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Gene Review

KRAS  -  Kirsten rat sarcoma viral oncogene homolog

Homo sapiens

Synonyms: C-K-RAS, CFC2, GTPase KRas, K-RAS2A, K-RAS2B, ...
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Disease relevance of KRAS


High impact information on KRAS

  • In 43 individuals with CFC, we identified two heterozygous KRAS mutations in three individuals and eight BRAF mutations in 16 individuals, suggesting that dysregulation of the RAS-RAF-ERK pathway is a common molecular basis for the three related disorders [9].
  • Germline KRAS mutations cause Noonan syndrome [10].
  • Furthermore, we found that whereas a gene-expression signature of KRAS2 activation was not identifiable when analyzing human tumors with known KRAS2 mutation status alone, integrating mouse and human data uncovered a gene-expression signature of KRAS2 mutation in human lung cancer [11].
  • An oncogenic KRAS2 expression signature identified by cross-species gene-expression analysis [11].
  • Serum HCV RNA was detected by a "nested" polymerase-chain-reaction (PCR) assay that used two sets of primers derived from the third (NS3) and fourth (NS4) non-structural gene regions of the HCV genome [12].

Chemical compound and disease context of KRAS


Biological context of KRAS


Anatomical context of KRAS


Associations of KRAS with chemical compounds

  • KRAS mutations (21% of tumors) were associated with significantly decreased TTP and survival in erlotinib plus chemotherapy-treated patients [14].
  • P14 was designed with a 15-base sequence complementary to the antisense strand of KRAS at the GAT (Asp) mutation and conjugated to the nuclear localization signal peptide PKKKRKV [16].
  • Compared to ICC that was not associated with Thorotrast, the frequency of mutation of the KRAS gene was lower, while that of the TP53 gene was more than two times higher [26].
  • Our results represent the first induction of KRAS gene rearrangement in cells of patients with familiar polyposis coli (FPC) treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 12-0-tetradecanoyl-phorbol-13-acetate (TPA) [27].
  • KRAS mutations were more common in African Americans with an odds ratio of 2.4 (P = 0.048), as were serine mutations, although the latter did not reach statistical significance (odds ratio, 2.6; P = 0.373) [28].

Physical interactions of KRAS

  • GRB7 binding may be involved in the activation of RAS signaling and KRAS2 maps to 12p, which is constitutively gained in TGCT and lies within a minimum overlapping region of amplification at 12p11.2-12.1, a region we have previously defined [29].
  • We previously demonstrated that an N-terminal portion of NS3 formed a complex with the tumor suppressor p53 and suppressed actinomycin D-induced apoptosis [30].

Enzymatic interactions of KRAS

  • We then determined whether the KRAS basic domain peptide plays a role similar to that of poly(L-lysine) and found that both the HRAS protein and calmodulin are phosphorylated by the receptor kinase in the presence of the KRAS basic domain peptide [31].

Regulatory relationships of KRAS


Other interactions of KRAS


Analytical, diagnostic and therapeutic context of KRAS


  1. Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Dews, M., Homayouni, A., Yu, D., Murphy, D., Sevignani, C., Wentzel, E., Furth, E.E., Lee, W.M., Enders, G.H., Mendell, J.T., Thomas-Tikhonenko, A. Nat. Genet. (2006) [Pubmed]
  2. Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. Tartaglia, M., Pennacchio, L.A., Zhao, C., Yadav, K.K., Fodale, V., Sarkozy, A., Pandit, B., Oishi, K., Martinelli, S., Schackwitz, W., Ustaszewska, A., Martin, J., Bristow, J., Carta, C., Lepri, F., Neri, C., Vasta, I., Gibson, K., Curry, C.J., Siguero, J.P., Digilio, M.C., Zampino, G., Dallapiccola, B., Bar-Sagi, D., Gelb, B.D. Nat. Genet. (2007) [Pubmed]
  3. Colorectal cancer with mutation in BRAF, KRAS, and wild-type with respect to both oncogenes showing different patterns of DNA methylation. Nagasaka, T., Sasamoto, H., Notohara, K., Cullings, H.M., Takeda, M., Kimura, K., Kambara, T., MacPhee, D.G., Young, J., Leggett, B.A., Jass, J.R., Tanaka, N., Matsubara, N. J. Clin. Oncol. (2004) [Pubmed]
  4. Similarity of the phenotypic patterns associated with BRAF and KRAS mutations in colorectal neoplasia. Yuen, S.T., Davies, H., Chan, T.L., Ho, J.W., Bignell, G.R., Cox, C., Stephens, P., Edkins, S., Tsui, W.W., Chan, A.S., Futreal, P.A., Stratton, M.R., Wooster, R., Leung, S.Y. Cancer Res. (2002) [Pubmed]
  5. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Shigematsu, H., Takahashi, T., Nomura, M., Majmudar, K., Suzuki, M., Lee, H., Wistuba, I.I., Fong, K.M., Toyooka, S., Shimizu, N., Fujisawa, T., Minna, J.D., Gazdar, A.F. Cancer Res. (2005) [Pubmed]
  6. Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma. Riely, G.J., Kris, M.G., Rosenbaum, D., Marks, J., Li, A., Chitale, D.A., Nafa, K., Riedel, E.R., Hsu, M., Pao, W., Miller, V.A., Ladanyi, M. Clin. Cancer Res. (2008) [Pubmed]
  7. KRAS mutation in stage III colon cancer and clinical outcome following intergroup trial CALGB 89803. Ogino, S., Meyerhardt, J.A., Irahara, N., Niedzwiecki, D., Hollis, D., Saltz, L.B., Mayer, R.J., Schaefer, P., Whittom, R., Hantel, A., Benson, A.B., Goldberg, R.M., Bertagnolli, M.M., Fuchs, C.S. Clin. Cancer Res. (2009) [Pubmed]
  8. Detection of KRAS oncogene in peripheral blood as a predictor of the response to cetuximab plus chemotherapy in patients with metastatic colorectal cancer. Yen, L.C., Yeh, Y.S., Chen, C.W., Wang, H.M., Tsai, H.L., Lu, C.Y., Chang, Y.T., Chu, K.S., Lin, S.R., Wang, J.Y. Clin. Cancer Res. (2009) [Pubmed]
  9. Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. Niihori, T., Aoki, Y., Narumi, Y., Neri, G., Cavé, H., Verloes, A., Okamoto, N., Hennekam, R.C., Gillessen-Kaesbach, G., Wieczorek, D., Kavamura, M.I., Kurosawa, K., Ohashi, H., Wilson, L., Heron, D., Bonneau, D., Corona, G., Kaname, T., Naritomi, K., Baumann, C., Matsumoto, N., Kato, K., Kure, S., Matsubara, Y. Nat. Genet. (2006) [Pubmed]
  10. Germline KRAS mutations cause Noonan syndrome. Schubbert, S., Zenker, M., Rowe, S.L., Böll, S., Klein, C., Bollag, G., van der Burgt, I., Musante, L., Kalscheuer, V., Wehner, L.E., Nguyen, H., West, B., Zhang, K.Y., Sistermans, E., Rauch, A., Niemeyer, C.M., Shannon, K., Kratz, C.P. Nat. Genet. (2006) [Pubmed]
  11. An oncogenic KRAS2 expression signature identified by cross-species gene-expression analysis. Sweet-Cordero, A., Mukherjee, S., Subramanian, A., You, H., Roix, J.J., Ladd-Acosta, C., Mesirov, J., Golub, T.R., Jacks, T. Nat. Genet. (2005) [Pubmed]
  12. A long-term study of hepatitis C virus replication in non-A, non-B hepatitis. Farci, P., Alter, H.J., Wong, D., Miller, R.H., Shih, J.W., Jett, B., Purcell, R.H. N. Engl. J. Med. (1991) [Pubmed]
  13. Germline missense mutations affecting KRAS Isoform B are associated with a severe Noonan syndrome phenotype. Carta, C., Pantaleoni, F., Bocchinfuso, G., Stella, L., Vasta, I., Sarkozy, A., Digilio, C., Palleschi, A., Pizzuti, A., Grammatico, P., Zampino, G., Dallapiccola, B., Gelb, B.D., Tartaglia, M. Am. J. Hum. Genet. (2006) [Pubmed]
  14. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. Eberhard, D.A., Johnson, B.E., Amler, L.C., Goddard, A.D., Heldens, S.L., Herbst, R.S., Ince, W.L., Jänne, P.A., Januario, T., Johnson, D.H., Klein, P., Miller, V.A., Ostland, M.A., Ramies, D.A., Sebisanovic, D., Stinson, J.A., Zhang, Y.R., Seshagiri, S., Hillan, K.J. J. Clin. Oncol. (2005) [Pubmed]
  15. Determination of TP53 mutation is more relevant than microsatellite instability status for the prediction of disease-free survival in adjuvant-treated stage III colon cancer patients. Westra, J.L., Schaapveld, M., Hollema, H., de Boer, J.P., Kraak, M.M., de Jong, D., ter Elst, A., Mulder, N.H., Buys, C.H., Hofstra, R.M., Plukker, J.T. J. Clin. Oncol. (2005) [Pubmed]
  16. Transcription inhibition of oncogenic KRAS by a mutation-selective peptide nucleic acid conjugated to the PKKKRKV nuclear localization signal peptide. Cogoi, S., Codognotto, A., Rapozzi, V., Meeuwenoord, N., van der Marel, G., Xodo, L.E. Biochemistry (2005) [Pubmed]
  17. The cardiofaciocutaneous syndrome. Roberts, A., Allanson, J., Jadico, S.K., Kavamura, M.I., Noonan, J., Opitz, J.M., Young, T., Neri, G. J. Med. Genet. (2006) [Pubmed]
  18. Inactivation of the mitogen-activated protein kinase pathway as a potential target-based therapy in ovarian serous tumors with KRAS or BRAF mutations. Pohl, G., Ho, C.L., Kurman, R.J., Bristow, R., Wang, T.L., Shih, I.e.M. Cancer Res. (2005) [Pubmed]
  19. A genetically defined model for human ovarian cancer. Liu, J., Yang, G., Thompson-Lanza, J.A., Glassman, A., Hayes, K., Patterson, A., Marquez, R.T., Auersperg, N., Yu, Y., Hahn, W.C., Mills, G.B., Bast, R.C. Cancer Res. (2004) [Pubmed]
  20. Aneuploidy Arises at Early Stages of Apc-Driven Intestinal Tumorigenesis and Pinpoints Conserved Chromosomal Loci of Allelic Imbalance between Mouse and Human. Alberici, P., de Pater, E., Cardoso, J., Bevelander, M., Molenaar, L., Jonkers, J., Fodde, R. Am. J. Pathol. (2007) [Pubmed]
  21. Characterization of active mitogen-activated protein kinase in ovarian serous carcinomas. Hsu, C.Y., Bristow, R., Cha, M.S., Wang, B.G., Ho, C.L., Kurman, R.J., Wang, T.L., Shih, I.e.M. Clin. Cancer Res. (2004) [Pubmed]
  22. KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas. Smit, V.T., Boot, A.J., Smits, A.M., Fleuren, G.J., Cornelisse, C.J., Bos, J.L. Nucleic Acids Res. (1988) [Pubmed]
  23. Loss of heterozygosity of chromosome 12p does not correlate with KRAS mutation in non-small cell lung cancer. Uchiyama, M., Usami, N., Kondo, M., Mori, S., Ito, M., Ito, G., Yoshioka, H., Imaizumi, M., Ueda, Y., Takahashi, M., Minna, J.D., Shimokata, K., Sekido, Y. Int. J. Cancer (2003) [Pubmed]
  24. APC and Oncogenic KRAS Are Synergistic in Enhancing Wnt Signaling in Intestinal Tumor Formation and Progression. Janssen, K.P., Alberici, P., Fsihi, H., Gaspar, C., Breukel, C., Franken, P., Rosty, C., Abal, M., El Marjou, F., Smits, R., Louvard, D., Fodde, R., Robine, S. Gastroenterology (2006) [Pubmed]
  25. Expression of wild-type and mutant simian virus 40 large tumor antigens in villus-associated enterocytes of transgenic mice. Kim, S.H., Roth, K.A., Coopersmith, C.M., Pipas, J.M., Gordon, J.I. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  26. Analysis of genetic changes in intrahepatic cholangiocarcinoma induced by thorotrast. Kamikawa, T., Amenomori, M., Itoh, T., Momoi, H., Hiai, H., Machinami, R., Ishikawa, Y., Mori, T., Shimahara, Y., Yamaoka, Y., Fukumoto, M. Radiat. Res. (1999) [Pubmed]
  27. Transformation of primate cells by chemicals and oncogenes: requirements for multiple factors. Khoobyarian, N., Marczynska, B. Anticancer Res. (1989) [Pubmed]
  28. Differences in KRAS mutation spectrum in lung cancer cases between African Americans and Caucasians after occupational or environmental exposure to known carcinogens. Hunt, J.D., Strimas, A., Martin, J.E., Eyer, M., Haddican, M., Luckett, B.G., Ruiz, B., Axelrad, T.W., Backes, W.L., Fontham, E.T. Cancer Epidemiol. Biomarkers Prev. (2002) [Pubmed]
  29. Activating mutations and/or expression levels of tyrosine kinase receptors GRB7, RAS, and BRAF in testicular germ cell tumors. McIntyre, A., Summersgill, B., Spendlove, H.E., Huddart, R., Houlston, R., Shipley, J. Neoplasia (2005) [Pubmed]
  30. Single-point mutations of hepatitis C virus NS3 that impair p53 interaction and anti-apoptotic activity of NS3. Tanaka, M., Nagano-Fujii, M., Deng, L., Ishido, S., Sada, K., Hotta, H. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  31. In vitro tyrosine phosphorylation studies on RAS proteins and calmodulin suggest that polylysine-like basic peptides or domains may be involved in interactions between insulin receptor kinase and its substrate. Fujita-Yamaguchi, Y., Kathuria, S., Xu, Q.Y., McDonald, J.M., Nakano, H., Kamata, T. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  32. Concomitant RASSF1A hypermethylation and KRAS/BRAF mutations occur preferentially in MSI sporadic colorectal cancer. Oliveira, C., Velho, S., Domingo, E., Preto, A., Hofstra, R.M., Hamelin, R., Yamamoto, H., Seruca, R., Schwartz, S. Oncogene (2005) [Pubmed]
  33. Hepatitis C core and nonstructural 3 proteins trigger toll-like receptor 2-mediated pathways and inflammatory activation. Dolganiuc, A., Oak, S., Kodys, K., Golenbock, D.T., Finberg, R.W., Kurt-Jones, E., Szabo, G. Gastroenterology (2004) [Pubmed]
  34. Transforming growth factor beta1 treatment leads to an epithelial-mesenchymal transdifferentiation of pancreatic cancer cells requiring extracellular signal-regulated kinase 2 activation. Ellenrieder, V., Hendler, S.F., Boeck, W., Seufferlein, T., Menke, A., Ruhland, C., Adler, G., Gress, T.M. Cancer Res. (2001) [Pubmed]
  35. Expression of cyclin D1 and c-Ki-ras gene product in human epithelial ovarian tumors. Hung, W.C., Chai, C.Y., Huang, J.S., Chuang, L.Y. Hum. Pathol. (1996) [Pubmed]
  36. Wild-type, but not mutant-type, p53 enhances nuclear accumulation of the NS3 protein of hepatitis C virus. Ishido, S., Muramatsu, S., Fujita, T., Iwanaga, Y., Tong, W.Y., Katayama, Y., Itoh, M., Hotta, H. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  37. BRAF mutations in papillary carcinomas of the thyroid. Fukushima, T., Suzuki, S., Mashiko, M., Ohtake, T., Endo, Y., Takebayashi, Y., Sekikawa, K., Hagiwara, K., Takenoshita, S. Oncogene (2003) [Pubmed]
  38. Frequent alterations of Ras signaling pathway genes in sporadic malignant melanomas. Reifenberger, J., Knobbe, C.B., Sterzinger, A.A., Blaschke, B., Schulte, K.W., Ruzicka, T., Reifenberger, G. Int. J. Cancer (2004) [Pubmed]
  39. Colorectal cancer with and without microsatellite instability involves different genes. Salahshor, S., Kressner, U., Pâhlman, L., Glimelius, B., Lindmark, G., Lindblom, A. Genes Chromosomes Cancer (1999) [Pubmed]
  40. The prevalence of PIK3CA mutations in gastric and colon cancer. Velho, S., Oliveira, C., Ferreira, A., Ferreira, A.C., Suriano, G., Schwartz, S., Duval, A., Carneiro, F., Machado, J.C., Hamelin, R., Seruca, R. Eur. J. Cancer (2005) [Pubmed]
  41. Advanced colorectal polyps with the molecular and morphological features of serrated polyps and adenomas: concept of a 'fusion' pathway to colorectal cancer. Jass, J.R., Baker, K., Zlobec, I., Higuchi, T., Barker, M., Buchanan, D., Young, J. Histopathology (2006) [Pubmed]
  42. Mutations of the BRAF gene in cholangiocarcinoma but not in hepatocellular carcinoma. Tannapfel, A., Sommerer, F., Benicke, M., Katalinic, A., Uhlmann, D., Witzigmann, H., Hauss, J., Wittekind, C. Gut (2003) [Pubmed]
  43. Mutation analysis of CDP, TP53, and KRAS in uterine leiomyomas. Patrikis, M.I., Bryan, E.J., Thomas, N.A., Rice, G.E., Quinn, M.A., Baker, M.S., Campbell, I.G. Mol. Carcinog. (2003) [Pubmed]
  44. RAS mutation in acute myeloid leukemia is associated with distinct cytogenetic subgroups but does not influence outcome in patients younger than 60 years. Bowen, D.T., Frew, M.E., Hills, R., Gale, R.E., Wheatley, K., Groves, M.J., Langabeer, S.E., Kottaridis, P.D., Moorman, A.V., Burnett, A.K., Linch, D.C. Blood (2005) [Pubmed]
  45. N- and KRAS mutations in primary testicular germ cell tumors: incidence and possible biological implications. Olie, R.A., Looijenga, L.H., Boerrigter, L., Top, B., Rodenhuis, S., Langeveld, A., Mulder, M.P., Oosterhuis, J.W. Genes Chromosomes Cancer (1995) [Pubmed]
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