Gene Detail

Gene Symbol SMO
Synonyms CRJS | FZD11 | Gx | SMOH
Gene Description SMO, smoothened, frizzled class receptor, is a G-protein coupled receptor and member of the Hedgehog signaling pathway, which is involved in cell fate, proliferation, and survival (PMID: 16881963). SMO gain-of-function mutations are associated with basal cell carcinoma (PMID: 25085664) and several missense mutations are associated with resistance to Hedgehog pathway inhibitors (PMID: 29175550, PMID: 25306392).
Entrez Id 6608
Chromosome 7
Map Location 7q32.1
Canonical Transcript NM_005631

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
H577Q missense unknown SMO H577Q lies within the C-terminal cytoplasmic tail of the Smo protein (PMID: 20207148). H577Q has not been characterized in the scientific literature and therefore, its effect on Smo protein function is unknown (PubMed, Mar 2018).
mutant unknown unknown SMO mutant indicates an unspecified mutation in the SMO gene.
E194K missense no effect - predicted SMO E194K lies within an extracellular domain of the Smo protein (UniProt.org). E194K has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Smo (PMID: 29533785).
wild-type none no effect Wild-type SMO indicates that no mutation has been detected within the SMO gene.
R726Q missense unknown SMO R726Q lies within C-terminal cytoplasmic tail the Smo protein (PMID: 20207148). R726Q has been identified in the scientific literature (PMID: 23349881), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Mar 2018).
A250D missense unknown SMO A250D lies within transmembrane domain 1 of the Smo protein (UniProt.org). A250D has not been characterized in the scientific literature and therefore, its effect on Smo protein function is unknown (PubMed, Mar 2018).
I637T missense unknown SMO I637T lies within the C-terminal cytoplasmic tail of the Smo protein (PMID: 20207148). I637T has not been characterized in the scientific literature and therefore, its effect on Smo protein function is unknown (PubMed, Mar 2018).
A338V missense unknown SMO A338V lies within the heptahelical domain of the Smo protein (PMID: 20207148). A338V has been identified in sequencing studies (PMID: 25148578), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Sep 2018).
V54M missense no effect - predicted SMO V54M lies within an extracellular domain of the Smo protein (UniProt.org). V54M has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Smo (PMID: 29533785).
K575M missense gain of function - predicted SMO K575M lies within the C-terminal cytoplasmic tail of the Smo protein (PMID: 16339184). K575M is predicted to confer a gain of function to the Smo protein, as demonstrated by increased expression of the Hedgehog pathway targets PTCH1 and GLI1 in human tumor samples (PMID: 16339184).
R199W missense unknown SMO R199W lies within the NH2-terminal region of the Smo protein (PMID: 9581815). R199W has been identified in sequencing studies (PMID: 15656799), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Sep 2018).
W535L missense unknown SMO W535L lies within the seventh transmembrane domain of the Smo protein (PMID: 9422511). The functional effect of W535L is conflicting, as W535L results in constitutive activation of Smo and is transforming in cell culture, and has been demonstrated to confer Hh pathway inhibitor resistance (PMID: 9422511, PMID: 10607393, PMID: 25759020), however in another study, W535L resulted in similar cell proliferation and viability levels as wild-type Smo (PMID: 29533785). Y
H692fs frameshift unknown SMO H692fs results in a change in the amino acid sequence of the Smo protein beginning at aa 692 of 787, likely resulting is a premature truncation of the functional protein (UniProt.org). H692fs has not been characterized and therefore, its effect on Smo protein function is unknown (PubMed, Mar 2018).
I408V missense unknown SMO I408V lies within the drug-binding pocket of the Smo protein (PMID: 25759019). I408V has been demonstrated to confer resistance to Hedgehog pathway inhibitors (PMID: 25759019), but has not been biochemically characterized, and therefore, its effect on Smo protein function is unknown (PubMed, Sep 2018). Y
S533N missense unknown SMO S533N lies within helical transmembrane domain 7 of the Smo protein (UniProt.org). S533N (corresponding to S539N in mouse) results in increased Hedgehog (Hh) pathway activation in mouse models and human tumor samples (PMID: 10984056, PMID: 9581815), and has been demonstrated to confer resistance to Hh pathway inhibitors (PMID: 26546616, PMID: 9581815), but also results in similar cell proliferation and viability levels as wild-type Smo (PMID: 29533785). Y
V329F missense unknown SMO V329F lies within one of the transmembrane domain of the Smo protein (UniProt.org). V329F has been demonstrated to confer resistance due to reduced Smo inhibitor binding (PMID: 25636740), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Sep 2018). Y
amp unknown no effect SMO amp indicates an increased number of copies of the SMO gene. However, the mechanism causing the increase is unspecified.
T640A missense no effect - predicted SMO T640A lies within the cytoplasmic domain of the Smo protein (UniProt.org). T640A has activity similar to wild-type Smo in cultured cells (PMID: 17287906) and therefore, is predicted to have no effect on Smo protein function.
C169G missense unknown SMO C169G lies within the FZ domain of the Smo protein (UniProt.org). C169G has not been characterized in the scientific literature and therefore, its effect on Smo protein function is unknown (PubMed, Mar 2018).
act mut unknown gain of function SMO act mut indicates that this variant results in a gain of function in the SMO protein. However, the specific amino acid change has not been identified.
T179M missense unknown SMO T179M lies within the FZ domain of the Smo protein (UniProt.org). T179M has not been characterized in the scientific literature and therefore, its effect on Smo protein function is unknown (PubMed, Mar 2018).
E518A missense gain of function - predicted SMO E518A lies within an extracellular domain of the Smo protein (UniProt.org). E518A is predicted to confer a gain of function to the Smo protein as demonstrated by increased Gli1 transcription in a reporter assay (PMID: 21123452) and has been demonstrated to confer resistance to Hedgehog pathway inhibitors (PMID: 21123452, PMID: 25008467). Y
S387N missense unknown SMO S387N lies within the drug-binding pocket of the Smo protein (PMID: 25759019). S387N has been demonstrated to confer resistance to Hh pathway inhibitors (PMID: 25759019), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Jul 2018). Y
V414A missense no effect - predicted SMO V414A lies within helical domain 5 of the Smo protein (UniProt.org). V414A has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Smo (PMID: 29533785).
R173H missense unknown SMO R173H lies within the FZ domain of the Smo domain (UniProt.org). R173H has not been characterized in the scientific literature and therefore, its effect on Smo protein function is unknown (PubMed, Sep 2018).
D384A missense unknown SMO D384A lies within the type I binding site of the Smo protein (PMID: 25636740). D384A has been demonstrated to confer resistance due to reduced Smo inhibitor binding (PMID: 25636740), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Sep 2018). Y
dec exp none no effect SMO dec exp indicates decreased expression of the Smo protein and/or mRNA. However, the mechanism causing the decreased expression is unspecified.
L221R missense unknown SMO L221R lies within the extracellular domain of the Smo protein (UniProt.org). L221R has been described as a resistance mutation (PMID: 25759020), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Jul 2018). Y
P768fs frameshift unknown SMO P768fs results in a change in the amino acid sequence of the Smo protein beginning at aa 768 of 787, likely resulting is a premature truncation of the functional protein (UniProt.org). P768fs has not been characterized in the scientific literature and therefore, its effect on Smo protein function is unknown (PubMed, Sep 2018).
D25G missense unknown SMO D25G lies within the signal peptide of the Smo protein (UniProt.org). D25G has been identified in the scientific literature (PMID: 23349881), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Sep 2018).
Q477E missense no effect - predicted SMO Q477E lies within the ligand binding pocket of the Smo protein (PMID: 25759020). Q477E is predicted to have no effect on Smo protein function as demonstrated by the lack of increased basal Hedgehog (Hh) pathway signaling in cell culture, but has been demonstrated to confer resistance to Hh pathway inhibitors (PMID: 25759020). Y
N219D missense unknown SMO N219D lies within the drug-binding pocket of the Smo protein (PMID: 25759019). N219D has been demonstrated to confer resistance to Hedgehog pathway inhibitors (PMID: 25759019), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Jul 2018). Y
P694fs frameshift unknown SMO P694fs results in a change in the amino acid sequence of the Smo protein beginning at aa 694 of 787, likely resulting is a premature truncation of the functional protein (UniProt.org). P694fs has been identified in sequencing studies (PMID: 25344691), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Sep 2018).
Y394A missense loss of function - predicted SMO Y394A lies within the type I binding site of the Smo protein (PMID: 25636740). Y394A has been demonstrated to confer resistance due to reduced Smo inhibitor binding (PMID: 25636740), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Sep 2018). Y
R161L missense unknown SMO R161L lies within the FZ domain of the Smo protein (UniProt.org). R161L has not been characterized and therefore, its effect on Smo protein function is unknown (PubMed, Mar 2018).
V404M missense no effect - predicted SMO V404M lies within a helical transmembrane domain of the Smo protein (UniProt.org). V404M has activity similar to wild-type Smo in cultured cells (PMID: 17287906) and therefore, is predicted to have no effect on Smo protein function.
L221F missense no effect - predicted SMO L221F lies within an extracellular domain of the Smo protein (UniProt.org). L221F has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Smo (PMID: 29533785).
P634L missense unknown SMO P634L lies within the C-terminal cytoplasmic tail of the Smo protein (PMID: 20207148). P634L has not been characterized in the scientific literature and therefore, its effect on Smo protein function is unknown (PubMed, Mar 2018).
P647S missense unknown SMO P647S lies within the C-terminal cytoplasmic tail of the Smo protein (PMID: 20207148). P647S has been identified in sequencing studies (PMID: 27624470), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Sep 2018).
W281C missense no effect - predicted SMO W281C lies within the ligand binding pocket of the Smo protein (PMID: 25759020). W281C is predicted to have no effect on Smo protein function, as demonstrated by lack of increased basal Hedgehog (Hh) pathway signaling in cell culture, but has been demonstrated to confer resistance to Hh pathway inhibitors (PMID: 25759020). Y
R762H missense unknown SMO R762H lies within the C-terminal cytoplasmic tail of the Smo protein (PMID: 20207148). R762H has not been characterized in the scientific literature and therefore, its effect on Smo protein function is unknown (PubMed, Sep 2018).
S574C missense unknown SMO S574C does not lie within any known functional domains of the Smo protein (UniProt.org). S574C has not been characterized in the scientific literature and therefore, its effect on Smo protein function is unknown (PubMed, Sep 2018).
P753L missense unknown SMO P753L lies within the cytoplasmic domain of the Smo protein (UniProt.org). P753L has not been characterized in the scientific literature and therefore, its effect on Smo protein function is unknown (PubMed, Sep 2018).
R628Q missense unknown SMO R628Q lies within the cytoplasmic tail domain of the Smo protein (PMID: 20207148). R628Q has not been characterized in the scientific literature and therefore, its effect on Smo protein function is unknown (PubMed, Sep 2018).
I408F missense unknown SMO I408F lies within transmembrane domain 5 of the Smo protein (UniProt.org). I408F has been identified in the scientific literature (PMID: 25636740), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Mar 2018).
H231R missense no effect - predicted SMO H231R lies within the ligand binding pocket of the Smo protein (PMID: 25759020). H231R is predicted to have no effect on Smo protein function as demonstrated by the lack of increased basal Hedgehog (Hh) pathway signaling in cell culture, but has been demonstrated to confer resistance to Hh pathway inhibitors (PMID: 25759020). Y
F460L missense gain of function - predicted SMO F460L lies within the pivot region of transmembrane helix 6 in the Smo protein (PMID: 25759020). F460L is predicted to confer a gain of function to the Smo protein as demonstrated by ligand-independent activation of Hedgehog signaling in cell culture and has also been demonstrated to confer resistance to Hedgehog pathway inhibitors (PMID: 25759020). Y
D473H missense no effect - predicted SMO D473H lies within the ligand binding pocket of the Smo protein (PMID: 25759020). D473H shows similar activity to wild-type Smo in cell culture, and therefore, is predicted to have no effect on Smo protein function, but has been demonstrated to confer resistance to Hedgehog pathway inhibitors (PMID: 19726788, PMID: 29175550). Y
R400C missense no effect - predicted SMO R400C does not lie within any known functional domains of the Smo protein (UniProt.org). R400C has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Smo (PMID: 29533785).
E518D missense no effect - predicted SMO E518D lies within an extracellular domain of the Smo protein (UniProt.org). E518D has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Smo (PMID: 29533785).
V270I missense unknown SMO V270I lies within helical domain 2 of the Smo protein (PMID: 20207148). V270I is a common Smo polymorphism (PMID: 23780909, PMID: 23349881), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Sep 2018).
N396S missense no effect - predicted SMO N396S lies within an extracellular domain of the Smo protein (UniProt.org). N396S has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Smo (PMID: 29533785).
T336P missense no effect - predicted SMO T336P lies within a cytoplasmic domain of the Smo protein (UniProt.org). T336P has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Smo (PMID: 29533785).
A729V missense no effect - predicted SMO A729V lies within a cytoplasmic domain of the Smo protein (UniProt.org). A729V has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Smo (PMID: 29533785) and therefore, is predicted to have no effect on Smo protein function.
A459V missense gain of function - predicted SMO A459V does not lie within any known functional domains of the Smo protein (UniProt.org). A459V is predicted to confer a gain of function to the Smo protein as demonstrated by increased Smo activity and also confers resistance to Hedgehog inhibitors in cell culture (PMID: 25759019). Y
G527E missense no effect - predicted SMO G527E lies within helical domain 7 of the Smo protein (UniProt.org). G527E has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Smo (PMID: 29533785).
T466F missense unknown SMO T466F lies within one of the transmembrane domains of the Smo protein (UniProt.org). T466F has been demonstrated to confer resistance due to reduced Smo inhibitor binding (PMID: 25636740), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Sep 2018). Y
D473G missense no effect - predicted SMO D473G lies within the ligand binding pocket of the Smo protein (PMID: 25759020). D473G does not result in activation of Smo, as indicated by the lack of increased basal Hedgehog (Hh) pathway signaling in cell culture, and therefore, is predicted to have no effect on Smo protein function, but has been demonstrated to confer resistance to Hedgehog pathway inhibitors (PMID: 25759020). Y
H227Y missense no effect - predicted SMO H227Y lies within an extracellular domain of the Smo protein (UniProt.org). H227Y has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Smo (PMID: 29533785).
R576W missense unknown SMO R576W lies within the C-terminal cytoplasmic tail of the Smo protein (PMID: 20207148). R576W has not been characterized in the scientific literature and therefore, its effect on Smo protein function is unknown (PubMed, Mar 2018).
L325F missense unknown SMO L325F lies within one of the transmembrane domains of the Smo protein (UniProt.org). L325F has been demonstrated to confer resistance due to reduced Smo inhibitor binding (PMID: 25636740), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Jul 2018). Y
over exp none no effect SMO over exp indicates an over expression of the Ptch1 protein and/or mRNA. However, the mechanism causing the over expression is unspecified.
A324T missense no effect - predicted SMO A324T lies within helical domain 3 of the Smo protein (UniProt.org). A324T has activity similar to wild-type Smo in cultured cells (PMID: 17287906) and therefore, is predicted to have no effect on Smo protein function.
Q651K missense unknown SMO Q651K lies within the cytoplasmic domain of the Smo protein (UniProt.org). Q651K has not been characterized in the scientific literature and therefore, its effect on Smo protein function is unknown (PubMed, Sep 2018).
V321M missense gain of function - predicted SMO V321M lies within helical domain 3 of the Smo protein (UniProt.org). V321M is predicted to confer a gain of function to the Smo protein, as demonstrated by constitutive activation of Hedgehog (Hh) signaling in cell culture and has been demonstrated to confer Hh pathway inhibitor resistance (PMID: 25759020). Y
Q635E missense unknown SMO Q635E lies within the cytoplasmic domain of the Smo protein (UniProt.org). Q635E has been described as a resistance mutation (PMID: 25759020), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Jul 2018). Y
R562Q missense no effect - predicted SMO R562Q lies within a cytoplasmic domain of the Smo protein (UniProt.org). R562Q has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Smo (PMID: 29533785).
L412F missense gain of function - predicted SMO L412F lies within the pivot region of transmembrane helix 5 in the Smo protein (PMID: 25759020). L412F is predicted to confer a gain of function to the Smo protein, as indicated by constitutive activation of Hedgehog (Hh) signaling in cell culture and has been demonstrated to confer Hh pathway inhibitor resistance (PMID: 25759020). Y
S387A missense unknown SMO S387A lies within the type I binding site of the Smo protein (PMID: 25636740). S387A has not been characterized and therefore, its effect on Smo protein function is unknown (PubMed, Mar 2018).
D473R missense gain of function - predicted SMO D473R lies within the ligand binding pocket of the Smo protein (PMID: 25759020). D473R is predicted to confer a gain of function to the Smo protein as demonstrated by increased Gli1 transcription in a reporter assay (PMID: 21123452) and has also been demonstrated to confer resistance to Hedgehog pathway inhibitors (PMID: 21123452). Y
del deletion loss of function SMO del indicates a deletion of the SMO gene.
R290H missense unknown SMO R290H lies within an extracellular domain of the Smo protein (UniProt.org). R290H has been identified in sequencing studies (PMID: 29854313), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Sep 2018).
L23dup duplication no effect - predicted SMO L23dup (also referred to as L23_G24insL) indicates the insertion of the duplicate amino acid, lysine (L)-23, in an unknown region of the Smo protein (UniProt.org) L23dup has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Smo (PMID: 29533785).
T241M missense gain of function - predicted SMO T241M does not lie within any known functional domains of the Smo protein (UniProt.org). T241M is predicted to confer a gain of function to the Smo protein, as demonstrated by increased Smo activity and also confers resistance to Hedgehog inhibitors in cell culture (PMID: 25759019). Y
R398Q missense no effect - predicted SMO R398Q lies within an extracellular domain of the Smo protein (UniProt.org). R398Q has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Smo (PMID: 29533785).
C469Y missense unknown SMO C469Y lies within the drug-binding pocket of the Smo protein (PMID: 25759019). C469Y has been demonstrated to confer resistance to Hedgehog pathway inhibitors (PMID: 25759019), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Jul 2018). Y
E518K missense unknown SMO E518K lies within an extracellular domain of the Smo protein (UniProt.org). E518K has been described as a resistance mutation (PMID: 23940421), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Jul 2018). Y
M525G missense unknown SMO M525G lies within one of the transmembrane domains of the Smo protein (UniProt.org). M525G has been demonstrated to confer resistance due to reduced Smo inhibitor binding (PMID: 25636740), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Jul 2018). Y
D613N missense no effect - predicted SMO D613N lies within a cytoplasmic domain of the Smo protein (UniProt.org). D613N has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Smo (PMID: 29533785).
P641A missense no effect - predicted SMO P641A lies within the C-terminal cytoplasmic tail of the Smo protein (PMID: 20207148). P641A has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Smo (PMID: 29533785).
R628W missense no effect - predicted SMO R628W lies within a cytoplasmic domain of the Smo protein (UniProt.org). R628W has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Smo (PMID: 29533785).
R400A missense unknown SMO R400A lies within the type I binding site of the Smo protein (PMID: 25636740). R400A has been demonstrated to confer resistance due to reduced Smo inhibitor binding (PMID: 25636740), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Sep 2018). Y
D384N missense unknown SMO D384N lies within the drug-binding pocket of the Smo protein (PMID: 25759019). D384N has been demonstrated to confer resistance to Hedgehog pathway inhibitors (PMID: 25759019), but has not been biochemically characterized and therefore, its effect on Smo protein function is unknown (PubMed, Jul 2018). Y
E208K missense loss of function - predicted SMO E208K lies within an extracellular domain of the Smo protein (UniProt.org). E208K has not been biochemically characterized, but is predicted to confer a loss of function on the Smo protein as demonstrated by decreased transformation ability in cell culture as compared to wild-type Smo (PMID: 29533785).
G328V missense no effect - predicted SMO G328V lies within helical domain 3 of the Smo protein (UniProt.org). G328V has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Smo (PMID: 29533785).
H577R missense unknown SMO H577R lies within the C-terminal cytoplasmic tail of the Smo protein (PMID: 20207148). H577R has not been characterized in the scientific literature and therefore, its effect on Smo protein function is unknown (PubMed, Mar 2018).
Molecular Profile Protein Effect Treatment Approaches
SMO H577Q unknown
SMO mutant unknown
SMO E194K no effect - predicted
SMO wild-type no effect
SMO R726Q unknown
SMO A250D unknown
SMO I637T unknown
SMO A338V unknown
SMO V54M no effect - predicted
SMO K575M gain of function - predicted GLI1/2 inhibitor SMO Inhibitor
SMO R199W unknown
SMO W535L unknown
SMO H692fs unknown
SMO I408V unknown
SMO S533N unknown
SMO V329F unknown
EGFR E746_A750del SMO amp
SMO amp no effect SMO Inhibitor
SMO T640A no effect - predicted
SMO C169G unknown
SMO act mut gain of function GLI1/2 inhibitor SMO Inhibitor
SMO T179M unknown
SMO E518A gain of function - predicted GLI1/2 inhibitor SMO Inhibitor
SMO S387N unknown
SMO V414A no effect - predicted
SMO R173H unknown
SMO D384A unknown
SMO dec exp no effect
SMO L221R unknown
SMO P768fs unknown
SMO D25G unknown
SMO Q477E no effect - predicted
SMO N219D unknown
SMO P694fs unknown
SMO Y394A loss of function - predicted
SMO R161L unknown
SMO V404M no effect - predicted
SMO L221F no effect - predicted
SMO P634L unknown
SMO P647S unknown
SMO W281C no effect - predicted
SMO R762H unknown
SMO S574C unknown
SMO P753L unknown
SMO R628Q unknown
SMO I408F unknown
SMO H231R no effect - predicted
SMO F460L gain of function - predicted GLI1/2 inhibitor SMO Inhibitor
SMO D473H no effect - predicted
SMO R400C no effect - predicted
SMO E518D no effect - predicted
SMO V270I unknown
SMO N396S no effect - predicted
SMO T336P no effect - predicted
SMO A729V no effect - predicted
SMO A459V gain of function - predicted GLI1/2 inhibitor SMO Inhibitor
SMO G527E no effect - predicted
SMO T466F unknown
SMO D473G no effect - predicted
SMO H227Y no effect - predicted
SMO R576W unknown
SMO L325F unknown
SMO over exp no effect
SMO A324T no effect - predicted
SMO Q651K unknown
SMO V321M gain of function - predicted GLI1/2 inhibitor SMO Inhibitor
SMO Q635E unknown
SMO R562Q no effect - predicted
SMO L412F gain of function - predicted GLI1/2 inhibitor SMO Inhibitor
SMO S387A unknown
SMO D473R gain of function - predicted
SMO del loss of function
SMO R290H unknown
SMO L23dup no effect - predicted
SMO T241M gain of function - predicted GLI1/2 inhibitor SMO Inhibitor
SMO R398Q no effect - predicted
SMO C469Y unknown
SMO E518K unknown
SMO M525G unknown
SMO D613N no effect - predicted
SMO P641A no effect - predicted
SMO R628W no effect - predicted
SMO R400A unknown
SMO D384N unknown
SMO E208K loss of function - predicted
SMO G328V no effect - predicted
SMO H577R unknown
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
SMO wild-type medulloblastoma sensitive Taladegib Preclinical Actionable In a preclinical study, LY2940680 was demonstrated to bind to the Smo receptor and inhibit hedgehog signaling in a human medulloblastoma tumor cell line (Cancer Research: April 15, 2011; Volume 71, Issue 8, Supplement 1, Abstract #2819). detail...
SMO wild-type stomach cancer predicted - sensitive Vismodegib Preclinical Actionable In a preclinical study, Vismodegib (GDC-0449) inhibited Hedgehog pathway signaling, increased apoptosis, and decreased proliferation of a gastric cancer cell line in culture (PMID: 26676867). 26676867
SMO W535L basal cell carcinoma predicted - sensitive Sonidegib Phase I Actionable In an open-label clinical trial, treatment with Sonidegib (LDE225) resulted in stable disease in a basal cell carcinoma patient harboring SMO W535L with resistance to Erivedge (vismodegib) (PMID: 26546616). 26546616
SMO W535L Advanced Solid Tumor resistant Vismodegib Preclinical Actionable In a preclinical study, a transformed cell line expressing SMO W535L demonstrated resistance to Erivedge (vismodegib) (PMID: 25759020). 25759020
SMO W535L Advanced Solid Tumor resistant Posaconazole Preclinical Actionable In a preclinical study, Posaconazole did not inhibit Hedghog signaling in mouse fibroblasts over expressing murine SMO W539L (corresponding to human SMO W535L) in culture (PMID: 26823493). 26823493
SMO W535L medulloblastoma sensitive Arsenic trioxide Preclinical Actionable In a preclinical study, treatment with arsenic trioxide resulted in improved survival in a transgenic mouse model of medulloblastoma expressing SMO W535L (PMID: 21183792). 21183792
SMO I408V Advanced Solid Tumor decreased response Taladegib Preclinical Actionable In a preclinical study, primary cerebellar granule neuron precursor cells over expressing SMO I408V on the background of PTCH1 and TP53 deletion demonstrated reduced response to LY2940680 induced growth inhibition in cell culture (PMID: 25759019). 25759019
SMO I408V Advanced Solid Tumor decreased response Vismodegib Preclinical Actionable In a preclinical study, primary cerebellar granule neuron precursor cells over expressing SMO I408V on the background of PTCH1 and TP53 deletion demonstrated reduced response to Erivedge (vismodegib) induced growth inhibition in cell culture (PMID: 25759019). 25759019
SMO I408V Advanced Solid Tumor decreased response Sonidegib Preclinical Actionable In a preclinical study, primary cerebellar granule neuron precursor cells over expressing SMO I408V on the background of PTCH1 and TP53 deletion demonstrated reduced response to Odomzo (sonidegib) induced growth inhibition in cell culture (PMID: 25759019). 25759019
SMO I408V Advanced Solid Tumor sensitive JQ1 Preclinical Actionable In a preclinical study, JQ1 inhibited proliferation of primary cerebellar granule neuron precursor cells over expressing SMO I408V on the background of PTCH1 and TP53 deletion in cell culture (PMID: 25759019). 25759019
SMO S533N basal cell carcinoma resistant Sonidegib Phase I Actionable In an open-label clinical trial, treatment with Sonidegib (LDE225) resulted in progressive disease in a basal cell carcinoma patient with resistance to Erivedge (vismodegib) harboring SMO D533N (PMID: 26546616). 26546616
SMO V329F Advanced Solid Tumor predicted - resistant MRT-92 Preclinical Actionable In a preclinical study, transformed human cells expressing SMO V329F displayed reduced binding to MRT-92 (PMID: 25636740). 25636740
EGFR E746_A750del SMO amp non-small cell lung carcinoma resistant Gefitinib Preclinical Actionable In a preclinical study, amplification of SMO conferred acquired resistance to Iressa (gefitinib) in non-small cell lung cancer cells harboring EGFR E746_A750del in culture (PMID: 26124204). 26124204
EGFR E746_A750del SMO amp non-small cell lung carcinoma sensitive PHA-665752 + Sonidegib Preclinical Actionable In a preclinical study, the combination of Odomzo (sonidegib) and PHA-665752 decreased viability and migration of non-small cell lung cancer (NSCLC) cells harboring EGFR E746_A750del and SMO amplification in culture, and resulted in complete response in 100% (8/8) of NSCLC xenograft models with EGFR E746_A750del and SMO amplification (PMID: 26124204). 26124204
EGFR E746_A750del SMO amp non-small cell lung carcinoma no benefit Sonidegib Preclinical Actionable In a preclinical study, Odomzo (sonidegib) did not decrease viability or migration of non-small cell lung cancer cells harboring EGFR E746_A750del and amplification of SMO in culture (PMID: 26124204). 26124204
EGFR E746_A750del SMO amp non-small cell lung carcinoma sensitive Gefitinib + Sonidegib Preclinical Actionable In a preclinical study, the combination of Odomzo (sonidegib) and Iressa (gefitinib) decreased viability and migration of non-small cell lung cancer (NSCLC) cells harboring an EGFR E746_A750del mutation and SMO amplification in culture and inhibited tumor growth in NSCLC xenograft models with EGFR E746_A750del and SMO amplification (PMID: 26124204). 26124204
SMO S387N Advanced Solid Tumor resistant Vismodegib Preclinical Actionable In a preclinical study, transformed mouse fibroblast cells over expressing murine SMO S391N (corresponding to human SMO S387N) were resistant to Erivedge (vismodegib) induced Hedgehog pathway inhibition in cell culture (PMID: 26823493). 26823493
SMO S387N Advanced Solid Tumor sensitive Arsenic trioxide + Posaconazole Preclinical Actionable In a preclinical study, combination of Posaconazole and Trisenox (Arsenic trioxide) demonstrated enhanced inhibition of Hedghog signaling in mouse fibroblasts over expressing murine SMO S391N (corresponding to human SMO S387N) in culture (PMID: 26823493). 26823493
SMO S387N sarcoma decreased response Vismodegib Preclinical Actionable In a preclinical study, mouse sarcoma cell lines over expressing SMO S387N demonstrated reduced response to Erivedge (vismodegib) induced Hedgehog pathway inhibition in cell culture (PMID: 25759019). 25759019
SMO S387N Advanced Solid Tumor resistant Sonidegib Preclinical Actionable In a preclinical study, transformed mouse fibroblast cells over expressing murine SMO S391N (corresponding to human SMO S387N) were resistant to Odomzo (sonidegib) induced Hedgehog pathway inhibition in cell culture (PMID: 26823493). 26823493
SMO S387N Advanced Solid Tumor sensitive Posaconazole Preclinical Actionable In a preclinical study, Posaconazole inhibited Hedghog signaling in mouse fibroblasts over expressing murine SMO S391N (corresponding to human SMO S387N) in culture (PMID: 26823493). 26823493
SMO D384A Advanced Solid Tumor predicted - resistant MRT-92 Preclinical Actionable In a preclinical study, transformed human cells expressing SMO D384A displayed reduced binding to MRT-92 (PMID: 25636740). 25636740
SMO dec exp osteosarcoma predicted - sensitive SANT1 Preclinical Actionable In a preclinical study, SANT1 inhibited survival of osteosarcoma cell lines with reduced SMO mRNA level in culture (PMID: 26781311). 26781311
SMO Q477E basal cell carcinoma no benefit Sonidegib Phase I Actionable In an open-label clinical trial, treatment with Sonidegib (LDE225) resulted in progressive disease in a basal cell carcinoma patient harboring SMO Q477E with resistance to Erivedge (vismodegib) (PMID: 26546616). 26546616
SMO Q477E basal cell carcinoma resistant Vismodegib Preclinical Actionable In a preclinical study, a transformed cell line expressing SMO Q477E was resistant to Erivedge (vismodegib) as demonstrated by elevated gene expression levels of GLI1 resulting in increased signaling of the hedgehog pathway (PMID: 25759020). 25759020
SMO N219D Advanced Solid Tumor resistant Sonidegib Preclinical Actionable In a preclinical study, transformed mouse fibroblast cells over expressing murine SMO N223D (corresponding to human SMO N219D) were resistant to Odomzo (sonidegib) induced Hedgehog pathway inhibition in cell culture (PMID: 26823493). 26823493
SMO N219D Advanced Solid Tumor sensitive Posaconazole Preclinical Actionable In a preclinical study, Posaconazole inhibited Hedghog signaling in mouse fibroblasts over expressing murine SMO N223D (corresponding to human SMO N219D) in culture (PMID: 26823493). 26823493
SMO N219D sarcoma decreased response Vismodegib Preclinical Actionable In a preclinical study, mouse sarcoma cell lines over expressing SMO N219D demonstrated reduced response to Erivedge (vismodegib) induced Hedgehog pathway inhibition in cell culture (PMID: 25759019). 25759019
SMO N219D Advanced Solid Tumor sensitive Arsenic trioxide + Posaconazole Preclinical Actionable In a preclinical study, combination of Posaconazole and Trisenox (Arsenic trioxide) demonstrated enhanced inhibition of Hedghog signaling in mouse fibroblasts over expressing murine SMO N223D (corresponding to human SMO N219D) in culture (PMID: 26823493). 26823493
SMO Y394A Advanced Solid Tumor predicted - resistant MRT-92 Preclinical Actionable In a preclinical study, transformed human cells expressing SMO Y394A displayed reduced binding to MRT-92 (PMID: 25636740). 25636740
SMO W281C Advanced Solid Tumor decreased response Taladegib Preclinical Actionable In a preclinical study, primary cerebellar granule neuron precursor cells over expressing SMO W281C on the background of PTCH1 and TP53 deletion demonstrated reduced response to LY2940680 induced growth inhibition in cell culture (PMID: 25759019). 25759019
SMO W281C Advanced Solid Tumor decreased response Sonidegib Preclinical Actionable In a preclinical study, primary cerebellar granule neuron precursor cells over expressing SMO W281C on the background of PTCH1 and TP53 deletion demonstrated reduced response to Odomzo (sonidegib) induced growth inhibition in cell culture (PMID: 25759019). 25759019
SMO W281C Advanced Solid Tumor sensitive JQ1 Preclinical Actionable In a preclinical study, JQ1 inhibited proliferation of primary cerebellar granule neuron precursor cells over expressing SMO W281C on the background of PTCH1 and TP53 deletion in cell culture (PMID: 25759019). 25759019
SMO W281C basal cell carcinoma resistant Vismodegib Preclinical Actionable In a preclinical study, a transformed cell line expressing SMO W281C was resistant to Erivedge (vismodegib) as demonstrated by elevated gene expression levels of GLI1 resulting in increased signaling of the hedgehog pathway (PMID: 25759020). 25759020
SMO H231R basal cell carcinoma resistant Vismodegib Preclinical Actionable In a preclinical study, a transformed cell line expressing SMO H231R was resistant to Erivedge (vismodegib) as demonstrated by elevated gene expression levels of GLI1 resulting in increased signaling of the hedgehog pathway (PMID: 25759020). 25759020
SMO F460L Advanced Solid Tumor resistant Vismodegib Preclinical Actionable In a preclinical study, a transformed cell line expressing SMO F460L demonstrated resistance to Erivedge (vismodegib) as compared to wild-type (PMID: 25759020). 25759020
SMO D473H Advanced Solid Tumor predicted - sensitive TAK-441 Preclinical Actionable In a preclinical study, TAK-441 inhibited Gli-reporter activation in cells transfected with SMO D473H in culture (PMID: 24291104). 24291104
SMO D473H basal cell carcinoma resistant Sonidegib Phase I Actionable In an open-label clinical trial, treatment with Sonidegib (LDE225) resulted in progressive disease in a basal cell carcinoma patient harboring SMO D473H with resistance to Erivedge (vismodegib) (PMID: 26546616). 26546616
SMO D473H medulloblastoma resistant Vismodegib Clinical Study Actionable In a single patient study, the SMO D473H mutant conferred secondary resistance to the hedgehog pathway inhibitor Erivedge (vismodegib) in a medulloblastoma patient (PMID: 19726788). 19726788
SMO D473H Advanced Solid Tumor sensitive Taladegib Preclinical Actionable In a preclinical study, LY2940680, inhibited the activity of SMO D473H, which is a mutant that confers resistance to the treatment of vismodegib (Cancer Research: April 15, 2011; Volume 71, Issue 8, Supplement 1, Abstract #2819). detail...
SMO A459V Advanced Solid Tumor decreased response Sonidegib Preclinical Actionable In a preclinical study, primary cerebellar granule neuron precursor cells over expressing SMO A459V on the background of PTCH1 and TP53 deletion demonstrated reduced response to Odomzo (sonidegib) induced growth inhibition in cell culture (PMID: 25759019). 25759019
SMO A459V Advanced Solid Tumor decreased response Vismodegib Preclinical Actionable In a preclinical study, primary cerebellar granule neuron precursor cells over expressing SMO A459V on the background of PTCH1 and TP53 deletion demonstrated reduced response to Erivedge (vismodegib) induced growth inhibition in cell culture (PMID: 25759019). 25759019
SMO A459V Advanced Solid Tumor sensitive JQ1 Preclinical Actionable In a preclinical study, JQ1 inhibited proliferation of primary cerebellar granule neuron precursor cells over expressing SMO A459V on the background of PTCH1 and TP53 deletion in cell culture (PMID: 25759019). 25759019
SMO A459V Advanced Solid Tumor decreased response Taladegib Preclinical Actionable In a preclinical study, primary cerebellar granule neuron precursor cells over expressing SMO A459V on the background of PTCH1 and TP53 deletion demonstrated reduced response to LY2940680 induced growth inhibition in cell culture (PMID: 25759019). 25759019
SMO T466F Advanced Solid Tumor predicted - resistant MRT-92 Preclinical Actionable In a preclinical study, transformed human cells expressing SMO T466F displayed reduced binding to MRT-92 (PMID: 25636740). 25636740
SMO D473G basal cell carcinoma resistant Sonidegib Phase I Actionable In an open-label clinical trial, treatment with Sonidegib (LDE225) resulted in progressive disease in a basal cell carcinoma patient harboring SMO D473G with resistance to Erivedge (vismodegib) (PMID: 26546616). 26546616
SMO D473G basal cell carcinoma resistant Vismodegib Preclinical Actionable In a preclinical study, a transformed cell line expressing SMO D473G was resistant to Erivedge (vismodegib) as demonstrated by elevated gene expression levels of GLI1 resulting in increased signaling of the hedgehog pathway (PMID: 25759020). 25759020
SMO D473G Advanced Solid Tumor resistant Vismodegib Preclinical Actionable In a preclinical study, transformed mouse fibroblast cells over expressing murine SMO D477G (corresponding to human SMO D473G) were resistant to Erivedge (vismodegib) induced Hedgehog pathway inhibition in cell culture (PMID: 26823493). 26823493
SMO D473G Advanced Solid Tumor sensitive Posaconazole Preclinical Actionable In a preclinical study, Posaconazole inhibited Hedghog signaling in mouse fibroblasts over expressing murine SMO D477G (corresponding to human SMO D473G) in culture (PMID: 26823493). 26823493
SMO D473G Advanced Solid Tumor sensitive Arsenic trioxide + Posaconazole Preclinical Actionable In a preclinical study, combination of Posaconazole and Trisenox (Arsenic trioxide) demonstrated enhanced inhibition of Hedghog signaling in mouse fibroblasts over expressing murine SMO D477G (corresponding to human SMO D473G) in culture (PMID: 26823493). 26823493
SMO L325F Advanced Solid Tumor predicted - resistant MRT-92 Preclinical Actionable In a preclinical study, transformed human cells expressing SMO L325F displayed reduced binding to MRT-92 (PMID: 25636740). 25636740
SMO V321M Advanced Solid Tumor resistant Vismodegib Preclinical Actionable In a preclinical study, a transformed cell line expressing SMO V321M demonstrated resistance to Erivedge (vismodegib) (PMID: 25759020). 25759020
SMO V321M Advanced Solid Tumor decreased response Sonidegib Preclinical Actionable In a preclinical study, primary cerebellar granule neuron precursor cells over expressing SMO C469Y on the background of PTCH1 and TP53 deletion demonstrated reduced response to Odomzo (sonidegib) induced growth inhibition in cell culture (PMID: 25759019). 25759019
SMO V321M Advanced Solid Tumor sensitive JQ1 Preclinical Actionable In a preclinical study, JQ1 inhibited proliferation of primary cerebellar granule neuron precursor cells over expressing SMO V321M on the background of PTCH1 and TP53 deletion in cell culture (PMID: 25759019). 25759019
SMO V321M Advanced Solid Tumor decreased response Taladegib Preclinical Actionable In a preclinical study, primary cerebellar granule neuron precursor cells over expressing SMO T241M on the background of PTCH1 and TP53 deletion demonstrated reduced response to LY2940680 induced growth inhibition in cell culture (PMID: 25759019). 25759019
SMO L412F Advanced Solid Tumor resistant Vismodegib Preclinical Actionable In a preclinical study, a transformed cell line expressing SMO L412F demonstrated resistance to Erivedge (vismodegib) (PMID: 25759020). 25759020
SMO T241M Advanced Solid Tumor decreased response Vismodegib Preclinical Actionable In a preclinical study, primary cerebellar granule neuron precursor cells over expressing SMO T241M on the background of PTCH1 and TP53 deletion demonstrated reduced response to Erivedge (vismodegib) induced growth inhibition in cell culture (PMID: 25759019). 25759019
SMO T241M Advanced Solid Tumor decreased response Sonidegib Preclinical Actionable In a preclinical study, primary cerebellar granule neuron precursor cells over expressing SMO T241M on the background of PTCH1 and TP53 deletion demonstrated reduced response to Odomzo (sonidegib) induced growth inhibition in cell culture (PMID: 25759019). 25759019
SMO T241M Advanced Solid Tumor sensitive JQ1 Preclinical Actionable In a preclinical study, JQ1 inhibited proliferation of primary cerebellar granule neuron precursor cells over expressing SMO T241M on the background of PTCH1 and TP53 deletion in cell culture (PMID: 25759019). 25759019
SMO T241M Advanced Solid Tumor decreased response Taladegib Preclinical Actionable In a preclinical study, primary cerebellar granule neuron precursor cells over expressing SMO T241M on the background of PTCH1 and TP53 deletion demonstrated reduced response to LY2940680 induced growth inhibition in cell culture (PMID: 25759019). 25759019
SMO C469Y Advanced Solid Tumor decreased response Taladegib Preclinical Actionable In a preclinical study, primary cerebellar granule neuron precursor cells over expressing SMO C469Y on the background of PTCH1 and TP53 deletion demonstrated reduced response to LY2940680 induced growth inhibition in cell culture (PMID: 25759019). 25759019
SMO C469Y Advanced Solid Tumor decreased response Vismodegib Preclinical Actionable In a preclinical study, primary cerebellar granule neuron precursor cells over expressing SMO C469Y on the background of PTCH1 and TP53 deletion demonstrated reduced response to Erivedge (vismodegib) induced growth inhibition in cell culture (PMID: 25759019). 25759019
SMO C469Y Advanced Solid Tumor decreased response Sonidegib Preclinical Actionable In a preclinical study, primary cerebellar granule neuron precursor cells over expressing SMO C469Y on the background of PTCH1 and TP53 deletion demonstrated reduced response to Odomzo (sonidegib) induced growth inhibition in cell culture (PMID: 25759019). 25759019
SMO C469Y Advanced Solid Tumor sensitive JQ1 Preclinical Actionable In a preclinical study, JQ1 inhibited proliferation of primary cerebellar granule neuron precursor cells over expressing SMO C469Y on the background of PTCH1 and TP53 deletion in cell culture (PMID: 25759019). 25759019
SMO E518K Advanced Solid Tumor resistant Vismodegib Preclinical Actionable In a preclinical study, transformed mouse fibroblast cells over expressing murine SMO E522K (corresponding to human SMO E518K) were resistant to Erivedge (vismodegib) induced Hedgehog pathway inhibition in cell culture (PMID: 26823493). 26823493
SMO E518K Advanced Solid Tumor sensitive Posaconazole Preclinical Actionable In a preclinical study, Posaconazole inhibited Hedghog signaling in mouse fibroblasts over expressing murine SMO E522K (corresponding to human SMO E518K) in culture (PMID: 26823493). 26823493
SMO E518K Advanced Solid Tumor sensitive Arsenic trioxide + Posaconazole Preclinical Actionable In a preclinical study, combination of Posaconazole and Trisenox (Arsenic trioxide) demonstrated enhanced inhibition of Hedghog signaling in mouse fibroblasts over expressing murine SMO E522K (corresponding to human SMO E518K) in culture (PMID: 26823493). 26823493
SMO E518K Advanced Solid Tumor predicted - resistant MRT-92 Preclinical Actionable In a preclinical study, transformed human cells expressing SMO E518K displayed reduced binding to MRT-92 (PMID: 25636740). 25636740
SMO E518K Advanced Solid Tumor decreased response Sonidegib Preclinical Actionable In a preclinical study, transformed mouse fibroblast cells over expressing murine SMO E522K (corresponding to human SMO E518K) demonstrated decreased response to Odomzo (sonidegib) induced Hedgehog pathway inhibition in cell culture (PMID: 26823493). 26823493
SMO M525G Advanced Solid Tumor predicted - resistant MRT-92 Preclinical Actionable In a preclinical study, transformed human cells expressing SMO M525G displayed reduced binding to MRT-92 (PMID: 25636740). 25636740
SMO R400A Advanced Solid Tumor predicted - sensitive MRT-92 Preclinical Actionable In a preclincal, transformed human cells expressing SMO R400A displayed reduced binding to MRT-92 (PMID: 25636740). 25636740
SMO D384N Advanced Solid Tumor resistant Sonidegib Preclinical Actionable In a preclinical study, transformed mouse fibroblast cells over expressing murine SMO D388N (corresponding to human SMO D384N) were resistant to Odomzo (sonidegib) induced Hedgehog pathway inhibition in cell culture (PMID: 26823493). 26823493
SMO D384N Advanced Solid Tumor sensitive Arsenic trioxide + Posaconazole Preclinical Actionable In a preclinical study, combination of Posaconazole and Trisenox (Arsenic trioxide) demonstrated enhanced inhibition of Hedghog signaling in mouse fibroblasts over expressing murine SMO D388N (corresponding to human SMO D384N) in culture (PMID: 26823493). 26823493
SMO D384N sarcoma decreased response Vismodegib Preclinical Actionable In a preclinical study, mouse sarcoma cell lines over expressing SMO D384N demonstrated reduced response to Erivedge (vismodegib) induced Hedgehog pathway inhibition in cell culture (PMID: 25759019). 25759019
SMO D384N Advanced Solid Tumor resistant Vismodegib Preclinical Actionable In a preclinical study, transformed mouse fibroblast cells over expressing murine SMO D388N (corresponding to human SMO D384N) were resistant to Erivedge (vismodegib) induced Hedgehog pathway inhibition in cell culture (PMID: 26823493). 26823493
SMO D384N Advanced Solid Tumor sensitive Posaconazole Preclinical Actionable In a preclinical study, Posaconazole inhibited Hedghog signaling in mouse fibroblasts over expressing murine SMO D388N (corresponding to human SMO D384N) in culture (PMID: 26823493). 26823493