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TLX3 (T-cell leukemia, homeobox protein 3)

Identity

Other namesRNX
HOX11L2
HGNC (Hugo) TLX3
Location 5q35.1
Location_base_pair Starts at 170668893 and ends at 170671743 bp from pter ( according to hg18-Mar_2006)  [Mapping]
 
  TLX3 (5q35.1): FISH with BAC clone ctb-45L16 (red) showing a breakpoint signal in the consensus breakpoint region split between der(5) and der(14) partners. Analysis was performed on the pediatric T-ALL cell line HPB-ALL (DSMZ ACC-483) which carries t(5;14)(q35.1;q32.2) as part of a complex 4-way rearrangement involving chromosomes 1 and 16. Normally (in the absence of secondary translocations) the breakpoints on both partners lie closely equidistant to the q-arm telomeres rendering the translocation cryptic and difficult to detect even with chromosome painting.

DNA/RNA

 
Description 3 exons on 2.23 kb
Transcription In a centromeric --> telomeric orientation; 876 bp mRNA (coding)

Protein

 
Description 291 amino acids, 31.8 kDa; contains one homeobox domain (residues 166-221)
Expression Narrowly restricted to brain.
Localisation Probably nuclear
Function Murine Tlx-3 and Tlx-1 together sustain expression of Drg-11, and control development of somatic and visceral relay sensory neurons.
Homology With homeobox genes, especially with those of the NK-like family.

Implicated in

Entity t(5;14)(q35;q32) in T-ALL-->TLX3 - BCL11B
Disease T-cell acute lymphocytic leukemia (T-ALL)
Prognosis TLX3 expression may denote poor prognosis.
Cytogenetics Cryptic translocation detectable by locus specific FISH. t(5;14) may exclude del(1)(p32) SIL-TAL1 fusion.
Hybrid/Mutated Gene 5' TLX3-3' BCL11B on der(14).
Oncogenesis Ectopic expression in T-cells
  
Entity t(5;14)(q35;q11) in T-ALL --> TLX3 - TCRD
Disease T-cell acute lymphocytic leukemia (T-ALL)
Cytogenetics Apparent variant of t(5;14)
Hybrid/Mutated Gene 5' TLX3-TCRD on der(14)
  

Breakpoints

 
 
Note Within the upstream region or within the neighboring gene RanBP17.

External links

Nomenclature
HGNC (Hugo)TLX3   13532
Entrez_Gene (NCBI)TLX3  30012  T-cell leukemia homeobox 3
Cards
AtlasTLX3ID398
GeneCards (Weizmann)TLX3
Ensembl (Hinxton)ENSG00000164438 [Gene_View]  TLX3 [Vega]
AceView (NCBI)TLX3
Genatlas (Paris)TLX3
euGene (Indiana)30012
SOURCE (Stanford)NM_021025
Genomic and cartography
GoldenPath (UCSC)TLX3  -  5q35.1   chr5:170668893-170671743 +  5q35.1   [Description]    (hg18-Mar_2006)
EnsemblTLX3 - 5q35.1 [CytoView]
Mapping of homologs : NCBITLX3 [Mapview]
OMIM604640   
Gene and transcription
Gene : Genbank (Entrez)BC017291 DQ892654 DQ895893 DQ896085
Reference sequence (RefSeq transcript) :SRSNM_021025
Reference transcript : EntrezNM_021025
RefSeq genomic : SRSAC_000048 AC_000137 NC_000005 NT_023133 NW_001838954 NW_922784
RefSeq genomic : EntrezAC_000048 AC_000137 NC_000005 NT_023133 NW_001838954 NW_922784
Consensus coding sequences : CCDS NCBITLX3
Cluster EST : UnigeneHs.249125 [ SRS ] Hs.249125 [ NCBI ]
Alternative Splicing : Fast-db (Paris)12997
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtO43711 (SRS) O43711 (Expasy) O43711 (Uniprot)
With graphics : InterProO43711
Splice isoforms : VarSplice FASTAO43711(VarSplice FASTA)
Domaine pattern : Prosite (SRS)HOMEOBOX_1 (PS00027)    HOMEOBOX_2 (PS50071)   
Domain pattern : Prosite (Expaxy)HOMEOBOX_1 (PS00027)    HOMEOBOX_2 (PS50071)   
Domains : Interpro (SRS)Homeobox    Homeodomain-rel   
Domains : Interpro (EBI)Homeobox    Homeodomain-rel   
Related proteins : CluSTrO43711
Domain families : Pfam SRSHomeobox (PF00046)   
Domain families : Pfam SangerHomeobox (PF00046)   
Domain families : Pfam NCBIpfam00046   
Domain families : Smart EMBLHOX (SM00389)
Domain structure : Prodom (Prabi Lyon)Homeobox (PD000010)   
Blocks (Seattle)O43711
Crystal structure of protein : PDB SRS
Crystal structure of protein : PDBSum
Crystal structure of protein : IMB
Crystal structure of protein : PDB RSDB
HPRD06868
Protein Interaction databases
DIP (DOE-UCLA)O43711
IntAct (EBI)O43711
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBITLX3
SNP : GeneSNP UtahTLX3
SNP : HGBaseTLX3
Genetic variants : HAPMAPTLX3
Somatic Mutations in Cancer : COSMICTLX3 
Mutations and Diseases : HGMDTLX3
Hereditary diseases : OMIM604640   
Hereditary diseases : GENETests604640   
Diseases : Genetic AssociationTLX3
General knowledge
Homologs : HomoloGeneTLX3
Homology/Alignments : Family Browser UCSCTLX3
Phylogenetic Trees/Animal Genes : TreeFamTLX3
Chemical/Protein Interactions : CTD30012
Keywords Ontology : AmiGOneuron migration  regulation of respiratory gaseous exchange by neurological process  transcription factor activity  protein binding  nucleus  regulation of transcription, DNA-dependent  multicellular organismal development  central nervous system development  respiratory gaseous exchange  sequence-specific DNA binding  negative regulation of neuron differentiation  neuron fate specification  
Keywords Ontology : EGO-EBIneuron migration  regulation of respiratory gaseous exchange by neurological process  transcription factor activity  protein binding  nucleus  regulation of transcription, DNA-dependent  multicellular organismal development  central nervous system development  respiratory gaseous exchange  sequence-specific DNA binding  negative regulation of neuron differentiation  neuron fate specification  
Pathways : BIOCARTA
Pathways : KEGG
Other databases
Probes
Probes : ImagenesTLX3 Related clones (RZPD - Berlin)
Literature
PubMed19 Pubmed reference(s) in Entrez
PubGeneTLX3

Bibliography

Assignment of the HOX11L2 gene to human chromosome band 5q35.1 and of its murine homolog to mouse chromosome bands 11A4-A5 by in situ hybridization.
Cinti R, Fava M, Sancandi M, Matera I, Ravazzolo R, Ceccherini I
Cytogenetics and cell genetics. 2001 ; 92 (3-4) : 354-355.
PMID 11435716
 
Assignment of the human homeobox 11-like 2 gene (HOX11L2) to chromosome 5q34-->q35 by radiation hybrid mapping.
Lee-Kirsch MA, Engel K, Paditz E, Rˆsen-Wolff A, Lee YA, Gahr M
Cytogenetics and cell genetics. 2001 ; 92 (3-4) : page 358.
PMID 11435718
 
A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia.
Bernard OA, Busson-LeConiat M, Ballerini P, Mauchauffˆ© M, Della Valle V, Monni R, Nguyen Khac F, Mercher T, Penard-Lacronique V, Pasturaud P, Gressin L, Heilig R, Daniel MT, Lessard M, Berger R
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2001 ; 15 (10) : 1495-1504.
PMID 11587205
 
Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia.
Ferrando AA, Neuberg DS, Staunton J, Loh ML, Huard C, Raimondi SC, Behm FG, Pui CH, Downing JR, Gilliland DG, Lander ES, Golub TR, Look AT
Cancer cell. 2002 ; 1 (1) : 75-87.
PMID 12086890
 
HOX11L2 expression defines a clinical subtype of pediatric T-ALL associated with poor prognosis.
Ballerini P, Blaise A, Busson-Le Coniat M, Su XY, Zucman-Rossi J, Adam M, van den Akker J, Perot C, Pellegrino B, Landman-Parker J, Douay L, Berger R, Bernard OA
Blood. 2002 ; 100 (3) : 991-997.
PMID 12130513
 
Disruption of the RanBP17/Hox11L2 region by recombination with the TCRdelta locus in acute lymphoblastic leukemias with t(5;14)(q34;q11).
Hansen-Hagge TE, Schˆ§fer M, Kiyoi H, Morris SW, Whitlock JA, Koch P, Bohlmann I, Mahotka C, Bartram CR, Janssen JW
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 ; 16 (11) : 2205-2212.
PMID 12399963
 
High incidence of Hox11L2 expression in children with T-ALL.
Mauvieux L, Leymarie V, Helias C, Perrusson N, Falkenrodt A, Lioure B, Lutz P, Lessard M
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 ; 16 (12) : 2417-2422.
PMID 12454747
 
Activation of HOX11L2 by juxtaposition with 3'-BCL11B in an acute lymphoblastic leukemia cell line (HPB-ALL) with t(5;14)(q35;q32.2).
MacLeod RA, Nagel S, Kaufmann M, Janssen JW, Drexler HG
Genes, chromosomes & cancer. 2003 ; 37 (1) : 84-91.
PMID 12661009
 
t(5;14)/HOX11L2-positive T-cell acute lymphoblastic leukemia. A collaborative study of the Groupe Franˆßais de Cytogˆ©nˆ©tique Hˆ©matologique (GFCH).
Berger R, Dastugue N, Busson M, Van Den Akker J, Pˆ©rot C, Ballerini P, Hagemeijer A, Michaux L, Charrin C, Pages MP, Mugneret F, Andrieux J, Talmant P, Hˆ©lias C, Mauvieux L, Lafage-Pochitaloff M, Mozziconacci MJ, Cornillet-Lefebvre P, Radford I, Asnafi V, Bilhou-Nabera C, Nguyen Khac F, Lˆ©onard C, Speleman F, Poppe B, Bastard C, Taviaux S, Quilichini B, Herens C, Grˆ©goire MJ, Cavˆ© H, Groupe Franˆßais de Cytogˆ©nˆ©tique Hˆ©matologique (GFCH), Bernard OA
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 ; 17 (9) : 1851-1857.
PMID 12970786
 
The cardiac homeobox gene NKX2-5 is deregulated by juxtaposition with BCL11B in pediatric T-ALL cell lines via a novel t(5;14)(q35.1;q32.2).
Nagel S, Kaufmann M, Drexler HG, MacLeod RA
Cancer research. 2003 ; 63 (17) : 5329-5334.
PMID 14500364
 
Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951.
Cavˆ© H, Suciu S, Preudhomme C, Poppe B, Robert A, Uyttebroeck A, Malet M, Boutard P, Benoit Y, Mauvieux L, Lutz P, Mˆ©chinaud F, Grardel N, Mazingue F, Dupont M, Margueritte G, Pages MP, Bertrand Y, Plouvier E, Brunie G, Bastard C, Plantaz D, Vande Velde I, Hagemeijer A, Speleman F, Lessard M, Otten J, Vilmer E, EORTC-CLG, Dastugue N
Blood. 2004 ; 103 (2) : 442-450.
PMID 14504110
 
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Contributor(s)

Written03-2004Roderick AF MacLeod, Stefan Nagel

Citation

This paper should be referenced as such :
MacLeod RAF, Nagel S . TLX3 (T-cell leukemia, homeobox protein 3). Atlas Genet Cytogenet Oncol Haematol. March 2004 .
URL : http://AtlasGeneticsOncology.org/Genes/TLX3ID398.html

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indexed on : Sat Jun 27 16:36:56 CEST 2009

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