KRAS (Kirsten rat sarcoma 2 viral oncogene homolog)
1999-02-01 Franz Watzinger , Thomas Lion AffiliationChildrens 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
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
Entity name
pancreas (80-90%)
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colon and rectum (25-60%)
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lung (25-60%)
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prostate (0-25%)
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skin (0-25%)
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thyroid (0-60%)
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liver (10-25%)
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ovary (0-50%)
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endometrium (10-40%)
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kidney (0-50%)
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brain (0-15%)
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testis (seminoma) (10-45%)
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acute non lymphocytic leukemia and myelodysplasia (5-15%)
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urinary bladder (5%)
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head and neck (10%)
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breast (10%)
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 2114981 | 1990 | ras oncogenes: their role in neoplasia. | Barbacid M et al |
| 2547513 | 1989 | ras oncogenes in human cancer: a review. | Bos JL et al |
| 1421167 | 1992 | ras activation in experimental carcinogenesis. | Mangues R et al |
| 3307760 | 1987 | Human 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
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA10040 | cetuximab | Chemical | ClinicalAnnotation, LabelAnnotation, VipGene | associated | PD | 20978259, 22537608, 22734028, 23071293, 23090619, 23324806, 24727325, 25183481, 25210463, 26162609, 26371285, 26438111, 26812186, 27897268 | |
| PA162373091 | panitumumab | Chemical | ClinicalAnnotation, LabelAnnotation, VipGene | associated | PD | 20978259, 22537608, 22734028, 23071293, 23090619, 23324806, 24727325, 25183481, 25210463, 26162609, 26371285, 26438111, 26812186, 27897268 | |
| PA165946873 | vemurafenib | Chemical | LabelAnnotation | associated | |||
| PA166114911 | dabrafenib | Chemical | LabelAnnotation | associated | |||
| PA166114943 | regorafenib | Chemical | LabelAnnotation | associated | |||
| PA166115364 | trametinib | Chemical | LabelAnnotation | associated | |||
| PA166154663 | rs112445441 | Variant | VipGene | associated | 22734028, 23071293, 23090619, 25122432, 26371285, 20978259 | ||
| PA166154665 | rs121913529 | Variant | VipGene | associated | 22734028, 25122432, 20978259 | ||
| PA166184558 | ramucirumab | Chemical | LabelAnnotation | associated | |||
| PA166184566 | tipiracil / trifluridine | Chemical | LabelAnnotation | associated | |||
| PA24928 | ARAF | Gene | Pathway | associated | |||
| PA25408 | BRAF | Gene | MultilinkAnnotation, Pathway | associated | 14513361, 28362716 | ||
| PA26880 | CRK | Gene | Pathway | associated | 20124951 | ||
| PA28127 | FGFR1 | Gene | Pathway | associated | 28362716 | ||
| PA28180 | FLT1 | Gene | Pathway | associated | 28362716 | ||
| PA28181 | FLT3 | Gene | Pathway | associated | 28362716 | ||
| PA28183 | FLT4 | Gene | Pathway | associated | 28362716 | ||
| PA30086 | KDR | Gene | Pathway | associated | 28362716 | ||
| PA30128 | KIT | Gene | Pathway | associated | 28362716 | ||
| PA30592 | MAP3K1 | Gene | Pathway | associated | |||
| PA33148 | PDGFRB | Gene | Pathway | associated | 28362716 | ||
| PA34183 | RAF1 | Gene | Pathway | associated | 20124951, 28362716 | ||
| PA34335 | RET | Gene | Pathway | associated | 28362716 | ||
| PA443622 | Carcinoma, Non-Small-Cell Lung | Disease | VipGene | associated | 25122432 | ||
| PA445062 | Neoplasms | Disease | ClinicalAnnotation | associated | PD | 23324806, 24727325, 25183481, 25210463, 26162609, 27897268 | |
| PA445742 | Stomach Neoplasms | Disease | MultilinkAnnotation | associated | 14513361 | ||
| PA446108 | Colorectal Neoplasms | Disease | ClinicalAnnotation, MultilinkAnnotation, VipGene | associated | PD | 12198537, 20978259, 22537608, 22734028, 23071293, 23090619, 26371285, 26812186 | |
| PA7360 | EGFR | Gene | Pathway | associated |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37589222 | 2024 | Increased KRAS G12C Prevalence, High Tumor Mutational Burden, and Specific Mutational Signatures Are Associated With MUTYH Mutations: A Pan-Cancer Analysis. | 0 |
| 37721193 | 2024 | Overall signature of acquired KRAS gene changes in advanced non-small cell lung cancer patient with EGFR-TKI resistance. | 1 |
| 37771286 | 2024 | KRAS mutations in pancreatic cancer: could we talk about a risk factor for the development of thromboembolic phenomena? | 0 |
| 37817679 | 2024 | Impact of the STK11/KRAS co-mutation on the response to immunotherapy in a real-world pan-cancer cohort. | 1 |
| 37852325 | 2024 | NRF2 interacts with distal enhancer and inhibits nitric oxide synthase 2 expression in KRAS-driven pancreatic cancer cells. | 1 |
| 37857983 | 2024 | Conditional Overall Survival After Diagnosis of Non-Metastatic Colon Cancer: Impact of Laterality, MSI, and KRAS Status. | 0 |
| 37897365 | 2024 | Mutual promotion of co-condensation of KRAS G-quadruplex and a well-folded protein HMGB1. | 2 |
| 37897621 | 2024 | An Updated Review on KRAS Mutation in Lung Cancer (NSCLC) and Its Effects on Human Health. | 0 |
| 37943166 | 2024 | Effects of KRAS Genetic Interactions on Outcomes in Cancers of the Lung, Pancreas, and Colorectum. | 0 |
| 37968341 | 2024 | STK11 loss leads to YAP1-mediated transcriptional activation in human KRAS-driven lung adenocarcinoma cell lines. | 1 |
| 38016110 | 2024 | One Mutation to Rule Them All: Mutant KRAS Controls Tumor Intrinsic and Microenvironment Signaling. | 0 |
| 38029547 | 2024 | Driver gene KRAS aggravates cancer-associated stroke outcomes. | 0 |
| 38040818 | 2024 | Opposing roles by KRAS and BRAF mutation on immune cell infiltration in colorectal cancer - possible implications for immunotherapy. | 3 |
| 38070788 | 2024 | Functional pri-miR-34b/c rs4938723 and KRAS 3'UTR rs61764370 SNPs: Novel phenotype modifiers in Li-Fraumeni Syndrome? | 0 |
| 38109937 | 2024 | The energetic and allosteric landscape for KRAS inhibition. | 8 |
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
