Gene

SMO

smoothened, frizzled class receptor

Explore in graph →CI-GENE-00031524HGNC:11119 ENSG00000128602 NCBI 6608 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (35)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–35 of 35 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
SMO A459V1
Vismodegib	Basal Cell Carcinoma	Predictive	D	Supports Resistance	—	submitted	EID4679 In an in vitro study, a C3H10T1/2 cell line expressing a SMO A459V mutation, demonstrated resistance to vismodegib treatment, compared to C3H10T1/2 cells expressing wild-type SMO. Resistance was deter…

Cohorts

Alteration frequency by cohort (88)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved88 cohort rows (showing 38, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Mixed Tumors Selpercatinib RET Trial (MSK, Nat Commun. 2022) mixed_selpercatinib_2020	unmapped	Ssm	1	60

Literature

Linked publications (6)

25 per page, newest first.

pubmedPublishedShowing 1–6 of 6 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Smoothened variants explain the majority of drug resistance in basal cell carcinoma.
· Cancer Cell · 2015 · PMID 25759020 · validated civic_curation pubmed
Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study.
· J Clin Oncol · 2018 · PMID 29320312 · validated civic_curation pubmed
An Investigator-Initiated Open-Label Trial of Sonidegib in Advanced Basal Cell Carcinoma Patients Resistant to Vismodegib.
· Clin Cancer Res · 2016 · PMID 26546616 · validated civic_curation pubmed
Segmental basal cell naevus syndrome caused by an activating mutation in smoothened.
· Br J Dermatol · 2016 · PMID 26822128 · validated civic_curation

SMO Amplification2
Gefitinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	3	submitted	EID2945 Activation of the Hh pathway was found in both models of EGFR-mutated and EGFR-WT NSCLC cell line resistant to EGFR-TKIs. In EGFR-WT NSCLC cell lines resistant to EGFR inhibitors, the combined inhibit… (full text at CIViC) PMID 26124204 · Della Corte et al., 2015 · Open in CIViC	civic
Gefitinib + SonidegibCombination	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	submitted	EID2946 Activation of the Hh pathway was found in both models of EGFR-mutated and EGFR-WT NSCLC cell line resistant to EGFR-TKIs. In EGFR-WT NSCLC cell lines resistant to EGFR inhibitors, the combined inhibit… (full text at CIViC) PMID 26124204 · Della Corte et al., 2015 · Open in CIViC	civic

SMO Amplification2

Gefitinib

Lung Non-Small Cell CarcinomaCURATED_BROADER

Predictive

Supports Resistance

submitted

EID2945

Activation of the Hh pathway was found in both models of EGFR-mutated and EGFR-WT NSCLC cell line resistant to EGFR-TKIs. In EGFR-WT NSCLC cell lines resistant to EGFR inhibitors, the combined inhibit… (full text at CIViC)

PMID 26124204 · Della Corte et al., 2015 · Open in CIViC

SMO D473H4
Patidegib	MedulloblastomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	accepted	EID1099 Saridegib treatment induced tumor reduction and significantly prolonged survival in a Shh-driven mouse medulloblastoma model, and was found to be active in cells with the D473H point mutation. PMID 22550175 · Lee et al., 2012 · Open in CIViC	civic
Vismodegib	MedulloblastomaCURATED_BROADER	Predictive	C	Supports Resistance	3	accepted	EID745 In this case report, the D473H mutation was reported as an acquired mechanism of resistance to the hedgehog pathway inhibitor GDC-0449 (vismodegib). PMID 19726788 · Yauch et al., 2009 · Open in CIViC	civic
〃	Basal Cell Carcinoma	Predictive	D	Supports Resistance	3	accepted	EID755 D473 mutations were identified in 5/30 resistant basal cell carcinomas. Crystal structure indicated this mutation interacts with a water molecule in the ligand binding pocket, putatively altering its … (full text at CIViC) PMID 25759020 · Atwood et al., 2015 · Open in CIViC	civic
〃	MedulloblastomaCURATED_BROADER	Predictive	D	Supports Resistance	—	submitted	EID4427 In an in vitro study, a C3H10T1/2 cell line expressing SMO D473H mutation, demonstrated resistance to vismodegib treatment (IC50: 3,000,000 nmol/L vs. 20 nmol/L) compared to C3H10T1/2 cells expressing… (full text at CIViC) PMID 21123452 · Dijkgraaf et al., 2011 · Open in CIViC	civic

SMO Mutation4
Arsenic Trioxide + PSISubstitutes	Basal Cell Carcinoma	Predictive	D	Supports Sensitivity Response	4	accepted	EID747 Basal cell carcinomas with ligand-binding pocket or constitutively active mutations in the SMO gene were sensitive to inhibition of downstream hedgehog signaling with PSI (aPKC-ι/λ/GLI inhibitor) or a… (full text at CIViC) PMID 25759020 · Atwood et al., 2015 · Open in CIViC	civic
Vismodegib	Basal Cell Carcinoma	Predictive	B	Supports Resistance	4	accepted	EID746 In basal cell carcinoma, H231R, D473G, W281C and Q477E mutations conferred resistance to SMO-inhibitor vismodegib. SMO mutations were identified in 22 of 44 resistant basal cell carcinomas in 15 patie… (full text at CIViC) PMID 25759020 · Atwood et al., 2015 · Open in CIViC	civic
〃	Malignant NeoplasmALIAS	Predictive	B	Does Not Support Sensitivity Response	2	accepted	EID5979 The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. Twenty-one p… (full text at CIViC) PMID 29320312 · Hainsworth et al., 2018 · Open in CIViC	civic
Sonidegib + VismodegibSequential	Basal Cell Carcinoma	Predictive	B	Supports Resistance	2	accepted	EID1477 Study explored the response to the SMO inhibitor sonidegib (LDE225) in a cohort of 9 patients with advanced basal cell carcinoma that exhibited treatment resistance with vismodegib (GDC0449). Sequenc… (full text at CIViC) PMID 26546616 · Danial et al., 2016 · Open in CIViC	civic

SMO W535L6
(diagnostic)	Olfactory Groove Meningioma	Diagnostic	C	Supports N/A	2	submitted	EID1928 Boetto et al used Sanger sequencing to query SMO mutations (W535L and L412F) in 79 confirmed olfactory groove meningiomas and identified 1 patient with W535L (and 21 with L412F). PMID 28082415 · Boetto et al., 2017 · Open in CIViC	civic
〃	Basal Cell Carcinoma	Diagnostic	C	Supports N/A	2	submitted	EID1929 Reifenberger et al used SSCP/Heteroduplex analysis and direct sequencing to identify mutations in PTCH or SMO in 31 sporadic basal cell carcinomas (BCCs) and 15 primitive neuroectodermal tumors (PNETs… (full text at CIViC) PMID 9581815 · Reifenberger et al., 1998 · Open in CIViC	civic
〃	Basal Cell Carcinoma	Diagnostic	D	Supports N/A	3	submitted	EID1926 Xie et al identified 3 / 47 sporadic basal cell carcinomas (BCC) with somatic mutations in SMO, 2 of which were W535L. Whole blood from these patients, as a normal control, did not contain this mutati… (full text at CIViC) PMID 9422511 · Xie et al., 1998 · Open in CIViC	civic
〃	Meningioma	Diagnostic	D	Supports N/A	3	submitted	EID1927 Brastianos et al identified SMO W535L in 2 tumors from a set of 65 meningiomas, notably in meningiomas lacking NF2 alterations and of the meningiothelial subtype. The variants displayed high somatic v… (full text at CIViC) PMID 23334667 · Brastianos et al., 2013 · Open in CIViC	civic
Vismodegib	Basal Cell Carcinoma	Predictive	C	Supports Resistance	—	submitted	EID3735 In 5 basal cell carcinoma patients harboring a SMO W535L mutation, SMO W535L was reported to be resistant to vismodegib treatment. In an in vitro study, mouse embryonic fibroblasts (MEFs) null for the… (full text at CIViC) PMID 25759020 · Atwood et al., 2015 · Open in CIViC	civic
〃	Basal Cell Carcinoma	Predictive	D	Supports Resistance	—	submitted	EID3734 In an in vitro study, a C3H10T1/2 cell line expressing a SMO W535L mutation, demonstrated resistance to vismodegib treatment, compared to C3H10T1/2 cells expressing wild-type SMO. Resistance was deter… (full text at CIViC) PMID 25759019 · Sharpe et al., 2015 · Open in CIViC	civic