Atlas of Genetics and Cytogenetics in Oncology and Haematology

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NRAS (neuroblastoma RAS viral oncogene homolog)

Written1999-02Franz Watzinger, Thomas Lion
Children's Cancer Research Institute (CCRI), Kinderspitalgasse 6, A-1090 Vienna, Austria

(Note : for Links provided by Atlas : click)


Alias (NCBI)N-RAS (neuroblastoma RAS viral oncogene homolog)
HGNC Alias symbN-ras
HGNC Previous nameneuroblastoma RAS viral (v-ras) oncogene homolog
 neuroblastoma RAS viral oncogene homolog
LocusID (NCBI) 4893
Atlas_Id 92
Location 1p13.2  [Link to chromosome band 1p13]
Location_base_pair Starts at 114704469 and ends at 114716771 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping NRAS.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
SS18 (18q11.2) / NRAS (1p13.2)
Note more on the RAS family is available as a deep insight


  evolution of two N-ras mRNA transcripts
the slightly differing consensus sequence of the poly A addition site (AATATA instead of AATAAA) leads to inefficient processing and to two different RNA transcripts; exons that encode protein are shown as black boxes, untranslated exons as white boxes; the upstream untranslated exon is indicated as Exon -1
Description consists of seven exons, spread over 8kb of genomic DNA
Transcription inefficient processing of pre-mRNA reveals two different transcripts of 4.3kb and 2kb (see Fig), differing in the extension of the 3 end of the smaller message; the longer transcript is probably a result of an RNA-extension through the termination site


Description p21N-ras; regular RAS protein - characterized in the page
Expression ubiquitously expressed
Localisation anchored to the inner surface of the plasma membrane
Function analogously to other GTP-binding proteins (such as Translation Elongation Factor EFTu or signal transducing G-Proteins) RAS proteins are involved in signal transduction pathways
Homology ras gene family is part of the ras superfamily including the mammalian RAS, RAL, RAC, RHO, RAP, and RAB gene families and the yeast homologs like SEC4 and YPT1 genes; genes encode small monomeric proteins of low molecular mass (20-30 kDa) which share at least 30% homology to RAS proteins

Implicated in

Entity tumor (frequency of N-RAS mutations); references in Full Bibliography
Entity acute non lymphocytic leukemia and myelodysplasia (20-40%)
Entity chronic myelogenous leukemia, acute lymphocytic leukemia (0-10%)
Entity brain (0-15%)
Entity skin (0-20%)
Entity thyroid (0-60%)
Entity testis (0-40%)
Entity stomach (gastric tumors) (5%)
Entity testis liver (0-15%)


Transforming ras genes from human melanoma: a manifestation of tumour heterogeneity?
Albino AP, Le Strange R, Oliff AI, Furth ME, Old LJ
Nature. 1984 ; 308 (5954) : 69-72.
PMID 6700714
Incidence of ras gene mutations in neuroblastoma.
Ballas K, Lyons J, Janssen JW, Bartram CR
European journal of pediatrics. 1988 ; 147 (3) : 313-314.
PMID 3292251
ras oncogenes: their role in neoplasia.
Barbacid M
European journal of clinical investigation. 1990 ; 20 (3) : 225-235.
PMID 2114981
ras oncogenes in human cancer: a review.
Bos JL
Cancer research. 1989 ; 49 (17) : 4682-4689.
PMID 2547513
Ras oncogene mutations in thyroid tumors: polymerase chain reaction-restriction-fragment-length polymorphism analysis from paraffin-embedded tissues.
Capella G, Matias-Guiu X, Ampudia X, de Leiva A, Perucho M, Prat J
Diagnostic molecular pathology : the American journal of surgical pathology, part B. 1996 ; 5 (1) : 45-52.
PMID 8919545
Infrequent point mutations in codons 12 and 61 of ras oncogenes in human hepatocellular carcinomas.
Challen C, Guo K, Collier JD, Cavanagh D, Bassendine MF
Journal of hepatology. 1992 ; 14 (2-3) : 342-346.
PMID 1323601
N-ras gene point mutations in Brazilian acute myelogenous leukemia patients correlate with a poor prognosis.
De Melo MB, Lorand-Metze I, Lima CS, Saad ST, Costa FF
Leukemia & lymphoma. 1997 ; 24 (3-4) : 309-317.
PMID 9156660
A new oncogene in human thyroid papillary carcinomas and their lymph-nodal metastases.
Fusco A, Grieco M, Santoro M, Berlingieri MT, Pilotti S, Pierotti MA, Della Porta G, Vecchio G
Nature. 1987 ; 328 (6126) : 170-172.
PMID 3600795
Mutation of ras oncogene in gastric adenocarcinoma: association with histological phenotype.
Kim TY, Bang YJ, Kim WS, Kang SH, Lee KU, Choe KJ, Kim NK
Anticancer research. 1997 ; 17 (2B) : 1335-1339.
PMID 9137494
High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis.
Lemoine NR, Mayall ES, Wyllie FS, Williams ED, Goyns M, Stringer B, Wynford-Thomas D
Oncogene. 1989 ; 4 (2) : 159-164.
PMID 2648253
Ras oncogene mutations in childhood brain tumors.
Maltzman TH, Mueller BA, Schroeder J, Rutledge JC, Patterson K, Preston-Martin S, Faustman EM
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 1997 ; 6 (4) : 239-243.
PMID 9107428
ras activation in experimental carcinogenesis.
Mangues R, Pellicer A
Seminars in cancer biology. 1992 ; 3 (4) : 229-239.
PMID 1421167
No N-ras mutations in human uveal melanoma: the role of ultraviolet light revisited.
Mooy CM, Van der Helm MJ, Van der Kwast TH, De Jong PT, Ruiter DJ, Zwarthoff EC
British journal of cancer. 1991 ; 64 (2) : 411-413.
PMID 1892776
Detection of RAS mutations in archival testicular germ cell tumors by polymerase chain reaction and oligonucleotide hybridization.
Moul JW, Theune SM, Chang EH
Genes, chromosomes & cancer. 1992 ; 5 (2) : 109-118.
PMID 1381946
Activated ras genes in human seminoma: evidence for tumor heterogeneity.
Mulder MP, Keijzer W, Verkerk A, Boot AJ, Prins ME, Splinter TA, Bos JL
Oncogene. 1989 ; 4 (11) : 1345-1351.
PMID 2682461
Multiple point mutation of N-ras and K-ras oncogenes in myelodysplastic syndrome and acute myelogenous leukemia.
Nakagawa T, Saitoh S, Imoto S, Itoh M, Tsutsumi M, Hikiji K, Nakamura H, Matozaki S, Ogawa R, Nakao Y
Oncology. 1992 ; 49 (2) : 114-122.
PMID 1574246
Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia.
Neubauer A, Dodge RK, George SL, Davey FR, Silver RT, Schiffer CA, Mayer RJ, Ball ED, Wurster-Hill D, Bloomfield CD
Blood. 1994 ; 83 (6) : 1603-1611.
PMID 8123851
Human cancer and cellular oncogenes.
Nishimura S, Sekiya T
The Biochemical journal. 1987 ; 243 (2) : 313-327.
PMID 3307760
RAS, FMS and p53 mutations and poor clinical outcome in myelodysplasias: a 10-year follow-up.
Padua RA, Guinn BA, Al-Sabah AI, Smith M, Taylor C, Pettersson T, Ridge S, Carter G, White D, Oscier D, Chevret S, West R
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 ; 12 (6) : 887-892.
PMID 9639416
K-ras oncogene codon 12 point mutations in testicular cancer.
Ridanpää M, Lothe RA, Onfelt A, Fosså S, B&oring;rresen AL, Husgafvel-Pursiainen K
Environmental health perspectives. 1993 ; 101 Suppl 3 : 185-187.
PMID 8143614
Investigation of the role of the ras protooncogene point mutation in human uveal melanomas.
Soparker CN, O'Brien JM, Albert DM
Investigative ophthalmology & visual science. 1993 ; 34 (7) : 2203-2209.
PMID 8505202
Detection of activated ras oncogenes in human thyroid carcinomas.
Su´rez HG, Du Villard JA, Caillou B, Schlumberger M, Tubiana M, Parmentier C, Monier R
Oncogene. 1988 ; 2 (4) : 403-406.
PMID 3283656
N-ras gene mutations in acute myeloid leukemia: accurate detection by solid-phase minisequencing.
Syvänen AC, Söderlund H, Laaksonen E, Bengtström M, Turunen M, Palotie A
International journal of cancer. Journal international du cancer. 1992 ; 50 (5) : 713-718.
PMID 1544704
High incidence of ras gene mutation in intrahepatic cholangiocarcinoma.
Tada M, Omata M, Ohto M
Cancer. 1992 ; 69 (5) : 1115-1118.
PMID 1739910
Absence of N-ras mutations in myeloid and lymphoid blast crisis of chronic myeloid leukemia.
Watzinger F, Gaiger A, Karlic H, Becher R, Pillwein K, Lion T
Cancer research. 1994 ; 54 (14) : 3934-3938.
PMID 8033117
Correlation of N-ras point mutations with specific chromosomal abnormalities in primary myelodysplastic syndrome.
de Souza Fernandez T, Menezes de Souza J, Macedo Silva ML, Tabak D, Abdelhay E
Leukemia research. 1998 ; 22 (2) : 125-134.
PMID 9593469
N-ras mutations in human cutaneous melanoma from sun-exposed body sites.
van 't Veer LJ, Burgering BM, Versteeg R, Boot AJ, Ruiter DJ, Osanto S, Schrier PI, Bos JL
Molecular and cellular biology. 1989 ; 9 (7) : 3114-3116.
PMID 2674680


This paper should be referenced as such :
Watzinger, F ; Lion, T
N-RAS (neuroblastoma RAS viral oncogene homolog)
Atlas Genet Cytogenet Oncol Haematol. 1999;3(2):68-70.
Free journal version : [ pdf ]   [ DOI ]

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 15 ]
  Classification of myelodysplastic syndromes 2015
Chronic Myelomonocytic Leukemia (CMML)
Early T-cell precursor acute lymphoblastic leukemia
i(17q) solely in myeloid malignancies
inv(3)(q21q26) RPN1/MECOM::t(3;3)(q21;q26) RPN1/MECOM::ins(3;3)(q26;q21q26) RPN1/MECOM
Juvenile myelomonocytic leukemia (JMML)
Acute lymphoblastic leukemia in Down syndrome
Mixed phenotype acute leukemia (MPAL)
Myelodysplastic/myeloproliferative neoplasms
Myeloid proliferations in Down syndrome
Plasma cell leukemia (PCL)
Primary cutaneous CD30+ anaplastic large cell lymphoma
t(3;21)(q26;q22) RUNX1/MECOM
t(6;11)(q27;q23) KMT2A/AFDN
t(14;16)(q32;q23) IGH/MAF

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 10 ]
  Thyroid: Anaplastic (undifferentiated) carcinoma
Nervous system: Astrocytic tumors
Breast tumors : an overview
Bone: Chordoma
Colon: Colorectal adenocarcinoma
Bone: Dedifferentiated chondrosarcoma
Breast: Ductal carcinoma
Thyroid: Medullary carcinoma
Head and Neck: Primary oral mucosal melanoma
Skin: Melanoma

Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ]
  Noonan syndrome

External links

HGNC (Hugo)NRAS   7989
LRG (Locus Reference Genomic)LRG_92
Entrez_Gene (NCBI)NRAS    "NRAS proto-oncogene, GTPase"
AliasesALPS4; CMNS; N-ras; NCMS; 
GeneCards (Weizmann)NRAS
Ensembl hg19 (Hinxton)ENSG00000213281 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000213281 [Gene_View]  ENSG00000213281 [Sequence]  chr1:114704469-114716771 [Contig_View]  NRAS [Vega]
ICGC DataPortalENSG00000213281
Genatlas (Paris)NRAS
SOURCE (Princeton)NRAS
Genetics Home Reference (NIH)NRAS
Genomic and cartography
GoldenPath hg38 (UCSC)NRAS  -     chr1:114704469-114716771 -  1p13.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)NRAS  -     1p13.2   [Description]    (hg19-Feb_2009)
GoldenPathNRAS - 1p13.2 [CytoView hg19]  NRAS - 1p13.2 [CytoView hg38]
genome Data Viewer NCBINRAS [Mapview hg19]  
OMIM114500   137550   162900   163200   164790   188470   249400   613224   614470   
Gene and transcription
Genbank (Entrez)AF493919 AW021410 AY941100 AY941101 BC005219
RefSeq transcript (Entrez)NM_002524
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)NRAS
Alternative Splicing GalleryENSG00000213281
Gene ExpressionNRAS [ NCBI-GEO ]   NRAS [ EBI - ARRAY_EXPRESS ]   NRAS [ SEEK ]   NRAS [ MEM ]
Gene Expression Viewer (FireBrowse)NRAS [ Firebrowse - Broad ]
GenevisibleExpression of NRAS in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4893
GTEX Portal (Tissue expression)NRAS
Human Protein AtlasENSG00000213281-NRAS [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP01111   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP01111  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP01111
Splice isoforms : SwissVarP01111
Domaine pattern : Prosite (Expaxy)RAS (PS51421)   
Domains : Interpro (EBI)P-loop_NTPase    Small_GTP-bd_dom    Small_GTPase    Small_GTPase_Ras-type   
Domain families : Pfam (Sanger)Ras (PF00071)   
Domain families : Pfam (NCBI)pfam00071   
Conserved Domain (NCBI)NRAS
Blocks (Seattle)NRAS
PDB (RSDB)2N9C    3CON    5UHV    6E6H    6MPP   
PDB Europe2N9C    3CON    5UHV    6E6H    6MPP   
PDB (PDBSum)2N9C    3CON    5UHV    6E6H    6MPP   
PDB (IMB)2N9C    3CON    5UHV    6E6H    6MPP   
Structural Biology KnowledgeBase2N9C    3CON    5UHV    6E6H    6MPP   
SCOP (Structural Classification of Proteins)2N9C    3CON    5UHV    6E6H    6MPP   
CATH (Classification of proteins structures)2N9C    3CON    5UHV    6E6H    6MPP   
Human Protein Atlas [tissue]ENSG00000213281-NRAS [tissue]
Peptide AtlasP01111
Protein Interaction databases
IntAct (EBI)P01111
Ontologies - Pathways
Ontology : AmiGOGolgi membrane  MAPK cascade  positive regulation of endothelial cell proliferation  stimulatory C-type lectin receptor signaling pathway  GTPase activity  GTPase activity  protein binding  GTP binding  Golgi apparatus  plasma membrane  plasma membrane  Ras protein signal transduction  Ras protein signal transduction  Ras protein signal transduction  membrane  GDP binding  neutrophil degranulation  protein-containing complex binding  extracellular exosome  tertiary granule membrane  
Ontology : EGO-EBIGolgi membrane  MAPK cascade  positive regulation of endothelial cell proliferation  stimulatory C-type lectin receptor signaling pathway  GTPase activity  GTPase activity  protein binding  GTP binding  Golgi apparatus  plasma membrane  plasma membrane  Ras protein signal transduction  Ras protein signal transduction  Ras protein signal transduction  membrane  GDP binding  neutrophil degranulation  protein-containing complex binding  extracellular exosome  tertiary granule membrane  
Pathways : KEGGMAPK signaling pathway    ErbB signaling pathway    Ras signaling pathway    Rap1 signaling pathway    Chemokine signaling pathway    FoxO signaling pathway    PI3K-Akt signaling pathway    Axon guidance    VEGF signaling pathway    Tight junction    Gap junction    Natural killer cell mediated cytotoxicity    T cell receptor signaling pathway    B cell receptor signaling pathway    Fc epsilon RI signaling pathway    Long-term potentiation    Neurotrophin signaling pathway    Cholinergic synapse    Serotonergic synapse    Long-term depression    Regulation of actin cytoskeleton    Insulin signaling pathway    GnRH signaling pathway    Estrogen signaling pathway    Melanogenesis    Prolactin signaling pathway    Thyroid hormone signaling pathway    Alcoholism    Hepatitis C    Hepatitis B    HTLV-I infection    Pathways in cancer    Viral carcinogenesis    Proteoglycans in cancer    MicroRNAs in cancer    Renal cell carcinoma    Endometrial cancer    Glioma    Prostate cancer    Thyroid cancer    Melanoma    Bladder cancer    Chronic myeloid leukemia    Acute myeloid leukemia    Non-small cell lung cancer   
REACTOMEP01111 [protein]
REACTOME PathwaysR-HSA-9634635 [pathway]   
NDEx NetworkNRAS
Atlas of Cancer Signalling NetworkNRAS
Wikipedia pathwaysNRAS
Orthology - Evolution
GeneTree (enSembl)ENSG00000213281
Phylogenetic Trees/Animal Genes : TreeFamNRAS
Homologs : HomoloGeneNRAS
Homology/Alignments : Family Browser (UCSC)NRAS
Gene fusions - Rearrangements
Fusion : Fusion_HubATG13--NRAS    CCND2--NRAS    CSDE1--NRAS    LYZ--NRAS    MAST2--NRAS    NRAS--BRAF    NRAS--CLDN14    NRAS--CSDE1    NRAS--IDH2    NRAS--KRAS    NRAS--PDE3B    SLC37A4--NRAS    SS18--NRAS   
Fusion : QuiverNRAS
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerNRAS [hg38]
Exome Variant ServerNRAS
GNOMAD BrowserENSG00000213281
Varsome BrowserNRAS
Genomic Variants (DGV)NRAS [DGVbeta]
DECIPHERNRAS [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisNRAS 
ICGC Data PortalNRAS 
TCGA Data PortalNRAS 
Broad Tumor PortalNRAS
OASIS PortalNRAS [ Somatic mutations - Copy number]
Cancer Gene: CensusNRAS 
Somatic Mutations in Cancer : COSMICNRAS  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DNRAS
Mutations and Diseases : HGMDNRAS
intOGen PortalNRAS
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)Mendelian genes
LOVD (Leiden Open Variation Database)**PUBLIC** CCHMC Molecular Genetics Laboratory Mutation Database
LOVD (Leiden Open Variation Database)MSeqDR-LSDB Mitochondrial Disease Locus Specific Database
BioMutasearch NRAS
DgiDB (Drug Gene Interaction Database)NRAS
DoCM (Curated mutations)NRAS (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)NRAS (select a term)
NCG6 (London) select NRAS
Cancer3DNRAS(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM114500    137550    162900    163200    164790    188470    249400    613224    614470   
Orphanet206    370    549    905    20165    11747   
Genetic Testing Registry NRAS
NextProtP01111 [Medical]
Target ValidationNRAS
Huge Navigator NRAS [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTD
Pharm GKB GenePA31768
Pharm GKB PathwaysPA154423660   PA162356267   PA165959584   PA165980050   PA2032   
Drug Sensitivity NRAS
Clinical trialNRAS
canSAR (ICR)NRAS (select the gene name)
DataMed IndexNRAS
Other database
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

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indexed on : Fri Feb 19 17:56:27 CET 2021

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