SMO
Chr 7ARsmoothened, frizzled class receptor
Also known as: CRJS, FZD11, Gx, PHLS, SMOH
The protein is a G protein-coupled receptor that transduces hedgehog signaling by interacting with the patched protein receptor complex. Gain-of-function mutations cause Curry-Jones syndrome and Pallister-Hall-like syndrome through autosomal recessive inheritance. The pathogenic mechanism involves disrupted hedgehog pathway signaling leading to developmental abnormalities.
Moderate evidence — consider for supplementary testing
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
161 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 2 | 7 | 21 | 0 | 30 |
Likely Pathogenic | 0 | 2 | 0 | 0 | 2 |
VUS | 2 | 49 | 4 | 3 | 58 |
Likely Benign | 0 | 5 | 20 | 14 | 39 |
Benign | 0 | 4 | 17 | 5 | 26 |
Conflicting | — | 3 | |||
| Total | 4 | 67 | 62 | 22 | 158 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SMO · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions)
ACTIVE NOT RECRUITINGA Study of Osimertinib With or Without Chemotherapy as 1st Line Treatment in Patients With Mutated Epidermal Growth Factor Receptor Non-Small Cell Lung Cancer (FLAURA2)
ACTIVE NOT RECRUITINGCanadian Profiling and Targeted Agent Utilization Trial (CAPTUR)
RECRUITINGA Study to Find a Suitable Dose of ASP5834 in Adults With Solid Tumors
RECRUITINGLINNOVATE: Lurbinectedin, Ipilimumab and Nivolumab for Soft Tissue Sarcoma
RECRUITINGStudy of CX-5461 in Patients With Solid Tumours and BRCA1/2, PALB2 or Homologous Recombination Deficiency (HRD) Mutation
RECRUITINGLong-Term Follow-up Protocol for Participants Treated With Gene-Modified T Cells
RECRUITINGIvosidenib in Participants With Locally Advanced or Metastatic Conventional Chondrosarcoma Untreated or Previously Treated With 1 Systemic Treatment Regimen
RECRUITINGA Study to Learn More About How Well Sevabertinib Works and How Safe it is Compared With Standard Treatment, in Participants Who Have Advanced Non-small Cell Lung Cancer (NSCLC) With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2)
RECRUITINGLimiFlex Clinical Trial for the Treatment of Degenerative Spondylolisthesis With Spinal Stenosis
ACTIVE NOT RECRUITINGHAELO: A Phase 3 Study to Evaluate NTLA-2002 in Participants With Hereditary Angioedema (HAE)
ACTIVE NOT RECRUITINGVismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas
RECRUITINGExternal Resources
Links to major genomics databases and tools