HRAS

The HRAS gene provides instructions for making a protein called H-Ras that is involved primarily in regulating cell division. Through a process known as signal transduction, the H-Ras protein relays signals from outside the cell to the cell's nucleus. These signals instruct the cell to grow or divide. The H-Ras protein is a GTPase, which means it converts a molecule called GTP into another molecule, called GDP. The H-Ras protein acts like a switch, and it is turned on and off by GTP and GDP molecules. To transmit signals, the protein must be turned on (activated) by binding to a molecule called GTP. The protein is turned off (inactivated) when it converts GTP to GDP. When the protein is bound to GDP, it does not relay signals to the cell's nucleus.

HRAS is a member of a class of genes called oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous. HRAS is in the Ras family of oncogenes, which also includes two other genes: KRAS and NRAS. The proteins produced from these three genes are GTPases. These proteins play important roles in cell division, the process by which cells mature to carry out specific functions (cell differentiation), and the self-destruction of cells (apoptosis).

Costello syndrome - caused by mutations in the HRAS gene

At least eight mutations in the HRAS gene have been identified in people with Costello syndrome. Each of these mutations changes a single protein building block (amino acid) in a critical region of the H-Ras protein. The most common mutation is responsible for at least 80 percent of all cases of Costello syndrome. This genetic change replaces the amino acid glycine with the amino acid serine at protein position 12 (written as Gly12Ser or G12S).

The HRAS mutations that cause Costello syndrome lead to the production of an H-Ras protein that is continuously active in cells throughout the body. Instead of triggering cell growth in response to signals from outside the cell, the overactive protein directs cells to grow and divide constantly. This uncontrolled cell division can result in the formation of noncancerous and cancerous tumors. Researchers are uncertain how mutations in the HRAS gene cause the other features of Costello syndrome (such as intellectual disability, distinctive facial features, and heart problems), but many of the signs and symptoms probably result from cell overgrowth and abnormal cell division.

bladder cancer - associated with the HRAS 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 HRAS mutations in bladder cells have been associated with some cases of bladder cancer. A particular genetic change has been identified in a significant percentage of bladder tumors; this mutation replaces the amino acid glycine with the amino acid valine at protein position 12 (written as Gly12Val or G12V). As a result of this change, the altered H-Ras protein becomes continuously active within the cell. The overactive H-Ras protein directs the cell to grow and divide abnormally, leading to uncontrolled cell division and the formation of a tumor. Mutations in the HRAS gene also have been associated with the progression of bladder cancer and an increased risk of tumor recurrence after treatment.

other cancers - associated with the HRAS gene

Noninherited (somatic) mutations in the HRAS gene are probably involved in the development of several additional types of cancer. These mutations lead to a version of the H-Ras protein that is always active and can direct cells to grow and divide without control. Studies suggest that HRAS mutations may be common in thyroid and kidney cancers. The H-Ras protein also may be produced at higher than normal levels (overexpressed) in other types of cancer cells.