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This gene, a Kirsten ras oncogene homolog from the mammalian ras gene family, encodes a protein that is a member of the small GTPase superfamily. A single amino acid substitution is responsible for an activating mutation. The transforming protein that results is implicated in various malignancies, including lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma. Alternative splicing leads to variants encoding two isoforms that differ in the C-terminal region. [provided by RefSeq, Jul 2008]
Mutations in the RAS family of proteins are frequently observed across cancer types. The amino acid positions that account for the overwhelming majority of these mutations are G12, G13 and Q61. The different protein isoforms, despite their raw similarity, also behave very differently when expressed in non-native tissue types, likely due to differences in the C-terminal hyper-variable regions. Mis-regulation of isoform expression has been shown to be a driving event in cancer, as well as missense mutations at the three hotspots previously mentioned. While highly recurrent in cancer, attempts to target these RAS mutants with inhibitors have not been successful, and has not yet become common practice in the clinic. The prognostic implications for KRAS mutations vary between cancer types, but have been shown to be associated with poor outcome in colorectal cancer, non-small cell lung cancer, and others.
KRAS (KRAS Proto-Oncogene, GTPase) is a Protein Coding gene. Diseases associated with KRAS include Oculoectodermal Syndrome and Schimmelpenning-Feuerstein-Mims Syndrome. Among its related pathways are MAPK Signaling: Oxidative Stress Pathway and Bladder cancer. Gene Ontology (GO) annotations related to this gene include GTP binding. An important paralog of this gene is NRAS.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0003924 | GTPase activity | IEA,IBA | 21873635 |
GO:0005515 | protein binding | IPI | 12732644 |
GO:0005525 | GTP binding | IEA,IBA | 21873635 |
GO:0016787 | hydrolase activity | IEA | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005737 | cytoplasm | IEA,IDA | 23698361 |
GO:0005739 | mitochondrion | IEA | -- |
GO:0005829 | cytosol | IEA | -- |
GO:0005886 | plasma membrane | TAS | -- |
GO:0005925 | focal adhesion | HDA | 21423176 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | RET signaling |
.92
|
.92
|
2 | Downstream signaling of activated FGFR2 | ||
3 | IL-2 Pathway |
ErbB Family Pathway
.59
ErbB4 Pathway
.59
Prolactin Signaling
.54
Thrombopoietin Pathway
.51
ErbB2-ErbB3 Heterodimers
.49
IL-2 Pathway
.48
|
LPS Stimulated MAPK Signaling
.47
UVC-Induced MAPK Signaling
.44
TREM1 Pathway
.43
HMGB1 Pathway
.36
PI3K Signaling in B-Lymphocyte
.35
IL-4 Pathway
.34
|
4 | Common Cytokine Receptor Gamma-Chain Family Signaling Pathways | ||
5 | Endometrial cancer |
.36
.32
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | TAS | -- |
GO:0001889 | liver development | IEA | -- |
GO:0001934 | positive regulation of protein phosphorylation | IMP | 22065586 |
GO:0002223 | stimulatory C-type lectin receptor signaling pathway | TAS | -- |
GO:0007165 | signal transduction | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Cetuximab | Approved | Pharma | Antibody, Biomarker, inhibitor | EGFR Inhibitors, Therapeutic Antibodies, Epidermal growth factor receptor (EGFR) inhibitors | 894 | |
Panitumumab | Approved, Investigational | Pharma | inhibitor, Biomarker, antibody | EGFR inhibitor, EGFR Inhibitors, Therapeutic Antibodies, Epidermal growth factor receptor (EGFR) inhibitors | 245 | |
Trametinib | Approved | Pharma | inhibitor, Biomarker | MEK 1/2 inhibitor, MEK Inhibitors, Kinase Inhibitors, Mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitors | 212 | |
Dabrafenib | Approved, Investigational | Pharma | BRAF kinase inhibitor, Kinase Inhibitors, Mutant BRAF Kinase | 133 | ||
Fludarabine | Approved | Pharma | DNA synthsis inhibitor | 1611,1611 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs |
---|
Compound | Action | Cas Number |
---|---|---|
6H05 | ||
AMG-47A | destabilizer of the KRAS oncoprotein | 882663-88-9 |
Deltarasin | KRAS-PDEδ interaction inhibitor | 1440898-61-2 |
Deltarasin hydrochloride | inhibitor of KRAS-PDEδ interaction, potent and selective | 1440898-82-7 |
Kobe0065 | Ras inhibitor | 436133-68-5 |
kobe2602 | Ras inhibitor | 454453-49-7 |
K-Ras(G12C) inhibitor 12 | 1469337-95-8 | |
K-Ras(G12C) inhibitor 6 | K-Ras (G12C) inhibitor | |
Salirasib | Inhibitor of active Ras protein | 162520-00-5 |
This gene was present in the common ancestor of animals and fungi.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | KRAS 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | KRAS 30 |
|
||
K-RAS 31 |
|
OneToOne | |||
Cow (Bos Taurus) |
Mammalia | KRAS 30 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | KRAS 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | KRAS 31 |
|
OneToMany | |
-- 31 |
|
OneToMany | |||
Rat (Rattus norvegicus) |
Mammalia | Kras 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Kras 30 17 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | KRAS 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | -- 31 |
|
OneToMany | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | LOC100485959 30 |
|
||
African clawed frog (Xenopus laevis) |
Amphibia | Xl.24980 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | kras 30 31 |
|
OneToOne | |
Fruit Fly (Drosophila melanogaster) |
Insecta | Ras85D 30 31 |
|
OneToMany | |
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP002219 30 |
|
||
Worm (Caenorhabditis elegans) |
Secernentea | let-60 30 31 |
|
OneToMany | |
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | RAS1 31 |
|
ManyToMany | |
RAS2 31 |
|
ManyToMany |
SNP ID | Clinical significance and condition | Chr 12 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
873193 | Uncertain Significance: Squamous cell lung carcinoma | 25,225,823(-) |
T/C NM_004985.5(KRAS):c.291-50A>G |
INTRON | |
883635 | Uncertain Significance: Noonan syndrome 3 | 25,245,266(-) |
A/C NM_004985.5(KRAS):c.111+8T>G |
INTRON | |
929160 | Uncertain Significance: not specified | 25,227,304(-) |
T/G NM_004985.5(KRAS):c.220A>C (p.Thr74Pro) |
MISSENSE | |
931154 | Uncertain Significance: Toriello-Lacassie-Droste syndrome | 25,209,825(-) |
CTTT/C NM_004985.5(KRAS):c.534_536del (p.Lys180del) |
INFRAME_DELETION,THREE_PRIME_UTR | |
935432 | Uncertain Significance: Rasopathy | 25,209,875(-) |
T/C NM_004985.5(KRAS):c.487A>G (p.Ile163Val) |
MISSENSE_VARIANT,THREE_PRIME_UTR |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv3580196 | CNV | loss | 25503493 |
esv3628892 | CNV | loss | 21293372 |
nsv1048631 | CNV | loss | 25217958 |
nsv470279 | CNV | gain | 18288195 |
nsv522233 | CNV | loss | 19592680 |
nsv557798 | CNV | loss | 21841781 |