MSI2

Chr 17

musashi RNA binding protein 2

Also known as: MSI2H

NCBI Gene: 124540UniProt: Q96DH6

This gene encodes an RNA-binding protein that is a member of the Musashi protein family. The encoded protein is transcriptional regulator that targets genes involved in development and cell cycle regulation. Mutations in this gene are associated with poor prognosis in certain types of cancers. This gene has also been shown to be rearranged in certain cancer cells. [provided by RefSeq, Apr 2016]

0
Active trials
45
ClinVar variants
15
Pathogenic / LP
2.3
Missense Z
0.24
LOEUF· LoF intolerant
11
Pubs (2 yr)
Clinical Summary— MSI2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 28 VUS of 45 total submissions
Some data sources returned errors (1)

ensembl: Error: Ensembl fetch failed: 500 for https://rest.ensembl.org/lookup/symbol/homo_sapiens/MSI2?content-type=application/json&expand=1

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.24LOEUF
pLI 0.995
Z-score 3.94
OE 0.05 (0.02–0.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.29Z-score
OE missense 0.55 (0.47–0.65)
114 obs / 206.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.05 (0.02–0.24)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.55 (0.47–0.65)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 1 / 20.0Missense obs/exp: 114 / 206.4Syn Z: -0.06

ClinVar Variant Classifications

45 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
VUS28
Likely Benign2
15
Pathogenic
28
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
0
0
0
VUS
0
23
5
0
28
Likely Benign
0
0
2
0
2
Benign
0
0
0
0
0
Total02322045

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MSI2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Inherited resilience to clonal hematopoiesis by modifying stem cell RNA regulation.
Agarwal G et al.·Science
2026
Circular RNA-based protein replacement therapy mitigates osteoarthritis in male mice.
Suo J et al.·Nat Commun
2025
RNA-Binding Proteins in Acute Leukemias.
Schuschel K et al.·Int J Mol Sci
2020Review
Correlates and consequences of clonal hematopoiesis expansion rate: a 16-year longitudinal study of 6976 women.
Pershad Y et al.·Blood
2025Natural history
Exploring the role of m6A methylation regulators in glioblastoma multiforme and their impact on the tumor immune microenvironment.
Deng X et al.·FASEB J
2023
Musashi-2 (MSI2) promotes neuroblastoma tumorigenesis through targeting MYC-mediated glucose-6-phosphate dehydrogenase (G6PD) transcriptional activation.
Jiang P et al.·Med Oncol
2023
The Novel KLF4/MSI2 Signaling Pathway Regulates Growth and Metastasis of Pancreatic Cancer.
Guo K et al.·Clin Cancer Res
2017
Musashi-2 potentiates colorectal cancer immune infiltration by regulating the post-translational modifications of HMGB1 to promote DCs maturation and migration.
Meng X et al.·Cell Commun Signal
2024
MSI2 expression in adrenocortical carcinoma: Association with unfavorable prognosis and correlation with steroid and immune-related pathways.
Veronez LC et al.·J Cell Biochem
2021
MSI2 is required for maintaining activated myelodysplastic syndrome stem cells.
Taggart J et al.·Nat Commun
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Musashi 2 (MSI2) expression as an independent prognostic biomarker in non-small cell lung cancer (NSCLC)
Topchu I et al.·J Thorac Dis
2021
Prognostic value of Musashi 2 (MSI2) in cancer patients: A systematic review and meta-analysis
Jiang L et al.·Front Oncol
2022Review
Potential Role of Musashi-2 RNA-Binding Protein in Cancer EMT
Sun J et al.·Onco Targets Ther
2021
MicroRNA-143 acts as a tumor suppressor through Musashi-2/DLL1/Notch1 and Musashi-2/Snail1/MMPs axes in acute myeloid leukemia
Li F et al.·J Transl Med
2023
LncRNA LINC00942 promotes chemoresistance in gastric cancer by suppressing MSI2 degradation to enhance c-Myc mRNA stability
Zhu Y et al.·Clin Transl Med
2022
Targeting Musashi-2 to counteract senescence and resistance in chronic myeloid leukemia: enhancing the efficacy of imatinib therapy
Arif K et al.·BMC Cancer
2025
Darwin, MSI2, and relapse in T-ALL.
Barata JT·Blood
2024
Electronic and Excitonic Properties of MSi2 Z4 Monolayers.
Woźniak T et al.·Small
2023
Musashi-2 in cancer-associated fibroblasts promotes non-small cell lung cancer metastasis through paracrine IL-6-driven epithelial-mesenchymal transition
Samart P et al.·Cell Biosci
2023
Regulation of VEGFR2 and AKT Signaling by Musashi-2 in Lung Cancer
Bychkov I et al.·Cancers (Basel)
2023
Top 10 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients