Aliases for FH Gene
External Ids for FH Gene
Previous GeneCards Identifiers for FH Gene
The protein encoded by this gene is an enzymatic component of the tricarboxylic acid (TCA) cycle, or Krebs cycle, and catalyzes the formation of L-malate from fumarate. It exists in both a cytosolic form and an N-terminal extended form, differing only in the translation start site used. The N-terminal extended form is targeted to the mitochondrion, where the removal of the extension generates the same form as in the cytoplasm. It is similar to some thermostable class II fumarases and functions as a homotetramer. Mutations in this gene can cause fumarase deficiency and lead to progressive encephalopathy. [provided by RefSeq, Jul 2008]
GeneCards Summary for FH Gene
FH (Fumarate Hydratase) is a Protein Coding gene. Diseases associated with FH include Fumarase Deficiency and Hereditary Leiomyomatosis And Renal Cell Cancer. Among its related pathways are Citrate cycle (TCA cycle) and Carbon metabolism. Gene Ontology (GO) annotations related to this gene include lyase activity and fumarate hydratase activity. An important paralog of this gene is ADSL.
UniProtKB/Swiss-Prot Summary for FH Gene
Catalyzes the reversible stereospecific interconversion of fumarate to L-malate (PubMed:30761759). Experiments in other species have demonstrated that specific isoforms of this protein act in defined pathways and favor one direction over the other (Probable).
[Isoform Mitochondrial]: Catalyzes the hydration of fumarate to L-malate in the tricarboxylic acid (TCA) cycle to facilitate a transition step in the production of energy in the form of NADH.
[Isoform Cytoplasmic]: Catalyzes the dehydration of L-malate to fumarate (By similarity). Fumarate metabolism in the cytosol plays a role during urea cycle and arginine metabolism; fumarate being a by-product of the urea cycle and amino-acid catabolism (By similarity). Also plays a role in DNA repair by promoting non-homologous end-joining (NHEJ) (PubMed:20231875, PubMed:26237645). In response to DNA damage and phosphorylation by PRKDC, translocates to the nucleus and accumulates at DNA double-strand breaks (DSBs): acts by catalyzing formation of fumarate, an inhibitor of KDM2B histone demethylase activity, resulting in enhanced dimethylation of histone H3 'Lys-36' (H3K36me2) (PubMed:26237645).