KRAS (Kirsten rat sarcoma 2 viral oncogene homolog)

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home Genes Leukemias Solid Tumors Cancer-Prone Deep Insight Case Reports Journals Portal Teaching

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

KRAS (Kirsten rat sarcoma 2 viral oncogene homolog)

Written	1999-02	Franz Watzinger, Thomas Lion
		Children's Cancer Research Institute (CCRI), Kinderspitalgasse 6, A-1090 Vienna, Austria

(Note : for Links provided by Atlas : click)

Identity

Alias_names	KRAS2
	v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog
	v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog
	Kirsten rat sarcoma viral oncogene homolog
Alias_symbol (synonym)	KRAS1
Other alias	K-RAS (Kirsten rat sarcoma 2 viral oncogene homolog)
	c-Ki-ras 2
HGNC (Hugo)	KRAS
LocusID (NCBI)	3845
Atlas_Id	91
Location	12p12.1 [Link to chromosome band 12p12]
Location_base_pair	Starts at 25204789 and ends at 25250931 bp from pter ( according to hg19-Feb_2009) [Mapping KRAS.png]

Fusion genes (updated 2016)	CDC42SE1 (1q21.3) / KRAS (12p12.1)	KRAS (12p12.1) / CDH13 (16q23.3)	KRAS (12p12.1) / KIAA0907 (1q22)
	KRAS (12p12.1) / KMT2A (11q23.3)	KRAS (12p12.1) / LMNTD1 (12p12.1)	KRAS (12p12.1) / RERGL (12p12.3)
	UBE2L3 (22q11.21) / KRAS (12p12.1)

Note	more on the RAS family is available as a deep insight

DNA/RNA



	K-ras splicing variants alternative splicing of K-ras precursor mRNA leads to the two transcripts which differ by the ex- or inclusion of Exon 4a; 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 six exons, spread over 35kb of genomic DNA.
Transcription	alternative RNA splicing reveals two different transcripts of 5.5 and 3.8kb (see Fig); if Exon 4a is skipped exon 4b is directly joined to exon 3; in 98% of the transcripts exon 4a is spliced out and only exon 4b is available for translation into protein.
Pseudogene	c-Ki-ras 1, inactivated, processed pseudogene which is located on Chromosome 6

Protein

Description	regular RAS protein - characterized in the RAS family 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

Note

Entity	tumor (frequency of K-RAS mutations); references in Full Bibliography


Entity	pancreas (80-90%)


Entity	colon and rectum (25-60%)


Entity	lung (25-60%)


Entity	prostate (0-25%)


Entity	skin (0-25%)


Entity	thyroid (0-60%)


Entity	liver (10-25%)


Entity	ovary (0-50%)


Entity	endometrium (10-40%)


Entity	kidney (0-50%)


Entity	brain (0-15%)


Entity	testis (seminoma) (10-45%)


Entity	acute non lymphocytic leukemia and myelodysplasia (5-15%)


Entity	urinary bladder (5%)


Entity	head and neck (10%)


Entity	breast (10%)

Bibliography

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 activation in experimental carcinogenesis.

Mangues R, Pellicer A

Seminars in cancer biology. 1992 ; 3 (4) : 229-239.

PMID 1421167

Human cancer and cellular oncogenes.

Nishimura S, Sekiya T

The Biochemical journal. 1987 ; 243 (2) : 313-327.

PMID 3307760

Citation

This paper should be referenced as such :

Watzinger, F ; Lion, T

KRAS (Kirsten rat sarcoma viral oncogene homolog)

Atlas Genet Cytogenet Oncol Haematol. 1999;3(2):66-67.

Free journal version : [ pdf ] [ DOI ]

On line version : http://AtlasGeneticsOncology.org/Genes/KRASID91.html

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 9 ]

Classification of myelodysplastic syndromes 2015
Chronic Myelomonocytic Leukemia (CMML)
Early T-cell precursor acute lymphoblastic leukemia
Juvenile Chronic Myelogenous Leukemia (JCML)
Acute basophilic leukemia::t(X;6)(p11;q23) MYB/GATA1
Plasma cell leukemia (PCL)
t(3;21)(q26;q22) RUNX1/MECOM
t(4;11)(q21;p15) NUP98/RAP1GDS1
t(4;11)(q23;p15) NUP98/RAP1GDS1

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 26 ]

Head and Neck: Odontogenic tumor: Ameloblastoma
Thyroid: Anaplastic (undifferentiated) carcinoma
Breast tumors : an overview
Neuro-Endocrine/Endocrine System: Carcinoid tumors
Colon: Colorectal adenocarcinoma
Bone: Dedifferentiated chondrosarcoma
Breast: Ductal carcinoma
Gallbladder: Carcinoma of the gallbladder and extrahepatic bile ducts
Head and Neck: Epidermoid carcinoma
Liver: Combined hepatocellular and cholangiocarcinoma
Gallbladder: Intrahepatic cholangiocarcinoma
Lung: Non-small cell carcinoma with inv(2)(p21p23) EML4/ALK
Liver tumors: an overview
Lung: Non-small cell carcinoma
Lung tumors: an overview
Thyroid: Medullary carcinoma
Ovary: Germ cell tumors
Ovarian tumours : an overview
Ovary: Sex cord-stromal tumors
Ovary: Epithelial tumors
Pancreatic tumors: an overview
Skin: Melanoma
Lung: Adenocarcinoma with t(6;12)(q22;q14.1) LRIG3/ROS1
Lung: Translocations in Adenocarcinoma
Lung: Translocations in Squamous Cell Carcinoma
Uterus Tumours: an Overview

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

Noonan syndrome

External links

	Nomenclature
HGNC (Hugo)	KRAS 6407
LRG (Locus Reference Genomic)	LRG_344
	Cards
Atlas	KRASID91
Entrez_Gene (NCBI)	KRAS 3845 KRAS proto-oncogene, GTPase
Aliases	C-K-RAS; CFC2; K-RAS2A; K-RAS2B;
	K-RAS4A; K-RAS4B; KI-RAS; KRAS1; KRAS2; NS; NS3; RALD; RASK2; c-Ki-ras2
GeneCards (Weizmann)	KRAS
Ensembl hg19 (Hinxton)	ENSG00000133703 [Gene_View]
Ensembl hg38 (Hinxton)	ENSG00000133703 [Gene_View] chr12:25204789-25250931 [Contig_View] KRAS [Vega]
ICGC DataPortal	ENSG00000133703
TCGA cBioPortal	KRAS
AceView (NCBI)	KRAS
Genatlas (Paris)	KRAS
WikiGenes	3845
SOURCE (Princeton)	KRAS
Genetics Home Reference (NIH)	KRAS
	Genomic and cartography
GoldenPath hg38 (UCSC)	KRAS - chr12:25204789-25250931 - 12p12.1 [Description] (hg38-Dec_2013)
GoldenPath hg19 (UCSC)	KRAS - 12p12.1 [Description] (hg19-Feb_2009)
Ensembl	KRAS - 12p12.1 [CytoView hg19] KRAS - 12p12.1 [CytoView hg38]
Mapping of homologs : NCBI	KRAS [Mapview hg19] KRAS [Mapview hg38]
OMIM	109800 114480 137215 163200 190070 211980 260350 601626 609942 615278
	Gene and transcription
Genbank (Entrez)	AA812162 AF493917 AI539465 AK292510 AW117295
RefSeq transcript (Entrez)	NM_004985 NM_033360
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)	KRAS
Cluster EST : Unigene	Hs.505033 [ NCBI ]
CGAP (NCI)	Hs.505033
Alternative Splicing Gallery	ENSG00000133703
Gene Expression	KRAS [ NCBI-GEO ] KRAS [ EBI - ARRAY_EXPRESS ] KRAS [ SEEK ] KRAS [ MEM ]
Gene Expression Viewer (FireBrowse)	KRAS [ Firebrowse - Broad ]
SOURCE (Princeton)	Expression in : [Datasets] [Normal Tissue Atlas] [carcinoma Classsification] [NCI60]
Genevisible	Expression in : [tissues] [cell-lines] [cancer] [perturbations]
BioGPS (Tissue expression)	3845
GTEX Portal (Tissue expression)	KRAS
	Protein : pattern, domain, 3D structure
UniProt/SwissProt	P01116 [function] [subcellular_location] [family_and_domains] [pathology_and_biotech] [ptm_processing] [expression] [interaction]
NextProt	P01116 [Sequence] [Exons] [Medical] [Publications]
With graphics : InterPro	P01116
Splice isoforms : SwissVar	P01116
PhosPhoSitePlus	P01116
Domaine pattern : Prosite (Expaxy)	RAS (PS51421)
Domains : Interpro (EBI)	P-loop_NTPase Small_GTP-bd_dom Small_GTPase Small_GTPase_Ras
Domain families : Pfam (Sanger)	Ras (PF00071)
Domain families : Pfam (NCBI)	pfam00071
Conserved Domain (NCBI)	KRAS
DMDM Disease mutations	3845
Blocks (Seattle)	KRAS
PDB (SRS)	1D8D 1D8E 1KZO 1KZP 3GFT 4DSN 4DSO 4EPR 4EPT 4EPV 4EPW 4EPX 4EPY 4L8G 4LDJ 4LPK 4LRW 4LUC 4LV6 4LYF 4LYH 4LYJ 4M1O 4M1S 4M1T 4M1W 4M1Y 4M21 4M22 4NMM 4OBE 4PZY 4PZZ 4Q01 4Q02 4Q03 4QL3 4TQ9 4TQA 4WA7 5F2E 5TAR 5TB5
PDB (PDBSum)	1D8D 1D8E 1KZO 1KZP 3GFT 4DSN 4DSO 4EPR 4EPT 4EPV 4EPW 4EPX 4EPY 4L8G 4LDJ 4LPK 4LRW 4LUC 4LV6 4LYF 4LYH 4LYJ 4M1O 4M1S 4M1T 4M1W 4M1Y 4M21 4M22 4NMM 4OBE 4PZY 4PZZ 4Q01 4Q02 4Q03 4QL3 4TQ9 4TQA 4WA7 5F2E 5TAR 5TB5
PDB (IMB)	1D8D 1D8E 1KZO 1KZP 3GFT 4DSN 4DSO 4EPR 4EPT 4EPV 4EPW 4EPX 4EPY 4L8G 4LDJ 4LPK 4LRW 4LUC 4LV6 4LYF 4LYH 4LYJ 4M1O 4M1S 4M1T 4M1W 4M1Y 4M21 4M22 4NMM 4OBE 4PZY 4PZZ 4Q01 4Q02 4Q03 4QL3 4TQ9 4TQA 4WA7 5F2E 5TAR 5TB5
PDB (RSDB)	1D8D 1D8E 1KZO 1KZP 3GFT 4DSN 4DSO 4EPR 4EPT 4EPV 4EPW 4EPX 4EPY 4L8G 4LDJ 4LPK 4LRW 4LUC 4LV6 4LYF 4LYH 4LYJ 4M1O 4M1S 4M1T 4M1W 4M1Y 4M21 4M22 4NMM 4OBE 4PZY 4PZZ 4Q01 4Q02 4Q03 4QL3 4TQ9 4TQA 4WA7 5F2E 5TAR 5TB5
Structural Biology KnowledgeBase	1D8D 1D8E 1KZO 1KZP 3GFT 4DSN 4DSO 4EPR 4EPT 4EPV 4EPW 4EPX 4EPY 4L8G 4LDJ 4LPK 4LRW 4LUC 4LV6 4LYF 4LYH 4LYJ 4M1O 4M1S 4M1T 4M1W 4M1Y 4M21 4M22 4NMM 4OBE 4PZY 4PZZ 4Q01 4Q02 4Q03 4QL3 4TQ9 4TQA 4WA7 5F2E 5TAR 5TB5
SCOP (Structural Classification of Proteins)	1D8D 1D8E 1KZO 1KZP 3GFT 4DSN 4DSO 4EPR 4EPT 4EPV 4EPW 4EPX 4EPY 4L8G 4LDJ 4LPK 4LRW 4LUC 4LV6 4LYF 4LYH 4LYJ 4M1O 4M1S 4M1T 4M1W 4M1Y 4M21 4M22 4NMM 4OBE 4PZY 4PZZ 4Q01 4Q02 4Q03 4QL3 4TQ9 4TQA 4WA7 5F2E 5TAR 5TB5
CATH (Classification of proteins structures)	1D8D 1D8E 1KZO 1KZP 3GFT 4DSN 4DSO 4EPR 4EPT 4EPV 4EPW 4EPX 4EPY 4L8G 4LDJ 4LPK 4LRW 4LUC 4LV6 4LYF 4LYH 4LYJ 4M1O 4M1S 4M1T 4M1W 4M1Y 4M21 4M22 4NMM 4OBE 4PZY 4PZZ 4Q01 4Q02 4Q03 4QL3 4TQ9 4TQA 4WA7 5F2E 5TAR 5TB5
Superfamily	P01116
Human Protein Atlas	ENSG00000133703
Peptide Atlas	P01116
HPRD	01817
IPI	IPI00423568 IPI00423570 IPI01026223 IPI01026118
	Protein Interaction databases
DIP (DOE-UCLA)	P01116
IntAct (EBI)	P01116
FunCoup	ENSG00000133703
BioGRID	KRAS
STRING (EMBL)	KRAS
ZODIAC	KRAS
	Ontologies - Pathways
QuickGO	P01116
Ontology : AmiGO	MAPK cascade liver development positive regulation of protein phosphorylation stimulatory C-type lectin receptor signaling pathway GTPase activity protein binding GTP binding cytoplasm mitochondrion cytosol plasma membrane focal adhesion epidermal growth factor receptor signaling pathway Ras protein signal transduction axon guidance female pregnancy positive regulation of cell proliferation visual learning positive regulation of gene expression membrane GMP binding GDP binding cytokine-mediated signaling pathway forebrain astrocyte development actin cytoskeleton organization LRR domain binding extrinsic component of cytoplasmic side of plasma membrane regulation of protein stability regulation of synaptic transmission, GABAergic protein complex binding positive regulation of Rac protein signal transduction response to isolation stress endocrine signaling Fc-epsilon receptor signaling pathway ERBB2 signaling pathway positive regulation of MAP kinase activity negative regulation of neuron apoptotic process membrane raft negative regulation of cell differentiation regulation of long-term neuronal synaptic plasticity homeostasis of number of cells within a tissue leukocyte migration positive regulation of nitric-oxide synthase activity positive regulation of NF-kappaB transcription factor activity striated muscle cell differentiation response to glucocorticoid response to mineralocorticoid epithelial tube branching involved in lung morphogenesis positive regulation of cellular senescence
Ontology : EGO-EBI	MAPK cascade liver development positive regulation of protein phosphorylation stimulatory C-type lectin receptor signaling pathway GTPase activity protein binding GTP binding cytoplasm mitochondrion cytosol plasma membrane focal adhesion epidermal growth factor receptor signaling pathway Ras protein signal transduction axon guidance female pregnancy positive regulation of cell proliferation visual learning positive regulation of gene expression membrane GMP binding GDP binding cytokine-mediated signaling pathway forebrain astrocyte development actin cytoskeleton organization LRR domain binding extrinsic component of cytoplasmic side of plasma membrane regulation of protein stability regulation of synaptic transmission, GABAergic protein complex binding positive regulation of Rac protein signal transduction response to isolation stress endocrine signaling Fc-epsilon receptor signaling pathway ERBB2 signaling pathway positive regulation of MAP kinase activity negative regulation of neuron apoptotic process membrane raft negative regulation of cell differentiation regulation of long-term neuronal synaptic plasticity homeostasis of number of cells within a tissue leukocyte migration positive regulation of nitric-oxide synthase activity positive regulation of NF-kappaB transcription factor activity striated muscle cell differentiation response to glucocorticoid response to mineralocorticoid epithelial tube branching involved in lung morphogenesis positive regulation of cellular senescence
Pathways : BIOCARTA	Telomeres, Telomerase, Cellular Aging, and Immortality [Genes]
Pathways : KEGG
REACTOME	P01116 [protein]
REACTOME Pathways	R-HSA-8853338 [pathway]
NDEx Network	KRAS
Atlas of Cancer Signalling Network	KRAS
Wikipedia pathways	KRAS
	Orthology - Evolution
OrthoDB	3845
GeneTree (enSembl)	ENSG00000133703
Phylogenetic Trees/Animal Genes : TreeFam	KRAS
HOVERGEN	P01116
HOGENOM	P01116
Homologs : HomoloGene	KRAS
Homology/Alignments : Family Browser (UCSC)	KRAS
	Gene fusions - Rearrangements
Fusion : Mitelman	KRAS/CDH13 [12p12.1/16q23.3]
Fusion : Mitelman	KRAS/LMNTD1 [12p12.1/12p12.1] [t(12;12)(p12;p12)]
Fusion : Mitelman	KRAS/RERGL [12p12.1/12p12.3] [t(12;12)(p12;p12)]
Fusion : COSMIC	UBE2L3 [22q11.21] - KRAS [12p12.1] [fusion_1298] [fusion_1299]
Fusion: TCGA	KRAS 12p12.1 IFLTD1 OV
Fusion: TCGA	KRAS 12p12.1 RERGL 12p12.3 BRCA
	Polymorphisms : SNP and Copy number variants
NCBI Variation Viewer	KRAS [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)	KRAS
dbVar	KRAS
ClinVar	KRAS
1000_Genomes	KRAS
Exome Variant Server	KRAS
ExAC (Exome Aggregation Consortium)	KRAS (select the gene name)
Genetic variants : HAPMAP	3845
Genomic Variants (DGV)	KRAS [DGVbeta]
DECIPHER	KRAS [patients] [syndromes] [variants] [genes]
CONAN: Copy Number Analysis	KRAS
	Mutations
ICGC Data Portal	KRAS
TCGA Data Portal	KRAS
Broad Tumor Portal	KRAS
OASIS Portal	KRAS [ Somatic mutations - Copy number]
Cancer Gene: Census	KRAS
Somatic Mutations in Cancer : COSMIC	KRAS [overview] [genome browser] [tissue] [distribution]
Mutations and Diseases : HGMD	KRAS
intOGen Portal	KRAS
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
BioMuta	search KRAS
DgiDB (Drug Gene Interaction Database)	KRAS
DoCM (Curated mutations)	KRAS (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)	KRAS (select a term)
intoGen	KRAS
NCG5 (London)	KRAS
Cancer3D	KRAS(select the gene name)
Impact of mutations	[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
	Diseases
OMIM	109800 114480 137215 163200 190070 211980 260350 601626 609942 615278
Orphanet	206 549 905 1559 19659 20165 2962 3245 3708 22213 22214 11747
Medgen	KRAS
Genetic Testing Registry	KRAS
NextProt	P01116 [Medical]
TSGene	3845
GENETests	KRAS
Target Validation	KRAS
Huge Navigator	KRAS [HugePedia]
snp3D : Map Gene to Disease	3845
BioCentury BCIQ	KRAS
ClinGen	KRAS (curated)
	Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD	3845
Chemical/Pharm GKB Gene	PA30196
Drug Sensitivity	KRAS
Clinical trial	KRAS
	Miscellaneous
canSAR (ICR)	KRAS (select the gene name)
Other database	http://cancergenome.broadinstitute.org/index.php?tgene=KRAS
	Probes
	Litterature
PubMed	499 Pubmed reference(s) in Entrez
GeneRIFs	Gene References Into Functions (Entrez)
CoreMine	KRAS
EVEX	KRAS
GoPubMed	KRAS
iHOP	KRAS

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Search in all EBI NCBI

indexed on : Fri Jun 30 11:10:15 CEST 2017

Home Genes Leukemias Solid Tumors Cancer-Prone Deep Insight Case Reports Journals Portal Teaching

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.