FAH Gene: Fumarylacetoacetate Hydrolase – Function, Mutations & Tyrosinemia Type I

The FAH gene encodes fumarylacetoacetate hydrolase, the final enzyme in the tyrosine catabolic pathway. It catalyzes the hydrolysis of 4-fumarylacetoacetate into fumarate and acetoacetate. Mutations in FAH cause hereditary tyrosinemia type I (HT1), a severe autosomal recessive disorder characterized by progressive liver disease, renal tubular dysfunction, and neurological crises. FAH deficiency leads to accumulation of toxic metabolites such as succinylacetone.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Tyrosine degradation (KEGG: hsa00350)

• Metabolism of amino acids (Reactome: R-HSA-71291)

Fumarylacetoacetate hydrolase (FAH) is a homodimeric enzyme (419 amino acids, ~45 kDa) localized in the cytosol. It catalyzes the final step of tyrosine catabolism, converting 4-fumarylacetoacetate into fumarate and acetoacetate. Deficiency due to FAH mutations causes hereditary tyrosinemia type I. The protein contains a conserved catalytic domain with a metal-binding site.