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Gene Symbol NRAS
Synonyms ALPS4 | CMNS | KRAS | 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).
NCBI Gene ID Chromosome Map Location Canonical Transcript Gene Role
4893 1 1p13.2 NM_002524 Oncogene (PMID: 30606230)

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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, Dec 2023).
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 characterized, but can be predicted to lead to a gain of Nras protein 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 no effect - predicted NRAS A18T lies within a GTP-binding region of the Nras protein (UniProt.org). A18T results in MAPK/ERK pathway activation similar to wild-type Nras in an in vitro assay (PMID: 34117033), and therefore, is predicted to have no effect on Nras protein function.
A59T missense gain of function - predicted NRAS A59T lies within the GTP-binding domain of the Nras protein (UniProt.org). A59T has not been characterized, but can be predicted to lead to a gain of Nras function based on the effects of HRAS A59T, which results in increased nucleotide exchange rate and transformation of cultured cells (PMID: 21779495, PMID: 3004741).
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, Dec 2023).
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, Dec 2023).
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, Dec 2023).
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, Dec 2023).
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, Dec 2023).
D57A missense unknown NRAS D57A lies within a GTP-binding region of the Nras protein (UniProt.org). D57A results in increased phosphorylation of Akt in the presence of growth factor but loss of enrichment in the GTP-bound state and does not activate the MAPK pathway in cultured cells (PMID: 34215961), and therefore, its effect on Nras protein function is unknown.
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 lead to 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: 6087162, PMID: 21924373), E162* is predicted to lead to a loss of Nras protein function resulting in inactivation of downstream signaling.
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: 6087162, PMID: 21924373), G115Efs*46 is predicted to lead to a loss of Nras protein function resulting in inactivation of downstream signaling.
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 to the 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 to the 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 to the 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 characterized, 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 NRAS G12R is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G12R results in increased MAPK/ERK pathway activation in an in vitro assay, is transforming in culture (PMID: 34117033), and is predicted to lead to a loss of Nras protein function based on the effects of HRAS G12R (PMID: 3042780, PMID: 6092966).
G12S missense loss of function - predicted NRAS G12S is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G12S results in increased Erk phosphorylation and cell proliferation, is transforming in culture (PMID: 17823240), and is predicted to lead to a loss of Nras protein function based on the effects of HRAS G12S (PMID: 24224811, PMID: 21850009, PMID: 6330729).
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 G12 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 to the 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, Dec 2023).
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 to the 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).
G13F missense unknown NRAS G13F lies within a GTP-binding region of the Nras protein (UniProt.org). G13F has been identified in sequencing studies (PMID: 26189770), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, Dec 2023).
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 results in increased MAPK/ERK pathway activation in an in vitro assay, is transforming in culture (PMID: 34117033), and can be predicted to lead to a loss of Nras protein function based on the effects of other NRAS G13 mutations.
G13S missense gain 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 lead to a gain of Nras protein function and activation of downstream signaling based on the effects of HRAS G13S (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 to the 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 G13 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 loss of function - predicted NRAS G60R lies within a GTP binding region of the Nras protein (UniProt.org). G60R has not been characterized, but can be predicted to lead to a loss of Nras protein function and activation of downstream signaling based on the effects of KRAS G60R (PMID: 20949621).
G60V missense unknown NRAS G60V lies within a GTP binding region of the Nras protein (UniProt.org). G60V has been identified in the scientific literature (PMID: 35494035, PMID: 30177804, PMID: 33588147), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, Dec 2023).
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, Dec 2023).
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, Dec 2023).
I24N missense loss of function - predicted NRAS I24N lies within the G domain of the Nras protein (PMID: 17384584). I24N results in autoactivation of Sos comparable to wild-type Nras under an autoinhibitory-free condition of Sos, but leads to deregulation of Sos activation under an autoinhibitory condition of Sos in an in vitro assay (PMID: 32753483), and results in increased GTP-bound Nras and activation of downstream signaling in cell culture, demonstrated by increased phosphorylation of Mek, and impaired cell migration in a zebrafish model (PMID: 21263000), and therefore, is predicted to lead to a loss of Nras protein function.
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 NRAS K135N lies within the G domain of the Nras protein (PMID: 17384584). K135N results in similar cell proliferation and viability levels to wild-type Nras in cultured cells (PMID: 29533785, PMID: 34117033) and shows similar MAPK/ERK pathway activation to wild-type Nras in an in vitro assay (PMID: 34117033).
L95H missense unknown NRAS L95H does not lie within any known functional domains of the Nras protein (UniProt.org). L95H has been identified in the scientific literature (PMID: 37258666), but has not been biochemically characterized and therefore, its effect on Nras protein function is unknown (PubMed, Jan 2024).
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, Dec 2023).
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 and inactivation of downstream signaling based on the effect of KRAS P34L (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, Dec 2023).
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, Dec 2023).
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, Dec 2023).
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 to the Nras protein leading to activation of downstream signaling based on the effect of HRAS Q61E, which results in decreased GTPase activity and cell transformation in culture (PMID: 3510078).
Q61H missense loss of function - predicted NRAS Q61H is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). Q61H results in increased GTP-bound Nras, downstream pathway activation, and increased cell proliferation in culture (PMID: 23103856), and is predicted to lead to a loss of Nras protein function based on the effects of HRAS Q61H (PMID: 3510078) and KRAS Q61H (PMID: 20147967).
Q61K missense loss of function - predicted NRAS Q61K is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). Q61K results in activation of downstream pathway signaling, increased survival, and transformation of cultured cells (PMID: 22718121, PMID: 34117033, PMID: 33431353), and is predicted to lead to a loss of Nras protein function based on the effects of HRAS Q61K (PMID: 3510078).
Q61L missense loss of function - predicted NRAS Q61L is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). Q61L results in increase Erk and Mek phosphorylation, and activation of Ck2alpha in cell culture (PMID: 27251789), and is predicted to lead to a loss of Nras protein function based on the effects of HRAS Q61L (PMID: 23487764) and KRAS Q61L (PMID: 26037647).
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 to the Nras protein based on the effect of HRAS Q61P, which results in decreased GTPase activity and activation of downstream signaling (PMID: 3510078).
Q61R missense loss of function - predicted NRAS Q61R is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). Q61R results in increased GTP-bound Nras, which leads to activation of Mapk signaling and cell transformation in culture (PMID: 16818621, PMID: 34117033), and is predicted to lead to a loss of GTPase activity based on the effect of HRAS Q61R (PMID: 3510078).
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 Q61 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 no effect - predicted NRAS R164C lies within the G domain of the Nras protein (PMID: 17384584). R164C results in MAPK/ERK pathway activation similar to wild-type Nras in an in vitro assay (PMID: 34117033), and therefore, is predicted to have no effect on Nras protein function.
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, Dec 2023).
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, Dec 2023).
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 is predicted to confer a loss of function to the Nras protein 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, Dec 2023).
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 increases 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), and therefore, is predicted to lead to a gain of Nras protein function.
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, Dec 2023).
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, Dec 2023).
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 (UniProt.org), Y40* is predicted to lead to a loss of Nras protein function resulting in inactivation of downstream signaling.
Y64D missense loss of function - 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 a gene expression signature similar to wild-type Nras protein in culture in one study (PMID: 27147599), and is predicted to lead to a loss of Nras protein function based on the effects of HRAS Y64D, which results in a loss of Hras GTPase activity in in vitro assays and failure to transform cells in culture (PMID: 1730690).