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The official name of this gene is “fumarylacetoacetate hydrolase (fumarylacetoacetase).”
FAH is the gene's official symbol. The FAH gene is also known by other names, listed below.
The FAH gene provides instructions for making an enzyme called fumarylacetoacetate hydrolase. This enzyme is abundant in the liver and kidneys, and smaller amounts are found in many tissues throughout the body. Fumarylacetoacetate hydrolase is the last in a series of five enzymes needed to break down the amino acid tyrosine, a protein building block found in many foods. Specifically, fumarylacetoacetate hydrolase converts a tyrosine byproduct called fumarylacetoacetate into smaller molecules that are either excreted by the kidneys or used in reactions that produce energy.
Researchers have identified more than 40 FAH mutations that cause type I tyrosinemia. The altered FAH gene produces an unstable or inactive enzyme, which results in reduced or absent fumarylacetoacetate hydrolase activity. The most common FAH mutation disrupts how genetic information is spliced together to make the blueprint for producing fumarylacetoacetate hydrolase. This particular mutation, called a splice-site mutation, is written as IVS12 + 5G>A. Without sufficient fumarylacetoacetate hydrolase activity, tyrosine is not processed completely. Instead of being converted to harmless molecules, fumarylacetoacetate, a tyrosine byproduct, accumulates in the liver and kidneys. Elevated levels of fumarylacetoacetate are thought to be toxic and to cause the liver and kidney problems characteristic of type I tyrosinemia. Individuals with this disorder are also at risk of liver cancer (hepatocarcinoma). Research studies suggest that elevated levels of fumarylacetoacetate in liver cells initiate or promote tumor development.
In several cases of type I tyrosinemia, the FAH gene mutation has been observed to revert to the normal state in some liver cells. If enough cells have the reverted gene, some fumarylacetoacetate hydrolase activity is restored. Researchers have found a correlation between the severity of symptoms and the extent of reversion in liver cells. People with severe symptoms of type I tyrosinemia have few reverted cells, while those with milder symptoms have many cells with the reverted FAH gene.
Cytogenetic Location: 15q25.1
Molecular Location on chromosome 15: base pairs 80,152,890 to 80,186,581
The FAH gene is located on the long (q) arm of chromosome 15 at position 25.1.
More precisely, the FAH gene is located from base pair 80,152,890 to base pair 80,186,581 on chromosome 15.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about FAH helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
amino acid ; cancer ; enzyme ; gene ; hepatocarcinoma ; hydrolase ; kidney ; liver cancer ; mutation ; protein ; reversion ; splice-site mutation ; toxic ; tumor ; tyrosine
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.