Gene

NRAS

NRAS proto-oncogene, GTPase

Explore in graph →CI-GENE-00017216HGNC:7989 ENSG00000213281 NCBI 4893 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (144)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 51–100 of 144 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
NRAS Mutation10
Cetuximab	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Resistance	2

Cohorts

Alteration frequency by cohort (150)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved150 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Melanoma (Broad/Dana Farber, Nature 2012) skcm_broad_dfarber	Cutaneous Melanoma	Ssm	9

Literature

Linked publications (37)

25 per page, newest first.

pubmedPublishedShowing 1–25 of 37 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology.
· J Natl Compr Canc Netw · 2017 · PMID 28275037 · validated civic_curation pubmed
FOLFOX4 Plus Cetuximab for Patients With Previously Untreated Metastatic Colorectal Cancer According to Tumor RAS and BRAF Mutation Status: Updated Analysis of the CECOG/CORE 1.2.002 Study.
· Clin Colorectal Cancer · 2015 · PMID 25666295 · validated civic_curation pubmed
Genomic Classification and Prognosis in Acute Myeloid Leukemia.
· N Engl J Med · 2016 · PMID 27276561 · validated civic_curation pubmed
Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial.
· Lancet Oncol · 2017 · PMID 28284557 · validated

BRAF Mutation + KRAS Mutation + NRAS MutationKRAS NRAS BRAF2
(prognostic)	Colorectal Adenocarcinoma	Prognostic	B	Supports Poor Outcome	4	submitted	EID11061 The Medical Research Council (MRC) COIN trial consisted of patients with histologically confirmed adenocarcinoma of the colon or rectum, inoperable metastatic or locoregional measurable disease, and w… (full text at CIViC) PMID 21641636 · Maughan et al., 2011 · Open in CIViC	civic
Lifirafenib	Solid NeoplasmCURATED_BROADER	Predictive	B	Supports Sensitivity Response	2	submitted	EID12641 In a first in human open label phase 1 dose escalation and expansion study of lifirafenib in advanced solid tumors (NCT02610361; n = 131; BRAF-mutated n = 53, KRAS/NRAS-mutated n = 66; biomarker BRAF … (full text at CIViC) PMID 32182156 · Desai et al., 2020 · Open in CIViC	civic

BRAF Mutation + KRAS Mutation + NRAS MutationKRAS NRAS BRAF2

(prognostic)

Colorectal Adenocarcinoma

Prognostic

Supports Poor Outcome

submitted

EID11061

The Medical Research Council (MRC) COIN trial consisted of patients with histologically confirmed adenocarcinoma of the colon or rectum, inoperable metastatic or locoregional measurable disease, and w… (full text at CIViC)

PMID 21641636 · Maughan et al., 2011 · Open in CIViC

KRAS Mutation + MAP2K1 Mutation + MAP2K2 Mutation + NRAS Mutation + RAF1 MutationRAF1 MAP2K1 MAP2K2 KRAS NRAS2
Cobimetinib	Erdheim-Chester Disease	Predictive	B	Supports Sensitivity Response	4	submitted	EID11328 In an open-label, phase II trial, 18 patients with histiocytosis of any mutational status were enrolled. The overall response rate was 89% (90% CI: 73 - 100). Responses were durable, with no acquired … (full text at CIViC) PMID 30867592 · Diamond et al., 2019 · Open in CIViC	civic
〃	Langerhans Cell Histiocytosis	Predictive	B	Supports Sensitivity Response	4	submitted	EID11329 In an open-label, phase II trial, 18 patients with histiocytosis of any mutational status were enrolled. Patients received cobimetinib at a starting dose of 60 mg daily for 21 days of each 28-day cycl… (full text at CIViC) PMID 30867592 · Diamond et al., 2019 · Open in CIViC	civic

NRAS Q619
(diagnostic)	Melanoma	Diagnostic	B	Supports Positive	3	accepted	EID10 Melanoma associated with NRAS Q61 mutation was more often associated with those at the extremity than those at the trunk. PMID 23861977 · Tschandl et al., 2013 · Open in CIViC	civic
(prognostic)	Thyroid Gland Follicular CarcinomaALIAS	Prognostic	B	Supports N/A	3	accepted	EID497 In patients with follicular thyroid carcinoma, those with mutations in NRAS at codon 61 did not have significantly different overall survival than patients with wild-type NRAS (p=0.36). PMID 22650231 · Fukahori et al., 2012 · Open in CIViC	civic
〃	Thyroid Gland Follicular CarcinomaALIAS	Prognostic	B	Does Not Support Poor Outcome	2	accepted	EID6959 Follicular thyroid cancers harboring RAS mutations have limited aggressiveness in the absence of TERT mutations. 2/2 follicular thyroid cancer patients with co-mutations in NRAS (10 Q61R and 1 Q61K) o… (full text at CIViC) PMID 25448848 · Muzza et al., 2015 · Open in CIViC	civic
〃	Thyroid Gland Follicular CarcinomaALIAS	Prognostic	B	Supports Poor Outcome	2	submitted	EID7104 Retrospective analysis of thyroid carcinoma patients from a single institution identified 33/58 patients with follicular carcinomas had any RAS mutations (NRAS, KRAS, or HRAS at codons 12 or 61), 22 o… (full text at CIViC) PMID 22650231 · Fukahori et al., 2012 · Open in CIViC	civic
Binimetinib	Cutaneous MelanomaALIAS	Predictive	B	Supports Sensitivity Response	2	accepted	EID1226 Phase 2 study of MEK162 in patients with advanced melanoma and NRAS or BRAF mutation. 71 patients were enrolled, 6/30 patients with NRAS mutation had a partial response (Gln61Leu 1 Patient, Gln61Lys 9… (full text at CIViC) PMID 23414587 · Ascierto et al., 2013 · Open in CIViC	civic
Cetuximab	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Does Not Support Resistance	3	accepted	EID124 In chemotherapy-refractory patients with colorectal cancer, NRAS mutation status (primarily Q61, N=13) was not informative for disease control rate, progression free survival or overall survival follo… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
Cetuximab + ChemotherapyCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	2	accepted	EID36 Chemotherapy-refractory patients with KRAS wt metastatic colorectal cancer harboring NRAS mutation (primarily Q61, n=10) have a significantly lower response rate to cetuximab than patients wildtype fo… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
Selumetinib	Cutaneous MelanomaALIAS	Predictive	C	Supports Sensitivity Response	2	accepted	EID1473 Phase 1 trial in 57 patients with advanced cancers treated with selumetinib. 4 melanoma patients had NRAS Q61 mutations. One patient with NRAS mutation had 70% tumor shrinkage after three cycles of se… (full text at CIViC) PMID 18390968 · Adjei et al., 2008 · Open in CIViC	civic
Vemurafenib	Melanoma	Predictive	B	Supports Resistance	4	accepted	EID14 Vemurafenib resistance is associated with gain of Q61 mutation in NRAS. PMID 23569304 · Trunzer et al., 2013 · Open in CIViC	civic

NRAS Q61H11
(diagnostic)	Pleural Malignant MesotheliomaALIAS	Diagnostic	D	Supports Positive	3	submitted	EID7332 Mice that carried the Q61H variant had Malignant Pleural Mesothelioma and Lewis Lung Carincoma. The malignant cells where taken and each cell line was shown to readily promote lung colonization compar… (full text at CIViC) PMID 28341702 · Giannou et al., 2017 · Open in CIViC	civic
Belvarafenib	Melanoma	Predictive	C	Supports Resistance	2	submitted	EID13216 A patient with melanoma harboring NRAS Q61H received belvarafenib monotherapy after two prior lines of systemic therapy and had progressive disease as the best RECIST response. The patient received be… (full text at CIViC) PMID 38470950 · Kim et al., 2024 · Open in CIViC	civic
Cetuximab	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	—	rejected	EID3823 In a retrospective study of 368 chemotherapy-refractory metastatic colorectal cancer, patients with a NRAS mutation (n=13) treated with cetuximab in combination with standard chemotherapy were associa… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
Cetuximab + IrinotecanCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	2	accepted	EID3690 One patient participating in a large retrospective study of cetuximab in metastatic, treatment refractory colorectal cancer had a tumor which harbored NRAS Q61H was wildtype for KRAS, BRAF and PIK3CA.… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
Dactolisib	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Sensitivity Response	—	rejected	EID2172 NRAS mutations have also been observed in melanoma and biliary tract, bladder, cervix, liver, lung, myeloid leukemia, ovarian, pancreatic, and thyroid cancer. PMID 17384584 · Schubbert et al., 2007 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Sensitivity Response	—	rejected	EID2173 In chemotherapy-resistant colorectal cancer patients treated with cetuximab-based therapy, NRAS mutations were associated with a lower objective response (7.7% vs. 38.1%, odds ratio (OR):0.14, 95% CI:… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Sensitivity Response	—	submitted	EID2171 In 28 out of 40 (70%) metastatic colorectal cancer tumors implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the PI3K/mTor inhibitor BEZ235 resulted in disease stabiliza… (full text at CIViC) PMID 22392911 · Migliardi et al., 2012 · Open in CIViC	civic
Ipilimumab	Melanoma	Predictive	B	Supports Sensitivity Response	4	submitted	EID7333 The researchers quantified ctDNA in time-intervals during the treatment of 6 patients with stage IV melanoma. The patient carrying the NRAS Q61H mutation was started on ipilimumab and responded well. … (full text at CIViC) PMID 26095797 · Tsao et al., 2015 · Open in CIViC	civic
Selumetinib	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Sensitivity Response	—	rejected	EID2175 NRAS mutations have also been observed in melanoma and biliary tract, bladder, cervix, liver, lung, myeloid leukemia, ovarian, pancreatic, and thyroid cancer. PMID 17384584 · Schubbert et al., 2007 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Sensitivity Response	—	rejected	EID2176 In chemotherapy-resistant colorectal cancer patients treated with cetuximab-based therapy, NRAS mutations were associated with a lower objective response (7.7% vs. 38.1%, odds ratio (OR):0.14, 95% CI:… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Sensitivity Response	—	submitted	EID2174 In 28 out of 40 (70%) metastatic colorectal cancer tumors implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the PI3K/mTor inhibitor BEZ235 resulted in disease stabiliza… (full text at CIViC) PMID 22392911 · Migliardi et al., 2012 · Open in CIViC	civic

NRAS Q61K15
(predisposing)	Melanoma	Predisposing	D	Supports Likely Pathogenic	4	submitted	EID7169 Established a novel mouse model for melanoma that shows for the first time that over expression of a mutant form of human N-ras (N-RasQ61K) in melanocytes results in a hyper pigmented skin phenotype a… (full text at CIViC) PMID 15899789 · Ackermann et al., 2005 · Open in CIViC	civic
〃	Melanoma	Predisposing	D	Supports Likely Pathogenic	4	submitted	EID7172 Recent studies in mouse have also shown that NRAS Q61K is capable of promoting melanoma formation and cooperates with INK4A loss to accelerate tumor onset. PMID 19954345 · Dovey et al., 2009 · Open in CIViC	civic
Belvarafenib	Melanoma	Predictive	C	Supports Resistance	2	submitted	EID13217 Two patients with NRAS Q61K-mutant melanoma treated with belvarafenib had progressive disease as their best RECIST response. One patient progressed after 1.6 months and the other after 1.4 months of t… (full text at CIViC) PMID 38470950 · Kim et al., 2024 · Open in CIViC	civic
〃	Acral Lentiginous Melanoma	Predictive	C	Supports Sensitivity Response	2	accepted	EID13218 A patient with acral melanoma harboring NRAS Q61K received belvarafenib as first-line therapy for metastatic disease after progression on adjuvant pembrolizumab and achieved stable disease as the best… (full text at CIViC) PMID 38470950 · Kim et al., 2024 · Open in CIViC	civic
Cetuximab	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	—	submitted	EID3833 In 11 melanoma patients harboring BRAF mutations, one patient with a Q61K NRAS mutation acquired resistance to the BRAF inhibitor vemurafenib. Q61K and/or A146T NRAS mutations have also shown resista… (full text at CIViC) PMID 21107323 · Nazarian et al., 2010 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Resistance	—	submitted	EID3834 In 28 out of 40 (70%) metastatic colorectal cancer tumors implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the PI3K/mTor inhibitor BEZ235 resulted in disease stabiliza… (full text at CIViC) PMID 22392911 · Migliardi et al., 2012 · Open in CIViC	civic
Cetuximab + ChemotherapyCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	3	accepted	EID2189 Four patients participating in a large retrospective study of cetuximab in metastatic, treatment refractory colorectal cancer had tumors which harbored NRAS Q61K and were wildtype for KRAS, BRAF and P… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
Dabrafenib + TrametinibCombination	Melanoma	Predictive	B	Supports Resistance	4	submitted	EID7678 In a retrospective study, authors analyzed BRAF V600 mutated melanoma metastases derived from 10 patients treated with the combination of dabrafenib and trametinib for resistance mechanisms and geneti… (full text at CIViC) PMID 25452114 · Long et al., 2014 · Open in CIViC	civic
Dactolisib	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Sensitivity Response	—	submitted	EID2194 In 11 melanoma patients harboring BRAF mutations, one patient with a Q61K NRAS mutation acquired resistance to the BRAF inhibitor vemurafenib. Q61K and/or A146T NRAS mutations have also shown resista… (full text at CIViC) PMID 21107323 · Nazarian et al., 2010 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Sensitivity Response	—	rejected	EID2195 NRAS mutations have also been observed in melanoma and biliary tract, bladder, cervix, liver, lung, myeloid leukemia, ovarian, pancreatic, and thyroid cancer. PMID 17384584 · Schubbert et al., 2007 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Sensitivity Response	—	submitted	EID2196 In 28 out of 40 (70%) metastatic colorectal cancer tumors implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the PI3K/mTor inhibitor BEZ235 resulted in disease stabiliza… (full text at CIViC) PMID 22392911 · Migliardi et al., 2012 · Open in CIViC	civic
Dactolisib + SelumetinibCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	accepted	EID2192 In 28 out of 40 (70%) metastatic colorectal cancer tumors harboring mutations in KRAS, NRAS, BRAF, or PIK3CA and implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the P… (full text at CIViC) PMID 22392911 · Migliardi et al., 2012 · Open in CIViC	civic
Erlotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	—	submitted	EID3839 In an in vitro study, a PC-9 cell line expressing NRAS Q61K mutation demonstrated decreased sensitivity to erlotinib treatment compared to PC-9 cells expressing NRAS wild-type. Sensitivity was determi… (full text at CIViC) PMID 22773810 · Ohashi et al., 2012 · Open in CIViC	civic
Binimetinib + EverolimusCombination	Neuroblastoma	Predictive	D	Supports Sensitivity Response	3	accepted	EID1002 In-vitro study in 5 neuroblastoma cell lines (2 with NRAS Q61K mutation). The combination of mTOR and MEK Inhibitors synergistically blocked cell growth in NRAS mutant but not wild type cell lines. Si… (full text at CIViC) PMID 26821351 · Kiessling et al., 2016 · Open in CIViC	civic
Selumetinib	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Sensitivity Response	—	rejected	EID2190 NRAS mutations have also been observed in melanoma and biliary tract, bladder, cervix, liver, lung, myeloid leukemia, ovarian, pancreatic, and thyroid cancer. PMID 17384584 · Schubbert et al., 2007 · Open in CIViC	civic