FH Gene

FH (fumarate hydratase) is a protein-coding gene located on chromosome 1q43.

The protein encoded by this gene is an enzymatic component of the citric acid cycle (tricarboxylic acid cycle/TCA) Catalyzes the hydration of fumarate to L-malate in the tricarboxylic acid cycle (TCA) to facilitate a transition step in energy production in the form of NADH (Ajalla Aleixo MA et al. 2019). Fumarate is a byproduct of the urea cycle and amino acid catabolism.

It exists in both a cytosolic form and an N-terminal extended form, differing only in the translational start site used. The N-terminal extended form is destined for the mitochondrion, where removal of the extension results in the same form as in the cytoplasm.

Mutations in this gene can cause fumarase deficiency and lead to progressive encephalopathy. Furthermore, Hereditary Leiomyomatosis And Renal Cell Cancer is associated with mutations in this gene. Also plays a role in DNA repair by promoting non-homologous end joining (NHEJ) (Jiang Y et al. 2015; Yogev O et al. 2010).

1. Ajalla Aleixo MA et al (2019) Structural, biochemical and biophysical characterization of recombinant human fumarate hydratase. FEBS J 286:1925-1940.
2. Jiang Y et al (2015) Local generation of fumarate promotes DNA repair through inhibition of histone H3 demethylation. Nat Cell Biol 17:1158-1168.
3. Yogev O et al (2010) Fumarase: a mitochondrial metabolic enzyme and a cytosolic/nuclear component of the DNA damage response. PLoS Biol 8:e1000328.