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 101–144 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 Q61K11
Selumetinib	Cutaneous MelanomaALIAS	Predictive	D	Supports Sensitivity Response	2	accepted

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 G466V + NRAS Q61KNRAS BRAF2
Cetuximab	Malignant NeoplasmALIAS	Predictive	D	Supports Resistance	3	submitted	EID12450 Expression of mutant (Q61K) but not wildtype NRAS in the non-small cell lung carcinoma cell line, H1666 (BRAF G466V), resulted in reduced sensitivity to cetuximab as measured by cell growth and RAS-GT… (full text at CIViC) PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic
Trametinib	Malignant NeoplasmALIAS	Predictive	D	Does Not Support Resistance	3	submitted	EID12451 Expression of mutant (Q61K) but not wildtype NRAS in the non-small cell lung carcinoma cell line, H1666 (BRAF G466V), resulted in reduced sensitivity to cetuximab but not trametinib as measured by cel… (full text at CIViC) PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic

BRAF G466V + NRAS Q61KNRAS BRAF2

Cetuximab

Malignant NeoplasmALIAS

Predictive

Supports Resistance

submitted

EID12450

Expression of mutant (Q61K) but not wildtype NRAS in the non-small cell lung carcinoma cell line, H1666 (BRAF G466V), resulted in reduced sensitivity to cetuximab as measured by cell growth and RAS-GT… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

NRAS Q61L11
Belvarafenib	Mucosal Melanoma	Predictive	C	Supports Sensitivity Response	2	accepted	EID13215 A patient with mucosal melanoma harboring NRAS Q61L received belvarafenib monotherapy after five prior lines of systemic therapy and achieved a confirmed partial response by RECIST. The patient receiv… (full text at CIViC) PMID 38470950 · Kim et al., 2024 · Open in CIViC	civic
Cetuximab + IrinotecanCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	3	accepted	EID2181 Two patients participating in a large retrospective study of cetuximab in metastatic, treatment refractory colorectal cancer had tumors which harbored NRAS Q61L and were wildtype for KRAS, BRAF and PI… (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	EID2179 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	EID2177 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
Pan-RAF/MEK Molecular Glue NST-628	Melanoma	Predictive	D	Supports Sensitivity Response	4	submitted	EID13154 In the NRAS Q61L-mutant IPC-298 melanoma model, NST-628 inhibited cell viability and induced apoptosis in vitro. In IPC-298 xenografts, NST-628 at 5 mg/kg once daily or 1.5 mg/kg twice daily produced … (full text at CIViC) PMID 38588399 · Ryan et al., 2024 · Open in CIViC	civic
Selumetinib	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Sensitivity Response	—	rejected	EID2182 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	EID2180 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
Temozolomide	Melanoma	Predictive	C	Supports Sensitivity Response	2	accepted	EID22 In a melanoma patient with NRAS Q61L mutation, treatment with temozolomide resulted in disease free survival of 14 months. PMID 21576590 · Soon et al., 2011 · Open in CIViC	civic
Selumetinib + TrametinibSubstitutes	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	2	submitted	EID3018 Of the 4,562 patients with lung cancers, 30 showed NRAS mutations, which corresponded to 9 different amino acid substitutions. Cell lines were developed for 6 of these mutations and 5/6 were sensitivi… (full text at CIViC) PMID 23515407 · Ohashi et al., 2013 · Open in CIViC	civic
Vemurafenib	Melanoma	Predictive	C	Supports Resistance	—	submitted	EID3825 In a retrospective study of 44 malignant melanoma patients, NRAS Q61L was associated with acquired resistance to vemurafenib monotherapy in one patient with disease progressive tumors harboring NRAS Q… (full text at CIViC) PMID 24265155 · Shi et al., 2014 · Open in CIViC	civic
〃	Melanoma	Predictive	D	Supports Resistance	—	submitted	EID3826 In an in vitro study, the YULOVY and YUFULO cell lines expressing NRAS Q61L were associated with reduced sensitivity to vemurafenib (PLX4032) treatment, as compared to cells expressing wild-type BRAF.… (full text at CIViC) PMID 20149136 · Halaban et al., 2010 · Open in CIViC	civic

NRAS Q61R16
(functional)	—UNRESOLVED	Functional	D	Supports Gain Of Function	5	submitted	EID12978 NRAS p.Gln61Arg (NM_002524.5:c.182A>G) causes decreased GTPase activity, and impaired nucleotide exchange. PMID 25252692 · Burd et al., 2014 · Open in CIViC	civic
〃	—UNRESOLVED	Functional	D	Supports Gain Of Function	5	submitted	EID12979 NRAS p.Gln61Arg (NM_002524.5:c.182A>G) causes increased pERK/ERK ratio, and increased BRAF binding affinity. PMID 35672316 · Murphy et al., 2022 · Open in CIViC	civic
Belvarafenib	Melanoma	Predictive	C	Supports Resistance	2	submitted	EID13219 A patient with cutaneous melanoma harboring NRAS Q61R received belvarafenib monotherapy after two prior lines of systemic therapy and had progressive disease as the best RECIST response. The patient r… (full text at CIViC) PMID 38470950 · Kim et al., 2024 · Open in CIViC	civic
〃	Melanoma	Predictive	C	Supports Sensitivity Response	2	accepted	EID13220 A patient with melanoma harboring NRAS Q61R received belvarafenib monotherapy after one prior line of systemic therapy and achieved stable disease as the best RECIST response. At the October 2023 data… (full text at CIViC) PMID 38470950 · Kim et al., 2024 · Open in CIViC	civic
Cetuximab	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	2	accepted	EID2184 Five patients participating in a large retrospective study of cetuximab in metastatic, treatment refractory colorectal cancer had tumors which harbored NRAS Q61R and were wildtype for KRAS, BRAF and P… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Resistance	—	submitted	EID3828 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	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Sensitivity Response	—	rejected	EID2188 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	EID2186 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
Pan-RAF/MEK Molecular Glue NST-628	Melanoma	Predictive	D	Supports Sensitivity Response	4	submitted	EID13155 In NRAS Q61R-mutant SK-MEL-2 melanoma cells, NST-628 showed potent antiproliferative activity, increased apoptosis, and durably suppressed MAPK-pathway signaling. In an intracranial SK-MEL-2-luc xenog… (full text at CIViC) PMID 38588399 · Ryan et al., 2024 · Open in CIViC	civic
Selumetinib	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Sensitivity Response	—	rejected	EID2185 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
Temozolomide	Melanoma	Predictive	C	Supports Sensitivity Response	2	accepted	EID23 In a melanoma patient with Q61R mutation, treatment with temozolomide resulted in overall survival of 16 months. PMID 21576590 · Soon et al., 2011 · Open in CIViC	civic
Selumetinib + TrametinibSubstitutes	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	2	submitted	EID3019 Of the 4,562 patients with lung cancers, 30 showed NRAS mutations, which corresponded to 9 different amino acid substitutions. Cell lines were developed for 6 of these mutations and 5/6 were sensitivi… (full text at CIViC) PMID 23515407 · Ohashi et al., 2013 · Open in CIViC	civic
Vemurafenib	Melanoma	Predictive	C	Supports Resistance	—	submitted	EID3829 In a retrospective study of 44 malignant melanoma patients, NRAS Q61R was associated with acquired resistance to vemurafenib monotherapy in three patients with disease progressive tumors harboring NRA… (full text at CIViC) PMID 24265155 · Shi et al., 2014 · Open in CIViC	civic
〃	Malignant NeoplasmALIAS	Predictive	D	Supports Resistance	3	submitted	EID12438 Several BRAF mutant cell lines were treated with vemurafenib, A375 (BRAF V600E) was used as a positive control. The SK-MEL-2 cell line (NRAS Q61R) was not inhibited. PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic
〃	Cutaneous MelanomaALIAS	Predictive	D	Supports Resistance	—	submitted	EID3830 In an in vitro study of single-cell clones derived from a cutaneous melanoma patient expressing a BRAF V600E mutation (a known sensitizing mutation to vemurafenib) and NRAS Q61R co-mutations, NRAS Q61… (full text at CIViC) PMID 23948972 · Romano et al., 2013 · Open in CIViC	civic
〃	Thyroid Gland Carcinoma	Predictive	D	Supports Resistance	—	submitted	EID3831 In an in vitro study, a HTH7 cell line expressing NRAS Q61R demonstrated reduced sensitivity to vemurafenib treatment, compared to BRAF V600E expressing cells (8505C, SWI1736, BHT101 and BCPAP). Sensi… (full text at CIViC) PMID 19880792 · Salerno et al., 2010 · Open in CIViC	civic

NRAS Wildtype4
Cetuximab	Malignant Breast Neoplasm	Predictive	B	Does Not Support Sensitivity Response	3	submitted	EID11656 In a clinical study of 49 patients, 10 patients with Breast Cancer (BC) and wild-type NRAS gene were treated with Cetuximab. After 16 weeks, no clinical activity was observed. PFS of 6.7 weeks (95% CI… (full text at CIViC) PMID 33090333 · Fisher et al., 2020 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Does Not Support Sensitivity Response	3	submitted	EID11660 In a clinical study of 49 patients, 10 patients with Non-Small Cell Lung Cancer (NSCLC) and wild-type NRAS gene were treated with Cetuximab. After 16 weeks, no clinical activity was observed. A PFS of… (full text at CIViC) PMID 33090333 · Fisher et al., 2020 · Open in CIViC	civic
〃	Malignant Ovarian Neoplasm	Predictive	B	Does Not Support Sensitivity Response	3	submitted	EID11662 In a clinical study of 49 patients, 29 patients with Ovarian Cancer and wild-type NRAS gene were treated with Cetuximab. After 16 weeks, no clinical activity was observed. A PFS of 8 weeks (95% CI, 6.… (full text at CIViC) PMID 33090333 · Fisher et al., 2020 · Open in CIViC	civic
Chemotherapy + PanitumumabCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	A	Supports Sensitivity Response	4	submitted	EID11270 In this phase III, randomized, open-label trial, 377 patients with wild-type KRAS exon two were randomized 1:1 to receive panitumumab 6 mg/kg IV on day 1 of each 14-day cycle plus BSC or BSC alone. Th… (full text at CIViC) PMID 27736842 · Kim et al., 2016 · Open in CIViC	civic