MSTN
protein-codingmyostatin, the group of Transforming growth factor beta superfamily
Gene summary
This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein negatively regulates skeletal muscle cell proliferation and differentiation. Mutations in this gene are associated with increased skeletal muscle mass in humans and other mammals. [provided by RefSeq, Jul 2016]
- GDF8
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0013598
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0013598
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MSTN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005259.3. 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 | 5 | 5 | 1 | 11 | ||
| missense | 38 | 7 | 2 | 47 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 43 | 12 | 3 | 58 |
Highest pathogenic variant AF is 0.000008060976
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005250.1 | 3 | MANE Select | |
| Ensembl | ENSP00000260950.3 | 3 | MANE Select | |
| Ensembl | ENSP00000803080.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| mstnb | Danio rerio | Structure: skeletal muscle cell Quality: increased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling
- Hypertrophy Model
- GPCR signaling-G alpha q
- GPCR signaling-cholera toxin
- GPCR signaling-pertussis toxin
Biological Process
- transforming growth factor beta receptor signaling pathway
- muscle organ development
- response to heat
- response to gravity
- regulation of signaling receptor activity
Molecular Function
- signaling receptor binding
- cytokine activity
- transforming growth factor beta receptor binding
- protein binding
- growth factor activity
Cellular Component
- extracellular space
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000260950
- Coding exons
- 3
- Length
- 7033
- Individuals with no LoFs
- 125683
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 125699
- p
- 0.0000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.778 | 170 | 201 | 0.846 | 0.0000101 | 2465 |
| Missense (PolyPhen) | 21 | 43.247 | 0.48558 | 510 | ||
| Synonymous | -1.21 | 85 | 72.0 | 1.18 | 0.00000389 | 710 |
| Loss of Function | 2.85 | 3 | 14.8 | 0.202 | 8.13e-7 | 181 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00051 | 0.00051 | rare |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts specifically as a negative regulator of skeletal muscle growth. {ECO:0000250|UniProtKB:O08689}.;
- Disease
- DISEASE: Muscle hypertrophy (MSLHP) [MIM:614160]: A condition characterized by increased muscle bulk and strength. Affected individuals are exceptionally strong. {ECO:0000269|PubMed:15215484}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.744
Intolerance Scores
- LoFtool
- 0.236
- RVIS EVS
- 0.66
- RVIS percentile EVS
- 84.55
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.772
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |