FH gene
The FH gene provides instructions for making the enzyme fumarase, which is critical for cellular energy production.
Normal Function
The FH gene provides instructions for making an enzyme called fumarase (also known as fumarate hydratase). Fumarase participates in an important series of reactions known as the citric acid cycle or Krebs cycle, which allows cells to use oxygen and generate energy. Specifically, fumarase helps convert a molecule called fumarate to a molecule called malate.
Health Conditions Related to Genetic Changes
Fumarase deficiency
More than 20 FH gene mutations have been identified in people with fumarase deficiency, a condition that primarily affects the brain and is often fatal in infancy. Fumarase deficiency occurs in individuals who inherit two mutated copies of the FH gene in each cell. These mutations disrupt the enzyme's ability to convert fumarate to malate, impairing the process that generates energy for cells, which is particularly harmful to the developing brain.
Hereditary leiomyomatosis and renal cell cancer
More than 70 mutations in the FH gene cause hereditary leiomyomatosis and renal cell cancer (HLRCC). This disorder is characterized by:
- Leiomyomas: Benign tumors containing smooth muscle tissue in the skin and, in females, the uterus.
- Kidney cancer: An increased risk of developing renal cell cancer.
People with HLRCC are born with one mutated copy of the FH gene. The second copy may acquire a somatic mutation later in life due to environmental factors or DNA replication errors. These mutations may lead to a buildup of fumarate, which researchers believe interferes with the regulation of oxygen levels in the cell. Chronic oxygen deficiency (hypoxia) in these cells may encourage tumor formation.
Primary macronodular adrenal hyperplasia
The FH gene is also associated with primary macronodular adrenal hyperplasia.
Other Names for This Gene
- fumarase
- fumarase hydratase
- FUMH_HUMAN
- HLRCC
- LRCC
- MCL
- MCUL1