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 exte... See more...

Aliases for FH Gene

Aliases for FH Gene

  • Fumarate Hydratase 2 3 5
  • Fumarase 2 3 4
  • Fumarate Hydratase, Mitochondrial 3 4
  • EC 4.2.1.2 4 52
  • HsFH 3 4
  • Epididymis Secretory Sperm Binding Protein 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 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).

Additional gene information for FH Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for FH Gene

Genomics for FH Gene

GeneHancer (GH) Regulatory Elements for FH Gene

Promoters and enhancers for FH Gene
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 500.7 +0.8 785 4 HNRNPK EP300 NRF1 POLR2G SP1 PHF8 ZFX POLR2A RBM34 FOS FH lnc-OPN3-1 CHML lnc-OPN3-2
GH01J241507 Enhancer 0.5 FANTOM5 Ensembl 0.4 +12.4 12384 2 FOS KAT8 KMO CHML lnc-OPN3-2 FH ENSG00000287738
GH01J241515 Enhancer 0.2 Ensembl 0.7 +4.6 4584 0.4 lnc-OPN3-2 CHML FH lnc-OPN3-1
GH01J241529 Enhancer 0.2 FANTOM5 0.4 -10.2 -10151 0 KMO FH
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around FH on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for FH

Top Transcription factor binding sites by QIAGEN in the FH gene promoter:
  • FOXD3
  • FOXI1
  • FOXO1
  • FOXO4
  • HFH-3
  • NF-kappaB1
  • NRSF form 1
  • NRSF form 2
  • p53

Genomic Locations for FH Gene

Genomic Locations for FH Gene
chr1:241,497,557-241,519,785
(GRCh38/hg38)
Size:
22,229 bases
Orientation:
Minus strand
chr1:241,660,857-241,683,085
(GRCh37/hg19)
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 (PubMed:21445611, PubMed:30761759). Interacts with H2AZ1 (PubMed:26237645).
    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.

    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

  • [Isoform Cytoplasmic]: Phosphorylation at Thr-236 by PRKDC in response to DNA damage promotes translocation to the nucleus and recruitment to DNA double-strand breaks (DSBs).
  • Ubiquitination at Lys94
  • Modification sites at PhosphoSitePlus

Other Protein References for FH Gene

ENSEMBL proteins:
REFSEQ proteins:

Domains & Families for FH Gene

Gene Families for FH Gene

Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Enzymes
  • Plasma proteins
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for FH Gene

Blocks:
  • Fumarate lyase
  • Delta crystallin signature
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for FH Gene

GenScript: Design optimal peptide antigens:
  • cDNA, FLJ92753, Homo sapiens fumarate hydratase (FH), nuclear gene encodingmitochondrial protein, mRNA (B1ANK7_HUMAN)
  • Fumarate hydratase, mitochondrial (FUMH_HUMAN)
  • Fumarate hydratase (Q7Z6G0_HUMAN)

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

Function for FH Gene

Molecular function for FH Gene

UniProtKB/Swiss-Prot Function:
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).
UniProtKB/Swiss-Prot Function:
[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.
UniProtKB/Swiss-Prot Function:
[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).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(S)-malate = fumarate + H2O; Xref=Rhea:RHEA:12460, ChEBI:CHEBI:15377, ChEBI:CHEBI:15589, ChEBI:CHEBI:29806; EC=4.2.1.2; Evidence=. ; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12461; Evidence=. ; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:12462; Evidence=. ;.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=1.4 mM for L-malate (at pH 8.5) {ECO:0000269 PubMed:30761759}; KM=0.2 mM for fumarate (at pH 8.5) {ECO:0000269 PubMed:30761759}; Note=Kcat is 280 sec(-1) with L-malate (at pH 8.5) (PubMed:30761759). Kcat is 170 sec(-1) with fumarate (at pH 8.5) (PubMed:30761759). {ECO:0000269 PubMed:30761759}; pH dependence: Optimum pH is 7.5-8.0. {ECO:0000269 PubMed:30761759};
GENATLAS Biochemistry:
fumarate hydratase,mitochondrial,catalyzing the seventh step of citric acid cycle

Enzyme Numbers (IUBMB) for FH Gene

Phenotypes From GWAS Catalog for FH Gene

Gene Ontology (GO) - Molecular Function for FH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004333 fumarate hydratase activity TAS,IDA 30761759
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:
  • Fh1 Fh1<tm1.1Pjp>

miRNA for FH Gene

Clone Products

  • Addgene plasmids for FH
  • Addgene plasmids 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, cytosol. Nucleus. Chromosome. Note=Translocates to the nucleus in response to DNA damage: localizes to DNA double-strand breaks (DSBs) following phosphorylation by PRKDC. {ECO:0000269 PubMed:26237645}.

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
mitochondrion 5
nucleus 5
cytosol 5
plasma membrane 2
extracellular 2
cytoskeleton 2
peroxisome 2
endoplasmic reticulum 2
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for FH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005694 chromosome IEA --
GO:0005737 cytoplasm TAS 8200987
GO:0005739 mitochondrion IDA,TAS --
GO:0005759 mitochondrial matrix TAS --
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 TAS,IDA 30761759
GO:0006108 malate metabolic process IDA 30761759
GO:0006281 DNA repair IEA --
GO:0006974 cellular response to DNA damage stimulus 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

(33) 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 1028
Miconazole Approved, Investigational, Vet_approved Pharma Antagonist, Pore Blocker, Channel blocker 4175
Mipomersen Approved, Investigational Pharma 19
Water Approved Pharma 0
Maleic acid Experimental, Investigational Pharma 336

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
L-Malic acid
  • (-)-L-Malic acid
  • (S)-(-)-Hydroxysuccinic acid
  • L-2-Hydroxybutanedioic acid
  • L-Apple acid
  • Malate
97-67-6
genes like me logo Genes that share compounds with FH: view

Transcripts for FH Gene

mRNA/cDNA for FH Gene

1 REFSEQ mRNAs :
17 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Clone Products

  • Addgene plasmids for FH
  • Addgene plasmids 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

Expression for FH Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and 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, MaxQB, and MOPED for FH Gene



Protein tissue co-expression partners for FH Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for 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
Regions:
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 31 30
  • 99.35 (n)
OneToOne
cow
(Bos Taurus)
Mammalia FH 31 30
  • 91.75 (n)
OneToOne
dog
(Canis familiaris)
Mammalia FH 31 30
  • 91.6 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia FH 31
  • 90 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia FH 31
  • 88 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Fh1 17 31 30
  • 87.38 (n)
rat
(Rattus norvegicus)
Mammalia Fh 30
  • 85.73 (n)
chicken
(Gallus gallus)
Aves FH 31 30
  • 78.37 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia FH 31
  • 91 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100491219 30
  • 77.32 (n)
Str.10251 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.24299 30
zebrafish
(Danio rerio)
Actinopterygii fh 31 30
  • 73.86 (n)
OneToOne
zgc66253 30
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.8748 30
fruit fly
(Drosophila melanogaster)
Insecta CG4094 32
  • 70 (a)
CG4095 31
  • 68 (a)
OneToMany
CG6140 31 32
  • 67 (a)
OneToMany
l(1)G0255 31 30
  • 65.6 (n)
OneToMany
CG31874 31
  • 57 (a)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP001884 30
  • 63.74 (n)
worm
(Caenorhabditis elegans)
Secernentea fum-1 31 30
  • 67.25 (n)
OneToOne
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0D00902g 30
  • 62.81 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes FUM1 33 31 30
  • 61.33 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ACR013C 30
  • 58.7 (n)
thale cress
(Arabidopsis thaliana)
eudicotyledons FUM2 30
  • 66.09 (n)
soybean
(Glycine max)
eudicotyledons Gma.16566 30
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.9657 30
corn
(Zea mays)
Liliopsida Zm.3679 30
barley
(Hordeum vulgare)
Liliopsida Hv.4136 30
wheat
(Triticum aestivum)
Liliopsida Ta.20449 30
rice
(Oryza sativa)
Liliopsida Os.6783 30
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes fum1 30
  • 60.59 (n)
bread mold
(Neurospora crassa)
Ascomycetes NCU10008 30
  • 59.38 (n)
sea squirt
(Ciona savignyi)
Ascidiacea Cin.8482 30
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.8482 30
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)
Aminode:
Evolutionary constrained regions (ECRs) for FH: view image

Paralogs for FH Gene

Paralogs for FH Gene

Pseudogenes.org Pseudogenes for FH Gene

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

Variants for FH Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for FH Gene

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 SPLICE_DONOR_VARIANT
639170 Uncertain Significance: Fumarase deficiency 241,506,054(-) T/C MISSENSE_VARIANT
639646 Uncertain Significance: Fumarase deficiency 241,513,712(-) G/A MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for FH Gene

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)

Additional Variant Information for FH Gene

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

SNP Genotyping and Copy Number Assay Products

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

Disorders for FH Gene

MalaCards: The human disease database

(54) MalaCards diseases for FH Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

- 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.23}. 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, ECO:0000269 PubMed:26237645, ECO:0000269 PubMed:8200987}. Note=The disease is caused by mutations affecting the gene represented in this entry. Isoform Cytoplasmic: HLRCC is probably caused by an accumulation of fumarate (PubMed:30718813). Accumulation of fumarate coupled with protonation promotes the formation of non-enzymatic post-translational modification cysteine S-succination (S-(2-succinyl)cysteine) on proteins, such as SMARCC1 (PubMed:30718813). {ECO:0000269 PubMed:30718813}.

Genatlas disease for FH Gene

fumaricaciduria,mitochondrial encephalomyopathy

Additional Disease Information for FH

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

Publications for FH Gene

  1. Fumarase: a mitochondrial metabolic enzyme and a cytosolic/nuclear component of the DNA damage response. (PMID: 20231875) Yogev O … Pines O (PLoS biology 2010) 3 4 23 54
  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 JR (Archives of dermatology 2008) 3 23 41 54
  3. Germline SDHB mutations and familial renal cell carcinoma. (PMID: 18728283) Ricketts C … Maher ER (Journal of the National Cancer Institute 2008) 3 23 41 54
  4. Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America. (PMID: 12772087) Toro JR … Zbar B (American journal of human genetics 2003) 3 23 41 54
  5. Germline fumarate hydratase mutations in families with multiple cutaneous and uterine leiomyomata. (PMID: 14632190) Martinez-Mir A … Zlotogorski A (The Journal of investigative dermatology 2003) 3 23 41 54

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