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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, PMID: 30154648, PMID: 28860801).

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
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, May 2020).
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
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).
A146X missense unknown NRAS A146X indicates any NRAS missense mutation that results in replacement of the alanine (A) at amino acid 146 by a different amino acid.
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, PMID: 27642091, PMID: 26216163), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, May 2020).
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.
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, PMID: 30458888), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, May 2020).
act mut unknown unknown NRAS act mut indicates that the variant results in activation of NRAS downstream signaling. The mechanism causing the activation can include either loss of GTP hydrolysis activity (loss of function) or increased nucleotide exchange rate (gain of function).
amp none no effect NRAS amplification indicates an increased number of copies of the NRAS gene. However, the mechanism causing the increase is unspecified.
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, PMID: 22037554), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, May 2020).
D154H missense unknown NRAS D154H lies within the G domain of the Nras protein (PMID: 17384584). D154H has been identified in sequencing studies (PMID: 27693639), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, May 2020).
D175N missense unknown NRAS D175N lies within the hypervariable region of the Nras protein (PMID: 17384584). D175N has not been characterized and therefore, its effect on Nras protein function is unknown (PubMed, May 2020).
D54N missense unknown NRAS D54N does not lie within any known functional domains of the Nras protein (UniProt.org). D54N has been identified in the scientific literature (PMID: 32028967), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, Mar 2020).
D57A missense unknown NRAS D57A lies within the G domain of the Nras protein (PMID: 17384584). D57A has been identified in sequencing studies (PMID: 30352278), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, May 2020).
dec exp none no effect NRAS dec exp indicates decreased expression of the Nras protein and/or mRNA. However, the mechanism causing the decreased expression is unspecified.
E132K missense loss of function - predicted NRAS E132K lies within the G domain of the Nras protein (PMID: 17384584). E132K does not affect cell proliferation or migration, but results in cytoskeletal disruption, decreased expression and aberrant localization of E-cadherin, and decreased cell adhesion compared to wild-type Nras in culture (PMID: 32620824), and therefore, is predicted to result in a loss of Nras GTPase function.
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.
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
exon2 unknown unknown NRAS exon 2 indicates an unspecified mutation has occurred in exon 2 of the NRAS gene.
exon3 unknown unknown NRAS exon 3 indicates an unspecified mutation has occurred in exon 3 of the NRAS gene.
exon4 unknown unknown NRAS exon 4 indicates an unspecified mutation has occurred in exon 4 of the NRAS gene.
G115Efs*46 frameshift loss of function - predicted NRAS G115Efs*46 indicates a shift in the reading frame starting at amino acid 115 and terminating 46 residues downstream causing a premature truncation of the 189 amino acid Nras protein (UniProt.org). Due to the loss of the CAAX motif (PMID: 10412982), G115Efs*46 is predicted to lead to a loss of Nras protein function.
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 KRAS G12A, which results in decreased GTPase activity, loss of response to GTPase-activating proteins, and transformation of cultured cells (PMID: 6092966, PMID: 26037647).
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).
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).
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).
G12P missense loss of function - predicted NRAS G12P is a hotspot 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).
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).
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).
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).
G12X missense unknown NRAS G12X indicates any NRAS missense mutation that results in replacement of the glycine (G) at amino acid 12 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).
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).
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 2019).
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).
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).
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).
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).
G13V missense loss of function - predicted NRAS G13V is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G13V has not been characterized, but can be predicted to confer a loss of function on Nras protein based on the effects of HRAS G13V, which results in a loss of response to GTPase-activating proteins, leading to increased GTP-bound Hras in culture (PMID: 24224811).
G13X missense unknown NRAS G13X indicates any NRAS missense mutation that results in replacement of the glycine (G) at amino acid 13 by a different amino acid. NRAS codon 13 mutations are hotspot mutations that often result in decreased Nras GTPase activity and transformation of cultured cells (PMID: 17517660, PMID: 26985062).
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).
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: 30603682, PMID: 27251789), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, May 2020).
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, PMID: 22817889), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, May 2020).
I24L missense unknown NRAS I24L lies within the G domain of the Nras protein (PMID: 17384584). I24L has been identified in sequencing studies (PMID: 22495314), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, May 2020).
inact mut unknown loss of function NRAS inact mut indicates that the variant results in failure to activate NRAS downstream signaling. However, the specific amino acid change has not been identified.
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.
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.
mutant unknown unknown NRAS mutant indicates an unspecified mutation in the NRAS gene.
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.
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, May 2020).
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).
positive unknown unknown NRAS positive indicates the presence of the NRAS gene, mRNA, and/or protein.
Q129E missense unknown NRAS Q129E lies within the G domain of the Nras protein (PMID: 17384584). Q129E has been identified in the scientific literature (PMID: 31101826), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, Jul 2020).
Q150H missense unknown NRAS Q150H lies within the G domain of the Nras protein (PMID: 17384584). Q150H has been identified in sequencing studies (PMID: 28108514, PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, May 2020).
Q22K missense unknown NRAS Q22K lies within the G domain of the Nras protein (PMID: 17384584). Q22K has been identified in the scientific literature (PMID: 31795494, PMID: 27168466, PMID: 22817889), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, May 2020).
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).
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).
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).
Q61L missense loss of function NRAS Q61L is a hotspot 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).
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).
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 unknown NRAS Q61X indicates any NRAS missense mutation that results in replacement of the glutamine (Q) at amino acid 61 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).
R164C missense unknown NRAS R164C lies within the G domain of the Nras protein (PMID: 17384584). R164C has not been characterized and therefore, its effect on Nras protein function is unknown (PubMed, May 2020).
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, May 2020).
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 2020).
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).
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, May 2020).
S89A missense loss of function NRAS S89A does not lie within any known functional domains of the Nras protein (UniProt.org). S89A demonstrates loss of both Nras phosphorylation and activation of downstream signaling as compared to wild-type Nras in cell culture (PMID: 30712867).
S89D missense unknown NRAS S89D does not lie within any known functional domains of the Nras protein (UniProt.org). S89D results in cell proliferation, colony formation and activation of Nras signaling similar to wild-type Nras in culture, but results in increased NRAS signaling and colony formation when combined with NRAS Q61R (PMID: 30712867), and therefore, its effect on Nras protein function is unknown.
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).
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).
T58_A59insTDV insertion unknown NRAS T58_A59insTDV results in the insertion of three amino acids within 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, May 2020).
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, May 2020).
wild-type none no effect Wild-type NRAS indicates that no mutation has been detected within the NRAS gene.
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 GTP binding regions Y40* is predicted to lead to a loss of Nras protein function (UniProt.org).
Y64D missense unknown 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 a gene expression signature similar to wild-type Nras protein in culture in one study (PMID: 27147599), but has not been fully biochemically characterized, and therefore, its effect on Nras protein function is unknown (PubMed, Jul 2020).