KRAS

The KRAS gene provides instructions for making a protein called K-Ras that is involved primarily in regulating cell division. Through a process known as signal transduction, 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 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. KRAS is in the Ras family of oncogenes, which also includes two other genes: HRAS and NRAS. The proteins produced from these three genes are GTPases. These proteins play important roles in cell division, cell differentiation, and the self-destruction of cells (apoptosis).

Noonan syndrome - caused by mutations in the KRAS gene

Mutations in the KRAS gene have caused a small number of cases of severe or atypical Noonan syndrome. Intellectual disability is more common in people who have Noonan syndrome with a KRAS mutation than in people with Noonan syndrome caused by a mutation in a different gene.

Each of the KRAS mutations changes a single protein building block (amino acid) in a critical region of the K-Ras protein, which causes the protein to be continuously active. Instead of triggering cell growth in response to particular signals from outside the cell, the overactive protein directs cells to grow and divide constantly. During embryonic development, the overactive K-Ras protein disrupts the normal growth and maturation of certain tissues. Researchers believe that increased K-Ras activation leading to defective cell movement and differentiation could play a role in the signs and symptoms of Noonan syndrome, including short stature and facial abnormalities.

cancers - increased risk from variations of the KRAS gene

Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. Somatic mutations in the KRAS gene are involved in the development of several types of cancer. These mutations lead to a K-Ras protein that is always active and can direct cells to grow and divide without control. Studies suggest that KRAS gene mutations are common in pancreatic, lung, and colorectal cancers. Mutations in the KRAS gene have also been found in other types of cancer.

other disorders - caused by mutations in the KRAS gene

KRAS mutations also cause a disorder whose major features overlap with those of Noonan syndrome and two other genetic conditions, cardiofaciocutaneous (CFC) 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. Each of these mutations changes a single amino acid 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.