Gene: NRAS
Alternate names for this Gene: ALPS4|CMNS|N-ras|NCMS|NRAS1|NS6
Gene Summary: This is an N-ras oncogene encoding a membrane protein that shuttles between the Golgi apparatus and the plasma membrane. This shuttling is regulated through palmitoylation and depalmitoylation by the ZDHHC9-GOLGA7 complex. The encoded protein, which has intrinsic GTPase activity, is activated by a guanine nucleotide-exchange factor and inactivated by a GTPase activating protein. Mutations in this gene have been associated with somatic rectal cancer, follicular thyroid cancer, autoimmune lymphoproliferative syndrome, Noonan syndrome, and juvenile myelomonocytic leukemia.
Gene is located in Chromosome: 1
Location in Chromosome : 1p13.2
Description of this Gene: NRAS proto-oncogene, GTPase
Type of Gene: protein-coding
rs11554290 in
NRAS gene and
Adenocarcinoma of lung (disorder)
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs11554290 in
NRAS gene and
Adrenocortical carcinoma
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs7549358 in
NRAS gene and
Body mass index
PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.
rs11554290 in
NRAS gene and
Brain Neoplasms
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs11554290 in
NRAS gene and
Chronic Lymphocytic Leukemia
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs11554290 in
NRAS gene and
Colorectal Neoplasms
PMID 20736745 2010 NRAS mutations are rare in colorectal cancer.
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
PMID 21305640 2011 Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer.
PMID 17699718 2007 AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models.
PMID 21729679 2011 Development of molecular biomarkers in individualized treatment of colorectal cancer.
PMID 20619739 2010 Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis.
PMID 16273091 2006 BRAF mutation predicts sensitivity to MEK inhibition.
PMID 21829508 2011 PIK3CA mutations frequently coexist with RAS and BRAF mutations in patients with advanced cancers.
PMID 25157968 2014 Prospective enterprise-level molecular genotyping of a cohort of cancer patients.
rs11554290 in
NRAS gene and
Cutaneous Melanoma
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs121434595 in
NRAS gene and
GIANT PIGMENTED HAIRY NEVUS
PMID 18633438 2009 Genotypic and gene expression studies in congenital melanocytic nevi: insight into initial steps of melanotumorigenesis.
PMID 23392294 2013 Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS.
rs11554290 in
NRAS gene and
Gastric Adenocarcinoma
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs11554290 in
NRAS gene and
Glioblastoma
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs121434596 in
NRAS gene and
Juvenile Myelomonocytic Leukemia
PMID 24493721 2014 American Society of Clinical Oncology Expert Statement: collection and use of a cancer family history for oncology providers.
PMID 17332249 2007 Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations.
PMID 10598665 2000 Juvenile myelomonocytic leukemia and Noonan syndrome.
PMID 19047918 2009 Correlation of clinical features with the mutational status of GM-CSF signaling pathway-related genes in juvenile myelomonocytic leukemia.
PMID 16518851 2006 Mutations of the PTPN11 and RAS genes in rhabdomyosarcoma and pediatric hematological malignancies.
PMID 19966803 2010 A restricted spectrum of NRAS mutations causes Noonan syndrome.
PMID 17384584 2007 Hyperactive Ras in developmental disorders and cancer.
rs11554290 in
NRAS gene and
Leukemia, Myelocytic, Acute
PMID 16434492 2006 Implications of NRAS mutations in AML: a study of 2502 patients.
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
PMID 19075190 2009 High-throughput sequencing screen reveals novel, transforming RAS mutations in myeloid leukemia patients.
PMID 2278970 1990 RAS gene mutations in childhood acute myeloid leukemia: a Pediatric Oncology Group study.
PMID 22407852 2012 RAS mutations are frequent in FAB type M4 and M5 of acute myeloid leukemia, and related to late relapse: a study of the Japanese Childhood AML Cooperative Study Group.
PMID 3122217 1987 RAS gene mutations in acute and chronic myelocytic leukemias, chronic myeloproliferative disorders, and myelodysplastic syndromes.
PMID 19657110 2009 Recurring mutations found by sequencing an acute myeloid leukemia genome.
PMID 22144181 2012 Inhibiting the palmitoylation/depalmitoylation cycle selectively reduces the growth of hematopoietic cells expressing oncogenic Nras.
PMID 25157968 2014 Prospective enterprise-level molecular genotyping of a cohort of cancer patients.
rs11554290 in
NRAS gene and
Liver carcinoma
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs121434595 in
NRAS gene and
Lymphoma, Non-Hodgkin, Familial
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs121434595 in
NRAS gene and
MYELODYSPLASTIC SYNDROME
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs11554290 in
NRAS gene and
Malignant Uterine Corpus Neoplasm
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs121434595 in
NRAS gene and
Medulloblastoma
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs11554290 in
NRAS gene and
Multiple Myeloma
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs121913250 in
NRAS gene and
Myeloid Leukemia, Chronic
PMID 23134356 2012 Progression of RAS-mutant leukemia during RAF inhibitor treatment.
PMID 25157968 2014 Prospective enterprise-level molecular genotyping of a cohort of cancer patients.
rs121913237 in
NRAS gene and
NEVUS, EPIDERMAL (disorder)
PMID 22499344 2012 Keratinocytic epidermal nevi are associated with mosaic RAS mutations.
rs11554290 in
NRAS gene and
Nasopharyngeal Neoplasms
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs121434596 in
NRAS gene and
Neoplasms
PMID 25157968 2014 Prospective enterprise-level molecular genotyping of a cohort of cancer patients.
rs121913254 in
NRAS gene and
Neurocutaneous melanosis
PMID 23392294 2013 Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS.
rs11554290 in
NRAS gene and
Non-Small Cell Lung Carcinoma
PMID 14508525 2003 BRAF mutations in papillary carcinomas of the thyroid.
PMID 22773810 2012 Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1.
PMID 19880792 2010 Cytostatic activity of adenosine triphosphate-competitive kinase inhibitors in BRAF mutant thyroid carcinoma cells.
PMID 23515407 2013 Characteristics of lung cancers harboring NRAS mutations.
PMID 18948947 2008 Somatic mutations affect key pathways in lung adenocarcinoma.
PMID 1654209 1991 ras gene mutations in non-small cell lung cancers are associated with shortened survival irrespective of treatment intent.
PMID 12460918 2002 BRAF and RAS mutations in human lung cancer and melanoma.
PMID 6587382 1984 Mechanism of activation of an N-ras oncogene of SW-1271 human lung carcinoma cells.
PMID 24370118 2014 Genetic mutation screen in early non--small-cell lung cancer (NSCLC) specimens.
PMID 18794081 2008 Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma.
rs121913237 in
NRAS gene and
Noonan Syndrome
PMID 14982869 2004 Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia.
PMID 15831708 2005 Repressible transgenic model of NRAS oncogene-driven mast cell disease in the mouse.
PMID 15046639 2004 Constitutive activation of the Ras-Raf signaling pathway in metastatic melanoma is associated with poor prognosis.
PMID 18952898 2009 RAS oncogene suppression induces apoptosis followed by more differentiated and less myelosuppressive disease upon relapse of acute myeloid leukemia.
PMID 19966803 2010 A restricted spectrum of NRAS mutations causes Noonan syndrome.
PMID 16518851 2006 Mutations of the PTPN11 and RAS genes in rhabdomyosarcoma and pediatric hematological malignancies.
PMID 17384584 2007 Hyperactive Ras in developmental disorders and cancer.
PMID 19047918 2009 Correlation of clinical features with the mutational status of GM-CSF signaling pathway-related genes in juvenile myelomonocytic leukemia.
PMID 10598665 2000 Juvenile myelomonocytic leukemia and Noonan syndrome.
PMID 21263000 2011 Recently, two mutations in NRAS were reported to be associated with Noonan syndrome, T50I and G60E.
rs267606920 in
NRAS gene and
Noonan Syndrome 6
PMID 19966803 2010 A restricted spectrum of NRAS mutations causes Noonan syndrome.
PMID 20876176 2010 Noonan syndrome: clinical features, diagnosis, and management guidelines.
rs121434596 in
NRAS gene and
RAS-ASSOCIATED AUTOIMMUNE LEUKOPROLIFERATIVE DISORDER
PMID 17517660 2007 NRAS mutation causes a human autoimmune lymphoproliferative syndrome.
rs11554290 in
NRAS gene and
Renal Cell Carcinoma
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs11554290 in
NRAS gene and
Serous cystadenocarcinoma ovary
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs121434595 in
NRAS gene and
Stomach Neoplasms
PMID 25157968 2014 Prospective enterprise-level molecular genotyping of a cohort of cancer patients.
rs11554290 in
NRAS gene and
Thyroid Neoplasm
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs11554290 in
NRAS gene and
Transitional cell carcinoma of bladder
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs1057519695 in
NRAS gene and
melanoma
PMID 8120410 1994 Ras mutations in human melanoma: a marker of malignant progression.
PMID 23538902 2013 Inhibition of Wee1, AKT, and CDK4 underlies the efficacy of the HSP90 inhibitor XL888 in an in vivo model of NRAS-mutant melanoma.
PMID 2674680 1989 N-ras mutations in human cutaneous melanoma from sun-exposed body sites.
PMID 22761467 2012 First-in-human, phase I dose-escalation study of the safety, pharmacokinetics, and pharmacodynamics of RO5126766, a first-in-class dual MEK/RAF inhibitor in patients with solid tumors.
PMID 23569304 2013 Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma.
PMID 23614898 2013 Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors.
PMID 20179705 2010 RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF.
PMID 23414587 2013 MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study.
PMID 20406486 2010 Differential sensitivity of melanoma cell lines with BRAFV600E mutation to the specific Raf inhibitor PLX4032.
PMID 25157968 2014 Prospective enterprise-level molecular genotyping of a cohort of cancer patients.
PMID 20130576 2010 RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth.
PMID 18390968 2008 Phase I pharmacokinetic and pharmacodynamic study of the oral, small-molecule mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancers.
PMID 16291983 2005 Distinct sets of genetic alterations in melanoma.
PMID 20149136 2010 Furthermore, PLX4032 increased the rate of proliferation of growth factor-dependent NRAS Q61L mutant primary melanoma cells, reduced cell adherence and increased mobility of cells from advanced lesions.
PMID 21576590 2011 NRAS-mutant melanoma: response to chemotherapy.
PMID 21107323 2010 Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation.
PMID 22962325 2012 Intratumoral molecular heterogeneity in a BRAF-mutant, BRAF inhibitor-resistant melanoma: a case illustrating the challenges for personalized medicine.
PMID 18375819 2008 BRAF and NRAS mutations in melanoma: potential relationships to clinical response to HSP90 inhibitors.
PMID 23431193 2013 Combined targeting of MEK and PI3K/mTOR effector pathways is necessary to effectively inhibit NRAS mutant melanoma in vitro and in vivo.
PMID 24918823 2014 Correlation of BRAF and NRAS mutation status with outcome, site of distant metastasis and response to chemotherapy in metastatic melanoma.
PMID 23076151 2012 We generated mutant BRAF(V600E) melanoma cells that exhibit resistance to PLX4720, the tool compound for vemurafenib, that co-expressed mutant (Q61K) NRAS.
PMID 23076151 2012 SHOC2 and CRAF mediate ERK1/2 reactivation in mutant NRAS-mediated resistance to RAF inhibitor.