HRAS

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HRAS is a human gene that provides instructions for making a protein that is involved in cell division. In a process called signal transduction, the protein relays signals from outside the cell to the cell nucleus and instructs the cell to grow or divide. The HRAS protein is a GTPase, which means it converts a molecule called GTP into another molecule called GDP. The protein acts like a switch; to transmit signals, the HRAS protein must be turned on (activated) by binding to GTP. The HRAS 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 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, which also includes two other oncogenes: KRAS and NRAS. The protein products of these three genes are GTPases. These proteins play important roles in cell division, cell specialization (the process by which cells mature to carry out specific functions), and controlled cell death (apoptosis).

The HRAS gene is located on the short (p) arm of chromosome 11 at position 15.5, from base pair 522,241 to base pair 525,549.

[edit] Related conditions

Costello syndrome: At least five inherited 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 HRAS protein. The most common mutation replaces the amino acid glycine with the amino acid serine at position 12 (written as Gly12Ser or G12S).

The mutations responsible for Costello syndrome lead to the production of an HRAS protein that is permanently 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. 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 mental retardation, distinctive facial features, and heart problems), but many of the signs and symptoms probably result from cell overgrowth and abnormal cell division.

Bladder cancer: Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes are called somatic mutations and are not inherited. Somatic mutations in the HRAS gene in bladder cells have been associated with bladder cancer. One specific mutation has been identified in a significant percentage of bladder tumors; this mutation substitutes one protein building block (amino acid) for another amino acid in the HRAS protein. Specifically, the mutation replaces the amino acid glycine with the amino acid valine at position 12 (written as Gly12Val or G12V). The altered HRAS protein is permanently activated within the cell. This overactive protein directs the cell to grow and divide in the absence of outside signals, 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: Somatic mutations in the HRAS gene are probably involved in the development of several other types of cancer. These mutations lead to an HRAS protein that is always active and can direct cells to grow and divide without control. Recent studies suggest that HRAS mutations may be common in thyroid and kidney cancers. The HRAS protein also may be produced at higher levels (overexpressed) in other types of cancer cells.