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Identification
HMDB Protein ID HMDBP02134
Secondary Accession Numbers
  • 7617
Name Thyrotropin receptor
Synonyms
  1. TSH-R
  2. Thyroid-stimulating hormone receptor
Gene Name TSHR
Protein Type Unknown
Biological Properties
General Function Involved in G-protein coupled receptor protein signaling pathway
Specific 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)
Pathways Not Available
Reactions Not Available
GO Classification
Component
cell part
membrane part
intrinsic to membrane
integral to membrane
Function
receptor activity
transmembrane receptor activity
protein-hormone receptor activity
molecular transducer activity
signal transducer activity
g-protein coupled receptor activity
Process
signaling
signaling pathway
cell surface receptor linked signaling pathway
g-protein coupled receptor protein signaling pathway
Cellular Location
  1. Cell membrane
  2. Multi-pass membrane protein
Gene Properties
Chromosome Location Chromosome:1
Locus 14q31
SNPs TSHR
Gene Sequence
>2295 bp
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
Protein Properties
Number of Residues 764
Molecular Weight 86829.0
Theoretical pI 6.98
Pfam Domain Function
Signals
  • 1-20
Transmembrane Regions
  • 414-441
  • 451-473
  • 495-517
  • 538-560
  • 581-602
  • 626-649
  • 661-682
Protein Sequence
>Thyrotropin receptor
MRPADLLQLVLLLDLPRDLGGMGCSSPPCECHQEEDFRVTCKDIQRIPSLPPSTQTLKLI
ETHLRTIPSHAFSNLPNISRIYVSIDVTLQQLESHSFYNLSKVTHIEIRNTRNLTYIDPD
ALKELPLLKFLGIFNTGLKMFPDLTKVYSTDIFFILEITDNPYMTSIPVNAFQGLCNETL
TLKLYNNGFTSVQGYAFNGTKLDAVYLNKNKYLTVIDKDAFGGVYSGPSLLDVSQTSVTA
LPSKGLEHLKELIARNTWTLKKLPLSLSFLHLTRADLSYPSHCCAFKNQKKIRGILESLM
CNESSMQSLRQRKSVNALNSPLHQEYEENLGDSIVGYKEKSKFQDTHNNAHYYVFFEEQE
DEIIGFGQELKNPQEETLQAFDSHYDYTICGDSEDMVCTPKSDEFNPCEDIMGYKFLRIV
VWFVSLLALLGNVFVLLILLTSHYKLNVPRFLMCNLAFADFCMGMYLLLIASVDLYTHSE
YYNHAIDWQTGPGCNTAGFFTVFASELSVYTLTVITLERWYAITFAMRLDRKIRLRHACA
IMVGGWVCCFLLALLPLVGISSYAKVSICLPMDTETPLALAYIVFVLTLNIVAFVIVCCC
YVKIYITVRNPQYNPGDKDTKIAKRMAVLIFTDFICMAPISFYALSAILNKPLITVSNSK
ILLVLFYPLNSCANPFLYAIFTKAFQRDVFILLSKFGICKRQAQAYRGQRVPPKNSTDIQ
VQKVTHDMRQGLHNMEDVYELIENSHLTPKKQGQISEEYMQTVL
GenBank ID Protein 64085121
UniProtKB/Swiss-Prot ID P16473
UniProtKB/Swiss-Prot Entry Name TSHR_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_000369.2
GeneCard ID TSHR
GenAtlas ID TSHR
HGNC ID HGNC:12373
References
General References
  1. 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. [PubMed:12508121 ]
  2. 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. [PubMed:2558651 ]
  3. 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. [PubMed:2610690 ]
  4. 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. [PubMed:2302212 ]
  5. 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. [PubMed:2293030 ]
  6. 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. [PubMed:1530609 ]
  7. 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. [PubMed:11502179 ]
  8. 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. [PubMed:12045258 ]
  9. 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. [PubMed:15775968 ]
  10. 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. [PubMed:8747461 ]
  11. 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. [PubMed:11887032 ]
  12. 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. [PubMed:12593721 ]
  13. 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. [PubMed:12930595 ]
  14. 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. [PubMed:10870027 ]
  15. 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. [PubMed:1955520 ]
  16. 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. [PubMed:8413627 ]
  17. 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. [PubMed:7508946 ]
  18. 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. [PubMed:8045989 ]
  19. 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. [PubMed:7989485 ]
  20. 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. [PubMed:7920658 ]
  21. 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. [PubMed:7556878 ]
  22. 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. [PubMed:7800007 ]
  23. 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. [PubMed:7528344 ]
  24. 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. [PubMed:7647578 ]
  25. 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. [PubMed:7488864 ]
  26. 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. [PubMed:8636266 ]
  27. 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. [PubMed:8964822 ]
  28. 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. [PubMed:8954020 ]
  29. 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. [PubMed:9062474 ]
  30. 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. [PubMed:9100579 ]
  31. 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. [PubMed:9253356 ]
  32. 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. [PubMed:9329388 ]
  33. 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. [PubMed:9360555 ]
  34. 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. [PubMed:9398746 ]
  35. 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. [PubMed:9185526 ]
  36. 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. [PubMed:9294132 ]
  37. 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. [PubMed:9349581 ]
  38. 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. [PubMed:9589634 ]
  39. 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. [PubMed:9854118 ]
  40. 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. [PubMed:10199795 ]
  41. 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. [PubMed:10487707 ]
  42. 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. [PubMed:10037070 ]
  43. 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. [PubMed:10560955 ]
  44. 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. [PubMed:11022192 ]
  45. 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. [PubMed:10651846 ]
  46. 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. [PubMed:10720030 ]
  47. 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. [PubMed:10852462 ]
  48. 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. [PubMed:10946859 ]
  49. 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. [PubMed:11095460 ]
  50. 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. [PubMed:11127522 ]
  51. 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. [PubMed:11081252 ]
  52. 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. [PubMed:11128715 ]
  53. 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. [PubMed:11201847 ]
  54. 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. [PubMed:11517004 ]
  55. 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. [PubMed:11549687 ]
  56. 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. [PubMed:11434721 ]
  57. 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. [PubMed:11442002 ]
  58. 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. [PubMed:12213664 ]
  59. 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. [PubMed:12050212 ]
  60. 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. [PubMed:12589819 ]
  61. 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. [PubMed:12788902 ]
  62. 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. [PubMed:14759073 ]
  63. 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. [PubMed:14725684 ]
  64. 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. [PubMed:15163335 ]
  65. 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. [PubMed:15531543 ]