SET Nuclear Proto-Oncogene (SET)
A multifunctional protein involved in chromatin remodeling, transcription regulation, and cancer progression.
Gene Information Card
| Symbol | SET |
|---|---|
| Full Name | SET nuclear proto-oncogene |
| Gene Type | Protein coding |
| Chromosomal Location | 9q34.11 |
| NCBI Gene ID | 6418 ncbi.nlm.nih.gov/gene/6418 |
| Ensembl ID | ENSG00000107175 |
| UniProt ID | Q01105 |
| OMIM ID | 600960 |
| HGNC ID | 10760 |
| Aliases | I2PP2A, TAF-I, PHAPII, 2PP2A |
Description
The SET gene encodes a multifunctional nuclear protein that acts as a potent inhibitor of protein phosphatase 2A (PP2A) and is involved in chromatin remodeling, transcription regulation, histone chaperone activity, and apoptosis. It is a proto-oncogene frequently overexpressed or rearranged in various cancers, particularly acute myeloid leukemia (AML) and other hematologic malignancies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute Myeloid Leukemia (AML) | SET-CAN fusion gene (NUP214-SET) disrupts PP2A regulation and promotes leukemogenesis; SET overexpression inhibits PP2A tumor suppressor activity. | PMID: 15692054; COSMIC; ClinVar |
| Alzheimer's Disease | SET overexpression leads to PP2A inhibition, tau hyperphosphorylation, and amyloid-beta accumulation. | PMID: 18296642; OMIM 600960 |
| Non-Small Cell Lung Cancer | SET overexpression correlates with poor prognosis; promotes cell proliferation via PP2A inhibition. | PMID: 25944712 |
| Breast Cancer | SET upregulation associated with aggressive subtypes; contributes to chemoresistance. | PMID: 27626308 |
| Colorectal Cancer | SET overexpression linked to tumor progression and metastasis. | PMID: 28708999 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.5 | Medium |
| Lymph Node | 10.8 | Medium |
| Brain | 8.2 | Medium |
| Lung | 7.1 | Low |
| Breast | 6.5 | Low |
| Colon | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 15.3 | High expression; consistent with SET role in AML |
| HeLa (cervical) | 11.2 | Medium expression |
| A549 (lung) | 9.8 | Medium expression |
| MCF7 (breast) | 7.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| SET-CAN (NUP214-SET) fusion | Chromosomal rearrangement | Rare in AML | Oncogenic; disrupts PP2A regulation |
| SET p.Glu109Lys | Missense | <1% (COSMIC) | Unknown functional effect |
| SET p.Arg144Trp | Missense | <1% (COSMIC) | Unknown functional effect |
| SET p.Leu200Phe | Missense | <1% (COSMIC) | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported; SET is typically overexpressed or fused in cancer.
Gain of Function (GOF)
SET overexpression and SET-CAN fusion are considered gain-of-function events that inhibit PP2A and promote oncogenic signaling.
Dominant Negative (DN)
Not described for SET; the SET-CAN fusion may act as a dominant-negative regulator of PP2A.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • nucleus (GO:0005634) |
| • chromatin remodeling (GO:0006338) | • transcription factor binding (GO:0008134) |
| • regulation of lipid metabolic process (GO:0019216) | • intracellular ribonucleoprotein complex (GO:0030529) |
| • identical protein binding (GO:0042802) | • perinuclear region of cytoplasm (GO:0048471) |
Pathways
• PP2A signaling pathway
• Chromatin remodeling (SET/TAF-I complex)
• Apoptosis regulation
• Tau protein phosphorylation (Alzheimer's disease)
Protein Summary
The SET protein (also known as I2PP2A, TAF-I, PHAPII) is a 290-amino acid multifunctional nuclear phosphoprotein. It acts as a potent inhibitor of protein phosphatase 2A (PP2A), a major tumor suppressor phosphatase. SET also functions as a histone chaperone, facilitating chromatin assembly and transcription regulation. It is involved in DNA replication, repair, and apoptosis. Overexpression or fusion of SET (e.g., SET-CAN in AML) leads to PP2A inhibition, promoting cell proliferation and survival. SET is also implicated in Alzheimer's disease through tau hyperphosphorylation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SETD7 Knockout HEK293 Cell Line | EDJ-KQ965 | Human | 80854 | Details Get a Quote |
| SETDB1 Knockout HEK293 Cell Line | EDJ-KQ3430 | Human | 9869 | Details Get a Quote |
| SETD4 Knockout HEK293 Cell Line | EDJ-KQ3939 | Human | 54093 | Details Get a Quote |
| SETMAR Knockout HEK293 Cell Line | EDJ-KQ5737 | Human | 6419 | Details Get a Quote |
| SETX Knockout HEK293 Cell Line | EDJ-KQ7804 | Human | 23064 | Details Get a Quote |
| SETD1B Knockout HEK293 Cell Line | EDJ-KQ7807 | Human | 23067 | Details Get a Quote |
| SETBP1 Knockout HEK293 Cell Line | EDJ-KQ8369 | Human | 26040 | Details Get a Quote |
| SETD9 Knockout HEK293 Cell Line | EDJ-KQ9312 | Human | 133383 | Details Get a Quote |
| SETDB2 Knockout HEK293 Cell Line | EDJ-KQ9909 | Human | 83852 | Details Get a Quote |
| SETD3 Knockout HEK293 Cell Line | EDJ-KQ10009 | Human | 84193 | Details Get a Quote |
| SETD2 Knockout HEK293 Cell Line | EDJ-KQ15234 | Human | 29072 | Details Get a Quote |
| SETD5 Knockout HEK293 Cell Line | EDJ-KQ15235 | Human | 55209 | Details Get a Quote |
| SETD6 Knockout HEK293 Cell Line | EDJ-KQ15236 | Human | 79918 | Details Get a Quote |
| SETSIP Knockout HEK293 Cell Line | EDJ-KQ15237 | Human | 646817 | Details Get a Quote |
| SET Knockout HEK293 Cell Line | EDJ-KQ16505 | Human | 6418 | Details Get a Quote |
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