HRAS gene

The HRAS gene provides instructions for the H-Ras protein, a critical regulator of cell division, and mutations in this gene are linked to Costello syndrome, epidermal nevi, and various cancers.

Normal Function

The HRAS gene provides instructions for making a protein called H-Ras, which is involved in regulating cell division through a process known as signal transduction. H-Ras relays signals from outside the cell to the nucleus, instructing the cell to grow or divide. It acts as a switch, turned on by binding to GTP and turned off when it converts GTP to GDP.

HRAS belongs to a class of genes known as oncogenes. When mutated, these genes have the potential to cause normal cells to become cancerous. The H-Ras protein plays important roles in cell division, cell differentiation, and apoptosis (programmed cell death).

Health Conditions Related to Genetic Changes

Costello syndrome

At least 15 mutations in the HRAS gene have been identified in people with Costello syndrome, a condition that increases the risk of developing cancerous and noncancerous tumors. These mutations lead to an H-Ras protein that is abnormally turned on, directing cells to grow and divide constantly.

• Common Mutation: The most common mutation replaces the amino acid glycine with serine at position 12 (Gly12Ser or G12S).
• Clinical Impact: Uncontrolled cell division can result in tumor formation. While the exact cause of other features—such as intellectual disability, distinctive facial features, and heart problems—is uncertain, they are likely linked to cell overgrowth and abnormal division.

Epidermal nevus

Mutations in the HRAS gene are involved in the development of epidermal nevi, which are abnormal, noncancerous patches of skin caused by an overgrowth of cells in the epidermis.

• Nevus Sebaceous: A type of organoid epidermal nevus involving hair follicles, sweat glands, or sebaceous glands. HRAS mutations are found in a majority of these cases.
• Somatic Mutations: These mutations are acquired during early development before birth. They are present only in the cells of the nevus and are not inherited.
• Common Mutation: The most common mutation replaces glycine with valine at position 12 (Gly12Val or G12V), resulting in an H-Ras protein that is always active.

Other Disorders and Cancers

• Schimmelpenning syndrome: A type of epidermal nevus syndrome where somatic HRAS mutations cause nevus sebaceous alongside abnormalities of the brain, eyes, or bones.
• Other Cancers: Somatic mutations in HRAS are likely involved in several other cancers, including thyroid and kidney cancers, where the overactive H-Ras protein directs uncontrolled cell growth.

Other Names for This Gene

• C-H-RAS
• Harvey murine sarcoma virus oncogene
• Harvey rat sarcoma viral oncogene homolog
• HRAS1
• Oncogene, G-RAS
• RASH1
• RASH_HUMAN
• Transformation gene: Oncogene HaMSV
• Transforming protein P21/H-RAS-1 (C-H-RAS)
• v-Ha-ras Harvey rat sarcoma viral oncogene homolog