SETBP1 (SET binding protein 1)

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

Identity

HGNC

SETBP1

LOCATION

18q12.3

LOCUSID

26040

ALIAS

MRD29,SEB

FUSION GENES

Show Gene Fusions

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

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)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Protein levels (Protein atlas)

Not detected

Low

Medium

High

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-(set-binding-protein-1)