SETBP1 (SET binding protein 1)
2012-09-01 Ion Cristóbal , Laura García-Orti , María D Odero AffiliationDNA/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
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
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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 22873195 | 2012 | SETBP1 and miR_4319 dysregulation in primary myelofibrosis progression to acute myeloid leukemia. | Albano F et al |
| 19965692 | 2010 | SETBP1 overexpression is a novel leukemogenic mechanism that predicts adverse outcome in elderly patients with acute myeloid leukemia. | Cristóbal I et al |
| 20436468 | 2010 | De novo mutations of SETBP1 cause Schinzel-Giedion syndrome. | Hoischen A et al |
| 11231286 | 2001 | Identification and characterization of SEB, a novel protein that binds to the acute undifferentiated leukemia-associated protein SET. | Minakuchi M et al |
| 17233820 | 2007 | 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 et al |
| 21371013 | 2011 | SETBP1 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 ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000152217 | ENST00000426838 | Q9Y6X0 |
| ENSG00000152217 | ENST00000591940 | K7ES17 |
| ENSG00000152217 | ENST00000645568 | A0A2R8YH59 |
| ENSG00000152217 | ENST00000649279 | Q9Y6X0 |
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38165902 | 2024 | The landscape of SETBP1 gene expression and transcription factor activity across human tissues. | 1 |
| 38194688 | 2024 | First-hit SETBP1 mutations cause a myeloproliferative disorder with bone marrow fibrosis. | 0 |
| 38520002 | 2024 | Structural rearrangements as a recurrent pathogenic mechanism for SETBP1 haploinsufficiency. | 0 |
| 38165902 | 2024 | The landscape of SETBP1 gene expression and transcription factor activity across human tissues. | 1 |
| 38194688 | 2024 | First-hit SETBP1 mutations cause a myeloproliferative disorder with bone marrow fibrosis. | 0 |
| 38520002 | 2024 | Structural rearrangements as a recurrent pathogenic mechanism for SETBP1 haploinsufficiency. | 0 |
| 36805818 | 2023 | Impaired neurogenesis and neural progenitor fate choice in a human stem cell model of SETBP1 disorder. | 5 |
| 37150818 | 2023 | Identification of a novel de novo mutation of SETBP1 and new findings of SETBP1 in tumorgenesis. | 2 |
| 37354804 | 2023 | Co-occurring mutations in ASXL1, SRSF2, and SETBP1 define a subset of myelodysplastic/ myeloproliferative neoplasm with neutrophilia. | 0 |
| 37489294 | 2023 | The impact of SETBP1 mutations in neurological diseases and cancer. | 4 |
| 37535001 | 2023 | SETBP1 mutation determines sensitivity to immune checkpoint inhibitors in melanoma and NSCLC. | 1 |
| 37798664 | 2023 | Novel SETBP1 mutation in a chinese family with intellectual disability. | 0 |
| 36805818 | 2023 | Impaired neurogenesis and neural progenitor fate choice in a human stem cell model of SETBP1 disorder. | 5 |
| 37150818 | 2023 | Identification of a novel de novo mutation of SETBP1 and new findings of SETBP1 in tumorgenesis. | 2 |
| 37354804 | 2023 | Co-occurring mutations in ASXL1, SRSF2, and SETBP1 define a subset of myelodysplastic/ myeloproliferative neoplasm with neutrophilia. | 0 |
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
