NRAS

The NRAS gene provides instructions for making a protein called N-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 N-Ras protein is a GTPase, which means it converts a molecule called GTP into another molecule called GDP. The N-Ras protein acts like a switch, and it is turned on and off by the GTP and GDP molecules. To transmit signals, the N-Ras protein must be turned on by attaching (binding) to a molecule of GTP. The N-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 NRAS gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous. The NRAS gene is in the Ras family of oncogenes, which also includes two other genes: HRAS and KRAS. 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 NRAS gene

At least two mutations in the NRAS gene have been found to cause Noonan syndrome. These mutations replace single protein building blocks (amino acids) in the N-Ras protein. One mutation replaces the amino acid threonine with the amino acid isoleucine at position 50 (written Thr50Ile or T50I) in the N-Ras protein. The other mutation replaces the amino acid glycine with the amino acid glutamic acid at position 60 (written Gly60Glu or G60E) in the N-Ras protein.

Mutations in the NRAS gene that cause Noonan syndrome lead to the production of altered N-Ras proteins that show increased GTP-binding and a decreased ability to convert GTP to GDP. 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 N-Ras protein disrupts the normal growth and maturation of certain tissues. Researchers believe that increased N-Ras activation leading to defective cell movement and differentiation could play a role in the signs and symptoms of Noonan syndrome, including short stature, heart defects, and skeletal abnormalities.

cancers - increased risk from variations of the NRAS 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 NRAS gene are involved in the development of several types of cancer. These mutations lead to an N-Ras protein that is always active and can direct cells to grow and divide without control. Studies suggest that NRAS gene mutations are common in an aggressive form of skin cancer called melanoma. Mutations in the NRAS gene have also been found in other types of cancer.

However, for reasons that are unclear, inherited mutations in the NRAS gene do not appear to increase the risk of cancer in people with Noonan syndrome.