SMAD7: A Key Negative Regulator of TGF-β Signaling
Comprehensive genomic and functional overview of SMAD7, an inhibitor of TGF-β superfamily signaling involved in fibrosis, inflammation, and cancer.
Gene Information Card
| Symbol | SMAD7 |
|---|---|
| Full Name | SMAD family member 7 |
| Gene Type | Protein coding |
| Chromosomal Location | 18q21.1 |
| NCBI Gene ID | 4092 ncbi.nlm.nih.gov/gene/4092 |
| Ensembl ID | ENSG00000101665 |
| UniProt ID | O15105 |
| OMIM ID | 602932 |
| HGNC ID | 6773 |
| Aliases | MADH7, MADH8, SMAD7 |
Description
SMAD7 (SMAD family member 7) is a protein-coding gene that functions as a key negative regulator of transforming growth factor-beta (TGF-β) superfamily signaling. It inhibits signaling by preventing the phosphorylation and nuclear translocation of receptor-regulated SMADs (R-SMADs) and by promoting the degradation of TGF-β receptors. SMAD7 is involved in diverse biological processes including cell growth, differentiation, apoptosis, and immune regulation. Dysregulation of SMAD7 is associated with fibrosis, inflammatory diseases, and multiple cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | SMAD7 overexpression or amplification can inhibit TGF-β-mediated tumor suppression, promoting tumor progression. | NCBI Gene, COSMIC, ClinVar |
| Inflammatory bowel disease (IBD) | SMAD7 is upregulated in intestinal mucosa, blocking TGF-β1 anti-inflammatory signaling, contributing to chronic inflammation. | NCBI Gene, OMIM |
| Systemic sclerosis (scleroderma) | Increased SMAD7 expression in fibroblasts may contribute to fibrosis by modulating TGF-β signaling. | NCBI Gene, UniProt |
| Pancreatic cancer | SMAD7 alterations (e.g., amplification) are observed and may correlate with poor prognosis. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.3 | Medium |
| Colon | 10.8 | Medium |
| Small intestine | 9.5 | Medium |
| Spleen | 8.2 | Medium |
| Liver | 6.1 | Low |
| Kidney | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 (embryonic kidney) | 15.2 | High expression |
| HeLa (cervical carcinoma) | 12.8 | Medium expression |
| A549 (lung carcinoma) | 10.5 | Medium expression |
| HCT 116 (colorectal carcinoma) | 9.1 | Medium expression |
| MCF7 (breast carcinoma) | 7.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1135C>T (p.Arg379*) | Nonsense | <0.1% | Truncation, likely loss of function |
| c.1042G>A (p.Gly348Arg) | Missense | <0.1% | Unknown significance |
| Amplification (18q21.1) | Copy number gain | Variable | Potential gain of function in cancers |
Mutation functional classification
Loss of Function (LOF)
Nonsense mutations (e.g., p.Arg379*) are predicted to result in a truncated protein, reducing inhibitory activity on TGF-β signaling.
Gain of Function (GOF)
Gene amplification or overexpression may enhance SMAD7's inhibitory function, potentially contributing to tumor progression by blocking TGF-β-mediated growth suppression.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for SMAD7.
View complete mutation data：
Gene Ontology (GO)
| • GO:0007179 (transforming growth factor beta receptor signaling pathway) | • GO:0030512 (negative regulation of transforming growth factor beta receptor signaling pathway) |
| • GO:0005515 (protein binding) | • GO:0005634 (nucleus) |
| • GO:0005737 (cytoplasm) | • GO:0017015 (regulation of transforming growth factor beta receptor signaling pathway) |
Pathways
• TGF-beta signaling pathway (KEGG: hsa04350)
• SMAD signaling pathway (Reactome: R-HSA-9006936)
• Signaling by TGF-beta family members (Reactome: R-HSA-9006934)
Protein Summary
SMAD7 is a 426-amino acid protein (UniProt O15105) that acts as an intracellular antagonist of TGF-β signaling. It binds to the TGF-β receptor complex, preventing the phosphorylation of SMAD2 and SMAD3, and recruits E3 ubiquitin ligases such as SMURF2 to promote receptor degradation. SMAD7 also shuttles between the nucleus and cytoplasm. Its expression is induced by TGF-β itself, forming a negative feedback loop. The protein contains a conserved MH2 domain essential for its inhibitory function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SMAD7 Knockout HEK293 Cell Line | EDJ-KQ403 | Human | 4092 | Details Get a Quote |
| SMAD7 Knockout A-549 Cell Line | EDC90651 | Human | 4092 | Details Get a Quote |
| SMAD7 Knockout HCT 116 Cell Line | EDJ-KQ18651 | Human | 4092 | Details Get a Quote |
| SMAD7 Knockout HeLa Cell Line | EDJ-KQ18652 | Human | 4092 | Details Get a Quote |
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