SETBP1 (SET binding protein 1)

2012-09-01   Ion Cristóbal , Laura García-Orti , María D Odero 

Identity

HGNC
LOCATION
18q12.3
LOCUSID
ALIAS
MRD29,SEB
FUSION GENES

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).

Proteins

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 name
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 gene
5 NUP98 - 3 SETBP1
Fusion 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 name
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 name
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).
Atlas Image
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.

Bibliography

Pubmed IDLast YearTitleAuthors
228731952012SETBP1 and miR_4319 dysregulation in primary myelofibrosis progression to acute myeloid leukemia.Albano F et al
199656922010SETBP1 overexpression is a novel leukemogenic mechanism that predicts adverse outcome in elderly patients with acute myeloid leukemia.Cristóbal I et al
204364682010De novo mutations of SETBP1 cause Schinzel-Giedion syndrome.Hoischen A et al
112312862001Identification and characterization of SEB, a novel protein that binds to the acute undifferentiated leukemia-associated protein SET.Minakuchi M et al
172338202007Fusion 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 et al
213710132011SETBP1 mutations in two Thai patients with Schinzel-Giedion syndrome.Suphapeetiporn K et al

Other Information

Locus ID:

NCBI: 26040
MIM: 611060
HGNC: 15573
Ensembl: ENSG00000152217

Variants:

dbSNP: 26040
ClinVar: 26040
TCGA: ENSG00000152217
COSMIC: SETBP1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000152217ENST00000426838Q9Y6X0
ENSG00000152217ENST00000591940K7ES17
ENSG00000152217ENST00000645568A0A2R8YH59
ENSG00000152217ENST00000649279Q9Y6X0

Expression (GTEx)

0
5
10
15
20
25
30
35

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
165829162006Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1.404
204364682010De novo mutations of SETBP1 cause Schinzel-Giedion syndrome.152
232229562013Recurrent SETBP1 mutations in atypical chronic myeloid leukemia.111
238320122013Somatic SETBP1 mutations in myeloid malignancies.87
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
238320112013Exome sequencing identifies secondary mutations of SETBP1 and JAK3 in juvenile myelomonocytic leukemia.69
236042292013CSF3R T618I is a highly prevalent and specific mutation in chronic neutrophilic leukemia.66
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
246950572014ASXL1 and SETBP1 mutations and their prognostic contribution in chronic myelomonocytic leukemia: a two-center study of 466 patients.53
236289592013SETBP1 mutations occur in 9% of MDS/MPN and in 4% of MPN cases and are strongly associated with atypical CML, monosomy 7, isochromosome i(17)(q10), ASXL1 and CBL mutations.41

Citation

Ion Cristóbal ; Laura García-Orti ; María D Odero

SETBP1 (SET binding protein 1)

Atlas Genet Cytogenet Oncol Haematol. 2012-09-01

Online version: http://atlasgeneticsoncology.org/gene/44031/setbp1