Gene Detail

Gene Symbol NRAS
Synonyms ALPS4 | CMNS | N-ras | NCMS | NRAS1 | NS6
Gene Description NRAS, NRAS proto-oncogene, GTPase, is a member of the family of small GTPase that when activated by growth factors, stimulates multiple effector pathways such as RAF and PI3K to promote cell proliferation and survival (PMID: 29524560). NRAS mutations have been observed in a variety of cancers including melanoma, thyroid, breast, ovary cancer, and leukemia (PMID: 29524560).
Entrez Id 4893
Chromosome 1
Map Location 1p13.2
Canonical Transcript NM_002524

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
G12P missense loss of function - predicted NRAS G12P is a hotsopt mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G12P has not been characteried, but can be predicted to lead to a loss of Nras protein function based on the effect of HRAS G12P, which demonstrates intrinsic hydrolysis rate similar to wild-type protein but has decreased affinity for GTPase-activating proteins, and is not transforming in cell culture (PMID: 6092966, PMID: 8357792).
G12X missense loss of function - predicted NRAS G12X indicates any NRAS missense mutation that results in the glycine (G) at amino acid 12 being replaced by a different amino acid. NRAS codon 12 mutations are "hotspot" mutations that often result in a loss of Nras GTPase activity and activation of downstream pathways (PMID: 27664710, PMID: 28666118, PMID: 22589270, PMID: 26985062) and therefore, are predicted to result in a loss of Nras protein function.
A146X missense unknown NRAS A146X indicates any NRAS missense mutation that results in the replacement of the alanine (A) at amino acid 146 by a different amino acid.
G60R missense unknown NRAS G60R lies within a GTP-binding region of the Nras protein (UniProt.org). G60R has been identified in sequencing studies (PMID: 27251789), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
S65G missense unknown NRAS S65G lies within the switch II domain of the Nras protein (PMID: 17384584). S65G has not been characterized in the scientific literature and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
over exp none no effect NRAS over exp indicates an over expression of the Nras protein and/or mRNA. However, the mechanism causing the over expression is unspecified.
Q61K missense loss of function NRAS Q61K is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). Q61K confers a loss of function on Nras protein as indicated by activation of downstream pathway signaling, increased survival, and transformation of cultured cells (PMID: 22718121).
E132K missense unknown NRAS E132K lies within the G domain of the Nras protein (PMID: 17384584). E132K has been identified in sequencing studies (PMID: 25344691), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
G12D missense loss of function NRAS G12D is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G12D confers a loss of function on Nras protein as indicated by decreased intrinsic GTPase activity, reduced sensitivity to GTPase-activating proteins, leading to accumulation of GTP-bound Nras, activation of downstream signaling, and transformation of cultured cells (PMID: 19075190, PMID: 25252692).
Q22K missense unknown NRAS Q22K lies within the G domain of the Nras protein (PMID: 17384584). Q22K has been identified in sequencing studies (PMID: 22817889), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
A66V missense unknown NRAS A66V lies within the switch II domain of the Nras protein (PMID: 17384584). A66V has been identified in sequencing studies (PMID: 25127237) but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
G13V missense unknown NRAS G13V is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G13V is predicted to result in decreased GTPase activity by computational modeling (PMID: 25339142), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
T58I missense loss of function - predicted NRAS T58I lies within the GTP binding pocket of the Nras protein (UniProt.org). T58I has not been characterized, but can be predicted to confer a loss of function on Nras protein based on the effects of KRAS T58I, which results in defective intrinsic GTPase activity and decreased response to GTPase-activating proteins, leading to increased phosphorylation of of Mek and Akt, and transformation in cell culture (PMID: 16474405).
amp none no effect NRAS amplification indicates an increased number of copies of the NRAS gene. However, the mechanism causing the increase is unspecified.
R164C missense unknown NRAS R164C lies within the G domain of the Nras protein (PMID: 17384584). R164C has not been characterized in the scientific literature and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
E63K missense loss of function NRAS E63K does not lie within any known functional domains of the Nras protein (UniProt.org). E63K confers a loss of function on Nras protein as demonstrated by increased GTP-bound Nras leading to activation of downstream signaling, and is associated with resistance to Egfr inhibitors in culture (PMID: 25870145). Y
G13D missense loss of function NRAS G13D is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G13D confers a loss of function on Nras protein as indicated by increased GTP-bound Nras, which leads to activation of downstream pathway signaling in cell culture (PMID: 17517660).
I24L missense unknown NRAS I24L lies within the G domain of the Nras protein (PMID: 17384584). I24L has not been characterized in the scientific literature and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
G12S missense loss of function NRAS G12S is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G12S confers a loss of function on Nras protein as indicated by increased Erk phosphorylation, increased cell preliferation, and is transforming in culture (PMID: 17823240).
G13R missense loss of function - predicted NRAS G13R is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G13R has not been characterized, but can be predicted to confer a loss of function on Nras protein based on the effects of HRAS G13R, which results in increased GTP-bound Hras, constitutive activation of Mapk and Akt signaling, and increased cell proliferation in culture (PMID: 22683711).
S106L missense unknown NRAS S106L lies within the G domain of the Nras protein (PMID: 17384584). S106L has not been characterized in the scientific literature and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
D154G missense unknown NRAS D154G lies within the G domain of the Nras protein (PMID: 17384584). D154G has been identified in sequencing studies (PMID: 24816253), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
G13S missense loss of function - predicted NRAS G13S is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G13S has not been characterized, but can be predicted to confer a loss of function on Nras based on the effect of HRAS G13S, which demonstrates increased GTPase activity, lack of response to GTPase-activating proteins, and is transforming in Xenopus oocytes (PMID: 8430333).
Q61R missense loss of function NRAS Q61R is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). Q61R results in a loss of Nras GTPase function as indicated by increased GTP-bound Nras, which leads to activation of Mapk signaling in culture (PMID: 16818621).
Q61X missense loss of function - predicted NRAS Q61X indicates any NRAS missense mutation that results in the glutamine (Q) at amino acid 61 being replaced by a different amino acid. NRAS codon 61 mutations are "hotspot" mutations that often result in a loss of Nras GTPase activity and activation of downstream pathways (PMID: 27664710, PMID: 28666118, PMID: 22589270, PMID: 26985062) and therefore, are predicted to result in a loss of Nras protein function.
mutant unknown unknown NRAS mutant indicates an unspecified mutation in the NRAS gene.
G12N missense loss of function - predicted NRAS G12N is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G12N has not been characterized, but can be predicted to confer a loss of function on Nras protein based on the effects of HRAS G12N, which results in transformation in cell culture (PMID: 6092966).
G12V missense loss of function NRAS G12V is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G12V confers a loss of function on Nras protein as indicated by accumulation of GTP-bound Nras, loss of GTPase-activating protein sensitivity, leading to increased downstream pathway activation in cell culture (PMID: 19966803).
G13C missense loss of function - predicted NRAS G13C is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G13C has not been characterized, but can be predicted to confer a loss of function on Nras protein based on the effects of KRAS G13C and HRAS G13C, which result in increased GTP-bound Ras and activation of downstream signaling (PMID: 25705018, PMID: 21850009).
Q61P missense loss of function - predicted NRAS Q61P is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). Q61P has not been characterized, but can be predicted to confer a loss of function on Nras protein based on the effect of HRAS Q61P, which results in decreased GTPase activity (PMID: 3510078).
A59X missense unknown NRAS A59X indicates any NRAS missense mutation that results in the replacement of the alanine (A) at amino acid 59 by a different amino acid.
G12Y missense loss of function - predicted NRAS G12Y is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G12Y has not been characterized, but can be predicted to confer a loss of function on Nras protein based on the effects of HRAS G12Y, which is transforming in culture (PMID: 6092966).
T74S missense unknown NRAS T74S lies within the G domain of the Nras protein (PMID: 17384584). T74S has not been characterized in the scientific literature and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
D175N missense unknown NRAS D175N lies within the hypervariable region of the Nras protein (PMID: 17384584). D175N has not been characterized in the scientific literature and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
G12R missense loss of function - predicted NRAS G12R is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G12R has not been characterized, but can be predicted to confer a loss of function on Nras protein based on the effects of HRAS G12R and NRAS G12R, which results in decreased GTPase activity, activation of downstream pathways, and transformation of cultured cells (PMID: 6092966, PMID: 26037647, PMID: 23455880).
A18T missense unknown NRAS A18T lies within a GTP-binding region of the Nras protein (UniProt.org). A18T has been identified in the scientific literature (PMID: 11406571), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
P34L missense loss of function - predicted NRAS P34L lies within the effector region of the Nras protein (UniProt.org). P34L has not been chatacterized, but can be predicted to lead to a loss of Nras protein function based on the effect of HRAS P34L and KRAS P34L, which result in increased GTP-bound Ras, loss of sensitivity to GTPase-activating proteins, leading to activation of downstream signaling (PMID: 20949621).
exon3 unknown unknown NRAS exon 3 indicates an unspecified mutation has occurred in exon 3 of the NRAS gene.
R167L missense unknown NRAS R167L lies within the hypervariable region of the Nras protein (UniProt.org). R167L has been identified in the scientific literature (PMID: 26343583), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
K135N missense no effect - predicted NRAS K135N lies within the G domain of the Nras protein (PMID: 17384584). K135N results in similar cell proliferation and viability levels as wild-type Nras in one study (PMID: 29533785) and therefore, is predicted to have no effect on Nras protein function.
Q61E missense loss of function - predicted NRAS Q61E is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). Q61E has not been characterized, but can be predicted to confer a loss of function on Nras protein based on the effect of HRAS Q61E, which results in decreased GTPase activity (PMID: 3510078).
A11T missense unknown NRAS A11T lies within a GTP-binding region of the Nras protein (UniProt.org). A11T has been identified in the scientific literature (PMID: 2183888), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
E162* nonsense loss of function - predicted NRAS E162* results in a premature truncation of the Nras protein at amino acid 162 of 189 (UniProt.org). Due to the loss of the CAAX motif (PMID: 10412982), E162* is predicted to lead to a loss of Nras protein function.
G60E missense loss of function NRAS G60E lies within the nucleotide binding domain of the Nras protein (UniProt.org). G60E confers a loss of function on Nras as indicated by accumulation of GTP-bound Nras, loss of response to GTPase-activating proteins, leading to activation of downstream signaling and cell proliferation in culture (PMID: 19966803, PMID: 19075190).
G13A missense unknown NRAS G13A is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G13A has been identified in the scientific literature (PMID: 22589270) but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
wild-type none no effect Wild-type NRAS indicates that no mutation has been detected within the NRAS gene.
exon2 unknown unknown NRAS exon 2 indicates an unspecified mutation has occurred in exon 2 of the NRAS gene.
act mut unknown gain of function NRAS act mut indicates that this variant results in a gain of function in the Nras protein. However, the specific amino acid change has not been identified.
exon4 unknown unknown NRAS exon 4 indicates an unspecified mutation has occurred in exon 4 of the NRAS gene.
Y64D missense no effect - predicted NRAS Y64D does not lie within any known functional domains of the Nras protein (UniProt.org). Y64D does not promote tumor formation in animal models in a pooled screening assay and induces gene expression signature similar to wild-type Nras protein in culture in one study (PMID: 27147599) and therefore, is predicted to have no effect on Nras protein function.
A146V missense gain of function - predicted NRAS A146V lies within the G domain of the Nras protein (PMID: 17384584). A146V has not been chatacterized, but can be predicted to lead to a gain of Nras function based on the effects of HRAS A146V, which results in increased nucleotide exchange rates, activation of downstream signaling, and transformation of cultured cells (PMID: 24224811, PMID: 21850009, PMID: 3043178).
G12C missense loss of function - predicted NRAS G12C is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G12C has not been characterized, but can be predicted to confer a loss of function on Nras protein based on the effects of HRAS G12C and KRAS G12C, which result in a loss of response to GTPase-activating proteins, and transformation of cultured cells (PMID: 26037647, PMID: 6092966).
T58_A59insTDV insertion unknown NRAS T58_A59insTDV results in the insertion of three amino acids in a GTP binding region of the Nras protein between amino acids 58 and 59 (UniProt.org). T58_A59insTDV has not been characterized in the scientific literature and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
Y40* nonsense loss of function - predicted NRAS Y40* results in a premature truncation of the Nras protein at amino acid 40 of 189 (UniProt.org). Due to the loss of the majority of the functional protein, Y40* is predicted to lead to a loss of Nras protein function (UniProt.org).
K117X missense unknown NRAS K117X indicates any NRAS missense mutation that results in the replacement of the lysine (K) at amino acid 117 by a different amino acid.
T50I missense gain of function - predicted NRAS T50I does not lie within any known functional domains of the Nras protein (UniProt.org). T50I has no effect on the intrinsic Nras GTPase activity and sensitivity to GTPase-activating proteins or guanine nucleotide exchange factor, but increased phosphorylation of Erk and Mel in cell culture, potentially through altering Nras membrane orientation and strengthening effector binding based on structural modeling of the Hras protein (PMID: 19966803, PMID: 18273062).
Q150H missense unknown NRAS Q150H lies within the G domain of the Nras protein (PMID: 17384584). Q150H has not been characterized in the scientific literature and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
D154H missense unknown NRAS D154H lies within the G domain of the Nras protein (PMID: 17384584). D154H has not been characterized in the scientific literature and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
Q61H missense loss of function NRAS Q61H is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). Q61H confers a loss of function to Nras protein as indicated by increased GTP-bound Nras, which leads to increased downstream pathway activation and cell proliferation in cell culture (PMID: 23103856).
G12A missense loss of function - predicted NRAS G12A is hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G12A has not been characterized, but can be predicted to confer a loss of function on Nras protein based on the effects of HRAS G12A and NRAS G12A, which results in decreased GTPase activity, loss of response to GTPase-activating proteins, and transformation of cultured cells (PMID: 6092966, PMID: 26037647).
G13X missense loss of function - predicted NRAS G13X indicates any NRAS missense mutation that results in the glycine (G) at amino acid 13 being replaced by a different amino acid. NRAS codon 13 mutations are "hotspot" mutations that often result in decreased Hras GTPase activity and transformation of cultured cells (PMID: 17517660, PMID: 26985062) and therefore, are predicted to result in a loss of Nras protein function.
A146T missense gain of function NRAS A146T does not lie within any known functional domains of the Nras protein (UniProt.org). A146T results in increased Nras activity likely due to increased GDP/GTP exchange rate, activation of downstream signaling, and is identified as a secondary mutation conferring resistance to Braf and Mek inhibitors in culture (PMID: 22389471, PMID: 3043178). Y
Q61L missense loss of function NRAS Q61L is a hotsopt mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). Q61L confers a loss of function on Nras protein as indicated by increase Erk and Mek phosphorylation, and activation of Ck2alpha in cell culture (PMID: 27251789).
D57A missense unknown NRAS D57A lies within the G domain of the Nras protein (PMID: 17384584). D57A has not been characterized in the scientific literature and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
P34A missense unknown NRAS P34A lies within the switch I domain of the Nras protein (PMID: 17384584). P34A has not been characterized in the scientific literature and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
H131R missense unknown NRAS H131R lies within the G domain of the Nras protein (PMID: 17384584). H131R has been identified in sequencing studies (PMID: 24755198), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, Sep 2018).
S65C missense loss of function - predicted NRAS S65C does not lie within any known functional domains of the Nras protein (UniProt.org). S65C results in increased phosphorylation of Mek and Erk in cell culture (PMID: 24798740) and therefore, is predicted to confer a loss of function on Nras based on the effects of other activating Ras mutations (PMID: 22589270).
Molecular Profile Protein Effect Treatment Approaches
NRAS G12P loss of function - predicted
NRAS G12X loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
NRAS A146X unknown
NRAS G60R unknown
NRAS S65G unknown
FGFR1 amp NRAS over exp
NRAS over exp no effect
BRAF G466V NRAS Q61K
BRAF V600E NRAS Q61K NRAS A146T MAP2K1 P387S
BRAF G596R NRAS Q61K
NRAS Q61K loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
BRAF amp BRAF V600X NRAS Q61K
BRAF V600E NRAS Q61K NRAS A146T
EGFR exon 19 del EGFR T790M NRAS Q61K
EGFR exon 19 del NRAS Q61K
BRAF G469R NRAS Q61K
BRAF V600E MAP2K1 P387S NRAS Q61K
NRAS Q61K CDKN2A loss
EGFR L858R EGFR T790M NRAS Q61K
BRAF V600K NRAS Q61K
BRAF L597V NRAS Q61K
BRAF V600E NRAS Q61K
BRAF wild-type NRAS Q61K
NRAS E132K unknown
KMT2A-MLLT1 NRAS G12D
AKT1 E17K NRAS G12D
NRAS G12D loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
BRAF D594G NRAS G12D
NRAS Q22K unknown
NRAS A66V unknown
NRAS G13V unknown MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
NRAS T58I loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
BRAF V600X MAP2K1 V60E NRAS T58I NRAS Q61R
FGFR1 amp NRAS amp
EGFR exon 19 del NRAS amp
NRAS amp no effect
NRAS R164C unknown
EGFR exon 19 del NRAS E63K
NRAS E63K loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
NRAS G13D loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
NRAS I24L unknown
NRAS G12S loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
NRAS G13R loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
BRAF G596V NRAS G13R
NRAS S106L unknown
NRAS D154G unknown
NRAS G13S loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
ATM mut NRAS Q61R
KIT D816V NRAS Q61R
NRAS Q61R loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
AKT1 E17K NRAS Q61R
NRAS Q61X loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
BRAF mut NRAS mut
NRAS mut STAG2 dec exp
NRAS mutant unknown
BRAF wild-type NRAS mutant
CDKN2A loss NRAS mutant
CTNNB1 mut NRAS mut
NRAS mut PIK3CA wild-type
NRAS G12N loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
BRAF V600E NRAS G12V
NRAS G12V loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
EGFR exon 19 del NRAS G12V
NRAS G13C loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
NRAS Q61P loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
NRAS A59X unknown
NRAS G12Y loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
NRAS T74S unknown
NRAS D175N unknown
EGFR exon 19 del NRAS G12R
NRAS G12R loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
NRAS A18T unknown
NRAS P34L loss of function - predicted
NRAS exon 3 unknown
NRAS R167L unknown
NRAS K135N no effect - predicted
NRAS Q61E loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
NRAS A11T unknown
NRAS E162* loss of function - predicted
NRAS G60E loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
NRAS G13A unknown MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
NRAS wild-type no effect
NRAS BRAF wild-type
BRAF mut NRAS wild-type
BRAF wild-type NRAS wild-type
BRAF wild-type KRAS wild-type NRAS wild-type
MP BRAF KRAS NRAS PIK3CA
BRAF wild-type KRAS wild-type NRAS wild-type PIK3CA wild-type
NRAS exon 2 unknown
NRAS mut CDKN2A mut
NRAS act mut gain of function
NRAS exon 4 unknown
NRAS Y64D no effect - predicted
NRAS A146V gain of function - predicted
NRAS G12C loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
NRAS T58_A59insTDV unknown
NRAS Y40* loss of function - predicted
NRAS K117X unknown
NRAS T50I gain of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
NRAS Q150H unknown
NRAS D154H unknown
NRAS Q61H loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
NRAS G12A loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
NRAS G13X loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
NRAS A146T gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
BRAF V600E NRAS A146T MAP2K1 P387S
BRAF V600E NRAS A146T
NRAS Q61L loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
NRAS D57A unknown
NRAS P34A unknown
NRAS H131R unknown
NRAS S65C loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan)
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
NRAS G12X myelodysplastic syndrome not applicable N/A Guideline Prognostic NRAS G12X is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). detail...
FGFR1 amp NRAS over exp non-small cell lung carcinoma decreased response BGJ398 Preclinical - Cell culture Actionable In a preclinical study, overexpression of Nras in FGFR1-amplified non-small cell lung carcinoma cells resulted in decreased response to BGJ398 in culture (PMID: 28630215). 28630215
FGFR1 amp NRAS over exp non-small cell lung carcinoma sensitive BGJ398 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, BGJ398 and Mekinist (trametinib) combination treatment inhibited Erk signaling, resulting in growth inhibition in FGFR1-amplified non-small cell lung carcinoma cells overexpressing Nras in culture (PMID: 28630215). 28630215
BRAF G466V NRAS Q61K non-small cell lung carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) growth of a non-small cell lung cancer cell line harboring BRAF G466V and expressing NRAS Q61K in culture (PMID: 28783719). 28783719
BRAF V600E NRAS Q61K NRAS A146T MAP2K1 P387S melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K NRAS A146T MAP2K1 P387S melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K NRAS A146T MAP2K1 P387S melanoma resistant Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant to growth inhibition by Mekinist (trametinib) in culture (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K NRAS A146T MAP2K1 P387S melanoma decreased response GSK2126458 Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K NRAS A146T MAP2K1 P387S melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). 22389471
NRAS Q61K non-small cell lung carcinoma sensitive Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) inhibited proliferation of non-small cell lung cancer cells harboring NRAS Q61K in culture (PMID: 23629727). 23629727
NRAS Q61K melanoma predicted - sensitive RAF709 Preclinical - Cell culture Actionable In a preclinical study, RAF709 inhibited Erk signaling in melanoma cells harboring NRAS Q61K in culture (PMID: 29343524). 29343524
NRAS Q61K melanoma sensitive Selumetinib Preclinical Actionable In a preclinical study, Selumetinib (AZD6244) inhibited proliferation of human melanoma cell lines harboring NRAS Q61K in culture (PMID: 26343583). 26343583
NRAS Q61K non-small cell lung carcinoma decreased response Gedatolisib Preclinical Actionable In a preclinical study, human non-small cell lung cancer cells harboring NRAS Q61K had a decreased response to Gedatolisib (PKI-587) in culture (PMID: 21325073, PMID: 12068308). 21325073 12068308
NRAS Q61K lung cancer sensitive RAF709 Preclinical - Cell line xenograft Actionable In a preclinical study, RAF709 inhibited Erk signaling and proliferation of lung cancer cells harboring NRAS Q61K in culture, and resulted in tumor regression in cell line xenograft models (PMID: 29343524). 29343524
NRAS Q61K melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring NRAS Q61K were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). 26343583
NRAS Q61K non-small cell lung carcinoma sensitive Pimasertib + Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Stivarga (regorafenib) synergistically inhibited proliferation of non-small cell lung cancer cells harboring NRAS Q61K in culture (PMID: 23629727). 23629727
NRAS Q61K melanoma sensitive Binimetinib Phase II Actionable In a Phase II trial, Binimetinib (MEK162) treatment resulted in partial response in 20% (6/30), and stable disease in 43% (13/30) of melanoma patients harboring NRAS mutations, including Q61L (1/30), Q61K (9/30), and Q61R (15/30) (PMID: 23414587). 23414587
NRAS Q61K non-small cell lung carcinoma sensitive Pimasertib + Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Nexavar (sorafenib) synergistically inhibited proliferation of non-small cell lung cancer cells harboring NRAS Q61K in culture (PMID: 23629727). 23629727
NRAS Q61K non-small cell lung carcinoma sensitive Everolimus + Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Afinitor (everolimus) synergistically inhibited proliferation of non-small cell lung cancer cells harboring NRAS Q61K in culture (PMID: 23629727). 23629727
NRAS Q61K melanoma sensitive LY3009120 Preclinical Actionable In a preclinical study, LY3009120 inhibited soft agar growth of human melanoma cancer cells harboring NRAS Q61K in culture (PMID: 26343583). 26343583
BRAF amp BRAF V600X NRAS Q61K melanoma resistant Vemurafenib Clinical Study Actionable In a clinical study, a melanoma patient harboring a BRAF V600 mutation developed resistant mutations, BRAF amplification and NRAS Q61K, during treatment with Zelboraf (vemurafenib) (PMID: 24265153). 24265153
BRAF V600E NRAS Q61K NRAS A146T melanoma sensitive Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of human melanoma cells harboring BRAF V600E and NRAS A146T and NRAS Q61K in culture (PMID: 22389471). 22389471
EGFR exon 19 del EGFR T790M NRAS Q61K non-small cell lung carcinoma resistant Osimertinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR exon 19 deletion, EGFR T790M, and NRAS Q61K were resistant to Tagrisso (osimertinib) in culture (PMID: 25870145). 25870145
EGFR exon 19 del NRAS Q61K non-small cell lung carcinoma sensitive Selumetinib Preclinical Actionable In a preclinical study, Selumetinib inhibited proliferation of non-small cell lung cancer cells harboring EGFR exon 19 deletion and NRAS Q61K in culture (PMID: 25870145). 25870145
EGFR exon 19 del NRAS Q61K non-small cell lung carcinoma resistant WZ4002 Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR exon 19 deletion became resistant to WZ4002 after the emergence of NRAS Q61K in culture (PMID: 25870145). 25870145
EGFR exon 19 del NRAS Q61K non-small cell lung carcinoma resistant Osimertinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR exon 19 deletion and NRAS Q61K were resistant to Tagrisso (osimertinib) in culture (PMID: 25870145). 25870145
BRAF G469R NRAS Q61K melanoma sensitive LY3009120 Preclinical Actionable In a preclinical study, LY3009120 inhibited soft agar growth of human melanoma cancer cells harboring BRAF G469R and NRAS Q61K in culture (PMID: 26343583). 26343583
BRAF G469R NRAS Q61K melanoma decreased response Selumetinib Preclinical Actionable In a preclinical study, Selumetinib (AZD6244) modestly inhibited proliferation of human melanoma cells harboring BRAF G469R and NRAS Q61K in culture (PMID: 26343583). 26343583
BRAF G469R NRAS Q61K melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, human melanoma cells harboring BRAF G469R and NRAS G61K were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). 26343583
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma decreased response Trametinib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma decreased response GSK2126458 Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were resistant to growth inhibition by Zelboraf (vemurafenib) in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma conflicting Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, the response of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S to Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) was conflicting as one cell line with this mutation profile responded to the combination and another cell line with the mutation profile did not (PMID: 22389471). 22389471
NRAS Q61K CDKN2A loss melanoma sensitive SBI-0640756 Preclinical Actionable In a preclinical study, SBI-0640726 delayed tumor growth of melanomas in mice with a genetic background of NRAS Q61K and CDKN2A loss (PMID: 26603897). 26603897
NRAS Q61K CDKN2A loss melanoma sensitive Palbociclib + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Ibrance (palbociclib) and Mekinist (trametinib) induced tumor regression in a mouse melanoma model expressing NRAS Q61K and harboring CDKN2A loss (PMID: 22983396). 22983396
EGFR L858R EGFR T790M NRAS Q61K non-small cell lung carcinoma resistant Osimertinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR L858R, EGFR T790M, and NRAS Q61K were resistant to Tagrisso (osimertinib) in culture (PMID: 25870145). 25870145
BRAF V600K NRAS Q61K melanoma sensitive GSK2126458 Preclinical Actionable In a preclinical study, Omipalisib (GSK2126458) inhibited the growth of melanoma cell lines harboring BRAF V600K in culture (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma sensitive Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma decreased response Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600K and NRAS Q61K were 3-7 fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600K in culture (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma sensitive Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) inhibited growth of melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600K and NRAS Q61K were resistant to Tafinlar (dabrafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF L597V NRAS Q61K non-small cell lung carcinoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K in culture (PMID: 27523909). 27523909
BRAF L597V NRAS Q61K non-small cell lung carcinoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 27523909). 27523909
BRAF L597V NRAS Q61K non-small cell lung carcinoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K in culture (PMID: 27523909). 27523909
BRAF L597V NRAS Q61K non-small cell lung carcinoma decreased response PLX7904 Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61L demonstrated decreased sensitivity to PLX7904 in culture (PMID: 27523909). 27523909
BRAF L597V NRAS Q61K non-small cell lung carcinoma decreased response Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
BRAF V600E NRAS Q61K melanoma sensitive Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of melanoma cell lines harboring BRAF V600E and NRAS Q61K in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K lung adenocarcinoma predicted - resistant Trametinib + Dabrafenib Clinical Study Actionable In a clinical case study, a breast cancer patient with metastatic lung adenocarcinoma harboring BRAF V600E developed progressive disease after initial response to Talfinlar (dabrafenib) and Mekinist (trametinib) combination therapy, NRAS Q61K was identified as an acquired mutation after disease progression (PMID: 29631033). 29631033
BRAF V600E NRAS Q61K melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E expressing NRAS Q61K were resistant to Tafinlar (dabrafenib) mediated growth inhibition and retained MEK and ERK signaling (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, a NRAS Q61K mutation conferred resistance to Zelboraf (vemurafenib) in melanoma cells harboring BRAF V600E in culture (PMID: 21107323). 21107323
BRAF V600E NRAS Q61K melanoma sensitive XL888 Preclinical Actionable In a preclinical study, treatment with XL888 resulted in increased apoptosis and decreased growth of Zelboraf (vemurafenib)-resistant melanoma cells harboring BRAF V600E along with NRAS Q61K in cell culture (PMID: 22351686). 22351686
BRAF wild-type NRAS Q61K melanoma resistant GDC0879 Preclinical - Pdx Actionable In a preclinical study, GDC0879 failed to inhibit growth of BRAF wild-type melanoma cells harboring NRAS Q61K in patient-derived xenograft models (PMID: 19276360). 19276360
KMT2A-MLLT1 NRAS G12D acute myeloid leukemia sensitive Dinaciclib Preclinical Actionable In a preclinical study, acute myeloid leukemia cells co-harboring KMT2A-MLLT1 and NRAS G12D demonstrated a decrease in tumor burden, reduced colony formation, and an increase in cell death when treated with Dinaciclib in both culture and mouse models (PMID: 26627013). 26627013
KMT2A-MLLT1 NRAS G12D acute myeloid leukemia predicted - sensitive AZ20 Preclinical Actionable In a preclinical study, AZ20 treatment resulted in growth inhibition of tumor cells and prolonged survival in animal models of acute myeloid leukemia harboring KMT2A-MLLT1 fusion and NRAS G12D (PMID: 27625305). 27625305
KMT2A-MLLT1 NRAS G12D acute myeloid leukemia predicted - sensitive AZD0156 Preclinical Actionable In a preclinical study, AZD0156 treatment resulted in growth inhibition of tumor cells and prolonged survival in animal models of acute myeloid leukemia harboring KMT2A-MLLT1 fusion and NRAS G12D (PMID: 27625305). 27625305
AKT1 E17K NRAS G12D prostate cancer sensitive BAY1125976 Preclinical - Cell line xenograft Actionable In a preclinical study, BAY1125976 inhibited proliferation of a prostate cancer cell line harboring AKT E17K and NRAS G12D in culture, and demonstrated antitumor activity in xenograft models (PMID: 27699769). 27699769
NRAS G12D Advanced Solid Tumor sensitive N-Arachidonoyl Dopamine Preclinical - Cell culture Actionable In a preclinical study, N-Arachidonoyl Dopamine (NADA) disrupted NRAS protein membrane localization and decreased NRAS downstream signaling, and inhibited proliferation and induced cell death in transformed cells expressing NRAS G12D in culture (PMID: 27760835). 27760835
NRAS G12D acute myeloid leukemia sensitive Alpelisib + Binimetinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Binimetinib (MEK162) and Alpelisib (BYL719) inhibited proliferation in a human acute myeloid leukemia (AML) cell line harboring NRAS G12D in culture, and decreased disease burden in xenograft models (PMID: 24569456). 24569456
NRAS G12D acute myeloid leukemia sensitive Binimetinib Preclinical Actionable In a preclinical study, Binimetinib (MEK162) inhibited growth of acute myeloid leukemia cells that have been demonstrated to harbor NRAS G12D in culture and decreased disease burden in xenograft models with NRAS G12D (PMID: 24569456, PMID: 11238126). 24569456 11238126
BRAF D594G NRAS G12D melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma decreased response PLX7904 Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to PLX7904 in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring both BRAF D594G and NRAS G12D in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring both BRAF D594G and NRAS G12D in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma decreased response Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
NRAS G13V adult T-cell leukemia sensitive 3144 Preclinical - Pdx & cell culture Actionable In a preclinical study, 3144 inhibited growth of patient-derived T-cell acute lymphocytic leukemia cells harboring NRAS G13V in culture, and reduced tumor burden in xenograft models (PMID: 28235199). 28235199
BRAF V600X MAP2K1 V60E NRAS T58I NRAS Q61R melanoma resistant Vemurafenib Clinical Study Actionable In a clinical study, a melanoma patient harboring a BRAF V600 mutation developed resistant mutations, MAP2K1 V60E, NRAS T58I, and NRAS Q61R, after 18 weeks of treatment with Zelboraf (vemurafenib) (PMID: 24265153). 24265153
FGFR1 amp NRAS amp non-small cell lung carcinoma resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cells harboring both FGFR1 and NRAS amplification were resistant to Mekinist (trametinib) in culture (PMID: 28630215). 28630215
FGFR1 amp NRAS amp non-small cell lung carcinoma sensitive BGJ398 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, BGJ398 and Mekinist (trametinib) combination treatment inhibited Erk signaling, resulting in growth inhibition in non-small cell lung carcinoma cells harboring both FGFR1 and NRAS amplification in culture (PMID: 28630215). 28630215
FGFR1 amp NRAS amp non-small cell lung carcinoma resistant BGJ398 Preclinical - Cell culture Actionable In a preclinical study, amplification of NRAS was identified in a non-small cell lung cancer cell line harboring FGFR1 amplification that acquired resistance to BGJ398 in culture (PMID: 28630215). 28630215
EGFR exon 19 del NRAS amp non-small cell lung carcinoma resistant Afatinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR exon 19 deletion became resistant to Gilotrif (afatinib) after the emergence of amplified NRAS in culture (PMID: 25870145). 25870145
EGFR exon 19 del NRAS amp non-small cell lung carcinoma resistant Osimertinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR exon 19 deletion and amplified NRAS were resistant to Tagrisso (osimertinib) in culture (PMID: 25870145). 25870145
EGFR exon 19 del NRAS amp non-small cell lung carcinoma sensitive Selumetinib Preclinical Actionable In a preclinical study, Selumetinib inhibited proliferation of non-small cell lung cancer cells harboring EGFR exon 19 deletion and amplified NRAS in culture (PMID: 25870145). 25870145
EGFR exon 19 del NRAS E63K non-small cell lung carcinoma resistant Osimertinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR exon 19 deletion and NRAS E63K were resistant to Tagrisso (osimertinib) AZD9291 treatment in culture (PMID: 25870145). 25870145
EGFR exon 19 del NRAS E63K non-small cell lung carcinoma resistant Gefitinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR exon 19 deletion became resistant to Iressa (gefitinib) after the emergence of NRAS E63K in culture (PMID: 25870145). 25870145
EGFR exon 19 del NRAS E63K non-small cell lung carcinoma sensitive Selumetinib Preclinical Actionable In a preclinical study, Selumetinib inhibited proliferation of non-small cell lung cancer cells harboring EGFR exon 19 deletion and NRAS E63K in culture (PMID: 25870145). 25870145
NRAS G13D melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, human melanoma cells harboring NRAS G13D were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). 26343583
NRAS G13D melanoma sensitive LY3009120 Preclinical Actionable In a preclinical study, LY3009120 inhibited soft agar growth of human melanoma cancer cells harboring NRAS G13D in culture (PMID: 26343583). 26343583
NRAS G13D melanoma sensitive Selumetinib Preclinical Actionable In a preclinical study, Selumetinib (AZD6244) inhibited proliferation of human melanoma cells harboring NRAS G13D in culture (PMID: 26343583). 26343583
NRAS G13D adult T-cell leukemia sensitive 3144 Preclinical - Cell culture Actionable In a preclinical study, 3144 inhibited growth of patient-derived T-cell acute lymphocytic leukemia cells harboring NRAS G13D in culture (PMID: 28235199). 28235199
BRAF G596V NRAS G13R colorectal cancer sensitive Cetuximab + LSN3074753 Preclinical - Pdx Actionable In a preclinical study, LSN3074753 and Erbitux (cetuximab) worked synergistically, resulting in tumor regression in a patient-derived xenograft model of colorectal cancer harboring BRAF G596V and NRAS G13R (PMID: 28611205). 28611205
ATM mut NRAS Q61R melanoma sensitive Binimetinib Clinical Study Actionable In a clinical study, a melanoma patient harboring an ATM mutation and NRAS Q61R demonstrated a partial response and 16 month progression free survival when treated with Binimetinib (MEK162) (PMID: 28514312). 28514312
KIT D816V NRAS Q61R melanoma no benefit Pembrolizumab + Trametinib Clinical Study Actionable In a clinical study, a melanoma patient harboring KIT D816V and NRAS Q61R demonstrated progressive disease when treated with a combination of Mekinist (trametinib) and Keytruda (pembrolizumab) (PMID: 28514312). 28514312
NRAS Q61R thyroid cancer sensitive MK2206 Preclinical - Cell culture Actionable In a preclinical study, MK2206 inhibited AKT activation, proliferation, and growth of thyroid cancer cell lines with PI3K/AKT pathway alterations in culture, including an anaplastic thyroid cancer cell line harboring NRAS Q61R (PMID: 21289267). 21289267
NRAS Q61R melanoma sensitive Binimetinib Phase II Actionable In a Phase II trial, Binimetinib (MEK162) treatment resulted in partial response in 20% (6/30), and stable disease in 43% (13/30) of melanoma patients harboring NRAS mutations, including Q61L (1/30), Q61K (9/30), and Q61R (15/30) (PMID: 23414587). 23414587
AKT1 E17K NRAS Q61R bladder carcinoma sensitive BAY1125976 Preclinical - Cell culture Actionable In a preclinical study, BAY1125976 inhibited Akt activation and downstream signaling in bladder cancer cell lines carrying both Akt1 E17K and Nras Q61R mutations (AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3685). detail...
NRAS Q61X myelodysplastic syndrome not applicable N/A Guideline Prognostic NRAS Q61X is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). detail...
BRAF mut NRAS mut melanoma predicted - sensitive BI-847325 Preclinical - Cell culture Actionable In a preclinical study, treatment with BI-847325 inhibited growth of a BRAF-mutant melanoma cell line with BRAF-inhibitor resistance due to an NRAS mutation in culture (PMID: 25873592). 25873592
BRAF mut NRAS mut melanoma sensitive Lenvatinib Phase I Actionable In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 50% (1/2) of melanoma patients harboring both BRAF and NRAS mutations (PMID: 26169970). 26169970
NRAS mut STAG2 dec exp melanoma decreased response Trametinib Preclinical - Cell culture Actionable In a preclinical study, decreasing Stag2 expression level through shRNA knockdown in NRAS mutated melanoma cell lines resulted in decreased response to Mekinist (trametinib) in culture (PMID: 27500726). 27500726
NRAS mutant melanoma sensitive Buparlisib Preclinical - Cell line xenograft Actionable In a preclinical study, Buparlisib (BKM120) treatment in human melanoma cell line xenograft models with brain metastases and harboring an NRAS mutation resulted in inhibition of brain tumor growth and an improved survival benefit (PMID: 27307593). 27307593
NRAS mutant melanoma sensitive SBI-0640756 Preclinical Actionable In a preclinical study, SBI-0640756 inhibited proliferation and transformation of human melanoma cell lines harboring NRAS mutation in culture (PMID: 26603897). 26603897
NRAS mutant multiple myeloma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human multiple myeloma cells harboring mutant NRAS in culture (PMID: 26343583). 26343583
NRAS mutant melanoma sensitive BI-69A11 Preclinical Actionable In a preclinical study, BI-69A11 inhibited proliferation and transformation of human melanoma cell lines harboring NRAS mutation in culture (PMID: 26603897). 26603897
NRAS mutant biliary tract cancer predicted - sensitive Binimetinib Phase I Actionable In a Phase I trial, Binimetinib (MEK162) treatment resulted in partial response in a biliary tract cancer patient harboring NRAS mutation (PMID: 28152546) 28152546
NRAS mutant melanoma sensitive Binimetinib + BKM120 Preclinical - Cell culture Actionable In a preclinical study, the combination of Binimetinib (MEK162) and Buparlisib (BKM120) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line harboring an NRAS mutation (PMID: 27307593). 27307593
NRAS mutant leukemia sensitive Alpelisib + Binimetinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Alpelisib (BYL719) and Binimetinib (MEK162) led to a synergistic effect in leukemia cells harboring mutant NRAS, demonstrating cell death in culture (PMID: 29437705). 29437705
NRAS mutant Advanced Solid Tumor no benefit CC-90003 Phase I Actionable In a Phase Ia trial, CC-90003 treatment did not result in any objective responses and demonstrated toxicity in advanced solid tumor patients harboring KRAS, NRAS, or BRAF mutations (J Clin Oncol 35, 2017 (suppl; abstr 2577)). detail...
NRAS mutant lung adenocarcinoma resistant Trametinib Preclinical Actionable In a preclinical study, human lung adenocarcinoma cell lines harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
NRAS mutant melanoma sensitive SBI-0640726 Preclinical Actionable In a preclinical study, SBI-0640726 inhibited proliferation and transformation of human melanoma cell lines harboring NRAS mutation in culture (PMID: 26603897). 26603897
NRAS mutant leukemia sensitive HM95573 Preclinical - Cell culture Actionable In a preclinical study, HM95573 inhibited growth of NRAS mutant leukemia cells in culture (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). detail...
NRAS mutant central nervous system cancer sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human central nervous system cancer cells harboring mutant NRAS in culture (PMID: 26343583). 26343583
NRAS mutant non-small cell lung carcinoma predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of NRAS-mutant non-small cell lung cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
NRAS mutant melanoma conflicting Binimetinib Phase II Actionable In a Phase II trial, Binimetinib (MEK162) treatment resulted in partial response in 20% (6/30), and stable disease in 43% (13/30) of melanoma patients harboring NRAS mutations, including Q61L (1/30), Q61K (9/30), and Q61R (15/30) (PMID: 23414587). 23414587
NRAS mutant melanoma conflicting Binimetinib Phase III Actionable In a Phase III clinical trial, treatment with Binimetinib (MEK162) improved median progression-free survival compared to treatment with Deticene (dacarbazine) (2.8 mo. vs. 1.5 mo.), but did not improve overall survival in patients with NRAS-mutant melanoma (PMID: 28284557). 28284557
NRAS mutant hematologic cancer predicted - resistant SHP099 Preclinical Actionable In a preclinical study, hematopoietic cancer cell lines harboring NRAS mutations demonstrated resistance to SHP099 in cell culture (PMID: 27362227). 27362227
NRAS mutant skin melanoma sensitive Binimetinib Phase III Actionable In a Phase III trial, Binimetinib (MEK162) treatment resulted in improved progression free survival (2.8 months), objective response rate (15%, 40/269) and disease control rate (58%, 156/269) compared to Deticene (dacarbazine) (1.5 months, 7%, 25%, respectively) in NRAS-mutant cutaneous melanoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9500)). detail...
NRAS mutant melanoma no benefit PD-0325901 Preclinical - Cell line xenograft Actionable In a preclinical study, PD-0325901 treatment resulted in stable tumor growth in melanoma cell line xenograft models harboring an NRAS mutation, however, growth later ensued and thus, demonstrates a lack of benefit (PMID: 27488531). 27488531
NRAS mutant Advanced Solid Tumor no benefit NS1 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing an NRAS mutation did not respond to treatment with NS1 in culture, resulting in sustained downstream signaling and cell transformation (PMID: 27820802). 27820802
NRAS mutant melanoma no benefit Palbociclib Preclinical - Cell line xenograft Actionable In a preclinical study, Ibrance (palbociclib) treatment resulted in stable tumor growth in melanoma cell line xenograft models harboring an NRAS mutation, however, growth later ensued and thus, demonstrated a lack of benefit (PMID: 27488531). 27488531
NRAS mutant hepatocellular carcinoma sensitive Refametinib + Sorafenib Phase II Actionable In a Phase II trial, Refametinib (BAY86-9766) and Nexavar (sorafenib) combination treatment resulted in an objective response rate of 6.3% (1/16), a disease control rate of 43.8% (7/16), an overall survival of 12.7 months, and a progression-free survival of 1.5 months in patients unresectable or metastatic hepatocellular carcinoma harboring RAS (NRAS and KRAS) mutations (PMID: 29950351; NCT01915602). 29950351
NRAS mutant Advanced Solid Tumor sensitive RAF709 Preclinical - Cell culture Actionable In a preclinical study, cancer cell lines harboring NRAS mutations demonstrated increased sensitivity to RAF709 compared to NRAS wild-type cells in culture (PMID: 29343524). 29343524
NRAS mutant Advanced Solid Tumor sensitive Obatoclax Preclinical Actionable In a preclinical study, obatoclax decreased proliferation in human tumor cell lines with NRAS mutation in culture (PMID: 22460902). 22460902
NRAS mutant Advanced Solid Tumor predicted - sensitive BGB-283 Phase I Actionable In a Phase I trial, BGB-283 demonstrated safety and preliminary efficacy, resulted in partial response in 14% (4/29), and prolonged stable disease in 48% (14/29) of advanced solid tumor patients harboring mutations in KRAS, NRAS, and/or BRAF (AACR Annual Meeting, Apr 2016, abstract # CT005). detail...
NRAS mutant autonomic nervous system neoplasm sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human autonomic ganglia cancer cells harboring mutant NRAS in culture (PMID: 26343583). 26343583
NRAS mutant melanoma sensitive LY3009120 Preclinical Actionable In a preclinical study, LY3009120 inhibited growth of NRAS mutant human melanoma cell lines in culture (PMID: 26343583). 26343583
NRAS mutant melanoma predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of NRAS-mutant melanoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
NRAS mutant liver cancer sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of liver cancer cell lines harboring mutant NRAS in culture (PMID: 26343583). 26343583
NRAS mutant transitional cell carcinoma decreased response Trametinib Preclinical Actionable In a preclinical study, human urinary tract transitional cell carcinoma cells harboring mutant NRAS were moderately sensitive to Mekinist (trametinib) growth inhibition in culture (PMID: 26343583). 26343583
NRAS mutant melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring a mutation in NRAS were resistant to Zelboraf (vemurafenib) mediated growth inhibition in culture (PMID: 26343583). 26343583
NRAS mutant pancreatic cancer predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of NRAS-mutant pancreatic cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
NRAS mutant neuroblastoma sensitive Alpelisib + Binimetinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Alpelisib (BYL719) and Binimetinib (MEK162) led to a synergistic effect in neuroblastoma cells harboring mutant NRAS, demonstrating cell death in culture (PMID: 29437705). 29437705
NRAS mutant melanoma sensitive S63845 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, combination of S63845 and Mekinist (trametinib) resulted in potent cytotoxic effects in NRAS-mutated melanoma cells in culture compared to the cytostatic effect of Mekinist (trametinib) alone (PMID: 27760111). 27760111
NRAS mutant melanoma sensitive Adavosertib Preclinical Actionable In a preclinical study, MK-1775 showed efficacy in NRAS mutant melanoma and in mutant KRAS colorectal, pancreatic, and lung cancers (PMID: 24791855). 24791855
NRAS mutant acute myeloid leukemia sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human acute myeloid leukemia cell lines harboring mutant NRAS in culture (PMID: 26343583). 26343583
NRAS mutant melanoma sensitive PD-0325901 + Palbociclib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination treatment of PD-0325901 and Ibrance (palbociclib) resulted in tumor regression in 33% (2/6) of melanoma xenograft models harboring an NRAS mutation (PMID: 27488531). 27488531
NRAS mutant colon cancer resistant GDC0879 Preclinical - Cell culture Actionable In a preclinical study, colon cancer cells harboring NRAS mutations were resistant to GDC0879 induced growth inhibition in culture (PMID: 19276360). 19276360
NRAS mutant melanoma sensitive Binimetinib + Ribociclib Phase Ib/II Actionable In a Phase Ib trial, the combination of Binimetinib (MEK162) and Kisqali (ribociclib) resulted in a median progression-free survival of 6.7 months, a partial response in 25% (4/16), and stable disease in 44% (7/16) of NRAS mutant melanoma patients (J Clin Oncol 35, 2017 (suppl; abstr 9519)). detail...
NRAS mutant melanoma sensitive Binimetinib + Ribociclib Phase Ib/II Actionable In a Phase Ib/II trial, the combination of Binimetinib (MEK162) and Kisqali (ribociclib) resulted in a partial response in 43% (6/14) and stable disease in 43% (6/14) of NRAS mutant melanoma patients (J Clin Oncol 32:5s, 2014 (Suppl;abstr 9009)). detail...
NRAS mutant acute myeloid leukemia predicted - sensitive AZD5153 Preclinical - Cell line xenograft Actionable In a preclinical study, AZD5153 inhibited proliferation of acute myeloid leukemia cells harboring NRAS mutation in culture, resulted in tumor growth inhibition in cell line xenograft models (PMID: 27573426). 27573426
NRAS mutant colorectal cancer predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of NRAS-mutant colorectal cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
NRAS mutant leukemia predicted - sensitive Trametinib Phase Ib/II Actionable In a Phase Ib/II clinical trial, treatment with Mekinist (trametinib) resulted in an overall response rate of 28% in RAS-mutant leukemia patients, with 12% (7/57) of patients achieving complete remission (ASH 2015 Annual Meeting, Abst 677). detail...
NRAS mutant melanoma sensitive CCT241161 Preclinical Actionable In a preclinical study, CCT241161 inhibited growth of melanoma cells harboring NRAS mutations in culture (PMID: 25500121). 25500121
NRAS mutant melanoma predicted - sensitive Trametinib Phase I Actionable In a Phase I trial, Mekinist (trametinib) treatment resulted in stable disease in 29% (2/7) of patients with NRAS mutated melanoma (PMID: 22805292). 22805292
NRAS mutant melanoma predicted - sensitive Ulixertinib Phase I Actionable In a Phase I trial, treatment with BVD-523 (ulixertinib) resulted in a best response of stable disease in six melanoma patients and a partial response in three melanoma patients all harboring an NRAS mutation (PMID: 29247021). 29247021
NRAS mutant ovarian cancer sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of ovarian cancer cells harboring mutant NRAS in culture (PMID: 26343583). 26343583
NRAS mutant non-Hodgkin lymphoma resistant Trametinib Preclinical Actionable In a preclinical study, human non-Hodgkin lymphoma cells harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
NRAS mutant lymphoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human lymphoma cells harboring mutant NRAS in culture (PMID: 26343583). 26343583
NRAS mutant stomach carcinoma predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of NRAS-mutant gastric carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
NRAS mutant melanoma sensitive HM95573 Phase I Actionable In a Phase I trial, HM95573 treatment resulted in an unconfirmed partial response in a patient with NRAS mutant melanoma (Journal of Clinical Oncology 34, no. 15_suppl (May 20 2016) 2570-2570; NCT02405065). detail...
NRAS mutant melanoma sensitive CCT196969 Preclinical Actionable In a preclinical study, CCT196969 inhibited growth of melanoma cells harboring NRAS mutations in culture (PMID: 25500121). 25500121
NRAS mutant Advanced Solid Tumor predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 resulted in tumor regression in patient derived xenograft (PDX) models harboring either a BRAF mutation, NRAS mutation, or KRAS mutation (EJC Dec 2016, 69:1; S126). detail...
NRAS mutant sarcoma resistant Trametinib Preclinical Actionable In a preclinical study, human sarcoma cells harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
NRAS mutant colorectal cancer no benefit Cetuximab + FOLFIRI Phase III Actionable In a retrospective analysis of a Phase III trial, the combination of Erbitux (cetuximab) and FOLFIRI did not demonstrate an improved clinical benefit compared to FOLFIRI alone in colorectal cancer patients with RAS mutations (PMID: 25605843). 25605843
NRAS mutant acute myeloid leukemia sensitive LY3009120 Preclinical Actionable In a preclinical study, LY3009120 inhibited proliferation of human NRAS mutant acute myeloid leukemia cell lines in culture (PMID: 26343583). 26343583
NRAS mutant melanoma sensitive Tubastatin A Preclinical Actionable In a preclinical study, Tubastatin A inhibited proliferation of NRAS mutant melanoma cell lines in culture (PMID: 25957812). 25957812
NRAS mutant cervix carcinoma predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of NRAS-mutant cervical carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
NRAS mutant colorectal cancer predicted - resistant SYM004 Preclinical - Pdx Actionable In a preclinical study, patient-derived xenograft (PDX) models of colorectal cancer harboring KRAS, NRAS or BRAF mutations demonstrated poor response to SYM004 treatment compared to wild-type models (PMID: 29423521). 29423521
NRAS mutant thyroid cancer sensitive Selumetinib Phase I Actionable In a Phase I study, selumetinib demonstrated an increase in iodine uptake and retention in a subgroup of patients with thyroid cancer that was refractory to radioiodine; including patients with BRAF and NRAS mutations disease (PMID: 23406027). 23406027
BRAF wild-type NRAS mutant melanoma sensitive Lenvatinib Phase I Actionable In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 83% (5/6) of melanoma patients harboring NRAS mutations and wild-type BRAF (PMID: 26169970). 26169970
CDKN2A loss NRAS mutant melanoma sensitive Abemaciclib Phase I Actionable In a Phase I trial, Abemaciclib (LY2835219) resulted in a partial response in a melanoma patient with CDKN2A loss and NRAS mutation (PMID: 27217383). detail... 27217383
CTNNB1 mut NRAS mut liver cancer resistant Trametinib Preclinical Actionable In a preclinical study, human liver cancer cells harboring mutant NRAS and mutant CTNNB1 were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
NRAS mut PIK3CA wild-type colorectal cancer predicted - sensitive TAK-733 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cell lines harboring mutations in KRAS or NRAS and with wild-type PIK3CA demonstrated a trend toward increased sensitivity to TAK-733 in culture (PMID: 26439693). 26439693
BRAF V600E NRAS G12V melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, expression of NRAS G12V in melanoma cells harboring BRAF V600E conferred resistance to Zelboraf (vemurafenib) in culture (PMID: 26267534). 26267534
BRAF V600E NRAS G12V melanoma sensitive DEL-22379 Preclinical - Cell culture Actionable In a preclinical study, DEL-22379 inhibited growth of a melanoma cell line harboring BRAF V600E and over expressing NRAS G12V in culture (PMID: 26267534). 26267534
NRAS G12V colorectal cancer resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring NRAS G12V demonstrated resistance to Erbitux (cetuximab) in culture (PMID: 28179366). 28179366
NRAS G12V colorectal cancer sensitive Cetuximab + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Erbitux (cetuximab) and Mekinist (trametinib) decreased viability of colorectal cancer cells harboring NRAS G12V in culture (PMID: 28179366). 28179366
EGFR exon 19 del NRAS G12V non-small cell lung carcinoma resistant Osimertinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR exon 19 deletion and NRAS G12V were resistant to Tagrisso (osimertinib) in culture (PMID: 25870145). 25870145
EGFR exon 19 del NRAS G12R non-small cell lung carcinoma sensitive Selumetinib Preclinical Actionable In a preclinical study, Selumetinib inhibited proliferation of non-small cell lung cancer cells harboring EGFR exon 19 deletion and NRAS G12R in culture (PMID: 25870145). 25870145
EGFR exon 19 del NRAS G12R non-small cell lung carcinoma resistant Osimertinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR exon 19 deletion and NRAS G12R were resistant to Tagrisso (osimertinib) in culture (PMID: 25870145). 25870145
NRAS exon 3 colon cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab) is not indicated for use in colon cancer patients with NRAS exon 3 mutations (NCCN.org). detail...
NRAS exon 3 rectum cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab) is not indicated for use in rectum cancer patients with NRAS exon 3 mutations (NCCN.org). detail...
NRAS exon 3 colon cancer resistant Panitumumab Guideline Actionable Vectibix (panitumumab) is not indicated for use in colon cancer patients with NRAS exon 3 mutations (NCCN.org). detail...
NRAS exon 3 rectum cancer resistant Panitumumab Guideline Actionable Vectibix (panitumumab) is not indicated for use in rectum cancer patients with NRAS exon 3 mutations (NCCN.org). detail...
NRAS wild-type melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, an NRAS wild-type melanoma cell line demonstrated inhibition of cell growth when treated with Mekinist (trametinib) in culture (PMID: 27488531). 27488531
NRAS wild-type colorectal cancer predicted - sensitive Cetuximab + FOLFIRI Phase III Actionable In a Phase III trial, the combination of Erbitux (cetuximab) and FOLFIRI demonstrated a significant clinical benefit in OS, PFS, and objective response compared to FOLFIRI alone in colorectal cancer patients with RAS wild-type status (PMID: 25605843). 25605843
NRAS wild-type melanoma decreased response Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, an NRAS wild-type melanoma cell line demonstrated minimal sensitivity when treated with the combination of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 27488531). 27488531
NRAS wild-type melanoma sensitive Palbociclib Preclinical - Cell culture Actionable In a preclinical study, NRAS wild-type melanoma cells demonstrated decreased cell viability when treated with Ibrance (palbociclib) in culture (PMID: 27488531). 27488531
NRAS wild-type melanoma sensitive E6201 Preclinical Actionable In a preclinical study, E6201 inhibited proliferation of several melanoma cell lines in culture and hypersensitivity was associated with wild-type NRAS (PMID: 23039341). 23039341
NRAS wild-type colorectal cancer predicted - sensitive Panitumumab Phase III Actionable In a Phase III clinical trial, the combination of Vectibix (panitumumab) and FOLFIRI improved progression-free survival and median overall survival in patients with RAS wild-type colorectal cancer compared to FOLFIRI treatment alone (PMID: 26341920). 26341920
BRAF mut NRAS wild-type melanoma sensitive Lenvatinib Phase I Actionable In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 100% (5/5) of melanoma patients harboring BRAF mutations and wild-type NRAS (PMID: 26169970). 26169970
BRAF wild-type NRAS wild-type melanoma sensitive Lenvatinib Phase I Actionable In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 44% (4/9) and partial response in 22% (2/9) of melanoma patients carrying wild-type BRAF and NRAS (PMID: 26169970). 26169970
BRAF wild-type NRAS wild-type melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, BRAF and NRAS wild-type melanoma cells were resistant to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
BRAF wild-type NRAS wild-type melanoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of BRAF and NRAS wild-type melanoma cells in culture (PMID: 27523909). 27523909
BRAF wild-type NRAS wild-type melanoma resistant PLX7904 Preclinical - Cell culture Actionable In a preclinical study, BRAF and NRAS wild-type melanoma cells were resistant to PLX7904 in culture (PMID: 27523909). 27523909
BRAF wild-type NRAS wild-type melanoma sensitive Binimetinib + BKM120 Preclinical - Cell culture Actionable In a preclinical study, the combination of Binimetinib (MEK162) and Buparlisib (BKM120) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line with wild-type BRAF and wild-type NRAS in culture (PMID: 27307593). 27307593
BRAF wild-type NRAS wild-type melanoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of BRAF and NRAS wild-type melanoma cells in culture (PMID: 27523909). 27523909
BRAF wild-type KRAS wild-type NRAS wild-type colorectal cancer predicted - sensitive Cetuximab + FOLFIRI + Bevacizumab Phase II Actionable In a Phase II trial (MACBETH), first-line treatment with the combination of Erbitux (cetuximab) and FOLFIRI, followed by Avastin (bevacizumab) maintenance, demonstrated activity in BRAF/KRAS/NRAS wild-type metastatic colorectal cancer patients, resulting in a median overall survival in the intent-to-treat population of 32.2 mo and response rate of 75% (43/57), however, resulted in a 10-mo PFS rate of 40.4% (23/57), which did not meet the primary endpoint of 70% (PMID: 29450468; NCT02295930). 29450468
BRAF wild-type KRAS wild-type NRAS wild-type colorectal cancer predicted - sensitive Cetuximab + FOLFIRI Phase II Actionable In a Phase II trial (MACBETH), first-line treatment with the combination of Erbitux (cetuximab) and FOLFIRI, followed by Erbitux (cetuximab) maintenance, demonstrated activity in BRAF/KRAS/NRAS wild-type metastatic colorectal cancer patients, resulting in a median overall survival in the intent-to-treat population of 33.2 mo and response rate of 68% (40/59), however, resulted in a 10-mo PFS rate of 50.8% (30/59), which did not meet the primary endpoint of 70% (PMID: 29450468; NCT02295930). 29450468
BRAF wild-type KRAS wild-type NRAS wild-type PIK3CA wild-type colorectal cancer sensitive Cetuximab Preclinical Actionable In a preclinical study, Erbitux (cetuximab) inhibited growth of human colorectal cancer cells wild-type for BRAF, KRAS, NRAS and PIK3CA in culture (PMID: 25838391). 25838391
BRAF wild-type KRAS wild-type NRAS wild-type PIK3CA wild-type colorectal cancer predicted - sensitive Cetuximab + FOLFOX Phase II Actionable In a Phase II trial, Erbitux (cetuximab) in combination with FOLFOX resulted in improved median progression-free survival (6.9 months) comparing to FOLFOX alone (5.3 months) in BRAF, KRAS, NRAS, and PIK3CA wild-type colorectal cancer patients (hazard ratio =0.56) (PMID: 27002107). 27002107
BRAF wild-type KRAS wild-type NRAS wild-type PIK3CA wild-type colorectal cancer resistant Regorafenib Preclinical Actionable In a preclinical study, colorectal cancer cell lines with wild-type BRAF, KRAS, NRAS and PIK3CA were resistant to Stivarga (regorafenib) in culture (PMID: 25838391). 25838391
NRAS exon 2 rectum cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab) is not indicated for use in rectum cancer patients with NRAS exon 2 mutations (NCCN.org). detail...
NRAS exon 2 colon cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab) is not indicated for use in colon cancer patients with NRAS exon 2 mutations (NCCN.org). detail...
NRAS exon 2 rectum cancer resistant Panitumumab Guideline Actionable Vectibix (panitumumab) is not indicated for use in rectum cancer patients with NRAS exon 2 mutations (NCCN.org). detail...
NRAS exon 2 colon cancer resistant Panitumumab Guideline Actionable Vectibix (panitumumab) is not indicated for use in colon cancer patients with NRAS exon 2 mutations (NCCN.org). detail...
NRAS mut CDKN2A mut acute lymphocytic leukemia resistant Trametinib Preclinical Actionable In a preclinical study, human acute lymphoblastic leukemia cells harboring NRAS and CDKN2A mutations were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
NRAS act mut non-small cell lung carcinoma sensitive RAF709 Preclinical - Pdx Actionable In a preclinical study, RAF709 inhibited tumor growth in patient-derived xenograft (PDX) models of non-small cell lung cancer harboring NRAS activating mutations (PMID: 29343524). 29343524
NRAS exon 4 rectum cancer resistant Panitumumab Guideline Actionable Vectibix (panitumumab) is not indicated for use in rectum cancer patients with NRAS exon 4 mutations (NCCN.org). detail...
NRAS exon 4 colon cancer resistant Panitumumab Guideline Actionable Vectibix (panitumumab) is not indicated for use in colon cancer patients with NRAS exon 4 mutations (NCCN.org). detail...
NRAS exon 4 colon cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab) is not indicated for use in colon cancer patients with NRAS exon 4 mutations (NCCN.org). detail...
NRAS exon 4 rectum cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab) is not indicated for use in rectum cancer patients with NRAS exon 4 mutations (NCCN.org). detail...
NRAS Q61H rhabdomyosarcoma sensitive Alpelisib + Binimetinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Alpelisib (BYL719) and Binimetinib (MEK162) led to a synergistic effect in rhabdomyosarcoma cells harboring NRAS Q61H, demonstrating cell death in culture (PMID: 29437705). 29437705
NRAS G13X myelodysplastic syndrome not applicable N/A Guideline Prognostic NRAS G13X is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). detail...
BRAF V600E NRAS A146T MAP2K1 P387S melanoma no benefit Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Omipalisib (GSK2126458) did not improve the response to human melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T MAP2K1 P387S melanoma decreased response GSK2126458 Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T MAP2K1 P387S melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E NRAS A146T MAP2K1 P387S melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T MAP2K1 P387S melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T MAP2K1 P387S melanoma decreased response Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E and also had reduced sensitivity in comparison to cell lines harboring BRAF V600E and NRAS A146T in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E and NRAS A146T were resistant to Tafinlar (dabrafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma decreased response Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T were >10-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma decreased response GSK2126458 Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma sensitive Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of melanoma cell lines harboring BRAF V600E and NRAS A146T in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma sensitive Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E and NRAS A146T in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E and NRAS A146T in culture, compared to either agent alone (PMID: 22389471). 22389471
NRAS Q61L melanoma sensitive CCT196969 Preclinical - Cell line xenograft Actionable In a preclinical study, CCT196969 inhibited MEK and ERK activation and growth of a melanoma cell line harboring NRAS Q61L in culture, and inhibited tumor growth in a NRAS Q61L-mutant melanoma cell line xenograft model (PMID: 25500121, PMID: 23431193). 25500121 23431193
NRAS Q61L melanoma sensitive CCT241161 Preclinical - Cell line xenograft Actionable In a preclinical study, CCT241161 inhibited MEK and ERK activation and growth of a melanoma cell line harboring NRAS Q61L in culture, and inhibited tumor growth in a NRAS Q61L-mutant melanoma cell line xenograft model (PMID: 25500121, PMID: 23431193). 25500121 23431193
NRAS Q61L melanoma decreased response Selumetinib Preclinical Actionable In a preclinical study, Selumetinib (AZD6244) modestly inhibited proliferation of human melanoma cells harboring NRAS Q61L in culture (PMID: 26343583). 26343583
NRAS Q61L melanoma resistant PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX4720 did not inhibit growth of melanoma cells harboring NRAS Q61L in culture or in cell line xenograft models (PMID: 25500121, PMID: 23431193). 25500121 23431193
NRAS Q61L melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, human melanoma cells harboring NRAS Q61L were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). 26343583
NRAS Q61L melanoma sensitive Binimetinib Phase II Actionable In a Phase II trial, Binimetinib (MEK162) treatment resulted in partial response in 20% (6/30), and stable disease in 43% (13/30) of melanoma patients harboring NRAS mutations, including Q61L (1/30), Q61K (9/30), and Q61R (15/30) (PMID: 23414587). 23414587
NRAS Q61L melanoma sensitive RAF709 Preclinical - Cell culture Actionable In a preclinical study, RAF709 inhibited Erk signaling and proliferation of melanoma cells harboring NRAS Q61L in culture (PMID: 29343524). 29343524
NRAS Q61L melanoma decreased response LY3009120 Preclinical Actionable In a preclinical study, LY3009120 modestly inhibited soft agar growth of human melanoma cancer cells harboring NRAS Q61L in culture (PMID: 26343583). 26343583