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Aliases for FH Gene

Aliases for FH Gene

  • Fumarate Hydratase 2 3 5
  • EC 4.2.1.2 4 61
  • Fumarase 3 4
  • Fumarate Hydratase, Mitochondrial 3
  • HLRCC 3
  • MCUL1 3
  • FMRD 3
  • LRCC 3
  • MCL 3

External Ids for FH Gene

Previous GeneCards Identifiers for FH Gene

  • GC01M239746
  • GC01M237114
  • GC01M237957
  • GC01M238702
  • GC01M237986
  • GC01M241660
  • GC01M212119

Summaries for FH Gene

Entrez Gene Summary 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 Leiomyomatosis And Renal Cell Cancer and Fumarase Deficiency. Among its related pathways are Citrate cycle (TCA cycle) and Pyruvate metabolism and Citric Acid (TCA) cycle. GO annotations related to this gene include lyase activity and fumarate hydratase activity.

UniProtKB/Swiss-Prot for FH Gene

  • Also acts as a tumor suppressor.

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for FH Gene

Genomics for FH Gene

Regulatory Elements for FH Gene

Enhancers for FH Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH01G241517 1.1 ENCODE 0.7 +0.4 441 2.8 HDGF PKNOX1 CREB3L1 ARNT ARID4B SIN3A DMAP1 FEZF1 YY1 SLC30A9 LOC105373230 CHML FH GC01P241514
GH01G241518 0.2 Ensembl 0.7 +2.4 2385 0.4 CHML FH GC01P241514
GH01G241529 0.3 FANTOM5 0.4 -10.2 -10151 0.0 KMO FH
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around FH on UCSC Golden Path with GeneCards custom track

Promoters for FH Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000022651 485 2601 HDGF PKNOX1 CREB3L1 ARNT ARID4B SIN3A DMAP1 FEZF1 YY1 SLC30A9

Genomic Location for FH Gene

Chromosome:
1
Start:
241,497,557 bp from pter
End:
241,519,785 bp from pter
Size:
22,229 bases
Orientation:
Minus strand

Genomic View for FH Gene

Genes around FH on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FH Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FH Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for FH Gene

Proteins for FH Gene

  • Protein details for FH Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P07954-FUMH_HUMAN
    Recommended name:
    Fumarate hydratase, mitochondrial
    Protein Accession:
    P07954
    Secondary Accessions:
    • B1ANK7

    Protein attributes for FH Gene

    Size:
    510 amino acids
    Molecular mass:
    54637 Da
    Quaternary structure:
    • Homotetramer.
    Miscellaneous:
    • There are 2 substrate-binding sites: the catalytic A site, and the non-catalytic B site that may play a role in the transfer of substrate or product between the active site and the solvent. Alternatively, the B site may bind allosteric effectors (By similarity).

    Three dimensional structures from OCA and Proteopedia for FH Gene

    Alternative splice isoforms for FH Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for FH Gene

Selected DME Specific Peptides for FH Gene

P07954:
  • KIGRTHTQDA
  • QTGSGTQTNMN
  • VNKSQSSND
  • SGPRSGL
  • GLGELILP
  • GGTAVGTGLN
  • VHPNDHVN
  • KVPNDKY
  • ANTERINKLM
  • NEVISNRAIE
  • HIGYDKAA
  • EPGSSIMPGKVNPTQ
  • QVMGNHV
  • NKFEALA
  • LMKIAND
  • GKLNDHFPL
  • DKYYGAQTVRSTMNF
  • AKIAKTA
  • DTFGELKVP
  • FPLVVWQTGSGTQ
  • FPTAMHIA
  • NDIRFLGSGPR
  • ELNVFKP
  • PENEPGSSIMPGKVNP
  • QSSNDTFPTA
  • AIMKAADEV
  • KIANDIR
  • PLTLGQE
  • NMNVNEVI
  • LHSARLL
  • IKIGRTH
  • ELGYLTAEQFDEWVKP
  • GLDPKIA
  • SLMLVTAL
  • LGQEFSGY
  • LAAHDALVE
  • KRAAAEVN
  • TAPNKFE

Post-translational modifications for FH Gene

  • Ubiquitination at Lys94
  • Modification sites at PhosphoSitePlus

Other Protein References for FH Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for FH (FH)

Domains & Families for FH Gene

Graphical View of Domain Structure for InterPro Entry

P07954

UniProtKB/Swiss-Prot:

FUMH_HUMAN :
  • Belongs to the class-II fumarase/aspartase family. Fumarase subfamily.
Family:
  • Belongs to the class-II fumarase/aspartase family. Fumarase subfamily.
genes like me logo Genes that share domains with FH: view

No data available for Gene Families for FH Gene

Function for FH Gene

Molecular function for FH Gene

GENATLAS Biochemistry:
fumarate hydratase,mitochondrial,catalyzing the seventh step of citric acid cycle
UniProtKB/Swiss-Prot CatalyticActivity:
(S)-malate = fumarate + H(2)O.
UniProtKB/Swiss-Prot Function:
Also acts as a tumor suppressor.

Enzyme Numbers (IUBMB) for FH Gene

Gene Ontology (GO) - Molecular Function for FH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004333 fumarate hydratase activity EXP 8200987
GO:0005515 protein binding IPI 25416956
GO:0016829 lyase activity IEA --
genes like me logo Genes that share ontologies with FH: view
genes like me logo Genes that share phenotypes with FH: view

Human Phenotype Ontology for FH Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for FH Gene

MGI Knock Outs for FH:

Animal Model Products

miRNA for FH Gene

miRTarBase miRNAs that target FH

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for FH
  • Addgene plasmids for FH
  • Applied Biological Materials Clones for FH

No data available for Transcription Factor Targets and HOMER Transcription for FH Gene

Localization for FH Gene

Subcellular locations from UniProtKB/Swiss-Prot for FH Gene

Isoform Mitochondrial: Mitochondrion.
Isoform Cytoplasmic: Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for FH gene
Compartment Confidence
extracellular 5
mitochondrion 5
cytosol 3
nucleus 1

Gene Ontology (GO) - Cellular Components for FH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm TAS 8200987
GO:0005739 mitochondrion TAS,IDA 20833797
GO:0005759 mitochondrial matrix TAS --
GO:0045239 tricarboxylic acid cycle enzyme complex IEA --
GO:0070062 extracellular exosome IDA 20458337
genes like me logo Genes that share ontologies with FH: view

Pathways & Interactions for FH Gene

genes like me logo Genes that share pathways with FH: view

UniProtKB/Swiss-Prot P07954-FUMH_HUMAN

  • Pathway: Carbohydrate metabolism; tricarboxylic acid cycle; (S)-malate from fumarate: step 1/1.

Gene Ontology (GO) - Biological Process for FH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006099 tricarboxylic acid cycle TAS --
GO:0006106 fumarate metabolic process IBA,TAS --
GO:0006108 malate metabolic process IBA --
GO:0048873 homeostasis of number of cells within a tissue IEA --
genes like me logo Genes that share ontologies with FH: view

No data available for SIGNOR curated interactions for FH Gene

Drugs & Compounds for FH Gene

(24) Drugs for FH Gene - From: ClinicalTrials, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Heparin Approved, Investigational Pharma Antagonist 848,265
Miconazole Approved, Investigational, Vet_approved Pharma Antagonist, Pore Blocker 3706
Mipomersen Approved Pharma 19
Water Approved Pharma 0
SB-649868 Experimental Pharma Antagonist 0

(18) Additional Compounds for FH Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
L-Malic acid
  • (-)-(S)-Malate
  • (-)-(S)-Malic acid
  • (-)-Hydroxysuccinate
  • (-)-Hydroxysuccinic acid
  • (-)-L-Malic acid
97-67-6
genes like me logo Genes that share compounds with FH: view

Transcripts for FH Gene

Unigene Clusters for FH Gene

Fumarate hydratase:
Representative Sequences:

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for FH
  • Addgene plasmids for FH
  • Applied Biological Materials Clones for FH

Alternative Splicing Database (ASD) splice patterns (SP) for FH Gene

No ASD Table

Relevant External Links for FH Gene

GeneLoc Exon Structure for
FH
ECgene alternative splicing isoforms for
FH

Expression for FH Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for FH Gene

mRNA differential expression in normal tissues according to GTEx for FH Gene

This gene is overexpressed in Heart - Left Ventricle (x4.3).

Protein differential expression in normal tissues from HIPED for FH Gene

This gene is overexpressed in Liver, secretome (13.2), Nasal epithelium (8.2), and Heart (6.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for FH Gene



Protein tissue co-expression partners for FH Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of FH Gene:

FH

SOURCE GeneReport for Unigene cluster for FH Gene:

Hs.592490

mRNA Expression by UniProt/SwissProt for FH Gene:

P07954-FUMH_HUMAN
Tissue specificity: Expressed in red blood cells; underexpressed in red blood cells (cytoplasm) of patients with hereditary non-spherocytic hemolytic anemia of unknown etiology.

Evidence on tissue expression from TISSUES for FH Gene

  • Nervous system(4.8)
  • Liver(4.5)
  • Skin(4.3)
  • Kidney(2.9)
  • Muscle(2.9)
  • Intestine(2.8)
  • Heart(2.6)
  • Adrenal gland(2)
  • Eye(2)
  • Lung(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for FH Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Organs:
Head and neck:
  • brain
  • cerebellum
  • cranial nerve
  • ear
  • eye
  • face
  • forehead
  • head
  • larynx
  • meninges
  • middle ear
  • mouth
  • neck
  • nose
  • outer ear
  • skull
  • thyroid
  • tongue
  • vocal cord
Thorax:
  • heart
  • heart valve
  • lung
  • trachea
Abdomen:
  • abdominal wall
  • adrenal gland
  • biliary tract
  • gallbladder
  • kidney
  • liver
  • pancreas
Pelvis:
  • urinary bladder
  • uterus
General:
  • blood
  • blood vessel
  • coagulation system
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
  • skin
  • sweat gland
genes like me logo Genes that share expression patterns with FH: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery for FH Gene

Orthologs for FH Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for FH Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia FH 35 34
  • 99.35 (n)
OneToOne
cow
(Bos Taurus)
Mammalia FH 35 34
  • 91.75 (n)
OneToOne
dog
(Canis familiaris)
Mammalia FH 34 35
  • 91.6 (n)
oppossum
(Monodelphis domestica)
Mammalia FH 35
  • 90 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia FH 35
  • 88 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Fh1 16 35 34
  • 87.38 (n)
rat
(Rattus norvegicus)
Mammalia Fh 34
  • 85.73 (n)
chicken
(Gallus gallus)
Aves FH 34 35
  • 78.37 (n)
lizard
(Anolis carolinensis)
Reptilia FH 35
  • 91 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100491219 34
  • 77.32 (n)
Str.10251 34
African clawed frog
(Xenopus laevis)
Amphibia Xl.24299 34
zebrafish
(Danio rerio)
Actinopterygii fh 35 34
  • 73.86 (n)
OneToOne
zgc66253 34
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.8748 34
fruit fly
(Drosophila melanogaster)
Insecta CG4094 36
  • 70 (a)
CG6140 36 35
  • 68 (a)
CG4095 35
  • 68 (a)
OneToMany
l(1)G0255 34 35
  • 65.6 (n)
CG31874 35
  • 57 (a)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP001884 34
  • 63.74 (n)
worm
(Caenorhabditis elegans)
Secernentea fum-1 35 34
  • 67.25 (n)
OneToOne
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0D00902g 34
  • 62.81 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes FUM1 34 35 37
  • 61.33 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ACR013C 34
  • 58.7 (n)
thale cress
(Arabidopsis thaliana)
eudicotyledons FUM2 34
  • 66.09 (n)
soybean
(Glycine max)
eudicotyledons Gma.16566 34
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.9657 34
barley
(Hordeum vulgare)
Liliopsida Hv.4136 34
rice
(Oryza sativa)
Liliopsida Os.6783 34
wheat
(Triticum aestivum)
Liliopsida Ta.20449 34
corn
(Zea mays)
Liliopsida Zm.3679 34
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes fum1 34
  • 60.59 (n)
bread mold
(Neurospora crassa)
Ascomycetes NCU10008 34
  • 59.38 (n)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.8482 34
Species where no ortholog for FH was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)

Evolution for FH Gene

ENSEMBL:
Gene Tree for FH (if available)
TreeFam:
Gene Tree for FH (if available)

Paralogs for FH Gene

Pseudogenes.org Pseudogenes for FH Gene

genes like me logo Genes that share paralogs with FH: view

No data available for Paralogs for FH Gene

Variants for FH Gene

Sequence variations from dbSNP and Humsavar for FH Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type
rs121913118 Fumarase deficiency (FMRD) [MIM:606812] 241,504,228(-) TCACT(A/G)CTCCG reference, missense
rs121913121 Pathogenic, Hereditary leiomyomatosis and renal cell cancer (HLRCC) [MIM:150800] 241,513,661(-) AGTAA(A/C)CCAGG reference, missense
rs28933069 Hereditary leiomyomatosis and renal cell cancer (HLRCC) [MIM:150800]
rs752232718 Hereditary leiomyomatosis and renal cell cancer (HLRCC) [MIM:150800], Fumarase deficiency (FMRD) [MIM:606812] 241,508,652(+) CAATC(C/T)TGATG reference, missense
rs779707997 Likely pathogenic, Hereditary leiomyomatosis and renal cell cancer (HLRCC) [MIM:150800] 241,511,968(+) TGACC(C/T)GGCTT reference, missense

Structural Variations from Database of Genomic Variants (DGV) for FH Gene

Variant ID Type Subtype PubMed ID
nsv1002214 CNV gain 25217958
nsv549460 CNV gain 21841781

Variation tolerance for FH Gene

Residual Variation Intolerance Score: 18% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.31; 25.98% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for FH Gene

Human Gene Mutation Database (HGMD)
FH
SNPedia medical, phenotypic, and genealogical associations of SNPs for
FH

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for FH Gene

Disorders for FH Gene

MalaCards: The human disease database

(38) MalaCards diseases for FH Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
leiomyomatosis and renal cell cancer
  • hereditary leiomyomatosis and renal cell cancer
fumarase deficiency
  • fumarate hydratase deficiency
fumarate hydratase deficiency
  • fumarase deficiency
multiple cutaneous and uterine leiomyomas
  • hereditary leiomyomatosis and renal cell cancer
hereditary paraganglioma-pheochromocytoma syndromes
  • paragangliomas 4
- elite association - COSMIC cancer census association via MalaCards
Search FH in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

FUMH_HUMAN
  • Fumarase deficiency (FMRD) [MIM:606812]: A severe autosomal recessive metabolic disorder characterized by early-onset hypotonia, profound psychomotor retardation, and brain abnormalities, such as agenesis of the corpus callosum, gyral defects, and ventriculomegaly. Many patients show neonatal distress, metabolic acidosis, and/or encephalopathy. {ECO:0000269 PubMed:9635293, ECO:0000269 Ref.17}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Hereditary leiomyomatosis and renal cell cancer (HLRCC) [MIM:150800]: A disorder characterized by predisposition to cutaneous and uterine leiomyomas, and papillary type 2 renal cancer which occurs in about 20% of patients. {ECO:0000269 PubMed:11865300}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Genatlas disease for FH Gene

fumaricaciduria,mitochondrial encephalomyopathy

Relevant External Links for FH

Genetic Association Database (GAD)
FH
Human Genome Epidemiology (HuGE) Navigator
FH
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
FH
genes like me logo Genes that share disorders with FH: view

Publications for FH Gene

  1. Germline SDHB mutations and familial renal cell carcinoma. (PMID: 18728283) Ricketts C. … Maher E.R. (J. Natl. Cancer Inst. 2008) 3 22 46 64
  2. Association of germline mutations in the fumarate hydratase gene and uterine fibroids in women with hereditary leiomyomatosis and renal cell cancer. (PMID: 19075141) Stewart L. … Toro J.R. (Arch Dermatol 2008) 3 22 46 64
  3. Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America. (PMID: 12772087) Toro J.R. … Zbar B. (Am. J. Hum. Genet. 2003) 3 22 46 64
  4. Germline fumarate hydratase mutations in families with multiple cutaneous and uterine leiomyomata. (PMID: 14632190) Martinez-Mir A. … Zlotogorski A. (J. Invest. Dermatol. 2003) 3 22 46 64
  5. Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. (PMID: 11865300) Tomlinson I.P.M. … Aaltonen L.A. (Nat. Genet. 2002) 3 4 22 64

Products for FH Gene

  • Addgene plasmids for FH
  • Addgene plasmids for FH

Sources for FH Gene

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