MSTN (Myostatin) Gene: Function, Expression, and Clinical Significance
A comprehensive biomedical overview of the MSTN gene, encoding myostatin, a key regulator of muscle growth, with implications in muscle-related disorders and therapeutic targeting.
Gene Information Card
| Symbol | MSTN |
|---|---|
| Full Name | myostatin |
| Gene Type | protein coding |
| Chromosomal Location | 2q32.2 |
| NCBI Gene ID | 2660 ncbi.nlm.nih.gov/gene/2660 |
| Ensembl ID | ENSG00000138379 |
| UniProt ID | O14793 |
| OMIM ID | 601788 |
| HGNC ID | 4226 |
| Aliases | GDF8, GDF-8, MSLHP |
Description
The MSTN gene encodes myostatin, a secreted growth differentiation factor that belongs to the transforming growth factor beta (TGF-β) superfamily. Myostatin acts primarily as a negative regulator of skeletal muscle growth and development. It is synthesized as a precursor protein that undergoes proteolytic processing to form a mature active dimer. Myostatin signals through activin type II receptors (ACVR2A/ACVR2B) and downstream SMAD transcription factors to inhibit myoblast proliferation and differentiation. Mutations in MSTN can lead to increased muscle mass in animals and humans, while elevated myostatin levels are associated with muscle wasting conditions. The gene is a major focus for therapeutic interventions in muscle-related diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Muscle hypertrophy (MSTN-related) | Loss-of-function mutations in MSTN reduce myostatin activity, leading to increased muscle mass. The mechanism involves reduced inhibition of myogenesis and enhanced muscle fiber growth. | ClinVar, OMIM |
| Sarcopenia (age-related muscle loss) | Elevated myostatin expression in aging muscle contributes to muscle atrophy. Increased myostatin signaling activates SMAD pathways that promote protein degradation and inhibit satellite cell function. | PubMed, NCBI |
| Cachexia (cancer-associated muscle wasting) | Tumor-derived factors upregulate myostatin expression, leading to muscle wasting. Myostatin inhibition is being explored as a therapeutic strategy. | PubMed, COSMIC |
| Obesity and metabolic syndrome | Myostatin levels correlate with insulin resistance and fat accumulation. Reduced myostatin function improves metabolic profile in animal models, suggesting a role in energy metabolism. | PubMed, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal Muscle | High (nTPM ~ 2000) | Predominant expression; highest levels in skeletal muscle. |
| Adipose Tissue | Low (nTPM ~ 5) | Expressed in adipose tissue, but at much lower levels. |
| Heart | Low (nTPM ~ 3) | Minimal expression in cardiac muscle. |
| Liver | Not detected | No significant expression. |
| Brain | Not detected | No significant expression. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Skeletal Muscle Myotubes | High | Differentiated myotubes show high MSTN expression. |
| C2C12 Myoblasts | Moderate | Mouse myoblast cell line; expression decreases upon differentiation. |
| HepG2 (Liver) | Low | Hepatocellular carcinoma cell line with minimal expression. |
| A549 (Lung) | Low | Lung carcinoma cell line with low expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.313+1G>A (splice site) | Splice site variant | Rare | Loss-of-function; associated with muscle hypertrophy. |
| c.374T>C (p.Ile125Thr) | Missense | Rare | Loss-of-function; reduces myostatin activity. |
| c.563A>G (p.Asp188Gly) | Missense | Rare | Loss-of-function; impairs dimerization. |
| c.748T>C (p.Cys250Arg) | Missense | Rare | Loss-of-function; disrupts disulfide bond formation. |
Mutation functional classification
Loss of Function (LOF)
Most MSTN mutations are loss-of-function, leading to reduced or absent myostatin activity. This results in increased muscle mass due to enhanced myogenesis and reduced muscle protein breakdown.
Gain of Function (GOF)
Gain-of-function mutations are extremely rare and not well documented. Overexpression of wild-type myostatin can cause muscle wasting, but no activating mutations have been reported in humans.
Dominant Negative (DN)
Some missense mutations may exert a dominant-negative effect by forming non-functional dimers with wild-type myostatin, thereby reducing overall activity. This is seen in certain variants like p.Asp188Gly.
View complete mutation data：
Gene Ontology (GO)
| • growth factor activity | • cytokine activity |
| • protein binding | • transforming growth factor beta receptor binding |
| • extracellular space | • regulation of muscle cell differentiation |
| • negative regulation of cell proliferation | • SMAD protein signal transduction |
Pathways
• TGF-beta signaling pathway
• Regulation of skeletal muscle cell differentiation
• Myostatin signaling pathway
• Cytokine-cytokine receptor interaction
Protein Summary
Myostatin (UniProt O14793) is a 375-amino acid precursor protein with a signal peptide (aa 1-24), a propeptide domain (aa 25-266), and a mature C-terminal domain (aa 267-375). The mature protein forms a homodimer stabilized by disulfide bonds. It is secreted and cleaved by furin proteases to release the active C-terminal dimer. Myostatin binds to activin type II receptors (ACVR2A/ACVR2B) and recruits type I receptors (ALK4/ALK5), leading to SMAD2/3 phosphorylation and transcriptional regulation of target genes. The protein is highly conserved across species. Its expression is regulated by various factors including myogenic regulatory factors and hormones.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MSTN Knockout HEK293 Cell Line | EDJ-KQ2039 | Human | 2660 | Details Get a Quote |
| MSTN Knockout HeLa Cell Line | EDJ-KQ53324 | Human | 2660 | Details Get a Quote |
| MSTN Knockout A-549 Cell Line | EDJ-KQ61807 | Human | 2660 | Details Get a Quote |
| MSTN Knockout HCT 116 Cell Line | EDJ-KQ70293 | Human | 2660 | Details Get a Quote |
