HRas proto-oncogene, GTPase
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 by attaching (binding) to a molecule of GTP. The H-Ras 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.
The HRAS gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous. The HRAS gene 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).
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 gene mutations that occur in bladder cells have been associated with some cases of bladder cancer. A particular mutation 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 genetic 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.
At least 15 mutations in the HRAS gene have been identified in people with Costello syndrome, a rare condition that affects many parts of the body and increases the risk of developing cancerous and noncancerous tumors. The mutations change single protein building blocks (amino acids) in a critical region of the H-Ras protein. The most common mutation accounts for more than 80 percent of all cases of Costello syndrome; it replaces the amino acid glycine with the amino acid serine at protein position 12 (written as Gly12Ser or G12S).
The HRAS gene mutations that cause Costello syndrome lead to the production of an H-Ras protein that is abnormally turned on (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.
Genetics Home Reference provides information about head and neck squamous cell carcinoma.
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 gene mutations may be common in thyroid and kidney cancers. Increased activity (expression) of the HRAS gene has also been reported in other types of cancer.
- Harvey murine sarcoma virus oncogene
- Harvey rat sarcoma viral oncogene homolog
- Oncogene, G-RAS
- Transformation gene: Oncogene HaMSV
- Transforming protein P21/H-RAS-1 (C-H-RAS)
- v-Ha-ras Harvey rat sarcoma viral oncogene homolog