Home > A. Molecular pathology > TTF1


MIM.600635 14q13.3 HGNC:11825

Thursday 26 June 2008

NK2 homeobox 1, NKX2A, BCH, TITF1, thyroid transcription factor 1, TTF-1, TTF1; TTF1, thyroid transcription factor-1, TITF1; thyroid transcription factor-1 TTF-1NKX2-1 ; NKX2-1


Definition: Thyroid transcription factor-1 (TTF-1) is a 38-kd homeodomain containing DNA-binding protein originally identified in follicular cells of the thyroid and subsequently in pneumocytes. TTF-1 is one of the three most important transcription factors for thyroid gland organogenesis.

Expression in normal cells

- follicular cells of the thyroid

Expression in tumors

- pulmonary small cell carcinomas (82.7%)
- extrapulmonary small cell carcinomas (42.0%)
- brain anomalies


- germline mutations of TITF1 in

  • benign hereditary chorea (MIM.118700)
  • choreoathetosis and hypothyroidism (16507635)
  • choreoathetosis, hypothyroidism and respiratory distress (MIM.118700)
    • congenital alveolar proteinosis
  • congenital hypothyroidism and benign chorea without pulmonary distress (16507635)


- Differential diagtnosis


- TTF1-associated benign hereditary chorea (MIM.118700)
- TTF1-associated choreoathetosis, hypothyroidism, and respiratory distress (MIM.610978)
- TTF1-associated neonatal respiratory distress (MIM.610978)

  • TTF1-associated infantile pneumopathy


- TTF1-expressing thyroid tumors

- TTF1-expressing pulmonary tumors

  • pulmonary adenocarcinoma
  • small cell lung tumor
  • pulmonary neuroendocrine tumors

- TTF1-expressing pituitary tumors

- TTF1-expressing extra-pulmonary neuroendocrine tumors


- Chordoid Gliomas of the Third Ventricle Share TTF-1 Expression With Organum Vasculosum of the Lamina Terminalis. Bielle F, Villa C, Giry M, Bergemer-Fouquet AM, Polivka M, Vasiljevic A, Aubriot-Lorton MH, Bernier M, Lechapt-Zalcman E, Viennet G, Sazdovitch V, Duyckaerts C, Sanson M, Figarella-Branger D, Mokhtari K; RENOP. Am J Surg Pathol. 2015 Mar 16. PMID: 25786084

- TTF-1 in Embryonal Tumors: An Immunohistochemical Study of 117 Cases. Galliani CA, Bisceglia M, Lastilla G, Parafioriti A, Vita G, Rosai J. Am J Surg Pathol. 2011 Sep;35(9):1422-5. PMID: 21836486

- Lau SK, Luthringer DJ, Eisen RN. Thyroid transcription factor-1: a review. Appl Immunohistochem Mol Morphol. 2002 Jun;10(2):97-102. PMID: 12051643

- Thyroid transcription factor-1 expression in breast carcinomas. Robens J, Goldstein L, Gown AM, Schnitt SJ. Am J Surg Pathol. 2010 Dec;34(12):1881-5. PMID: 21107096

- DeFelice M, Silberschmidt D, DiLauro R, Xu Y, Wert SE, Weaver TE, Bachurski CJ, Clark JC, Whitsett JA. TTF-1 phosphorylation is required for peripheral lung morphogenesis, perinatal survival, and tissue-specific gene expression. J Biol Chem. 2003 Sep 12;278(37):35574-83. PMID: 12829717

- Acebron, A.; Aza-Blanc, P.; Rossi, D. L.; Lamas, L.; Santisteban, P. :
Congenital human thyroglobulin defect due to low expression of the thyroid-specific transcription factor TTF-1. J. Clin. Invest. 96: 781-785, 1995. PubMed ID : 7635972

- Asmus, F.; Horber, V.; Pohlenz, J.; Schwabe, D.; Zimprich, A.; Munz, M.; Schoning, M.; Gasser, T. : A novel TITF-1 mutation causes benign hereditary chorea with response to levodopa. Neurology 64: 1952-1954, 2005. PubMed ID : 15955952

- Breedveld, G. J.; van Dongen, J. W. F.; Danesino, C.; Guala, A.; Percy, A. K.; Dure, L. S.; Harper, P.; Lazarou, L. P.; van der Linde, H.; Joosse, M.; Gruters, A.; MacDonald, M. E.; de Vries, B. B. A.; Arts, W. F. M.; Oostra, B. A.; Krude, H.; Heutink, P. : Mutations in TITF-1 are associated with benign hereditary chorea. Hum. Molec. Genet. 11: 971-979, 2002. PubMed ID : 11971878

- Devriendt, K.; Vanhole, C.; Matthijs, G.; de Zegher, F. :
Deletion of thyroid transcription factor-1 gene in an infant with neonatal thyroid dysfunction and respiratory failure. (Letter) New Eng. J. Med. 338: 1317-1318, 1998. PubMed ID : 9565498

- do Carmo Costa, M.; Costa, C.; Silva, A. P.; Evangelista, P.; Santos, L.; Ferro, A.; Sequeiros, J.; Maciel, P. : Nonsense mutation in TITF1 in a Portuguese family with benign hereditary chorea. Neurogenetics 6: 209-215, 2005. PubMed ID : 16220345

- Doyle, D. A.; Gonzalez, I.; Thomas, B.; Scavina, M. :
Autosomal dominant transmission of congenital hypothyroidism, neonatal respiratory distress, and ataxia caused by a mutation of NKX2-1. J. Pediat. 145: 190-193, 2004. PubMed ID : 15289765

- Garcia-Barcelo, M.-M.; Lau, D. K.; Ngan, E. S.; Leon, T. Y.; Liu, T.; So, M.; Miao, X.; Lui, V. C.; Wong, K. K.; Ganster, R. W.; Cass, D. T.; Croaker, G. D. H.; Tam, P. K. : Evaluation of the thyroid transcription factor-1 gene (TITF1) as a Hirschsprung’s disease locus. Ann. Hum. Genet. 71: 746-754, 2007. PubMed ID : 17640327

- Iwatani, N.; Mabe, H.; Devriendt, K.; Kodama, M.; Miike, T. :
Deletion of NKX2.1 gene encoding thyroid transcription factor-1 in two siblings with hypothyroidism and respiratory failure. J. Pediat. 137: 272-276, 2000. PubMed ID : 10931427

- Kimura, S.; Hara, Y.; Pineau, T.; Fernandez-Salguero, P.; Fox, C. H.; Ward, J. M.; Gonzalez, F. J. : The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary. Genes Dev. 10: 60-69, 1996. PubMed ID : 8557195

- Krude, H.; Schutz, B.; Biebermann, H.; von Moers, A.; Schnabel, D.; Neitzel, H.; Tonnies, H.; Weise, D.; Lafferty, A.; Schwarz, S.; DeFelice, M.; von Deimling, A.; van Landeghem, F.; DiLauro, R.; Gruters, A. :
Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency. J. Clin. Invest. 109: 475-480, 2002. PubMed ID : 11854319

- Pohlenz, J.; Dumitrescu, A.; Zundel, D.; Martine, U.; Schonberger, W.; Koo, E.; Weiss, R. E.; Cohen, R. N.; Kimura, S.; Refetoff, S. :
Partial deficiency of thyroid transcription factor 1 produces predominantly neurological defects in humans and mice. J. Clin. Invest. 109: 469-473, 2002. PubMed ID : 11854318

- Seidman, J. G.; Seidman, C. : Transcription factor haploinsufficiency: when half a loaf is not enough. (Commentary) J. Clin. Invest. 109: 451-455, 2002. PubMed ID : 11854316

- Trueba, S. S.; Auge, J.; Mattei, G.; Etchevers, H.; Martinovic, J.; Czernichow, P.; Vekemans, M.; Polak, M.; Attie-Bitach, T. : PAX8, TITF1, and FOXE1 gene expression patterns during human development: new insights into human thyroid development and thyroid dysgenesis-associated malformations. J. Clin. Endocr. Metab. 90: 455-462, 2005. PubMed ID : 15494458

- Weir, B. A.; Woo, M. S.; Getz, G.; Perner, S.; Ding, L.; Beroukhim, R.; Lin, W. M.; Province, M. A.; Kraja, A.; Johnson, L. A.; Shah, K.; Sato, M.; and 58 others : Characterizing the cancer genome in lung adenocarcinoma. Nature 450: 893-898, 2007. PubMed ID : 17982442

- Zhu, N. L.; Li, C.; Xiao, J.; Minoo, P. : NKX2.1 regulates transcription of the gene for human bone morphogenetic protein-4 in lung epithelial cells. Gene 327: 25-36, 2004. PubMed ID : 14960358


  • TTF-1 labelling in infantile thyroid