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Gene NRAS
Variant Q129E
Impact List missense
Protein Effect unknown
Gene Variant Descriptions 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).
Associated Drug Resistance

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Transcript NM_002524
gDNA chr1:g.114709634G>C
cDNA c.385C>G
Protein p.Q129E
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_002524 chr1:g.114709634G>C c.385C>G p.Q129E RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
NRAS exon4 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 exon4 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 exon4 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 exon4 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 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 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 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 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 acute myeloid leukemia predicted - resistant Vemurafenib Preclinical - Patient cell culture Actionable In a preclinical study, NRAS mutations correlated with resistance to Zelboraf (vemurafenib) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). 30333627
NRAS mutant lung non-small cell 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 colorectal cancer no benefit Cetuximab + Fluorouracil + Irinotecan + Leucovorin 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 melanoma predicted - sensitive Cobimetinib + UNC2025 Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of UNC2025 and Cotellic (cobimetinib) resulted in greater inhibition of colony formation and apoptotic induction in melanoma cells harboring an NRAS mutation in culture when compared to either therapy alone (PMID: 30482852). 30482852
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 acute myeloid leukemia predicted - resistant Tivozanib Preclinical - Patient cell culture Actionable In a preclinical study, NRAS mutations correlated with resistance to Tivozanib (AV-951) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). 30333627
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 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 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 sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, NRAS-mutant melanoma cell lines were sensitive to treatment with Mekinist (trametinib) in culture, demonstrating decreased cell viability, colony formation, and pathway activity, and increased cell cycle arrest (PMID: 30819666). 30819666
NRAS mutant melanoma 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; NCT00687622). 22805292
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 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 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, Adavosertib (MK-1775) showed efficacy in NRAS mutant melanoma and in mutant KRAS colorectal, pancreatic, and lung cancers (PMID: 24791855). 24791855
NRAS mutant melanoma predicted - sensitive Belvarafenib Phase I Actionable In Phase I trials, Belvarafenib (HM95573) treatment resulted in partial response in 44% (4/9) of patients with NRAS-mutant melanoma in a dose escalation study, and partial response in 22% (2/9) of NRAS-mutant melanoma patients in a dose expansion study (J Clin Oncol 37, 2019 (suppl; abstr 3000); NCT02405065, NCT03118817). detail...
NRAS mutant melanoma predicted - sensitive Belvarafenib Case Reports/Case Series Actionable In a Phase I trial, Belvarafenib (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 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 predicted - sensitive Nivolumab Clinical Study - Cohort Actionable In a clinical study, NRAS mutations were associated with higher 6-month objective response rate (53.3% vs. 19.6% without NRAS mutations; p=0.019) following treatment with Keytruda (pembrolizumab) or Opdivo (nivolumab) in patients with metastatic melanoma, however, progression-free survival and overall survival were similar between patients with and without NRAS mutations (PMID: 29973670). 29973670
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 melanoma predicted - sensitive Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cell lines harboring an NRAS mutation were sensitive to the combination therapy of Ibrance (palbociclib) and Mekinist (trametinib) in culture, demonstrating reduced cell viability, colony formation, and pathway activity, and increased cell cycle arrest (PMID: 30819666). 30819666
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 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 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 skin melanoma sensitive Binimetinib Guideline Actionable Mektovi (binimetinib) is included in guidelines as second-line therapy for patients with metastatic or unresectable cutaneous melanoma harboring an NRAS mutation (NCCN.org). detail...
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 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 melanoma sensitive Binimetinib + Buparlisib 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 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 melanoma conflicting Palbociclib Preclinical - Cell culture Actionable In a preclinical study, NRAS-mutant melanoma cell lines were sensitive to treatment with Ibrance (palbociclib) in culture, demonstrating decreased cell viability, colony formation, and pathway activity, and increased cell cycle arrest (PMID: 30819666). 30819666
NRAS mutant melanoma conflicting 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 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 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 colorectal cancer no benefit Regorafenib Phase II Actionable In a Phase II clinical trial (PREVIUM), Stivarga (regorafenib) treatment resulted in 0% (0/15) 6-month progression free survival (PFS), a 2.2-month median PFS, and a median overall survival of 3.3 months in metastatic colorectal cancer patients with KRAS (n=9), NRAS (n=3) or BRAF (n=2) mutations who failed first line therapy; however, the trial was terminated early due to poor accrual (PMID: 30120161; NCT02175654). 30120161
NRAS mutant Advanced Solid Tumor no benefit LY3009120 Case Reports/Case Series Actionable In a Phase I trial, LY3009120 did not achieve expected pharmacodynamic effects, resulted in stable disease as best overall response in 1 of 5 patients with advanced or metastatic cancer harboring NRAS mutations (PMID: 31645440; NCT02014116). 31645440
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 acute myeloid leukemia predicted - resistant Pazopanib Preclinical - Patient cell culture Actionable In a preclinical study, NRAS mutations correlated with resistance to Votrient (pazopanib) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). 30333627
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 melanoma sensitive Palbociclib + PD-0325901 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 melanoma predicted - sensitive Pembrolizumab Clinical Study - Cohort Actionable In a clinical study, NRAS mutations were associated with higher 6-month objective response rate (53.3% vs. 19.6% without NRAS mutations; p=0.019) following treatment with Keytruda (pembrolizumab) or Opdivo (nivolumab) in patients with metastatic melanoma, however, progression-free survival and overall survival were similar between patients with and without NRAS mutations (PMID: 29973670). 29973670
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 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 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 leukemia sensitive Belvarafenib Preclinical - Cell culture Actionable In a preclinical study, Belvarafenib (HM95573) inhibited growth of NRAS mutant leukemia cells in culture (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). detail...
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 thyroid gland 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
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
Molecular Profile Protein Effect Treatment Approaches
NRAS Q129E unknown