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Genetics Home Reference: your guide to understanding genetic conditions
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FAH

Reviewed August 2015

What is the official name of the FAH gene?

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.

What is the normal function of the FAH gene?

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 that work 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 to produce energy or make other substances in the body.

How are changes in the FAH gene related to health conditions?

tyrosinemia - caused by mutations in the FAH gene

At least 86 FAH mutations have been found that cause tyrosinemia type I. This condition is characterized by severe liver and kidney disease, neurological problems, and other signs and symptoms that begin in infancy. The altered FAH gene that causes this condition produces an unstable or inactive enzyme, which results in reduced or absent fumarylacetoacetate hydrolase activity. The most common FAH mutation disrupts the way the gene's instructions are used to make the enzyme. This mutation (written IVS12 + 5G>A) is called a splice-site mutation and results in an abnormally short enzyme. Without sufficient fumarylacetoacetate hydrolase activity, tyrosine and its byproducts are not properly broken down. As a result, fumarylacetoacetate accumulates in the liver and kidneys. Elevated levels of fumarylacetoacetate are thought to be toxic to cells and accumulation of this substance likely causes the liver and kidney problems and other features that are characteristic of tyrosinemia type I.

In several cases of tyrosinemia type I, the FAH gene mutation has been observed to revert to the normal state in some liver cells. If enough cells have the reverted gene, which produces normal fumarylacetoacetate hydrolase, some level of enzyme activity is achieved. Researchers have found a correlation between the severity of symptoms and the extent of reversion in liver cells. People with severe symptoms of tyrosinemia type I have few reverted cells, while those with milder symptoms have many cells with the reverted FAH gene.

Where is the FAH gene located?

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.

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.

Where can I find additional information about FAH?

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.

What other names do people use for the FAH gene or gene products?

  • beta-diketonase
  • FAA
  • FAAA_HUMAN
  • fumarylacetoacetase

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding FAH?

amino acid ; enzyme ; gene ; hydrolase ; kidney ; mutation ; neurological ; protein ; reversion ; splice-site mutation ; toxic ; tyrosine

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References

  • Arranz JA, Piñol F, Kozak L, Pérez-Cerdá C, Cormand B, Ugarte M, Riudor E. Splicing mutations, mainly IVS6-1(G>T), account for 70% of fumarylacetoacetate hydrolase (FAH) gene alterations, including 7 novel mutations, in a survey of 29 tyrosinemia type I patients. Hum Mutat. 2002 Sep;20(3):180-8. (http://www.ncbi.nlm.nih.gov/pubmed/12203990?dopt=Abstract)
  • Demers SI, Russo P, Lettre F, Tanguay RM. Frequent mutation reversion inversely correlates with clinical severity in a genetic liver disease, hereditary tyrosinemia. Hum Pathol. 2003 Dec;34(12):1313-20. (http://www.ncbi.nlm.nih.gov/pubmed/14691918?dopt=Abstract)
  • Fernández-Lainez C, Ibarra-González I, Belmont-Martínez L, Monroy-Santoyo S, Guillén-López S, Vela-Amieva M. Tyrosinemia type I: clinical and biochemical analysis of patients in Mexico. Ann Hepatol. 2014 Mar-Apr;13(2):265-72. (http://www.ncbi.nlm.nih.gov/pubmed/24552869?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2184)
  • Pérez-Carro R, Sánchez-Alcudia R, Pérez B, Navarrete R, Pérez-Cerdá C, Ugarte M, Desviat LR. Functional analysis and in vitro correction of splicing FAH mutations causing tyrosinemia type I. Clin Genet. 2014 Aug;86(2):167-71. doi: 10.1111/cge.12243. Epub 2013 Aug 21. (http://www.ncbi.nlm.nih.gov/pubmed/23895425?dopt=Abstract)
  • Pérez-Carro R, Sánchez-Alcudia R, Pérez B, Navarrete R, Pérez-Cerdá C, Ugarte M, Desviat LR. Functional analysis and in vitro correction of splicing FAH mutations causing tyrosinemia type I. Clin Genet. 2014 Aug;86(2):167-71. doi: 10.1111/cge.12243. Epub 2013 Aug 21. (http://www.ncbi.nlm.nih.gov/pubmed/23895425?dopt=Abstract)

 

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.

 
Reviewed: August 2015
Published: September 1, 2015