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NRAS (neuroblastoma RAS viral oncogene homolog)

Identity

Other namesN-RAS (neuroblastoma RAS viral oncogene homolog)
HGNC (Hugo) NRAS
LocusID (NCBI) 4893
Location 1p13.2
Location_base_pair Starts at 115247085 and ends at 115259515 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Note more on the RAS family is available as a deep insight

DNA/RNA

 
  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

Protein

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%)
  

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias 11q23ChildAMLID1615 11q23ID1030 11q23secondLeukID1131 t1119ELLID1029

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors AmeloblastomID5945 MedulloblastomaID5065 rhab5004

External links

Nomenclature
HGNC (Hugo)NRAS   7989
Cards
AtlasNRASID92
Entrez_Gene (NCBI)NRAS  4893  neuroblastoma RAS viral (v-ras) oncogene homolog
GeneCards (Weizmann)NRAS
Ensembl (Hinxton)ENSG00000213281 [Gene_View]  chr1:115247085-115259515 [Contig_View]  NRAS [Vega]
ICGC DataPortalENSG00000213281
cBioPortalNRAS
AceView (NCBI)NRAS
Genatlas (Paris)NRAS
WikiGenes4893
SOURCE (Princeton)NM_002524
Genomic and cartography
GoldenPath (UCSC)NRAS  -  1p13.2   chr1:115247085-115259515 -  1p13.2   [Description]    (hg19-Feb_2009)
EnsemblNRAS - 1p13.2 [CytoView]
Mapping of homologs : NCBINRAS [Mapview]
OMIM114500   137550   162900   164790   188470   249400   613224   614470   
Gene and transcription
Genbank (Entrez)AF493919 AW021410 AY941100 AY941101 BC005219
RefSeq transcript (Entrez)NM_002524
RefSeq genomic (Entrez)AC_000133 NC_000001 NC_018912 NG_007572 NT_032977 NW_001838594 NW_004929290
Consensus coding sequences : CCDS (NCBI)NRAS
Cluster EST : UnigeneHs.486502 [ NCBI ]
CGAP (NCI)Hs.486502
Alternative Splicing : Fast-db (Paris)GSHG0002385
Alternative Splicing GalleryENSG00000213281
Gene ExpressionNRAS [ NCBI-GEO ]     NRAS [ SEEK ]   NRAS [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP01111 (Uniprot)
NextProtP01111  [Medical]
With graphics : InterProP01111
Splice isoforms : SwissVarP01111 (Swissvar)
Domaine pattern : Prosite (Expaxy)RAS (PS51421)   
Domains : Interpro (EBI)P-loop_NTPase [organisation]   Small_GTP-bd_dom [organisation]   Small_GTPase [organisation]   Small_GTPase_Ras [organisation]  
Related proteins : CluSTrP01111
Domain families : Pfam (Sanger)Ras (PF00071)   
Domain families : Pfam (NCBI)pfam00071   
Domain families : Smart (EMBL)RAS (SM00173)  
DMDM Disease mutations4893
Blocks (Seattle)P01111
PDB (SRS)3CON   
PDB (PDBSum)3CON   
PDB (IMB)3CON   
PDB (RSDB)3CON   
Human Protein AtlasENSG00000213281 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP01111
HPRD01273
IPIIPI00000005   
Protein Interaction databases
DIP (DOE-UCLA)P01111
IntAct (EBI)P01111
FunCoupENSG00000213281
BioGRIDNRAS
InParanoidP01111
Interologous Interaction database P01111
IntegromeDBNRAS
STRING (EMBL)NRAS
Ontologies - Pathways
Ontology : AmiGOGolgi membrane  MAPK cascade  activation of MAPKK activity  GTP binding  plasma membrane  GTP catabolic process  epidermal growth factor receptor signaling pathway  small GTPase mediated signal transduction  Ras protein signal transduction  axon guidance  blood coagulation  positive regulation of cell proliferation  insulin receptor signaling pathway  visual learning  fibroblast growth factor receptor signaling pathway  membrane  actin cytoskeleton organization  regulation of synaptic transmission, GABAergic  protein complex binding  positive regulation of Rac protein signal transduction  Fc-epsilon receptor signaling pathway  negative regulation of neuron apoptotic process  innate immune response  neurotrophin TRK receptor signaling pathway  regulation of long-term neuronal synaptic plasticity  leukocyte migration  striated muscle cell differentiation  extracellular vesicular exosome  
Ontology : EGO-EBIGolgi membrane  MAPK cascade  activation of MAPKK activity  GTP binding  plasma membrane  GTP catabolic process  epidermal growth factor receptor signaling pathway  small GTPase mediated signal transduction  Ras protein signal transduction  axon guidance  blood coagulation  positive regulation of cell proliferation  insulin receptor signaling pathway  visual learning  fibroblast growth factor receptor signaling pathway  membrane  actin cytoskeleton organization  regulation of synaptic transmission, GABAergic  protein complex binding  positive regulation of Rac protein signal transduction  Fc-epsilon receptor signaling pathway  negative regulation of neuron apoptotic process  innate immune response  neurotrophin TRK receptor signaling pathway  regulation of long-term neuronal synaptic plasticity  leukocyte migration  striated muscle cell differentiation  extracellular vesicular exosome  
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   
Protein Interaction DatabaseNRAS
Wikipedia pathwaysNRAS
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)NRAS
snp3D : Map Gene to Disease4893
SNP (GeneSNP Utah)NRAS
SNP : HGBaseNRAS
Genetic variants : HAPMAPNRAS
Exome VariantNRAS
1000_GenomesNRAS 
ICGC programENSG00000213281 
Cancer Gene: CensusNRAS 
Somatic Mutations in Cancer : COSMICNRAS 
CONAN: Copy Number AnalysisNRAS 
Mutations and Diseases : HGMDNRAS
Genomic VariantsNRAS  NRAS [DGVbeta]
dbVarNRAS
ClinVarNRAS
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM114500    137550    162900    164790    188470    249400    613224    614470   
MedgenNRAS
GENETestsNRAS
Disease Genetic AssociationNRAS
Huge Navigator NRAS [HugePedia]  NRAS [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneNRAS
Homology/Alignments : Family Browser (UCSC)NRAS
Phylogenetic Trees/Animal Genes : TreeFamNRAS
Chemical/Protein Interactions : CTD4893
Chemical/Pharm GKB GenePA31768
Drug Sensitivity NRAS
Clinical trialNRAS
Cancer Resource (Charite)ENSG00000213281
Other databases
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=NRAS
Probes
Litterature
PubMed280 Pubmed reference(s) in Entrez
CoreMineNRAS
iHOPNRAS
OncoSearchNRAS

Bibliography

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
 
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
 
Human cancer and cellular oncogenes.
Nishimura S, Sekiya T
The Biochemical journal. 1987 ; 243 (2) : 313-327.
PMID 3307760
 
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
 
The ras gene family and human carcinogenesis.
Bos JL
Mutation research. 1988 ; 195 (3) : 255-271.
PMID 3283542
 
Activated ras oncogenes in human thyroid cancers.
Lemoine NR, Mayall ES, Wyllie FS, Farr CJ, Hughes D, Padua RA, Thurston V, Williams ED, Wynford-Thomas D
Cancer research. 1988 ; 48 (16) : 4459-4463.
PMID 3293774
 
Detection of activated ras oncogenes in human thyroid carcinomas.
Suˆ°rez HG, Du Villard JA, Caillou B, Schlumberger M, Tubiana M, Parmentier C, Monier R
Oncogene. 1988 ; 2 (4) : 403-406.
PMID 3283656
 
ras oncogenes in human cancer: a review.
Bos JL
Cancer research. 1989 ; 49 (17) : 4682-4689.
PMID 2547513
 
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
 
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
 
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
 
ras oncogenes: their role in neoplasia.
Barbacid M
European journal of clinical investigation. 1990 ; 20 (3) : 225-235.
PMID 2114981
 
Analysis of ras gene mutations in human hepatic malignant tumors by polymerase chain reaction and direct sequencing.
Tada M, Omata M, Ohto M
Cancer research. 1990 ; 50 (4) : 1121-1124.
PMID 2153451
 
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
 
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
 
ras activation in experimental carcinogenesis.
Mangues R, Pellicer A
Seminars in cancer biology. 1992 ; 3 (4) : 229-239.
PMID 1421167
 
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
 
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
 
High incidence of ras gene mutation in intrahepatic cholangiocarcinoma.
Tada M, Omata M, Ohto M
Cancer. 1992 ; 69 (5) : 1115-1118.
PMID 1739910
 
N-ras gene mutations in acute myeloid leukemia: accurate detection by solid-phase minisequencing.
Syvˆ§nen AC, Sˆderlund H, Laaksonen E, Bengtstrˆm M, Turunen M, Palotie A
International journal of cancer. Journal international du cancer. 1992 ; 50 (5) : 713-718.
PMID 1544704
 
K-ras oncogene codon 12 point mutations in testicular cancer.
Ridanpˆ§ˆ§ M, Lothe RA, Onfelt A, Fossˆ€ S, Bˆ½rresen 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
 
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
 
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
 
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
 
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
 
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
 
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, 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
 
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
 
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Contributor(s)

Written02-1999Franz Watzinger and Thomas Lion

Citation

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 online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/NRASID92.html

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