SMO Gene (Smoothened, Frizzled Class Receptor): Structure, Function, and Clinical Significance
A comprehensive biomedical overview of the SMO gene, its protein product, associated diseases, expression patterns, mutations, and molecular pathways.
Gene Information Card
| Symbol | SMO |
|---|---|
| Full Name | Smoothened, Frizzled Class Receptor |
| Gene Type | Protein coding |
| Chromosomal Location | 7q32.1 |
| NCBI Gene ID | 6608 ncbi.nlm.nih.gov/gene/6608 |
| Ensembl ID | ENSG00000128602 |
| UniProt ID | Q99835 |
| OMIM ID | 601500 |
| HGNC ID | 11187 |
| Aliases | SMOH, FZD11, Gx, smoothened homolog |
Description
The SMO gene encodes Smoothened, a G protein-coupled receptor (GPCR) that is a critical component of the Hedgehog signaling pathway. It is a seven-transmembrane protein that, upon activation by the Hedgehog ligand (via Patched), initiates a signaling cascade that regulates cell differentiation, proliferation, and tissue patterning during development. Aberrant activation of SMO is implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Basal cell carcinoma | Activating mutations in SMO lead to constitutive activation of the Hedgehog pathway, promoting tumorigenesis. | COSMIC; PMID: 26912385 |
| Medulloblastoma | Somatic mutations in SMO (e.g., W535L) cause constitutive signaling, driving tumor growth in the SHH-subtype. | COSMIC; PMID: 12172542 |
| Gorlin syndrome (Nevoid basal cell carcinoma syndrome) | Germline mutations in PTCH1 (not SMO) are primary, but SMO mutations can contribute to tumor progression. | OMIM #601500; PMID: 10508505 |
| Rhabdomyosarcoma | SMO mutations or amplification can activate Hedgehog signaling, contributing to tumor development. | COSMIC; PMID: 24651015 |
| Breast cancer | Overexpression or activation of SMO has been observed, potentially driving cancer stem cell proliferation. | PMID: 21746838 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cerebellum | 8.2 | Medium |
| Skin | 5.1 | Low |
| Lung | 4.3 | Low |
| Kidney | 3.9 | Low |
| Liver | 2.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 6.5 | Moderate expression |
| A549 (lung cancer) | 5.2 | Low expression |
| HEK293 (embryonic kidney) | 4.8 | Low expression |
| HepG2 (liver cancer) | 3.1 | Low expression |
| U87MG (glioblastoma) | 7.0 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| W535L | Missense | ~10% in medulloblastoma | Constitutive activation of SMO, leading to uncontrolled Hedgehog signaling. |
| R562Q | Missense | Rare | Gain-of-function, associated with basal cell carcinoma. |
| S533N | Missense | Rare | Gain-of-function, observed in medulloblastoma. |
| G457D | Missense | Rare | Loss-of-function, reduces signaling activity. |
| V331A | Missense | Rare | Gain-of-function, found in basal cell carcinoma. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in SMO are rare and typically impair Hedgehog signaling, potentially leading to developmental defects. Examples include G457D, which reduces pathway activity.
Gain of Function (GOF)
Gain-of-function mutations are common in cancers, leading to constitutive activation of the Hedgehog pathway. These mutations often occur in the transmembrane domains and promote tumorigenesis (e.g., W535L, R562Q).
Dominant Negative (DN)
Dominant-negative mutations in SMO are not well-documented; most pathogenic mutations are gain-of-function. However, some variants may interfere with normal signaling in a dominant-negative manner, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • Hedgehog receptor activity |
| • signal transduction | • cell surface receptor signaling pathway |
| • positive regulation of cell proliferation | • embryonic development |
| • pattern specification process |
Pathways
• Hedgehog signaling pathway
• Signaling by GPCR
• Developmental biology
• Cancer pathways
Protein Summary
Smoothened (SMO) is a 787-amino acid G protein-coupled receptor with seven transmembrane domains. It is a key transducer of the Hedgehog signaling pathway. In the absence of Hedgehog ligand, Patched (PTCH1) inhibits SMO. Upon ligand binding, PTCH1's inhibition is relieved, allowing SMO to accumulate on the primary cilium and activate downstream transcription factors (GLI proteins). SMO is involved in embryonic patterning, cell differentiation, and stem cell maintenance. Dysregulation of SMO is linked to multiple cancers, making it a therapeutic target (e.g., vismodegib).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MSMO1 Knockout HEK293 Cell Line | EDJ-KQ5712 | Human | 6307 | Details Get a Quote |
| SMOX Knockout HEK293 Cell Line | EDJ-KQ11441 | Human | 54498 | Details Get a Quote |
| SMOC2 Knockout HEK293 Cell Line | EDJ-KQ12164 | Human | 64094 | Details Get a Quote |
| SMOC1 Knockout HEK293 Cell Line | EDJ-KQ12215 | Human | 64093 | Details Get a Quote |
| MOSMO Knockout HEK293 Cell Line | EDJ-KQ14289 | Human | 730094 | Details Get a Quote |
| SMO Knockout HEK293 Cell Line | EDJ-KQ17842 | Human | 6608 | Details Get a Quote |
| MSMO1 Knockout A-549 Cell Line | EDJ-KQ29089 | Human | 6307 | Details Get a Quote |
| MSMO1 Knockout HCT 116 Cell Line | EDJ-KQ29090 | Human | 6307 | Details Get a Quote |
| MSMO1 Knockout HeLa Cell Line | EDJ-KQ29091 | Human | 6307 | Details Get a Quote |
| SMOC1 Knockout A-549 Cell Line | EDJ-KQ40957 | Human | 64093 | Details Get a Quote |
| SMOC1 Knockout HeLa Cell Line | EDJ-KQ40958 | Human | 64093 | Details Get a Quote |
| MOSMO Knockout A-549 Cell Line | EDJ-KQ44337 | Human | 730094 | Details Get a Quote |
| MOSMO Knockout HCT 116 Cell Line | EDJ-KQ44338 | Human | 730094 | Details Get a Quote |
| MOSMO Knockout HeLa Cell Line | EDJ-KQ44339 | Human | 730094 | Details Get a Quote |
| SMO Knockout A-549 Cell Line | EDJ-KQ19767 | Human | 6608 | Details Get a Quote |
Displaying Records 1 To 15 Of 27 Records
