SMO

Chr 7

smoothened, frizzled class receptor

Also known as: CRJS, FZD11, Gx, PHLS, SMOH

The protein encoded by this gene is a G protein-coupled receptor that interacts with the patched protein, a receptor for hedgehog proteins. The encoded protein tranduces signals to other proteins after activation by a hedgehog protein/patched protein complex. [provided by RefSeq, Jul 2010]

187
ClinVar variants
10
Pathogenic / LP
0.00
pLI score
12
Active trials
Clinical SummarySMO
🧬
Gene-Disease Validity (ClinGen)
congenital hypothalamic hamartoma syndrome · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 122 VUS of 187 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.68LOEUF
pLI 0.000
Z-score 3.08
OE 0.46 (0.310.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.90Z-score
OE missense 0.75 (0.690.82)
345 obs / 459.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.46 (0.310.68)
00.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.690.82)
00.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
01.21.6
LoF obs/exp: 17 / 37.3Missense obs/exp: 345 / 459.4Syn Z: 0.10

ClinVar Variant Classifications

187 submitted variants in ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic2
VUS122
Likely Benign34
Benign20
Conflicting1
8
Pathogenic
2
Likely Pathogenic
122
VUS
34
Likely Benign
20
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
2
0
0
2
VUS
2
110
7
3
122
Likely Benign
0
2
24
8
34
Benign
0
1
17
2
20
Conflicting
1
Total21155613187

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.

Gene2Phenotype Curations

SMO-related Curry-Jones syndrome

definitive
ADGain Of FunctionAltered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗

SMO-related developmental disorder

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

No OMIM entries found.

📖
GeneReview available — SMO
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
[Meningioma].
Sasaki H·No Shinkei Geka
2023
Simpson-Golabi-Behmel syndrome.
Vaisfeld A et al.·Am J Med Genet C Semin Med Genet
2024Review
Clinical genetics of craniosynostosis.
Wilkie AOM et al.·Curr Opin Pediatr
2017Review
Genomic Landscape of Meningiomas.
Wang JZ et al.·Adv Exp Med Biol
2023
Ivosidenib in acute myeloid leukemia.
Bruzzese A et al.·Expert Opin Pharmacother
2023Review
Targeting of Smoothened for therapeutic gain.
Ruat M et al.·Trends Pharmacol Sci
2014Review
Top 10 resultsSearch PubMed ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Intracranial MeningiomaRecurrent MeningiomaNF2 Gene Mutation

Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas

RECRUITING
NCT02523014Phase PHASE2Alliance for Clinical Trials in OncologyStarted 2015-09-28
VismodegibFAK Inhibitor GSK2256098Capivasertib
Advanced LymphomaAdvanced Malignant Solid NeoplasmBladder Carcinoma

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

ACTIVE NOT RECRUITING
NCT02465060Phase PHASE2National Cancer Institute (NCI)Started 2015-08-17
AdavosertibAfatinibAfatinib Dimaleate
Degenerative SpondylolisthesisLumbar Spinal Stenosis

LimiFlex Clinical Trial for the Treatment of Degenerative Spondylolisthesis With Spinal Stenosis

ACTIVE NOT RECRUITING
NCT03115983Phase NAEmpirical Spine, Inc.Started 2017-07-17
LimiFlexFusion InstrumentationDecompression
Acute Coronary Syndrome

A Study of Milvexian in Participants After a Recent Acute Coronary Syndrome

ACTIVE NOT RECRUITING
NCT05754957Phase PHASE3Janssen Research & Development, LLCStarted 2023-04-07
MilvexianPlacebo
Melanoma

A Trial to See if the Combination of Fianlimab With Cemiplimab Works Better Than Pembrolizumab for Preventing or Delaying Melanoma From Coming Back After it Has Been Removed With Surgery

ACTIVE NOT RECRUITING
NCT05608291Phase PHASE3Regeneron PharmaceuticalsStarted 2023-01-16
FianlimabCemiplimabPembrolizumab
Non-small Cell Lung Cancer

Beamion LUNG-3: A Study to Test Whether Zongertinib Helps People With Surgically Removed, Non-small Cell Lung Cancer With HER2 Mutations Compared With Standard Treatment

RECRUITING
NCT07195695Phase PHASE3Boehringer IngelheimStarted 2026-01-16
ZongertinibPembrolizumabAtezolizumab
Breast CancerCognitive Impairments

Cognitive Training for Cancer Related Cognitive Impairment in Breast Cancer Survivors

RECRUITING
NCT05896189Phase NANRG OncologyStarted 2024-04-12
Arm 1: Computerized Cognitive Training-Global Stimulation GamesArm 2: Computerized Cognitive Training-Neuroplasticity Games
Non-Small Cell Lung Cancer

A 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 RECRUITING
NCT04035486Phase PHASE3AstraZenecaStarted 2019-07-02
OsimertinibPemetrexed/CarboplatinPemetrexed/Cisplatin
Neoplasms

Study of TSR-042, an Anti-programmed Cell Death-1 Receptor (PD-1) Monoclonal Antibody, in Participants With Advanced Solid Tumors

ACTIVE NOT RECRUITING
NCT02715284Phase PHASE1Tesaro, Inc.Started 2016-03-07
Dostarlimab
Anatomic Stage I Breast Cancer AJCC v8Anatomic Stage II Breast Cancer AJCC v8Anatomic Stage III Breast Cancer AJCC v8

Monitoring Symptoms to Help Young Women Take Hormone Therapy for Stage I-III Breast Cancer, ASPEN Study

ACTIVE NOT RECRUITING
NCT05568472Phase NASWOG Cancer Research NetworkStarted 2023-03-29
Best PracticeBiospecimen CollectionEndocrine Drug Therapy
TumorTumor, SolidMetastasis

Phase 2 Basket Trial of Nab-sirolimus in Patients With Malignant Solid Tumors With Pathogenic Alterations in TSC1/TSC2 Genes (PRECISION 1)

ACTIVE NOT RECRUITING
NCT05103358Phase PHASE2Aadi Bioscience, Inc.Started 2022-02-15
nab-sirolimus
Anatomic Stage I Breast Cancer AJCC v8Anatomic Stage II Breast Cancer AJCC v8Anatomic Stage III Breast Cancer AJCC v8

Pembrolizumab vs. Observation in People With Triple-negative Breast Cancer Who Had a Pathologic Complete Response After Chemotherapy Plus Pembrolizumab

RECRUITING
NCT05812807Phase PHASE3Alliance for Clinical Trials in OncologyStarted 2023-06-14
PembrolizumabPatient ObservationBiopsy