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SETBP1 (SET binding protein 1)

Identity

Other namesSEB
HGNC (Hugo) SETBP1
LocusID (NCBI) 26040
Location 18q12.3
Location_base_pair Starts at 42260138 and ends at 42457379 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order From centromere to telomere: SETBP1, SMAD2, SMAD4, BCL2.

DNA/RNA

Description SETBP1 has two isoforms: transcript variant a spans 387,61 kb on the genomic DNA and has 6 exons; transcript variant b spans 197,24 kb on the genomic DNA and includes 4 exons.
Transcription 9899 bp mRNA (isoform a); 1804 bp mRNA (isoform b).

Protein

Description Two isoforms: variant a (1596 amino acids); variant b (242 amino acids).
Expression Expressed in numerous tissues.
Localisation Predominantly in the nucleus (Minakuchi et al., 2001; Cristóbal et al., 2010).
Function SETBP1 overexpression promotes leukemogenesis by enhancing full-length SET protein and then impairing the phosphatase activity of the tumor suppressor PP2A in acute myeloid leukaemia. In addition, defects in SETBP1 have been described as the cause of Schinzel-Giedion syndrome.
Homology The protein contains a region homologous to the dimerization domain of the SKI oncoprotein, six PEST sequences, three AT-hook DNA binding domains, a SET-binding domain and three nuclear localization signals.

Mutations

Somatic De novo mutations have been decribed in patients with Schinzel-Giedion syndrome: I871T (5 unrelated patients), D868N (4 unrelated patients), D868A (one case), G870D (one case) and G870S (three unrelated patients) (Hoischen et al., 2010; Suphapeetiporn et al., 2011).

Implicated in

Entity Pediatric T-cell acute lymphoblastic leukemia (T-ALL) (Panagopoulos et al., 2007)
Cytogenetics t(11;18)(p15;q12); only one case decribed so far.
Hybrid/Mutated Gene 5' NUP98 - 3' SETBP1
Abnormal Protein The NUP98-SETBP1 fusion protein consists in the exon 12 of NUP98 fused in-frame with exon 5 of SETBP1.
Oncogenesis SETBP1/NUP98 expression was not detected, suggesting that the NUP98/SETBP1 transcript is pathogenetically important.
  
Entity Schinzel-Giedion syndrome
Prognosis Defects in SETBP1 caused by the presence of the novo mutations have been described as the cause of Schinzel-Giedion midface retraction syndrome.
Cytogenetics Normal karyotype.
  
Entity Acute myeloid leukemia (AML)
Prognosis SETBP1 overexpression associates with worse overall survival specially in the subgroup of elderly patients (older than 60 years).
Cytogenetics The presence of a t(12;18)(p13;q12) has been describe in one case with AML secondary to myelodysplastic syndrome (figure 1) (Cristóbal et al., 2010), and in one case with AML secondary to primary myelofibrosis (Albano et al., 2012).
 
Figure 1.
Oncogenesis SETBP1 overexpression promotes leukemogenesis by enhancing full-length SET protein and then impairing the phosphatase activity of the tumor suppressor PP2A through the formation of a SETBP1-SET-PP2A complex.
  

External links

Nomenclature
HGNC (Hugo)SETBP1   15573
Cards
AtlasSETBP1ID44031ch18q12
Entrez_Gene (NCBI)SETBP1  26040  SET binding protein 1
GeneCards (Weizmann)SETBP1
Ensembl (Hinxton)ENSG00000152217 [Gene_View]  chr18:42260138-42457379 [Contig_View]  SETBP1 [Vega]
ICGC DataPortalENSG00000152217
cBioPortalSETBP1
AceView (NCBI)SETBP1
Genatlas (Paris)SETBP1
WikiGenes26040
SOURCE (Princeton)NM_001130110 NM_015559
Genomic and cartography
GoldenPath (UCSC)SETBP1  -  18q12.3   chr18:42260138-42457379 +  18q21.1   [Description]    (hg19-Feb_2009)
EnsemblSETBP1 - 18q21.1 [CytoView]
Mapping of homologs : NCBISETBP1 [Mapview]
OMIM269150   611060   
Gene and transcription
Genbank (Entrez)AB007897 AB022660 AK123972 AL832945 BC062338
RefSeq transcript (Entrez)NM_001130110 NM_015559
RefSeq genomic (Entrez)AC_000150 NC_000018 NC_018929 NG_027527 NT_010966 NW_001838467 NW_004929410
Consensus coding sequences : CCDS (NCBI)SETBP1
Cluster EST : UnigeneHs.435458 [ NCBI ]
CGAP (NCI)Hs.435458
Alternative Splicing : Fast-db (Paris)GSHG0014019
Alternative Splicing GalleryENSG00000152217
Gene ExpressionSETBP1 [ NCBI-GEO ]     SETBP1 [ SEEK ]   SETBP1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9Y6X0 (Uniprot)
NextProtQ9Y6X0  [Medical]
With graphics : InterProQ9Y6X0
Splice isoforms : SwissVarQ9Y6X0 (Swissvar)
Domains : Interpro (EBI)AT_hook_DNA-bd_motif [organisation]  
Related proteins : CluSTrQ9Y6X0
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Domain families : Smart (EMBL)AT_hook (SM00384)  
DMDM Disease mutations26040
Blocks (Seattle)Q9Y6X0
Human Protein AtlasENSG00000152217 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ9Y6X0
HPRD10224
IPIIPI00159049   IPI00441195   IPI01021397   
Protein Interaction databases
DIP (DOE-UCLA)Q9Y6X0
IntAct (EBI)Q9Y6X0
FunCoupENSG00000152217
BioGRIDSETBP1
InParanoidQ9Y6X0
Interologous Interaction database Q9Y6X0
IntegromeDBSETBP1
STRING (EMBL)SETBP1
Ontologies - Pathways
Ontology : AmiGODNA binding  nucleus  
Ontology : EGO-EBIDNA binding  nucleus  
Protein Interaction DatabaseSETBP1
Wikipedia pathwaysSETBP1
Gene fusion - rearrangments
Rearrangement : TICdbNUP98 [11p15.4]  -  SETBP1 [3p25.2]
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)SETBP1
snp3D : Map Gene to Disease26040
SNP (GeneSNP Utah)SETBP1
SNP : HGBaseSETBP1
Genetic variants : HAPMAPSETBP1
Exome VariantSETBP1
1000_GenomesSETBP1 
ICGC programENSG00000152217 
Cancer Gene: CensusSETBP1 
Somatic Mutations in Cancer : COSMICSETBP1 
CONAN: Copy Number AnalysisSETBP1 
Mutations and Diseases : HGMDSETBP1
Genomic VariantsSETBP1  SETBP1 [DGVbeta]
dbVarSETBP1
ClinVarSETBP1
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM269150    611060   
MedgenSETBP1
GENETestsSETBP1
Disease Genetic AssociationSETBP1
Huge Navigator SETBP1 [HugePedia]  SETBP1 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneSETBP1
Homology/Alignments : Family Browser (UCSC)SETBP1
Phylogenetic Trees/Animal Genes : TreeFamSETBP1
Chemical/Protein Interactions : CTD26040
Chemical/Pharm GKB GenePA37982
Clinical trialSETBP1
Cancer Resource (Charite)ENSG00000152217
Other databases
Probes
Litterature
PubMed29 Pubmed reference(s) in Entrez
CoreMineSETBP1
iHOPSETBP1
OncoSearchSETBP1

Bibliography

Identification and characterization of SEB, a novel protein that binds to the acute undifferentiated leukemia-associated protein SET.
Minakuchi M, Kakazu N, Gorrin-Rivas MJ, Abe T, Copeland TD, Ueda K, Adachi Y.
Eur J Biochem. 2001 Mar;268(5):1340-51.
PMID 11231286
 
Fusion of NUP98 and the SET binding protein 1 (SETBP1) gene in a paediatric acute T cell lymphoblastic leukaemia with t(11;18)(p15;q12).
Panagopoulos I, Kerndrup G, Carlsen N, Strombeck B, Isaksson M, Johansson B.
Br J Haematol. 2007 Jan;136(2):294-6.
PMID 17233820
 
SETBP1 overexpression is a novel leukemogenic mechanism that predicts adverse outcome in elderly patients with acute myeloid leukemia.
Cristobal I, Blanco FJ, Garcia-Orti L, Marcotegui N, Vicente C, Rifon J, Novo FJ, Bandres E, Calasanz MJ, Bernabeu C, Odero MD.
Blood. 2010 Jan 21;115(3):615-25. Epub 2009 Nov 16.
PMID 19965692
 
De novo mutations of SETBP1 cause Schinzel-Giedion syndrome.
Hoischen A, van Bon BW, Gilissen C, Arts P, van Lier B, Steehouwer M, de Vries P, de Reuver R, Wieskamp N, Mortier G, Devriendt K, Amorim MZ, Revencu N, Kidd A, Barbosa M, Turner A, Smith J, Oley C, Henderson A, Hayes IM, Thompson EM, Brunner HG, de Vries BB, Veltman JA.
Nat Genet. 2010 Jun;42(6):483-5. Epub 2010 May 2.
PMID 20436468
 
SETBP1 mutations in two Thai patients with Schinzel-Giedion syndrome.
Suphapeetiporn K, Srichomthong C, Shotelersuk V.
Clin Genet. 2011 Apr;79(4):391-3. doi: 10.1111/j.1399-0004.2010.01552.x.
PMID 21371013
 
SETBP1 and miR_4319 dysregulation in primary myelofibrosis progression to acute myeloid leukemia.
Albano F, Anelli L, Zagaria A, Coccaro N, Casieri P, Minervini A, Specchia G.
J Hematol Oncol. 2012 Aug 8;5:48. doi: 10.1186/1756-8722-5-48.
PMID 22873195
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written09-2012Ion Cristóbal, Laura García-Orti, María D Odero
Translational Oncology Division, Health Research Institute and Oncology Department, University Hospital "Fundacion Jimenez Diaz", Autonomous University of Madrid, E-28040 Madrid, Spain (IC); Division of Oncology, Center for Applied Medical Research (CIMA), University of Navarra, E-31008 Pamplona, Spain (LGO, MDO); Department of Genetics, School of Sciences, University of Navarra E-31008 Pamplona, Spain (MDO)

Citation

This paper should be referenced as such :
Cristòbal, I ; Garcia-Orti, L ; Odero, MD
SETBP1 (SET binding protein 1)
Atlas Genet Cytogenet Oncol Haematol. 2013;17(3):159-160.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/SETBP1ID44031ch18q12.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Jul 30 14:26:55 CEST 2014

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