MSI1

Chr 12

musashi RNA binding protein 1

NCBI Gene: 4440ENSG00000135097UniProt: O43347OMIM: 603328

This protein is an RNA-binding protein that regulates mRNA translation, particularly controlling expression of NUMB (a NOTCH1 antagonist) and maintaining stem cells in the central nervous system. The gene is highly constrained against loss-of-function variants (pLI=0.99, LOEUF=0.26), but definitive human disease associations have not been established in the provided data.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.26
Clinical Summary— MSI1
⚡
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
13 unique Pathogenic / Likely Pathogenic· 39 VUS of 65 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.26LOEUF
pLI 0.994
Z-score 4.15
OE 0.08 (0.03–0.26)
Highly constrained

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

Missense Constraint
2.80Z-score
OE missense 0.46 (0.39–0.55)
100 obs / 215.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.08 (0.03–0.26)
0≤0.351.4
Missense OE0.46 (0.39–0.55)
0≤0.61.4
Synonymous OE0.94
0≤1.21.6
LoF obs/exp: 2 / 23.8Missense obs/exp: 100 / 215.5Syn Z: 0.45
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedMSI1-related microcephalyOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.5869th %ile
GOF
0.4184th %ile
LOF
0.70top 10%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

65 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic4
VUS39
Likely Benign1
Benign1
9
Pathogenic
4
Likely Pathogenic
39
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
4
0
4
VUS
0
34
5
0
39
Likely Benign
0
0
1
0
1
Benign
0
0
0
1
1
Total03419154

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

View in ClinVar →

Protein Context — Lollipop Plot

MSI1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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