin Endocrinol Metab. 1997 Apr;82(4):1094-100. 9100579
  34. Parma J, Duprez L, Van Sande J, Hermans J, Rocmans P, Van Vliet G, Costagliola S, Rodien P, Dumont JE, Vassart G: Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas. J Clin Endocrinol Metab. 1997 Aug;82(8):2695-701. 9253356
  35. Biebermann H, Schoneberg T, Krude H, Schultz G, Gudermann T, Gruters A: Mutations of the human thyrotropin receptor gene causing thyroid hypoplasia and persistent congenital hypothyroidism. J Clin Endocrinol Metab. 1997 Oct;82(10):3471-80. 9329388
  36. Holzapfel HP, Wonerow P, von Petrykowski W, Henschen M, Scherbaum WA, Paschke R: Sporadic congenital hyperthyroidism due to a spontaneous germline mutation in the thyrotropin receptor gene. J Clin Endocrinol Metab. 1997 Nov;82(11):3879-84. 9360555
  37. Fuhrer D, Wonerow P, Willgerodt H, Paschke R: Identification of a new thyrotropin receptor germline mutation (Leu629Phe) in a family with neonatal onset of autosomal dominant nonautoimmune hyperthyroidism. J Clin Endocrinol Metab. 1997 Dec;82(12):4234-8. 9398746
  38. Abramowicz MJ, Duprez L, Parma J, Vassart G, Heinrichs C: Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland. J Clin Invest. 1997 Jun 15;99(12):3018-24. 9185526
  39. Kopp P, Muirhead S, Jourdain N, Gu WX, Jameson JL, Rodd C: Congenital hyperthyroidism caused by a solitary toxic adenoma harboring a novel somatic mutation (serine281-->isoleucine) in the extracellular domain of the thyrotropin receptor. J Clin Invest. 1997 Sep 15;100(6):1634-9. 9294132
  40. Kopp P, Jameson JL, Roe TF: Congenital nonautoimmune hyperthyroidism in a nonidentical twin caused by a sporadic germline mutation in the thyrotropin receptor gene. Thyroid. 1997 Oct;7(5):765-70. 9349581
  41. Gruters A, Schoneberg T, Biebermann H, Krude H, Krohn HP, Dralle H, Gudermann T: Severe congenital hyperthyroidism caused by a germ-line neo mutation in the extracellular portion of the thyrotropin receptor. J Clin Endocrinol Metab. 1998 May;83(5):1431-6. 9589634
  42. Rodien P, Bremont C, Sanson ML, Parma J, Van Sande J, Costagliola S, Luton JP, Vassart G, Duprez L: Familial gestational hyperthyroidism caused by a mutant thyrotropin receptor hypersensitive to human chorionic gonadotropin. N Engl J Med. 1998 Dec 17;339(25):1823-6. 9854118
  43. Khoo DH, Parma J, Rajasoorya C, Ho SC, Vassart G: A germline mutation of the thyrotropin receptor gene associated with thyrotoxicosis and mitral valve prolapse in a Chinese family. J Clin Endocrinol Metab. 1999 Apr;84(4):1459-62. 10199795
  44. Gabriel EM, Bergert ER, Grant CS, van Heerden JA, Thompson GB, Morris JC: Germline polymorphism of codon 727 of human thyroid-stimulating hormone receptor is associated with toxic multinodular goiter. J Clin Endocrinol Metab. 1999 Sep;84(9):3328-35. 10487707
  45. Russo D, Wong MG, Costante G, Chiefari E, Treseler PA, Arturi F, Filetti S, Clark OH: A Val 677 activating mutation of the thyrotropin receptor in a Hurthle cell thyroid carcinoma associated with thyrotoxicosis. Thyroid. 1999 Jan;9(1):13-7. 10037070
  46. Esapa CT, Duprez L, Ludgate M, Mustafa MS, Kendall-Taylor P, Vassart G, Harris PE: A novel thyrotropin receptor mutation in an infant with severe thyrotoxicosis. Thyroid. 1999 Oct;9(10):1005-10. 10560955
  47. Kosugi S, Hai N, Okamoto H, Sugawa H, Mori T: A novel activating mutation in the thyrotropin receptor gene in an autonomously functioning thyroid nodule developed by a Japanese patient. Eur J Endocrinol. 2000 Oct;143(4):471-7. 11022192
  48. Kaczur V, Takacs M, Szalai C, Falus A, Nagy Z, Berencsi G, Balazs C: Analysis of the genetic variability of the 1st (CCC/ACC, P52T) and the 10th exons (bp 1012-1704) of the TSH receptor gene in Graves' disease. Eur J Immunogenet. 2000 Feb;27(1):17-23. 10651846
  49. Tonacchera M, Agretti P, Pinchera A, Rosellini V, Perri A, Collecchi P, Vitti P, Chiovato L: Congenital hypothyroidism with impaired thyroid response to thyrotropin (TSH) and absent circulating thyroglobulin: evidence for a new inactivating mutation of the TSH receptor gene. J Clin Endocrinol Metab. 2000 Mar;85(3):1001-8. 10720030
  50. Tonacchera M, Agretti P, Chiovato L, Rosellini V, Ceccarini G, Perri A, Viacava P, Naccarato AG, Miccoli P, Pinchera A, Vitti P: Activating thyrotropin receptor mutations are present in nonadenomatous hyperfunctioning nodules of toxic or autonomous multinodular goiter. J Clin Endocrinol Metab. 2000 Jun;85(6):2270-4. 10852462
  51. Muhlberg T, Herrmann K, Joba W, Kirchberger M, Heberling HJ, Heufelder AE: 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. J Clin Endocrinol Metab. 2000 Aug;85(8):2640-3. 10946859
  52. Russo D, Betterle C, Arturi F, Chiefari E, Girelli ME, Filetti S: 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. J Clin Endocrinol Metab. 2000 Nov;85(11):4238-42. 11095460
  53. Biebermann H, Schoneberg T, Krude H, Gudermann T, Gruters A: Constitutively activating TSH-receptor mutations as a molecular cause of non-autoimmune hyperthyroidism in childhood. Langenbecks Arch Surg. 2000 Oct;385(6):390-2. 11127522
  54. Tonacchera M, Agretti P, Rosellini V, Ceccarini G, Perri A, Zampolli M, Longhi R, Larizza D, Pinchera A, Vitti P, Chiovato L: Sporadic nonautoimmune congenital hyperthyroidism due to a strong activating mutation of the thyrotropin receptor gene. Thyroid. 2000 Oct;10(10):859-63. 11081252
  55. Camacho P, Gordon D, Chiefari E, Yong S, DeJong S, Pitale S, Russo D, Filetti S: A Phe 486 thyrotropin receptor mutation in an autonomously functioning follicular carcinoma that was causing hyperthyroidism. Thyroid. 2000 Nov;10(11):1009-12. 11128715
  56. Fuhrer D, Warner J, Sequeira M, Paschke R, Gregory J, Ludgate M: Novel TSHR germline mutation (Met463Val) masquerading as Graves' disease in a large Welsh kindred with hyperthyroidism. Thyroid. 2000 Dec;10(12):1035-41. 11201847
  57. Alberti L, Proverbio MC, Costagliola S, Weber G, Beck-Peccoz P, Chiumello G, Persani L: A novel germline mutation in the TSH receptor gene causes non-autoimmune autosomal dominant hyperthyroidism. Eur J Endocrinol. 2001 Sep;145(3):249-54. 11517004
  58. Biebermann H, Schoneberg T, Hess C, Germak J, Gudermann T, Gruters A: The first activating TSH receptor mutation in transmembrane domain 1 identified in a family with nonautoimmune hyperthyroidism. J Clin Endocrinol Metab. 2001 Sep;86(9):4429-33. 11549687
  59. Trulzsch B, Krohn K, Wonerow P, Chey S, Holzapfel HP, Ackermann F, Fuhrer D, Paschke R: Detection of thyroid-stimulating hormone receptor and Gsalpha mutations: in 75 toxic thyroid nodules by denaturing gradient gel electrophoresis. J Mol Med (Berl). 2001;78(12):684-91. 11434721
  60. Nagashima T, Murakami M, Onigata K, Morimura T, Nagashima K, Mori M, Morikawa A: Novel inactivating missense mutations in the thyrotropin receptor gene in Japanese children with resistance to thyrotropin. Thyroid. 2001 Jun;11(6):551-9. 11442002
  61. Vanvooren V, Uchino S, Duprez L, Costa MJ, Vandekerckhove J, Parma J, Vassart G, Dumont JE, Van Sande J, Noguchi S: Oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in the Japanese population. Eur J Endocrinol. 2002 Sep;147(3):287-91. 12213664
  62. Alberti L, Proverbio MC, Costagliola S, Romoli R, Boldrighini B, Vigone MC, Weber G, Chiumello G, Beck-Peccoz P, Persani L: Germline mutations of TSH receptor gene as cause of nonautoimmune subclinical hypothyroidism. J Clin Endocrinol Metab. 2002 Jun;87(6):2549-55. 12050212
  63. Sykiotis GP, Neumann S, Georgopoulos NA, Sgourou A, Papachatzopoulou A, Markou KB, Kyriazopoulou V, Paschke R, Vagenakis AG, Papavassiliou AG: Functional significance of the thyrotropin receptor germline polymorphism D727E. Biochem Biophys Res Commun. 2003 Feb 21;301(4):1051-6. 12589819
  64. Peeters RP, van Toor H, Klootwijk W, de Rijke YB, Kuiper GG, Uitterlinden AG, Visser TJ: Polymorphisms in thyroid hormone pathway genes are associated with plasma TSH and iodothyronine levels in healthy subjects. J Clin Endocrinol Metab. 2003 Jun;88(6):2880-8. 12788902
  65. Tonacchera M, Perri A, De Marco G, Agretti P, Montanelli L, Banco ME, Corrias A, Bellone J, Tosi MT, Vitti P, Martino E, Pinchera A, Chiovato L: TSH receptor and Gs(alpha) genetic analysis in children with Down's syndrome and subclinical hypothyroidism. J Endocrinol Invest. 2003 Oct;26(10):997-1000. 14759073
  66. Park SM, Clifton-Bligh RJ, Betts P, Chatterjee VK: Congenital hypothyroidism and apparent athyreosis with compound heterozygosity or compensated hypothyroidism with probable hemizygosity for inactivating mutations of the TSH receptor. Clin Endocrinol (Oxf). 2004 Feb;60(2):220-7. 14725684
  67. Vaidya B, Campbell V, Tripp JH, Spyer G, Hattersley AT, Ellard S: Premature birth and low birth weight associated with nonautoimmune hyperthyroidism due to an activating thyrotropin receptor gene mutation. Clin Endocrinol (Oxf). 2004 Jun;60(6):711-8. 15163335
  68. Tonacchera M, Perri A, De Marco G, Agretti P, Banco ME, Di Cosmo C, Grasso L, Vitti P, Chiovato L, Pinchera A: Low prevalence of thyrotropin receptor mutations in a large series of subjects with sporadic and familial nonautoimmune subclinical hypothyroidism. J Clin Endocrinol Metab. 2004 Nov;89(11):5787-93. 15531543