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TET2 (tet methylcytosine dioxygenase 2)

Written2014-08Franck Viguié
Laboratoire de Cytogenetique - Service d'Hematologie Biologique, Hopital Hotel-Dieu - 75181 Paris Cedex 04, France

(Note : for Links provided by Atlas : click)

Identity

Alias_namesKIAA1546
KIAA1546
tet oncogene family member 2
Alias_symbol (synonym)FLJ20032
Other aliasMDS
HGNC (Hugo) TET2
LocusID (NCBI) 54790
Atlas_Id 40597
Location 4q24  [Link to chromosome band 4q24]
Location_base_pair Starts at 105145875 and ends at 105242771 bp from pter ( according to hg19-Feb_2009)  [Mapping TET2.png]
Fusion genes
(updated 2017)		Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
NINJ1 (9q22.31) / TET2 (4q24)TET2 (4q24) / ADH6 (4q23)TET2 (4q24) / LANCL1 (2q34)
TET2 (4q24) / LARP7 (4q25)
Note The name of the TET family ("ten eleven translocation") comes from the TET1 gene involved in the translocation t(10;11)(q21;q23) which fuses TET1 with MLL, in 2 cases of acute myeloid leukemia.

DNA/RNA

Description Genomic size: 133942bp; Coding sequence: 6009 nt - 11 exons, 9 coding exons on plus strand.
Transcription From centromere to telomere.
Pre-mRNA alternative splicing produces at least 3 isoforms.

Protein

Note Name: 2-oxoglutarate tet methylcytosine dioxygenase 2.
Description The canonical isoform 1 is composed of 2002 amino acids.
The catalytic dioxygenase domain is located at the C-terminal part of the protein, inside a cysteine-rich region. Isoforms 2 and 3 appear as truncated proteins whose function is not yet well understood.
Expression Wide, mainly in haematopoietic tissues and in some specialized areas of the nervous tissue.
Localisation Nuclear.
 
Function Methylcytosine dioxygenase dependant of α-ketoglutarate (α-KG, also called 2-oxoglutarate) and Fe++, which catalyses conversion from 5-methylcytosine (5mC) to 5-dihydroxymethylcytosine (5hmC). TET proteins play a key role in epigenetic regulation of the transcription. The transition from 5mC to 5hmC, and later to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), is considered as a key step in the process of DNA demethylation at CpG islands and other sites. The enrichment in 5hmC in CpG islands near or inside promoter sites, as well as in intragenic regions, leads to increased gene expression. 5mC can be restored enzymatically from 5fC and 5caC, but not from 5hmC. The global epigenetic regulation of transcription seems to depend on the dynamic balance between 5mC and 5hmC (Branco et al., 2012; Kohli and Zhang, 2013) (figure 1).
The role of TET2 in haematopoiesis is pleiotropic, including self renewal of haematopoietic stem cells (HSCs), lineage commitment and cell line differentiation. TET2 is strongly expressed in progenitors and HSCs, and progressively repressed during differentiation. In mice the consequence of targeted inactivation of the Tet2 gene is a decrease of 5hmC and an increase of the number of mutated HSCs/progenitor cells, with a selective advantage over wt HSCs (Ko et al., 2011).
TET2 and TET3 proteins have a strong interaction with O-GlcNac transferase (OGT), independent from their catalytic activity on 5mC. OGT mediates the addition of O-GlcNac to ser and thr residues of many intracellular proteins. The link TET2/3-OGT promotes the activity of OGT: this complex binds to chromatin and contributes to promoters activation by enrichment in histone H3K4me3 (Solary et al., 2014).
Tet1 and Tet2 are also expressed in murine embryonic stem cells. To be noted the role of murine Tet2, in conjunction with the enzyme poly(ADP-ribose) polymerase-1 (Parp1), at an early stage of epigenetic reprogrammation of somatic cells into induced pluripotent stem cells (IPSCs) (Doege et al., 2012).
Homology TET2 is one member of a family comprising the 3 evolutionary conserved genes TET1, TET2 and TET3 in mammals. Only TET1 and TET2 are involved in malignant haematological diseases. The 3 proteins have two highly conserved domains in the middle of the protein and at the C-terminal extremity. TET1 and TET3 contain also a CXXC DNA binding zinc finger domain at the N-terminal extremity, which is not present in TET2. However there is a CXXC domain in a gene named CXXC4 or IDAX located 650kb proximal from TET2, which results from a chromosomal inversion affecting the ancestral TET2 gene. IDAX is oriented and transcribed in opposite direction from TET2, it regulates its expression and would be involved in its DNA binding (Ko et al., 2013).

Mutations

Note All types of somatic TET2 mutations were observed in cancer. The more prominent implication was described in haematological malignancies. However TET2 activity alteration, either by mutation or transcriptional mRNA reduction, was subsequently reported in a great variety of human tumours.
The implication of the gene in haematological malignancies was first detected after the observation of reciprocal translocations involving a sub microscopic 4q24 deletion in tumour cells (Viguié et al., 2005). All mutations alter the catalytic activity, leading to a loss-of-function of the enzyme. Nonsense and frame shift mutations, which result in a truncated protein, occur all over the gene. But critical missense mutations occur only in the two evolutionary conserved domains of TET2. Missense variations outside of these two domains are considered as germinal polymorphisms. Both copies of the gene are altered in less than half of the patients, suggesting a role for haploinsufficiency. Consequently TET2 must be considered as a tumour suppressor gene.
In murine models, the consequence of Tet2 inactivation is a depletion of 5hmC in bone marrow cells, an increase of the pool of HSCs, and an orientation of maturation towards monocyte/macrophage differentiation (Quivoron et al., 2011). The same effect is obtained in vitro on human cell lines or CD34+ cells, by shRNA knockdown of TET2 gene (Pronier et al., 2011).
Mutations of TET2 and of IDH1/IDH2 are mutually exclusive, suggesting that they act in the same pathway. IDH1 and IDH2 are the two genes coding for an isocitrate deshydrogenase, they catalyse the decarboxylation of isocitrate to α-ketoglutarate (α-KG) in the Krebs cycle. IDH mutations lead to a gain of function and the production of the R enantiomer of 2-hydroxyglutarate (R-2HG) instead of α-KG. As α-KG is a crucial cofactor for the activity of TET2, the protein is inactivated by the production of R-2HG instead of α-KG.
Mutations of IDH1/IDH2 are observed in many tumours including haematological malignancies with the same final epigenetic effect as TET2 inactivation, mainly a global promoter hypermethylation.

Implicated in

Note
  
Entity Ph negative myeloproliferative neoplasms (MPN)
Note Frequency: mutated in 10-16% of polycythemia vera, 4-11% of essential thrombocytemia, 7-17% of idiopathic myelofibrosis, 14% of myelofibrosis post PV or ET, 29% of mastocytosis. TET2 mutation is a very early event, preceding JAK2 mutation in the major part of cases with JAK2 V617F mutation. It is associated with the expansion of the mutated clone (Delhommeau et al., 2009; Tefferi et al., 2009b). However there is no notable correlation with prognosis.
TET2 mutations were also observed during the progression from MPN to AML, appearing as a later event.
  
  
Entity Ph positive chronic myeloproliferative leukemia (CML)
Note No TET2 mutation detected in chronic phase.
In contrast mutations were detected in 8-12% of accelerated or blastic phase (Makishima et al., 2011; Roche-Lestienne et al., 2011).
  
  
Entity Chronic myelomonocytic leukemia (CMML)
Note Frequency : TET2 mutated in 42-50%, being by far the most frequent molecular event in CMML.
Prognosis Controversial. In some clinical studies CMML with TET2 mutated have a shorter overall survival and a higher monocyte rate compared to wt CMML. However other studies show less genomic alterations and a better prognosis in TET2 mutated patients (Tefferi et al., 2009a; Smith et al., 2010).
Genome-wide DNA methylation studies show that TET2 mutated CMML express a lower level of hypermethylation than wt CMML and constitute a subtype with distinct epigenetic characteristics.
  
  
Entity Myelodysplastic syndrome (MDS)
Note Frequency : TET2 mutated in 12-26%. As in CMML, TET2 mutation is the most frequent molecular event, before ASXL1 (~ 14%) and RUNX1 (~ 8%) mutations. There is no significant association with either sub-type of MDS. However there is a correlation between TET2 mutation and MDS with a normal karyotype (Tefferi et al., 2009a; Langemeijer et al., 2009; Smith et al., 2010).
Prognosis So far, no independent prognosis value.
  
  
Entity Acute myeloid leukemia (AML)
Note Frequency : from 7 to 27% of primary AML.
Prognosis The impact of TET2 mutations on AML prognosis is controversial. TET2 mutations are significantly associated with normal karyotype, older medium age, hyperleucocytosis and blasts rate more elevated. According to European Leukemia Net criteria, TET2 mutation impairs the prognosis of cytogenetically normal AML with favourable risk (NPM1 and/or CEBPA mutated, FLT3-ITD negative), in comparison with wt-TET2 patients (Metzeler et al., 2011). A more recent study from the EORTC group in AML patients<60 years, shows that a TET2 mutation is an independent factor of poor prognosis. TET2 mutations confer an even worse prognosis when associated with other bad prognosis factors (FLT3-ITD(+), -5, -7, complex). The same worse prognosis is observed when associated with a DNMT3A mutation. They also show that patients with low TET2 mRNA expression, albeit without mutation, have also a decrease of their overall survival (Aslanyan et al., 2014).
  
  
Entity Blastic plasmacytoid dendritic cell neoplasm
Note One study of 13 cases of this rare haematopoietic neoplasm of uncertain lineage showed TET2 frame shift, nonsense or missense mutations in 7 cases (53%). In 3 cases at least the mutations were biallelic (Jardin et al., 2011).
  
  
Entity Lymphoproliferative disease
Note Frequency: TET2 mutations were observed largely more frequently in T-cell lymphomas than in B-cell lymphomas (12% vs 2%). One to 3 TET2 mutations were found in 47 to 76% of angioimmunoblastic T-cell lymphoma (AITL), often associated with mutations of DNMT3A, a gene involved in cytosine methylation. In peripheral not otherwise specified T-cell lymphoma (PTCL-NOS), 38% harboured a TET2 mutation (Odejide et al., 2014).
TET2 mutations can occur in early or advanced stages of lymphoid differentiation. Some patients have a concomitant or previous myelodysplastic syndrome, and the same TET2 mutation is found in both cell lineages, favouring a common origin from an early stem cell (Viguié et al., 2005; Delhommeau et al., 2009).
More recently TET2 mutations were observed in12% of diffuse large B-cell lymphomas, composed of 5% missense and 7% nonsense mutations (Asmar et al., 2013).
  
  
Entity Low grade diffuse glioma
Note More than 85% of low grade diffuse glioma have an IDH1/2 mutation. TET2 gene was explored in those lacking one of these two mutations. No TET2 mutation was found but TET2 promoter methylation was detected in 5 of 35 cases (14%). No TET2 alteration was observed in all cases with IDH1/2 mutation (Kim et al., 2011).
  
  
Entity Other cancer types
Note Some studies show that 5hmc reduction is significantly associated with tumorigenesis in a great variety of tumours, and that 5hmC depletion is frequently linked to a TET2 mutation or transcriptional inactivation, in cancers of breast, lung, pancreas, liver and probably colon and prostate (Yang et al., 2013).
  

Bibliography

Clinical and biological impact of TET2 mutations and expression in younger adult AML patients treated within the EORTC/GIMEMA AML-12 clinical trial.
Aslanyan MG, Kroeze LI, Langemeijer SM, Koorenhof-Scheele TN, Massop M, van Hoogen P, Stevens-Linders E, van de Locht LT, Tonnissen E, van der Heijden A, da Silva-Coelho P, Cilloni D, Saglio G, Marie JP, Tang R, Labar B, Amadori S, Muus P, Willemze R, Marijt EW, de Witte T, van der Reijden BA, Suciu S, Jansen JH.
Ann Hematol. 2014 Aug;93(8):1401-12. doi: 10.1007/s00277-014-2055-7. Epub 2014 Mar 29.
PMID 24994606
 
Genome-wide profiling identifies a DNA methylation signature that associates with TET2 mutations in diffuse large B-cell lymphoma.
Asmar F, Punj V, Christensen J, Pedersen MT, Pedersen A, Nielsen AB, Hother C, Ralfkiaer U, Brown P, Ralfkiaer E, Helin K, Gronbaek K.
Haematologica. 2013 Dec;98(12):1912-20. doi: 10.3324/haematol.2013.088740. Epub 2013 Jul 5.
PMID 23831920
 
Uncovering the role of 5-hydroxymethylcytosine in the epigenome.
Branco MR, Ficz G, Reik W.
Nat Rev Genet. 2011 Nov 15;13(1):7-13. doi: 10.1038/nrg3080. (REVIEW)
PMID 22083101
 
Mutation in TET2 in myeloid cancers.
Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Masse A, Kosmider O, Le Couedic JP, Robert F, Alberdi A, Lecluse Y, Plo I, Dreyfus FJ, Marzac C, Casadevall N, Lacombe C, Romana SP, Dessen P, Soulier J, Viguie F, Fontenay M, Vainchenker W, Bernard OA.
N Engl J Med. 2009 May 28;360(22):2289-301. doi: 10.1056/NEJMoa0810069.
PMID 19474426
 
Early-stage epigenetic modification during somatic cell reprogramming by Parp1 and Tet2.
Doege CA, Inoue K, Yamashita T, Rhee DB, Travis S, Fujita R, Guarnieri P, Bhagat G, Vanti WB, Shih A, Levine RL, Nik S, Chen EI, Abeliovich A.
Nature. 2012 Aug 30;488(7413):652-5. doi: 10.1038/nature11333.
PMID 22902501
 
TET2 and TP53 mutations are frequently observed in blastic plasmacytoid dendritic cell neoplasm.
Jardin F, Ruminy P, Parmentier F, Troussard X, Vaida I, Stamatoullas A, Lepretre S, Penther D, Duval AB, Picquenot JM, Courville P, Capiod JC, Tilly H, Bastard C, Marolleau JP.
Br J Haematol. 2011 May;153(3):413-6. doi: 10.1111/j.1365-2141.2010.08556.x. Epub 2011 Jan 31.
PMID 21275969
 
TET2 promoter methylation in low-grade diffuse gliomas lacking IDH1/2 mutations.
Kim YH, Pierscianek D, Mittelbronn M, Vital A, Mariani L, Hasselblatt M, Ohgaki H.
J Clin Pathol. 2011 Oct;64(10):850-2. doi: 10.1136/jclinpath-2011-200133. Epub 2011 Jun 20.
PMID 21690245
 
Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX.
Ko M, An J, Bandukwala HS, Chavez L, Aijo T, Pastor WA, Segal MF, Li H, Koh KP, Lahdesmaki H, Hogan PG, Aravind L, Rao A.
Nature. 2013 May 2;497(7447):122-6. doi: 10.1038/nature12052. Epub 2013 Apr 7.
PMID 23563267
 
Ten-Eleven-Translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice.
Ko M, Bandukwala HS, An J, Lamperti ED, Thompson EC, Hastie R, Tsangaratou A, Rajewsky K, Koralov SB, Rao A.
Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14566-71. doi: 10.1073/pnas.1112317108. Epub 2011 Aug 22.
PMID 21873190
 
TET enzymes, TDG and the dynamics of DNA demethylation.
Kohli RM, Zhang Y.
Nature. 2013 Oct 24;502(7472):472-9. doi: 10.1038/nature12750. (REVIEW)
PMID 24153300
 
Acquired mutations in TET2 are common in myelodysplastic syndromes.
Langemeijer SM, Kuiper RP, Berends M, Knops R, Aslanyan MG, Massop M, Stevens-Linders E, van Hoogen P, van Kessel AG, Raymakers RA, Kamping EJ, Verhoef GE, Verburgh E, Hagemeijer A, Vandenberghe P, de Witte T, van der Reijden BA, Jansen JH.
Nat Genet. 2009 Jul;41(7):838-42. doi: 10.1038/ng.391. Epub 2009 May 31.
PMID 19483684
 
CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations and additional chromosomal aberrations constitute molecular events in chronic myelogenous leukemia.
Makishima H, Jankowska AM, McDevitt MA, O'Keefe C, Dujardin S, Cazzolli H, Przychodzen B, Prince C, Nicoll J, Siddaiah H, Shaik M, Szpurka H, Hsi E, Advani A, Paquette R, Maciejewski JP.
Blood. 2011 May 26;117(21):e198-206. doi: 10.1182/blood-2010-06-292433. Epub 2011 Feb 23.
PMID 21346257
 
TET2 mutations improve the new European LeukemiaNet risk classification of acute myeloid leukemia: a Cancer and Leukemia Group B study.
Metzeler KH, Maharry K, Radmacher MD, Mrozek K, Margeson D, Becker H, Curfman J, Holland KB, Schwind S, Whitman SP, Wu YZ, Blum W, Powell BL, Carter TH, Wetzler M, Moore JO, Kolitz JE, Baer MR, Carroll AJ, Larson RA, Caligiuri MA, Marcucci G, Bloomfield CD.
J Clin Oncol. 2011 Apr 1;29(10):1373-81. doi: 10.1200/JCO.2010.32.7742. Epub 2011 Feb 22.
PMID 21343549
 
A targeted mutational landscape of angioimmunoblastic T-cell lymphoma.
Odejide O, Weigert O, Lane AA, Toscano D, Lunning MA, Kopp N, Kim S, van Bodegom D, Bolla S, Schatz JH, Teruya-Feldstein J, Hochberg E, Louissaint A, Dorfman D, Stevenson K, Rodig SJ, Piccaluga PP, Jacobsen E, Pileri SA, Harris NL, Ferrero S, Inghirami G, Horwitz SM, Weinstock DM.
Blood. 2014 Feb 27;123(9):1293-6. doi: 10.1182/blood-2013-10-531509. Epub 2013 Dec 17.
PMID 24345752
 
Inhibition of TET2-mediated conversion of 5-methylcytosine to 5-hydroxymethylcytosine disturbs erythroid and granulomonocytic differentiation of human hematopoietic progenitors.
Pronier E, Almire C, Mokrani H, Vasanthakumar A, Simon A, da Costa Reis Monte Mor B, Masse A, Le Couedic JP, Pendino F, Carbonne B, Larghero J, Ravanat JL, Casadevall N, Bernard OA, Droin N, Solary E, Godley LA, Vainchenker W, Plo I, Delhommeau F.
Blood. 2011 Sep 1;118(9):2551-5. doi: 10.1182/blood-2010-12-324707. Epub 2011 Jul 6.
PMID 21734233
 
TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis.
Quivoron C, Couronne L, Della Valle V, Lopez CK, Plo I, Wagner-Ballon O, Do Cruzeiro M, Delhommeau F, Arnulf B, Stern MH, Godley L, Opolon P, Tilly H, Solary E, Duffourd Y, Dessen P, Merle-Beral H, Nguyen-Khac F, Fontenay M, Vainchenker W, Bastard C, Mercher T, Bernard OA.
Cancer Cell. 2011 Jul 12;20(1):25-38. doi: 10.1016/j.ccr.2011.06.003. Epub 2011 Jun 30.
PMID 21723201
 
Mutation analysis of TET2, IDH1, IDH2 and ASXL1 in chronic myeloid leukemia.
Roche-Lestienne C, Marceau A, Labis E, Nibourel O, Coiteux V, Guilhot J, Legros L, Nicolini F, Rousselot P, Gardembas M, Helevaut N, Frimat C, Mahon FX, Guilhot F, Preudhomme C; Fi-LMC group.
Leukemia. 2011 Oct;25(10):1661-4. doi: 10.1038/leu.2011.139. Epub 2011 Jun 3.
PMID 21637286
 
Next-generation sequencing of the TET2 gene in 355 MDS and CMML patients reveals low-abundance mutant clones with early origins, but indicates no definite prognostic value.
Smith AE, Mohamedali AM, Kulasekararaj A, Lim Z, Gaken J, Lea NC, Przychodzen B, Mian SA, Nasser EE, Shooter C, Westwood NB, Strupp C, Gattermann N, Maciejewski JP, Germing U, Mufti GJ.
Blood. 2010 Nov 11;116(19):3923-32. doi: 10.1182/blood-2010-03-274704. Epub 2010 Aug 6.
PMID 20693430
 
The Ten-Eleven Translocation-2 (TET2) gene in hematopoiesis and hematopoietic diseases.
Solary E, Bernard OA, Tefferi A, Fuks F, Vainchenker W.
Leukemia. 2014 Mar;28(3):485-96. doi: 10.1038/leu.2013.337. Epub 2013 Nov 13. (REVIEW)
PMID 24220273
 
Detection of mutant TET2 in myeloid malignancies other than myeloproliferative neoplasms: CMML, MDS, MDS/MPN and AML.
Tefferi A, Lim KH, Abdel-Wahab O, Lasho TL, Patel J, Patnaik MM, Hanson CA, Pardanani A, Gilliland DG, Levine RL.
Leukemia. 2009a Jul;23(7):1343-5. doi: 10.1038/leu.2009.59. Epub 2009 Mar 19.
PMID 19295549
 
TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis.
Tefferi A, Pardanani A, Lim KH, Abdel-Wahab O, Lasho TL, Patel J, Gangat N, Finke CM, Schwager S, Mullally A, Li CY, Hanson CA, Mesa R, Bernard O, Delhommeau F, Vainchenker W, Gilliland DG, Levine RL.
Leukemia. 2009b May;23(5):905-11. doi: 10.1038/leu.2009.47. Epub 2009 Mar 5.
PMID 19262601
 
Common 4q24 deletion in four cases of hematopoietic malignancy: early stem cell involvement?
Viguie F, Aboura A, Bouscary D, Ramond S, Delmer A, Tachdjian G, Marie JP, Casadevall N.
Leukemia. 2005 Aug;19(8):1411-5.
PMID 15920487
 
Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation.
Yang H, Liu Y, Bai F, Zhang JY, Ma SH, Liu J, Xu ZD, Zhu HG, Ling ZQ, Ye D, Guan KL, Xiong Y.
Oncogene. 2013 Jan 31;32(5):663-9. doi: 10.1038/onc.2012.67. Epub 2012 Mar 5.
PMID 22391558
 

Citation

This paper should be referenced as such :
Franck Viguié
TET2 (tet methylcytosine dioxygenase 2)
Atlas Genet Cytogenet Oncol Haematol. 2015;19(6):405-409.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/TET2ID40597ch4q24.html

External links

Nomenclature
HGNC (Hugo)TET2   25941
LRG (Locus Reference Genomic)LRG_626
Cards
AtlasTET2ID40597ch4q24
Entrez_Gene (NCBI)TET2  54790  tet methylcytosine dioxygenase 2
AliasesKIAA1546; MDS
GeneCards (Weizmann)TET2
Ensembl hg19 (Hinxton)ENSG00000168769 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000168769 [Gene_View]  ENSG00000168769 [Sequence]  chr4:105145875-105242771 [Contig_View]  TET2 [Vega]
ICGC DataPortalENSG00000168769
TCGA cBioPortalTET2
AceView (NCBI)TET2
Genatlas (Paris)TET2
WikiGenes54790
SOURCE (Princeton)TET2
Genetics Home Reference (NIH)TET2
Genomic and cartography
GoldenPath hg38 (UCSC)TET2  -     chr4:105145875-105242771 +  4q24   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)TET2  -     4q24   [Description]    (hg19-Feb_2009)
GoldenPathTET2 - 4q24 [CytoView hg19]  TET2 - 4q24 [CytoView hg38]
ImmunoBaseENSG00000168769
Mapping of homologs : NCBITET2 [Mapview hg19]  TET2 [Mapview hg38]
OMIM612839   614286   
Gene and transcription
Genbank (Entrez)AB046766 AB075496 AI084057 AK000039 AK027819
RefSeq transcript (Entrez)NM_001127208 NM_017628
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)TET2
Cluster EST : UnigeneHs.706276 [ NCBI ]
CGAP (NCI)Hs.706276
Alternative Splicing GalleryENSG00000168769
Gene ExpressionTET2 [ NCBI-GEO ]   TET2 [ EBI - ARRAY_EXPRESS ]   TET2 [ SEEK ]   TET2 [ MEM ]
Gene Expression Viewer (FireBrowse)TET2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)54790
GTEX Portal (Tissue expression)TET2
Human Protein AtlasENSG00000168769-TET2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ6N021   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ6N021  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ6N021
Splice isoforms : SwissVarQ6N021
PhosPhoSitePlusQ6N021
Domains : Interpro (EBI)2OGFeDO_noxygenase_dom   
Domain families : Pfam (Sanger)Tet_JBP (PF12851)   
Domain families : Pfam (NCBI)pfam12851   
Domain families : Smart (EMBL)Tet_JBP (SM01333)  
Conserved Domain (NCBI)TET2
DMDM Disease mutations54790
Blocks (Seattle)TET2
PDB (RSDB)4NM6    5D9Y    5DEU   
PDB Europe4NM6    5D9Y    5DEU   
PDB (PDBSum)4NM6    5D9Y    5DEU   
PDB (IMB)4NM6    5D9Y    5DEU   
Structural Biology KnowledgeBase4NM6    5D9Y    5DEU   
SCOP (Structural Classification of Proteins)4NM6    5D9Y    5DEU   
CATH (Classification of proteins structures)4NM6    5D9Y    5DEU   
SuperfamilyQ6N021
Human Protein Atlas [tissue]ENSG00000168769-TET2 [tissue]
Peptide AtlasQ6N021
HPRD07876
IPIIPI00175151   IPI00026533   IPI00654641   IPI00794882   IPI00968180   IPI00963989   
Protein Interaction databases
DIP (DOE-UCLA)Q6N021
IntAct (EBI)Q6N021
FunCoupENSG00000168769
BioGRIDTET2
STRING (EMBL)TET2
ZODIACTET2
Ontologies - Pathways
QuickGOQ6N021
Ontology : AmiGODNA binding  iron ion binding  protein binding  nucleus  5-methylcytosine catabolic process  5-methylcytosine catabolic process  protein O-linked glycosylation  protein O-linked glycosylation  cell cycle  ferrous iron binding  zinc ion binding  response to organic cyclic compound  myeloid cell differentiation  myeloid cell differentiation  positive regulation of transcription by RNA polymerase II  positive regulation of transcription by RNA polymerase II  methylcytosine dioxygenase activity  methylcytosine dioxygenase activity  methylcytosine dioxygenase activity  methylcytosine dioxygenase activity  oxidative demethylation  DNA demethylation  DNA demethylation  histone H3-K4 trimethylation  
Ontology : EGO-EBIDNA binding  iron ion binding  protein binding  nucleus  5-methylcytosine catabolic process  5-methylcytosine catabolic process  protein O-linked glycosylation  protein O-linked glycosylation  cell cycle  ferrous iron binding  zinc ion binding  response to organic cyclic compound  myeloid cell differentiation  myeloid cell differentiation  positive regulation of transcription by RNA polymerase II  positive regulation of transcription by RNA polymerase II  methylcytosine dioxygenase activity  methylcytosine dioxygenase activity  methylcytosine dioxygenase activity  methylcytosine dioxygenase activity  oxidative demethylation  DNA demethylation  DNA demethylation  histone H3-K4 trimethylation  
REACTOMEQ6N021 [protein]
REACTOME PathwaysR-HSA-5221030 [pathway]   
NDEx NetworkTET2
Atlas of Cancer Signalling NetworkTET2
Wikipedia pathwaysTET2
Orthology - Evolution
OrthoDB54790
GeneTree (enSembl)ENSG00000168769
Phylogenetic Trees/Animal Genes : TreeFamTET2
HOGENOMQ6N021
Homologs : HomoloGeneTET2
Homology/Alignments : Family Browser (UCSC)TET2
Gene fusions - Rearrangements
Fusion PortalTET2 4q24 ADH6 4q23 LGG
Fusion PortalTET2 4q24 LANCL1 2q34 BRCA
Fusion PortalTET2 4q24 LARP7 4q25 PRAD
Fusion : FusionGDB24355    37768    37769    37770    37771    37772    37773   
Fusion : Fusion_HubLGALS8--TET2    NINJ1--TET2    PRKG1--TET2    TET2--ABCD3    TET2--ADH6    TET2--ANK2    TET2--CAMK2D    TET2--CSNK1D    TET2--JAK2    TET2--KLK3    TET2--LANCL1    TET2--LARP7    TET2--LMBRD1    TET2--MPP5    TET2--NDUFS4   
TET2--NFIL3    TET2--PALLD    TET2--PAPSS1    TET2--PPA2    TET2--PPP3CA    TET2--RAB7A    TET2--SEC24B    TET2--SNX25    TET2--TBCK    TET2--TRAPPC11    TET2--UGGT1   
Fusion : QuiverTET2
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTET2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TET2
dbVarTET2
ClinVarTET2
1000_GenomesTET2 
Exome Variant ServerTET2
ExAC (Exome Aggregation Consortium)ENSG00000168769
GNOMAD BrowserENSG00000168769
Varsome BrowserTET2
Genetic variants : HAPMAP54790
Genomic Variants (DGV)TET2 [DGVbeta]
DECIPHERTET2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisTET2 
Mutations
ICGC Data PortalTET2 
TCGA Data PortalTET2 
Broad Tumor PortalTET2
OASIS PortalTET2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTET2  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DTET2
Mutations and Diseases : HGMDTET2
intOGen PortalTET2
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch TET2
DgiDB (Drug Gene Interaction Database)TET2
DoCM (Curated mutations)TET2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TET2 (select a term)
intoGenTET2
NCG5 (London)TET2
Cancer3DTET2(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM612839    614286   
Orphanet3599    8745    8747    11088    11749    11752    13843   
DisGeNETTET2
MedgenTET2
Genetic Testing Registry TET2
NextProtQ6N021 [Medical]
TSGene54790
GENETestsTET2
Target ValidationTET2
Huge Navigator TET2 [HugePedia]
snp3D : Map Gene to Disease54790
BioCentury BCIQTET2
ClinGenTET2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD54790
Chemical/Pharm GKB GenePA162405634
Drug Sensitivity TET2
Clinical trialTET2
Miscellaneous
canSAR (ICR)TET2 (select the gene name)
DataMed IndexTET2
Probes
Litterature
PubMed264 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineTET2
EVEXTET2
GoPubMedTET2
iHOPTET2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Mon Aug 12 15:16:36 CEST 2019
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