MSLN
protein-codingmesothelin
Gene summary
This gene encodes a preproprotein that is proteolytically processed to generate two protein products, megakaryocyte potentiating factor and mesothelin. Megakaryocyte potentiating factor functions as a cytokine that can stimulate colony formation of bone marrow megakaryocytes. Mesothelin is a glycosylphosphatidylinositol-anchored cell-surface protein that may function as a cell adhesion protein. This protein is overexpressed in epithelial mesotheliomas, ovarian cancers and in specific squamous cell carcinomas. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MSLN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005823.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 5 | 3 | 11 | ||
| missense | 149 | 18 | 6 | 173 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 157 | 23 | 9 | 189 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005814.2 | 16 | MANE Select | |
| Ensembl | ENSP00000442965.2 | 16 | MANE Select | |
| RefSeq | NP_001170826.1 | 16 | Standard | |
| RefSeq | NP_037536.2 | 16 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein phosphorylation
- Post-translational modification: synthesis of GPI-anchored proteins
- Post-translational protein modification
- Metabolism of proteins
- Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
Biological Process
- cell adhesion
- cell-matrix adhesion
- pancreas development
- post-translational protein modification
- cellular protein metabolic process
Molecular Function
- protein binding
Cellular Component
- extracellular region
- extracellular space
- endoplasmic reticulum lumen
- Golgi apparatus
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000382862
- Coding exons
- 16
- Length
- 8104
- Individuals with no LoFs
- 124844
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 133
- Defined
- 124977
- p
- 0.000532
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.04 | 474 | 414 | 1.14 | 0.0000291 | 3944 |
| Missense (PolyPhen) | 111 | 104.96 | 1.0576 | 1233 | ||
| Synonymous | -2.69 | 242 | 194 | 1.25 | 0.0000138 | 1400 |
| Loss of Function | -0.590 | 35 | 31.4 | 1.11 | 0.00000149 | 338 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00063 | 0.00062 | rare |
| Latino/Admixed American | 0.0019 | 0.0019 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00071 | 0.00071 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00030 | 0.00029 | rare |
| South Asian | 0.00034 | 0.00029 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Membrane-anchored forms may play a role in cellular adhesion.;
- Disease
- DISEASE: Note=Antibodies against MSLN are detected in patients with mesothelioma and ovarian cancer. {ECO:0000269|PubMed:15897581}.;
Recessive Scores
- pRec
- 0.200
Intolerance Scores
- LoFtool
- 0.920
- RVIS EVS
- 0.73
- RVIS percentile EVS
- 85.99
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.282
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |