FH fumarate hydratase [Homo sapiens (human)] - Gene

Summary

Official Symbol: FHprovided by HGNC
Official Full Name: fumarate hydrataseprovided by HGNC
Primary source: HGNC:HGNC:3700
See related: Ensembl:ENSG00000091483 MIM:136850; AllianceGenome:HGNC:3700
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MCL; FMRD; HsFH; LRCC; HLRCC; MCUL1
Summary: 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]
Expression: Ubiquitous expression in heart (RPKM 49.3), liver (RPKM 41.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q43

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (241497603..241519755, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (240909033..240931170, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (241660903..241683055, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Uterine Leiomyomas with Specific Histology Features of Two Fumarate Hydratase/Succinate Dehydrogenase-Deficient Tumors: A Double Case Report.
Title: Uterine Leiomyomas with Specific Histology Features of Two Fumarate Hydratase/Succinate Dehydrogenase-Deficient Tumors: A Double Case Report.
Fumarate Hydratase-Deficient Leiomyoma of the Uterine Corpus: Comparative Morphologic Analysis of Protein-Deficient Tumors With and Without Pathogenic Germline Fumarate Hydratase Gene Mutations.
Title: Fumarate Hydratase-Deficient Leiomyoma of the Uterine Corpus: Comparative Morphologic Analysis of Protein-Deficient Tumors With and Without Pathogenic Germline Fumarate Hydratase Gene Mutations.
Genomic profile analysis of leiomyomas with bizarre nuclei and fumarate hydratase deficient leiomyomas: Strengths, weaknesses, and limitations of array-CGH interpretation.
Title: Genomic profile analysis of leiomyomas with bizarre nuclei and fumarate hydratase deficient leiomyomas: Strengths, weaknesses, and limitations of array-CGH interpretation.
Cryptic splice mutation in the fumarate hydratase gene in patients with clinical manifestations of Hereditary Leiomyomatosis and Renal Cell Cancer.
Title: Cryptic splice mutation in the fumarate hydratase gene in patients with clinical manifestations of Hereditary Leiomyomatosis and Renal Cell Cancer.
In deep bioinformatic characterization of a novel fumarate hydratase variant FH c.199T > G; (p.Tyr67Asp) in hereditary leiomyomatosis and renal cell carcinoma.
Title: In deep bioinformatic characterization of a novel fumarate hydratase variant FH c.199T > G; (p.Tyr67Asp) in hereditary leiomyomatosis and renal cell carcinoma.
FH Variant Pathogenicity Promotes Purine Salvage Pathway Dependence in Kidney Cancer.
Title: FH Variant Pathogenicity Promotes Purine Salvage Pathway Dependence in Kidney Cancer.
Fumarate Hydratase Variants and Their Association With Paraganglioma/Pheochromocytoma.
Title: Fumarate Hydratase Variants and Their Association With Paraganglioma/Pheochromocytoma.
A Missense Mutation c.1132G > A in Fumarate Hydratase (FH) Leads to Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) Syndrome and Insights into Clinical Management in Uterine Leiomyomata.
Title: A Missense Mutation c.1132G > A in Fumarate Hydratase (FH) Leads to Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) Syndrome and Insights into Clinical Management in Uterine Leiomyomata.
Macrophage fumarate hydratase restrains mtRNA-mediated interferon production.
Title: Macrophage fumarate hydratase restrains mtRNA-mediated interferon production.
Morphologic Characteristics and Mutational Analysis of Fumarate Hydratase Deficient Kidney and Smooth Muscle Tumors.
Title: Morphologic Characteristics and Mutational Analysis of Fumarate Hydratase Deficient Kidney and Smooth Muscle Tumors.

Submit: New GeneRIF Correction See all GeneRIFs (117)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Fumarase deficiency MedGen: C0342770 OMIM: 606812 GeneReviews: Fumarate Hydratase Deficiency	not available
Hereditary leiomyomatosis and renal cell cancer MedGen: C1708350 OMIM: 150800 GeneReviews: FH Tumor Predisposition Syndrome	not available

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2020-07-06) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2020-07-06) ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Vpr	vpr	A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies upregulation of fumarate hydratase (FH, mitochondrial) expression by HIV-1 Vpr in Vpr transduced macrophages	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH39631 (e-PCR)
- UniSTS:92180

SHGC-107202 (e-PCR)
- UniSTS:170296

RH64485 (e-PCR)
- UniSTS:9305

D1S258E (e-PCR)
- UniSTS:66232

AFM214xe11 (e-PCR)
- UniSTS:19424

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables fumarate hydratase activity	IBA Inferred from Biological aspect of Ancestor more info
enables fumarate hydratase activity	IDA Inferred from Direct Assay more info	PubMed
enables fumarate hydratase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables histone binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage response	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA repair	IEA Inferred from Electronic Annotation more info
involved_in fumarate metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in fumarate metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in homeostasis of number of cells within a tissue	IEA Inferred from Electronic Annotation more info
involved_in malate metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in malate metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of double-strand break repair via nonhomologous end joining	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of arginine metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in tricarboxylic acid cycle	IBA Inferred from Biological aspect of Ancestor more info
involved_in tricarboxylic acid cycle	IEA Inferred from Electronic Annotation more info
acts_upstream_of urea cycle	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in chromosome	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	TAS Traceable Author Statement more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in mitochondrion	HDA more info	PubMed
located_in mitochondrion	HTP more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in site of double-strand break	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: fumarate hydratase, mitochondrial

Names: epididymis secretory sperm binding protein; fumarase

NP_000134.2

EC 4.2.1.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.