KRAS (Kirsten rat sarcoma 2 viral oncogene homolog)

1999-02-01   Franz Watzinger , Thomas Lion 

Childrens Cancer Research Institute (CCRI), Kinderspitalgasse 6, A-1090 Vienna, Austria

Identity

HGNC
LOCATION
12p12.1
LOCUSID
ALIAS
C-K-RAS,C-K-RAS,CFC2,K-RAS2A,K-RAS2B,K-RAS4A,K-RAS4B,K-Ras,K-Ras
FUSION GENES

DNA/RNA

Atlas Image
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

Proteins

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

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

Bibliography

Pubmed IDLast YearTitleAuthors
21149811990ras oncogenes: their role in neoplasia.Barbacid M et al
25475131989ras oncogenes in human cancer: a review.Bos JL et al
14211671992ras activation in experimental carcinogenesis.Mangues R et al
33077601987Human cancer and cellular oncogenes.Nishimura S et al

Other Information

Locus ID:

NCBI: 3845
MIM: 190070
HGNC: 6407
Ensembl: ENSG00000133703

Variants:

dbSNP: 3845
ClinVar: 3845
TCGA: ENSG00000133703
COSMIC: KRAS

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000133703ENST00000256078P01116
ENSG00000133703ENST00000256078L7RSL8
ENSG00000133703ENST00000311936P01116
ENSG00000133703ENST00000311936A0A024RAV5
ENSG00000133703ENST00000556131G3V4K2
ENSG00000133703ENST00000557334G3V5T7

Expression (GTEx)

0
5
10
15
20
25
30
35

Pathways

PathwaySourceExternal ID
MAPK signaling pathwayKEGGko04010
ErbB signaling pathwayKEGGko04012
Autophagy - animalKEGGko04140
mTOR signaling pathwayKEGGko04150
ApoptosisKEGGko04210
Dorso-ventral axis formationKEGGko04320
Axon guidanceKEGGko04360
VEGF signaling pathwayKEGGko04370
Gap junctionKEGGko04540
Natural killer cell mediated cytotoxicityKEGGko04650
T cell receptor signaling pathwayKEGGko04660
B cell receptor signaling pathwayKEGGko04662
Fc epsilon RI signaling pathwayKEGGko04664
Long-term potentiationKEGGko04720
Long-term depressionKEGGko04730
Regulation of actin cytoskeletonKEGGko04810
Insulin signaling pathwayKEGGko04910
GnRH signaling pathwayKEGGko04912
Progesterone-mediated oocyte maturationKEGGko04914
MelanogenesisKEGGko04916
Colorectal cancerKEGGko05210
Renal cell carcinomaKEGGko05211
Pancreatic cancerKEGGko05212
Endometrial cancerKEGGko05213
GliomaKEGGko05214
Prostate cancerKEGGko05215
Thyroid cancerKEGGko05216
MelanomaKEGGko05218
Bladder cancerKEGGko05219
Chronic myeloid leukemiaKEGGko05220
Acute myeloid leukemiaKEGGko05221
Non-small cell lung cancerKEGGko05223
MAPK signaling pathwayKEGGhsa04010
ErbB signaling pathwayKEGGhsa04012
Autophagy - animalKEGGhsa04140
mTOR signaling pathwayKEGGhsa04150
ApoptosisKEGGhsa04210
Axon guidanceKEGGhsa04360
VEGF signaling pathwayKEGGhsa04370
Gap junctionKEGGhsa04540
Natural killer cell mediated cytotoxicityKEGGhsa04650
T cell receptor signaling pathwayKEGGhsa04660
B cell receptor signaling pathwayKEGGhsa04662
Fc epsilon RI signaling pathwayKEGGhsa04664
Long-term potentiationKEGGhsa04720
Long-term depressionKEGGhsa04730
Regulation of actin cytoskeletonKEGGhsa04810
Insulin signaling pathwayKEGGhsa04910
GnRH signaling pathwayKEGGhsa04912
MelanogenesisKEGGhsa04916
Pathways in cancerKEGGhsa05200
Colorectal cancerKEGGhsa05210
Renal cell carcinomaKEGGhsa05211
Pancreatic cancerKEGGhsa05212
Endometrial cancerKEGGhsa05213
GliomaKEGGhsa05214
Prostate cancerKEGGhsa05215
Thyroid cancerKEGGhsa05216
MelanomaKEGGhsa05218
Bladder cancerKEGGhsa05219
Chronic myeloid leukemiaKEGGhsa05220
Acute myeloid leukemiaKEGGhsa05221
Non-small cell lung cancerKEGGhsa05223
Chemokine signaling pathwayKEGGko04062
Chemokine signaling pathwayKEGGhsa04062
Neurotrophin signaling pathwayKEGGko04722
Neurotrophin signaling pathwayKEGGhsa04722
Dorso-ventral axis formationKEGGhsa04320
Progesterone-mediated oocyte maturationKEGGhsa04914
Aldosterone-regulated sodium reabsorptionKEGGko04960
Aldosterone-regulated sodium reabsorptionKEGGhsa04960
Hepatitis CKEGGko05160
Hepatitis CKEGGhsa05160
Cholinergic synapseKEGGhsa04725
HTLV-I infectionKEGGko05166
HTLV-I infectionKEGGhsa05166
Serotonergic synapseKEGGhsa04726
AlcoholismKEGGhsa05034
AlcoholismKEGGko05034
Viral carcinogenesisKEGGhsa05203
Viral carcinogenesisKEGGko05203
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
Hepatitis BKEGGhsa05161
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205
Estrogen signaling pathwayKEGGhsa04915
Estrogen signaling pathwayKEGGko04915
Prolactin signaling pathwayKEGGhsa04917
Prolactin signaling pathwayKEGGko04917
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206
Ras signaling pathwayKEGGhsa04014
Rap1 signaling pathwayKEGGhsa04015
Rap1 signaling pathwayKEGGko04015
FoxO signaling pathwayKEGGhsa04068
Thyroid hormone signaling pathwayKEGGhsa04919
Oxytocin signaling pathwayKEGGhsa04921
Oxytocin signaling pathwayKEGGko04921
Signaling pathways regulating pluripotency of stem cellsKEGGhsa04550
Signaling pathways regulating pluripotency of stem cellsKEGGko04550
Central carbon metabolism in cancerKEGGhsa05230
Choline metabolism in cancerKEGGhsa05231
Central carbon metabolism in cancerKEGGko05230
Choline metabolism in cancerKEGGko05231
Sphingolipid signaling pathwayKEGGhsa04071
Sphingolipid signaling pathwayKEGGko04071
DiseaseREACTOMER-HSA-1643685
Diseases of signal transductionREACTOMER-HSA-5663202
Signaling by EGFR in CancerREACTOMER-HSA-1643713
Signaling by Ligand-Responsive EGFR Variants in CancerREACTOMER-HSA-5637815
Constitutive Signaling by Ligand-Responsive EGFR Cancer VariantsREACTOMER-HSA-1236382
Signaling by EGFRvIII in CancerREACTOMER-HSA-5637812
Constitutive Signaling by EGFRvIIIREACTOMER-HSA-5637810
Signaling by FGFR in diseaseREACTOMER-HSA-1226099
Signaling by FGFR1 in diseaseREACTOMER-HSA-5655302
Signaling by FGFR2 in diseaseREACTOMER-HSA-5655253
Signaling by FGFR3 in diseaseREACTOMER-HSA-5655332
Signaling by FGFR4 in diseaseREACTOMER-HSA-5655291
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
Signaling by the B Cell Receptor (BCR)REACTOMER-HSA-983705
Downstream signaling events of B Cell Receptor (BCR)REACTOMER-HSA-1168372
Activation of RAS in B cellsREACTOMER-HSA-1169092
Innate Immune SystemREACTOMER-HSA-168249
DAP12 interactionsREACTOMER-HSA-2172127
DAP12 signalingREACTOMER-HSA-2424491
RAF/MAP kinase cascadeREACTOMER-HSA-5673001
RAF activationREACTOMER-HSA-5673000
MAP2K and MAPK activationREACTOMER-HSA-5674135
Negative regulation of MAPK pathwayREACTOMER-HSA-5675221
Regulation of RAS by GAPsREACTOMER-HSA-5658442
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
FCERI mediated MAPK activationREACTOMER-HSA-2871796
C-type lectin receptors (CLRs)REACTOMER-HSA-5621481
CD209 (DC-SIGN) signalingREACTOMER-HSA-5621575
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Interleukin-2 signalingREACTOMER-HSA-451927
Interleukin receptor SHC signalingREACTOMER-HSA-912526
Interleukin-3, 5 and GM-CSF signalingREACTOMER-HSA-512988
HemostasisREACTOMER-HSA-109582
Cell surface interactions at the vascular wallREACTOMER-HSA-202733
Tie2 SignalingREACTOMER-HSA-210993
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
GRB2 events in EGFR signalingREACTOMER-HSA-179812
SHC1 events in EGFR signalingREACTOMER-HSA-180336
Signaling by FGFRREACTOMER-HSA-190236
Signaling by FGFR1REACTOMER-HSA-5654736
Downstream signaling of activated FGFR1REACTOMER-HSA-5654687
FRS-mediated FGFR1 signalingREACTOMER-HSA-5654693
SHC-mediated cascade:FGFR1REACTOMER-HSA-5654688
Signaling by FGFR2REACTOMER-HSA-5654738
Downstream signaling of activated FGFR2REACTOMER-HSA-5654696
FRS-mediated FGFR2 signalingREACTOMER-HSA-5654700
SHC-mediated cascade:FGFR2REACTOMER-HSA-5654699
Signaling by FGFR3REACTOMER-HSA-5654741
Downstream signaling of activated FGFR3REACTOMER-HSA-5654708
FRS-mediated FGFR3 signalingREACTOMER-HSA-5654706
SHC-mediated cascade:FGFR3REACTOMER-HSA-5654704
Signaling by FGFR4REACTOMER-HSA-5654743
Downstream signaling of activated FGFR4REACTOMER-HSA-5654716
FRS-mediated FGFR4 signalingREACTOMER-HSA-5654712
SHC-mediated cascade:FGFR4REACTOMER-HSA-5654719
Signaling by Insulin receptorREACTOMER-HSA-74752
Insulin receptor signalling cascadeREACTOMER-HSA-74751
IRS-mediated signallingREACTOMER-HSA-112399
SOS-mediated signallingREACTOMER-HSA-112412
Signalling by NGFREACTOMER-HSA-166520
NGF signalling via TRKA from the plasma membraneREACTOMER-HSA-187037
Signalling to ERKsREACTOMER-HSA-187687
Signalling to RASREACTOMER-HSA-167044
p38MAPK eventsREACTOMER-HSA-171007
Signalling to p38 via RIT and RINREACTOMER-HSA-187706
Prolonged ERK activation eventsREACTOMER-HSA-169893
Frs2-mediated activationREACTOMER-HSA-170968
ARMS-mediated activationREACTOMER-HSA-170984
Signaling by PDGFREACTOMER-HSA-186797
Downstream signal transductionREACTOMER-HSA-186763
Signaling by VEGFREACTOMER-HSA-194138
VEGFA-VEGFR2 PathwayREACTOMER-HSA-4420097
VEGFR2 mediated cell proliferationREACTOMER-HSA-5218921
Signaling by SCF-KITREACTOMER-HSA-1433557
Signaling by ERBB2REACTOMER-HSA-1227986
SHC1 events in ERBB2 signalingREACTOMER-HSA-1250196
GRB2 events in ERBB2 signalingREACTOMER-HSA-1963640
Signaling by ERBB4REACTOMER-HSA-1236394
SHC1 events in ERBB4 signalingREACTOMER-HSA-1250347
MAPK family signaling cascadesREACTOMER-HSA-5683057
MAPK1/MAPK3 signalingREACTOMER-HSA-5684996
Signaling by GPCRREACTOMER-HSA-372790
Gastrin-CREB signalling pathway via PKC and MAPKREACTOMER-HSA-881907
EGFR Transactivation by GastrinREACTOMER-HSA-2179392
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)REACTOMER-HSA-2404192
IGF1R signaling cascadeREACTOMER-HSA-2428924
SHC-related events triggered by IGF1RREACTOMER-HSA-2428933
IRS-related events triggered by IGF1RREACTOMER-HSA-2428928
Signaling by LeptinREACTOMER-HSA-2586552
Developmental BiologyREACTOMER-HSA-1266738
Axon guidanceREACTOMER-HSA-422475
NCAM signaling for neurite out-growthREACTOMER-HSA-375165
Phospholipase D signaling pathwayKEGGko04072
Phospholipase D signaling pathwayKEGGhsa04072
AGE-RAGE signaling pathway in diabetic complicationsKEGGko04933
AGE-RAGE signaling pathway in diabetic complicationsKEGGhsa04933
Longevity regulating pathwayKEGGhsa04211
Longevity regulating pathway - multiple speciesKEGGko04213
Longevity regulating pathway - multiple speciesKEGGhsa04213
Signaling by PTK6REACTOMER-HSA-8848021
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinasesREACTOMER-HSA-8849471
Signaling by FGFR3 point mutants in cancerREACTOMER-HSA-8853338
Signaling by FGFR3 fusions in cancerREACTOMER-HSA-8853334
EGFR tyrosine kinase inhibitor resistanceKEGGko01521
Endocrine resistanceKEGGko01522
EGFR tyrosine kinase inhibitor resistanceKEGGhsa01521
Endocrine resistanceKEGGhsa01522
RET signalingREACTOMER-HSA-8853659
Breast cancerKEGGko05224
Breast cancerKEGGhsa05224
Oncogenic MAPK signalingREACTOMER-HSA-6802957
Signaling by RAS mutantsREACTOMER-HSA-6802949
Signaling by high-kinase activity BRAF mutantsREACTOMER-HSA-6802948
Signaling by moderate kinase activity BRAF mutantsREACTOMER-HSA-6802946
Paradoxical activation of RAF signaling by kinase inactive BRAFREACTOMER-HSA-6802955
Signaling by BRAF and RAF fusionsREACTOMER-HSA-6802952
RAS signaling downstream of NF1 loss-of-function variantsREACTOMER-HSA-6802953
Signaling by METREACTOMER-HSA-6806834
MET activates RAS signalingREACTOMER-HSA-8851805
Apelin signaling pathwayKEGGhsa04371
Mitophagy - animalKEGGko04137
Mitophagy - animalKEGGhsa04137

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA10040cetuximabChemicalClinicalAnnotation, LabelAnnotation, VipGeneassociatedPD20978259, 22537608, 22734028, 23071293, 23090619, 23324806, 24727325, 25183481, 25210463, 26162609, 26371285, 26438111, 26812186, 27897268
PA162373091panitumumabChemicalClinicalAnnotation, LabelAnnotation, VipGeneassociatedPD20978259, 22537608, 22734028, 23071293, 23090619, 23324806, 24727325, 25183481, 25210463, 26162609, 26371285, 26438111, 26812186, 27897268
PA165946873vemurafenibChemicalLabelAnnotationassociated
PA166114911dabrafenibChemicalLabelAnnotationassociated
PA166114943regorafenibChemicalLabelAnnotationassociated
PA166115364trametinibChemicalLabelAnnotationassociated
PA166154663rs112445441VariantVipGeneassociated22734028, 23071293, 23090619, 25122432, 26371285, 20978259
PA166154665rs121913529VariantVipGeneassociated22734028, 25122432, 20978259
PA166184558ramucirumabChemicalLabelAnnotationassociated
PA166184566tipiracil / trifluridineChemicalLabelAnnotationassociated
PA24928ARAFGenePathwayassociated
PA25408BRAFGeneMultilinkAnnotation, Pathwayassociated14513361, 28362716
PA26880CRKGenePathwayassociated20124951
PA28127FGFR1GenePathwayassociated28362716
PA28180FLT1GenePathwayassociated28362716
PA28181FLT3GenePathwayassociated28362716
PA28183FLT4GenePathwayassociated28362716
PA30086KDRGenePathwayassociated28362716
PA30128KITGenePathwayassociated28362716
PA30592MAP3K1GenePathwayassociated
PA33148PDGFRBGenePathwayassociated28362716
PA34183RAF1GenePathwayassociated20124951, 28362716
PA34335RETGenePathwayassociated28362716
PA443622Carcinoma, Non-Small-Cell LungDiseaseVipGeneassociated25122432
PA445062NeoplasmsDiseaseClinicalAnnotationassociatedPD23324806, 24727325, 25183481, 25210463, 26162609, 27897268
PA445742Stomach NeoplasmsDiseaseMultilinkAnnotationassociated14513361
PA446108Colorectal NeoplasmsDiseaseClinicalAnnotation, MultilinkAnnotation, VipGeneassociatedPD12198537, 20978259, 22537608, 22734028, 23071293, 23090619, 26371285, 26812186
PA7360EGFRGenePathwayassociated

References

Pubmed IDYearTitleCitations
193397202009Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer.1044
193397202009Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer.1044
189460612008K-ras mutations and benefit from cetuximab in advanced colorectal cancer.1039
189460612008K-ras mutations and benefit from cetuximab in advanced colorectal cancer.1039
183167912008Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer.910
198471662009Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1.707
206197392010Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis.666
206197392010Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis.666
166187172006KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer.634
240248392013Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer.629

Citation

Franz Watzinger ; Thomas Lion

KRAS (Kirsten rat sarcoma 2 viral oncogene homolog)

Atlas Genet Cytogenet Oncol Haematol. 1999-02-01

Online version: http://atlasgeneticsoncology.org/gene/91/kras-(kirsten-rat-sarcoma-2-viral-oncogene-homolog)