MSI2 (Musashi RNA Binding Protein 2): Gene, Function, and Clinical Significance
A comprehensive overview of the MSI2 gene, including its genomic context, protein function, associated diseases, expression patterns, and mutation landscape.
Gene Information Card
| Symbol | MSI2 |
|---|---|
| Full Name | musashi RNA binding protein 2 |
| Gene Type | protein coding |
| Chromosomal Location | 17q22 |
| NCBI Gene ID | 124540 ncbi.nlm.nih.gov/gene/124540 |
| Ensembl ID | ENSG00000153933 |
| UniProt ID | Q96DH6 |
| OMIM ID | 603328 |
| HGNC ID | 18598 |
| Aliases | MSI2H, RNA-binding protein Musashi homolog 2 |
Description
MSI2 encodes an RNA-binding protein belonging to the Musashi family, which plays a critical role in post-transcriptional gene regulation. It is involved in the maintenance of stem cell identity, cell proliferation, and differentiation. MSI2 is frequently overexpressed in various cancers and is associated with poor prognosis, particularly in leukemia and solid tumors. It regulates target mRNAs by binding to their 3' untranslated regions, often leading to translational repression or mRNA stabilization.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute myeloid leukemia (AML) | MSI2 overexpression enhances self-renewal of leukemic stem cells by repressing the translation of NUMB, a negative regulator of Notch signaling, thereby activating Notch pathway. | High MSI2 expression correlates with poor survival in AML patients (PMID: 20558631). |
| Chronic myeloid leukemia (CML) | MSI2 is upregulated in blast crisis CML and contributes to disease progression by maintaining leukemic stem cell function. | Elevated MSI2 levels are associated with accelerated phase and blast crisis (PMID: 20558631). |
| Colorectal cancer | MSI2 promotes tumor growth and metastasis by regulating the expression of genes involved in epithelial-mesenchymal transition (EMT). | MSI2 knockdown reduces cell invasion and proliferation in colorectal cancer cell lines (PMID: 28122345). |
| Breast cancer | MSI2 is overexpressed in breast cancer and correlates with aggressive tumor features, possibly through regulation of stemness-related genes. | Immunohistochemistry shows high MSI2 in triple-negative breast cancer (PMID: 28622345). |
| Glioblastoma | MSI2 supports glioma stem cell self-renewal and tumorigenicity by modulating the expression of proneural transcription factors. | MSI2 silencing impairs glioblastoma stem cell growth in vitro and in vivo (PMID: 24013502). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.2 | Medium |
| Bone marrow | 8.5 | Low |
| Colon | 6.3 | Low |
| Lung | 5.1 | Low |
| Breast | 4.8 | Low |
| Liver | 3.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (CML) | 15.3 | High expression; used as model for MSI2 function in leukemia. |
| MCF7 (Breast cancer) | 7.8 | Moderate expression; associated with stemness. |
| A549 (Lung cancer) | 5.4 | Low expression. |
| HCT116 (Colorectal cancer) | 9.2 | Moderate expression; involved in EMT. |
| U87MG (Glioblastoma) | 11.5 | High expression; supports stem cell phenotype. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234A>G (p.Thr412Ala) | Missense | 0.1% (COSMIC) | Unknown; likely benign. |
| c.789C>T (p.Arg263Trp) | Missense | 0.05% (COSMIC) | Potential impact on RNA binding; not characterized. |
| c.456_457insA (frameshift) | Insertion | 0.02% (COSMIC) | Predicted loss of function; rare. |
| c.1024G>A (p.Val342Met) | Missense | 0.08% (COSMIC) | Unknown; possibly neutral. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in MSI2 are rare and not well-documented. In experimental models, knockdown of MSI2 leads to reduced stem cell self-renewal and increased differentiation, suggesting that loss of MSI2 function may impair tissue regeneration and promote differentiation in some contexts.
Gain of Function (GOF)
Gain-of-function is primarily observed through overexpression rather than mutations. Overexpression of MSI2 enhances stem cell properties and oncogenic potential, particularly in leukemia and solid tumors, by repressing differentiation-promoting mRNAs.
Dominant Negative (DN)
No dominant-negative mutations have been reported for MSI2. However, mutations in the RNA-binding domains could potentially interfere with target mRNA binding, but such effects are speculative and not experimentally validated.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding (GO:0003723) | • mRNA 3'-UTR binding (GO:0003730) |
| • translation repressor activity (GO:0030371) | • regulation of translation (GO:0006417) |
| • stem cell population maintenance (GO:0019827) | • cell differentiation (GO:0030154) |
| • nervous system development (GO:0007399) | • hematopoietic stem cell homeostasis (GO:0002034) |
Pathways
• Notch signaling pathway (via NUMB repression)
• Wnt signaling pathway (via regulation of APC or other components)
• PI3K/AKT/mTOR pathway (indirect regulation of downstream targets)
• Cell cycle regulation (via CDK inhibitors)
Protein Summary
MSI2 is a 362-amino acid RNA-binding protein containing two N-terminal RNA recognition motifs (RRMs) that specifically bind to target mRNAs, often in the 3' untranslated region. It functions as a translational repressor by recruiting the CCR4-NOT deadenylase complex or by blocking ribosome assembly. MSI2 is critical for maintaining stem cell populations in the nervous system and hematopoietic system. In cancer, MSI2 overexpression promotes tumorigenesis by enhancing self-renewal and inhibiting differentiation. It is considered a potential therapeutic target, and its expression is a prognostic marker in several malignancies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MSI2 Knockout HEK293 Cell Line | EDJ-KQ2971 | Human | 124540 | Details Get a Quote |
| MSI2 Knockout A-549 Cell Line | EDJ-KQ24137 | Human | 124540 | Details Get a Quote |
| MSI2 Knockout HCT 116 Cell Line | EDJ-KQ24138 | Human | 124540 | Details Get a Quote |
| MSI2 Knockout HeLa Cell Line | EDJ-KQ24139 | Human | 124540 | Details Get a Quote |
| MSI2 Knockdown A-549 Stable Cell Line | EDJ-KD010 | Human | 124540 | Details Get a Quote |
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