autoimmune lymphoproliferative syndrome Genetics Home Reference provides information about autoimmune lymphoproliferative syndrome. cardiofaciocutaneous syndrome Mutations in the KRAS gene are an uncommon cause of cardiofaciocutaneous syndrome, accounting for less than 5 percent of cases. Several mutations in the KRAS gene have been identified in people with characteristic features of the disorder, which include heart defects, distinctive facial features, and skin abnormalities. The mutations change single protein building blocks (amino acids) in the K-Ras protein. The altered protein shows increased GTP binding and a decreased ability to convert GTP to GDP. These effects lead to prolonged activation of the K-Ras protein, which alters tightly regulated RAS/MAPK signaling during development. The altered signaling interferes with the development of organs and tissues throughout the body, leading to the varied signs and symptoms of cardiofaciocutaneous syndrome. cholangiocarcinoma Genetics Home Reference provides information about cholangiocarcinoma. core binding factor acute myeloid leukemia Genetics Home Reference provides information about core binding factor acute myeloid leukemia. epidermal nevus Genetics Home Reference provides information about epidermal nevus. lung cancer At least three mutations in the KRAS gene have been associated with lung cancer, a disease in which certain cells in the lung become abnormal and multiply uncontrollably to form a tumor. These mutations are somatic, which means they are acquired during a person's lifetime and are present only in tumor cells. Somatic mutations are not inherited. Nearly all of the KRAS gene 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 lead to a K-Ras protein that is constantly turned on (constitutively activated) and directing cells to grow and divide in an uncontrolled way, leading to tumor formation. When these gene changes occur in cells in the lungs, lung cancer develops. KRAS gene mutations are found in 15 to 25 percent of all lung cancer cases but are more frequent in affected white populations compared to affected Asian populations; 25 to 50 percent of whites with lung cancer have KRAS gene mutations, whereas 5 to 15 percent of Asians with lung cancer have KRAS gene mutations. While genetic, environmental, and lifestyle factors, including long-term tobacco smoking, contribute to a person's cancer risk, KRAS gene mutations are much more common in nonsmokers with lung cancer than in smokers. Lung cancers with KRAS gene mutations typically indicate a poor prognosis and resistance to several cancer treatments. Noonan syndrome Genetics Home Reference provides information about Noonan syndrome. other cancers Somatic mutations in the KRAS gene are involved in the development of several types of cancer, particularly pancreatic and colorectal cancers. These mutations lead to a K-Ras protein that is more strongly overactivated than the mutations that cause cardiofaciocutaneous syndrome (described above). The abnormal K-Ras protein is always active and can direct cells to grow and divide in an uncontrolled way. other disorders KRAS gene mutations also cause a disorder whose major features overlap with those of cardiofaciocutaneous syndrome and two related disorders called Noonan syndrome and Costello syndrome. This condition has been described as the KRAS mutation-associated phenotype. People with this condition have variable signs and symptoms that include mild to moderate intellectual disability, distinctive facial features, short stature, an unusually large head (macrocephaly), and hair that is sparse and thin. At least nine mutations in the KRAS gene have been reported in people with this disorder. These mutations are present in all of the body's cells and are known as germline mutations. Each of these mutations changes single amino acids in the K-Ras protein. These genetic changes abnormally activate the protein, which alters chemical signaling in cells throughout the body. The altered signaling interferes with the normal development of many organs and tissues, resulting in the characteristic features of the KRAS mutation-associated phenotype.

     The KRAS gene provides instructions for making a protein called K-Ras that is involved primarily in regulating cell division. As part of a signaling pathway known as the RAS/MAPK pathway, the protein relays signals from outside the cell to the cell's nucleus. These signals instruct the cell to grow and divide or to mature and take on specialized functions (differentiate). The K-Ras protein is a GTPase, which means it converts a molecule called GTP into another molecule called GDP. The K-Ras protein acts like a switch, and it is turned on and off by the GTP and GDP molecules. To transmit signals, the K-Ras protein must be turned on by attaching (binding) to a molecule of GTP. The K-Ras protein is turned off (inactivated) when it converts the GTP to GDP. When the protein is bound to GDP, it does not 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 the self-destruction of cells (apoptosis).

The following transcription factors affect gene expression:

• NF-kappaB
• PPAR-gamma1
• p53
• AP-1
• c-Jun
• NF-kappaB1
• STAT1
• STAT1beta
• STAT1alpha

Enzyme Regulation:

Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP). Interaction with SOS1 promotes exchange of bound GDP by GTP.

Molecular Function:

• Gtpase Activity
• Gtp Binding
• Gmp Binding
• Gdp Binding
• Protein Complex Binding

Biological Processes:

• Mapk Cascade
• Liver Development
• Positive Regulation Of Protein Phosphorylation
• Stimulatory C-Type Lectin Receptor Signaling Pathway
• Epidermal Growth Factor Receptor Signaling Pathway
• Ras Protein Signal Transduction
• Axon Guidance
• Positive Regulation Of Cell Proliferation
• Visual Learning
• Positive Regulation Of Gene Expression
• Cytokine-Mediated Signaling Pathway
• Forebrain Astrocyte Development
• Actin Cytoskeleton Organization
• Regulation Of Protein Stability
• Regulation Of Synaptic Transmission, Gabaergic
• Positive Regulation Of Rac Protein Signal Transduction
• Social Behavior
• Endocrine Signaling
• Fc-Epsilon Receptor Signaling Pathway
• Erbb2 Signaling Pathway
• Positive Regulation Of Map Kinase Activity
• Negative Regulation Of Neuron Apoptotic Process
• Negative Regulation Of Cell Differentiation
• Regulation Of Long-Term Neuronal Synaptic Plasticity
• Homeostasis Of Number Of Cells Within A Tissue
• Leukocyte Migration
• Positive Regulation Of Nitric-Oxide Synthase Activity
• Positive Regulation Of Nf-Kappab Transcription Factor Activity
• Striated Muscle Cell Differentiation
• Response To Glucocorticoid
• Response To Mineralocorticoid
• Epithelial Tube Branching Involved In Lung Morphogenesis
• Positive Regulation Of Cellular Senescence