Alt. symbols: KRAS2 | KRAS1

Approved name: KRAS proto-oncogene, GTPase
Alt. names: 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

Location: 12p12.1: 25205246 - 25250936 (-)
Gene type: protein_coding, 14 transcripts.

Scores: LoFtool: 0.190000 | pLI: 0.00106119 | LOEUF: 1.240

HGNC: 6407

NCBI: 3845, RefSeq: NG_007524.2

Ensembl: ENSG00000133703.14

LRG_344 | Status: public

OMIM: 190070

Expression | ProteinAtlas

Gene Ontology (GO)

• Molecular function: GTPase activity [GO:0003924]; GTP binding [GO:0005525]; GDP binding [GO:0019003]
• Cell component: plasma membrane [GO:0005886]
• Biological process: Ras protein signal transduction [GO:0007265]

Normal function

The KRAS gene encodes the protein K-Ras, which is part of the RAS/MAPK signaling pathway. This pathway relays extracellular signals to the cell's nucleus that instruct the cell to proliferate or to mature and differentiate. The K-Ras protein is a GTPase (it converts GTP into GDP molecules), which acts like a switch that is turned on and off by the presence of GTP and GDP molecules. That is, it must bind to a GTP molecule in order to be turned on and transmit signals. However, when the protein is bound to GDP, it gets inactivated and it cannot relay signals to the cell's nucleus. The KRAS gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous. The KRAS gene is in the Ras family of oncogenes, which also includes two other genes: HRAS and NRAS. These proteins play important roles in cell division, cell differentiation, and apoptosis.

Dysfunction and disease

Heterozygous germline and somatic mutations in this gene have been associated with various types of cancers and syndromes, such as Cardiofaciocutaneous syndrome 2 [MIM:615278], KRAS mutation-associated phenotype, or Noonan syndrome 3 [MIM:609942]. Germline mutations associated with any of these syndromes lead to the production of a protein with increased GTP binding capacity and a decreased ability to convert GTP to GDP. These effects lead to prolonged activation of the K-Ras protein, which alte rs tightly regulated RAS/MAPK signaling during development. The altered signaling interferes with the development of many body organs and tissues, leading to the features of CFCS. As stated above, somatic mutations in the KRAS gene are involved in the development of several types of cancer, particularly pancreatic, colorectal and lung cancers, or proliferative syndromes like the RAS-associated autoimmune leukoproliferative disorder (MIM#614470). These mutations lead to a K-Ras protein that is more strongly overactivated than the mutations that cause CFCS. The abnormal K-Ras protein is always active and can direct cells to proliferate in an uncontrolled way. Curiously, nearly all of the somatic KRAS mutations associated with lung cancer change the amino acid glycine at position 12 or 13 (Gly12 or Gly13) or change the amino acid glutamine at position 61 (Gln61) in the K-Ras protein. These mutations result in a K-Ras protein that is constitutively activated and directing cells to proliferate in an uncontrolled way, which leads to tumor formation. KRAS gene mutations are found in 15-25% of all lung cancer cases: KRAS mutations are found in 25-50% of whites with lung cancer, but only in 5-15% of Asians with lung cancers. Of note, KRAS mutations are much more common in long-term tobacco smokers with lung cancer than in nonsmokers. Lung cancers with KRAS gene mutations typically indicate a poor prognosis and are associated with resistance to several cancer treatments. [Load More]