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]

GeneReviewsResearchGenerating clinical summary…

Clinical highlights

Gene-disease validity (ClinGen)
congenital hypothalamic hamartoma syndrome · ARModerateconsider for supplementary testing2 gene-disease associations curated in total
Interpreting a novel variant
Curated mechanisms (Gene2Phenotype) include both loss of function and gain of function. Which applies is variant-dependent — do not assume a null variant is, or isn’t, the pathogenic class without checking the specific variant.Curated gene-level mechanism — a prior for triage, not a per-variant call.
12
Active trials
429
Pubs (1 yr)
P/LP submissions
P/LP missense
0.68
LOEUF
Multiple*
Mechanism· G2P
📖
GeneReview available — SMO
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
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?
0.68LOEUF
pLI 0.000
Z-score 3.08
OE 0.46 (0.310.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.90Z-score
OE missense 0.75 (0.690.82)
345 obs / 459.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.46 (0.310.68)
00.351.4
Missense OE?0.75 (0.690.82)
00.61.4
Synonymous OE?0.99
01.21.6
LoF obs/exp: 17 / 37.3Missense obs/exp: 345 / 459.4Syn Z: 0.10

ClinVar Variant Classifications

0 submitted variants 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Locally Advanced or Metastatic Conventional Chondrosarcoma With an IDH1 Mutation, Untreated or Previously Treated With 1 Systemic Treatment Regimen

Ivosidenib in Participants With Locally Advanced or Metastatic Conventional Chondrosarcoma Untreated or Previously Treated With 1 Systemic Treatment Regimen

RECRUITING
NCT06127407Phase PHASE3Servier Bio-Innovation LLCStarted 2024-07-09
Ivosidenib 500mgPlacebo
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
Unresectable or Metastatic Melanoma or Advanced Solid TumorsMelanomaUveal Melanoma

A Study of APG-115 in as a Monotherapy or Combination With Pembrolizumab in Patients With Metastatic Melanomas or Advanced Solid Tumors

ACTIVE NOT RECRUITING
NCT03611868Phase PHASE1, PHASE2Ascentage Pharma Group Inc.Started 2018-08-29
Phase 1b: APG-115+pembrolizumab
Solid Tumor, AdultOncology

Open-Label, Dose-Escalation With Expansion to Assess the Safety, Tolerability, and PK of TRE-515 in Subjects With Solid Tumors

RECRUITING
NCT05055609Phase PHASE1TretheraStarted 2021-09-23
TRE-515
Osteoarthritis (OA) of the Knee

A Study to Assess Safety and Tolerability of PCRX-201 in Subjects With Painful Osteoarthritis of the Knee

RECRUITING
NCT06884865Phase PHASE2Pacira Pharmaceuticals, IncStarted 2025-02-26
Enekinragene Inzadenovec (PCRX-201)Placebo
Advanced Non-small Cell Lung Cancer, HER2 Mutation

A 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)

RECRUITING
NCT06452277Phase PHASE3BayerStarted 2024-08-28
SevabertinibPembrolizumabCisplatin
MelanomaGliomaThyroid Cancer

A Study to Learn About the Study Medicine Called PF-07799544 as Monotherapy or in Combination in People With Advanced Solid Tumors

ACTIVE NOT RECRUITING
NCT05538130Phase PHASE1PfizerStarted 2022-11-30
PF-07799544PF-07799933
Advanced Soft-tissue Sarcoma

LINNOVATE: Lurbinectedin, Ipilimumab and Nivolumab for Soft Tissue Sarcoma

RECRUITING
NCT05876715Phase PHASE1, PHASE2ERLINDA M GORDONStarted 2023-06-07
Lurbinectedin
ChordomasChordoma

Pembrolizumab and Pemetrexed for Progressive Chordoma

RECRUITING
NCT06794645Phase PHASE2Saint John's Cancer InstituteStarted 2025-01
PembrolizumabPemetrexed Phase 2
Breast CancerCholangiocarcinomaColorectal Cancer

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 RECRUITING
NCT02568267Phase PHASE2Hoffmann-La RocheStarted 2015-11-19
Entrectinib
Locally Advanced or Metastatic Non-Small Cell Lung Cancer

A Study to Investigate the Efficacy and Safety of Trastuzumab Deruxtecan as the First Treatment Option for Unresectable, Locally Advanced/Metastatic Non-Small Cell Lung Cancer With HER2 Mutations

ACTIVE NOT RECRUITING
NCT05048797Phase PHASE3AstraZenecaStarted 2021-10-28
Trastuzumab DeruxtecanCisplatinCarboplatin
Advanced Solid Tumor

Study of CX-5461 in Patients With Solid Tumours and BRCA1/2, PALB2 or Homologous Recombination Deficiency (HRD) Mutation

RECRUITING
NCT04890613Phase PHASE1Senhwa Biosciences, Inc.Started 2021-09-08
CX-5461