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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]
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 ErbB signaling pathway. Gene Ontology (GO) annotations related to this gene include lyase activity and fumarate hydratase activity. An important paralog of this gene is ASL.
GeneHancer (GH) Identifier | GH Type | GH Score |
GH Sources | Gene Association Score | Total Score | TSS distance (kb) | Number of Genes Away | Size (kb) | Transcription Factor Binding Sites |
Gene Targets |
---|---|---|---|---|---|---|---|---|---|---|
GH01J241518 | Promoter/Enhancer | 2 | EPDnew Ensembl ENCODE CraniofacialAtlas | 600.7 | +0.8 | 755 | 4 | SP1 CREB1 GATAD2A HNRNPL REST ZNF512 IKZF1 POLR2A BACH1 FOS | FH lnc-OPN3-1 CHML lnc-OPN3-2 RGS7 | |
GH01J241482 | Enhancer | 1.1 | FANTOM5 Ensembl ENCODE | 0.3 | +36.3 | 36254 | 4.2 | IKZF1 JUND PKNOX1 CTCF DPF2 TCF12 EP300 RUNX3 CEBPB FOS | ENSG00000287738 KMO FH piR-30444-029 RGS7 | |
GH01J241423 | Promoter/Enhancer | 1.4 | Ensembl ENCODE | 0.2 | +95.8 | 95754 | 2 | PRDM10 ZNF629 ZNF692 PRDM1 ZIC2 ZSCAN4 POLR2A PATZ1 CTCF ZNF501 | LOC105373230 ENSG00000287516 RGS7 FH | |
GH01J241507 | Enhancer | 0.5 | FANTOM5 Ensembl | 0.4 | +12.4 | 12354 | 2 | KAT8 | KMO CHML lnc-OPN3-2 FH ENSG00000287738 RGS7 | |
GH01J241515 | Enhancer | 0.2 | Ensembl | 0.7 | +4.6 | 4554 | 0.4 | lnc-OPN3-2 CHML FH lnc-OPN3-1 RGS7 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0003824 | catalytic activity | IEA | -- |
GO:0004333 | fumarate hydratase activity | TAS,IMP | 29456767 |
GO:0005515 | protein binding | IPI | 25416956 |
GO:0016829 | lyase activity | IEA | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005634 | nucleus | IEA | -- |
GO:0005694 | chromosome | IEA | -- |
GO:0005737 | cytoplasm | TAS | 8200987 |
GO:0005739 | mitochondrion | TAS,IDA | -- |
GO:0005759 | mitochondrial matrix | TAS | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Citrate cycle (TCA cycle) |
.01
|
|
2 | Pyruvate metabolism and Citric Acid (TCA) cycle |
.01
|
|
3 | Metabolism |
.40
|
|
4 | Glucose / Energy Metabolism | ||
5 | Carbon metabolism |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0006099 | tricarboxylic acid cycle | TAS | -- |
GO:0006106 | fumarate metabolic process | TAS,IDA | 30761759 |
GO:0006108 | malate metabolic process | IDA | 30761759 |
GO:0006281 | DNA repair | IEA | -- |
GO:0006974 | cellular response to DNA damage stimulus | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Clotrimazole | Approved, Vet_approved | Pharma | Pore Blocker, Inhibition, Agonist, Antagonist, Channel blocker, Gating inhibitor | 3024 | ||
Heparin | Approved, Investigational | Pharma | Antagonist | 1058 | ||
Miconazole | Approved, Investigational, Vet_approved | Pharma | Channel blocker, Pore Blocker, Antagonist | 3024 | ||
Mipomersen | Approved, Investigational | Pharma | 19 | |||
Water | Approved | Pharma | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
L-Malic acid |
|
97-67-6 |
|
This gene was present in the common ancestor of eukaryotes.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | FH 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | FH 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | FH 30 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | FH 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | FH 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Fh1 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Fh 30 |
|
||
Chicken (Gallus gallus) |
Aves | FH 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | FH 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | LOC100491219 30 |
|
||
Str.10251 30 |
|
||||
African clawed frog (Xenopus laevis) |
Amphibia | Xl.24299 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | fh 30 31 |
|
OneToOne | |
zgc66253 30 |
|
||||
Rainbow Trout (Oncorhynchus mykiss) |
Actinopterygii | Omy.8748 30 |
|
||
Fruit Fly (Drosophila melanogaster) |
Insecta | CG4094 32 |
|
|
|
CG4095 31 |
|
OneToMany | |||
CG6140 31 32 |
|
OneToMany | |||
l(1)G0255 30 31 |
|
OneToMany | |||
CG31874 31 |
|
OneToMany | |||
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP001884 30 |
|
||
Worm (Caenorhabditis elegans) |
Secernentea | fum-1 30 31 |
|
OneToOne | |
K. Lactis Yeast (Kluyveromyces lactis) |
Saccharomycetes | KLLA0D00902g 30 |
|
||
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | FUM1 30 31 33 |
|
OneToOne | |
A. gosspyii yeast (Eremothecium gossypii) |
Saccharomycetes | AGOS_ACR013C 30 |
|
||
Thale Cress (Arabidopsis thaliana) |
eudicotyledons | FUM2 30 |
|
||
Alicante grape (Vitis vinifera) |
eudicotyledons | Vvi.9657 30 |
|
||
Soybean (Glycine max) |
eudicotyledons | Gma.16566 30 |
|
||
Barley (Hordeum vulgare) |
Liliopsida | Hv.4136 30 |
|
||
Rice (Oryza sativa) |
Liliopsida | Os.6783 30 |
|
||
Wheat (Triticum aestivum) |
Liliopsida | Ta.20449 30 |
|
||
Corn (Zea mays) |
Liliopsida | Zm.3679 30 |
|
||
Fission Yeast (Schizosaccharomyces pombe) |
Schizosaccharomycetes | fum1 30 |
|
||
Bread mold (Neurospora crassa) |
Ascomycetes | NCU10008 30 |
|
||
Sea Vase (Ciona intestinalis) |
Ascidiacea | Cin.8482 30 |
|
SNP ID | Clinical significance and condition | Chr 01 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
214380 | Uncertain Significance: Fumarase deficiency | 241,504,174(-) | C/T | MISSENSE_VARIANT | |
214385 | Pathogenic: Fumarase deficiency | 241,500,500(-) | C/A | NONSENSE | |
214412 | Likely Pathogenic: Fumarase deficiency | 241,506,002(-) | C/T | ||
639170 | Uncertain Significance: Fumarase deficiency | 241,506,054(-) | T/C | MISSENSE_VARIANT | |
639646 | Uncertain Significance: Fumarase deficiency | 241,513,712(-) | G/A | MISSENSE_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
nsv1002214 | CNV | gain | 25217958 |
nsv549460 | CNV | gain | 21841781 |
Disorder | Aliases | PubMed IDs |
---|---|---|
fumarase deficiency |
|
|
hereditary leiomyomatosis and renal cell cancer |
|
|
leiomyoma, uterine |
|
|
leiomyoma cutis |
|
|
hereditary paraganglioma-pheochromocytoma syndromes |
|
|