MST1
protein-codingmacrophage stimulating 1
Gene summary
The protein encoded by this gene contains four kringle domains and a serine protease domain, similar to that found in hepatic growth factor. Despite the presence of the serine protease domain, the encoded protein may not have any proteolytic activity. The receptor for this protein is RON tyrosine kinase, which upon activation stimulates ciliary motility of ciliated epithelial lung cells. This protein is secreted and cleaved to form an alpha chain and a beta chain bridged by disulfide bonds. [provided by RefSeq, Jan 2010]
- D3F15S2
- HGFL
- DNF15S2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0013934
Submitter: Ambry Genetics
Inheritance Pattern: Unknown
Disease ID:MONDO:0009176
Submitter: Genomics England PanelApp
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MST1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020998.4. 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 | 8 | 11 | |||
| missense | 128 | 8 | 1 | 137 | ||
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 138 | 16 | 2 | 156 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_066278.3 | 18 | MANE Select | |
| Ensembl | ENSP00000414287.2 | 18 | MANE Select | |
| RefSeq | NP_001380510.1 | 18 | Standard | |
| RefSeq | NP_001380511.1 | 18 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| mst1 | Danio rerio | Structure: intestinal epithelial cell Quality: increased rate abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- a6b1 and a6b4 Integrin signaling
- Signaling by MST1
- Signaling by Receptor Tyrosine Kinases
- amb2 Integrin signaling
Biological Process
- proteolysis
- regulation of macrophage chemotaxis
- positive regulation of mammary gland epithelial cell proliferation
- negative regulation of gluconeogenesis
- hepatocyte growth factor receptor signaling pathway
Molecular Function
- serine-type endopeptidase activity
- protein binding
- receptor tyrosine kinase binding
Cellular Component
- extracellular region
- extracellular space
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000449682
- Coding exons
- 18
- Length
- 5555
- Individuals with no LoFs
- 122424
- Homozygous LoFs
- 21
- Heterozygous LoFs
- 3170
- Defined
- 125615
- p
- 0.0128
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.531 | 482 | 450 | 1.07 | 0.0000282 | 4639 |
| Missense (PolyPhen) | 178 | 153.75 | 1.1577 | 1674 | ||
| Synonymous | -1.05 | 191 | 173 | 1.10 | 0.0000102 | 1408 |
| Loss of Function | 1.38 | 34 | 43.9 | 0.775 | 0.00000212 | 447 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0045 | 0.0043 | notable |
| Latino/Admixed American | 0.0076 | 0.0075 | notable |
| Ashkenazi Jewish | 0.022 | 0.022 | notable |
| East Asian | 0.00093 | 0.00092 | rare |
| Finnish | 0.0057 | 0.0057 | notable |
| European (Non-Finnish) | 0.017 | 0.017 | notable |
| South Asian | 0.017 | 0.017 | notable |
| Other | 0.015 | 0.015 | notable |
dbNSFP Gene Annotations
Source:
- Disease
- DISEASE: Note=MST1 variant Cys-689 may be associated with inflammatory bowel disease (IBD), a chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is unsure whether Cys-689 itself or a variation in linkage disequilibrium with Cys-689 is responsible for the association with IBD. {ECO:0000269|PubMed:19079170, ECO:0000269|PubMed:20228799}.;
Recessive Scores
- pRec
- 0.102
Intolerance Scores
- LoFtool
- 0.148
- RVIS EVS
- -0.42
- RVIS percentile EVS
- 25.79
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.421
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |