Fh1 fumarate hydratase 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Fh1provided by MGI
Official Full Name: fumarate hydratase 1provided by MGI
Primary source: MGI:MGI:95530
See related: Ensembl:ENSMUSG00000026526 AllianceGenome:MGI:95530
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Fh; Fh-1
Summary: Enables fumarate hydratase activity. Involved in several processes, including carboxylic acid metabolic process; positive regulation of cold-induced thermogenesis; and tricarboxylic acid cycle. Acts upstream of or within homeostasis of number of cells within a tissue. Located in mitochondrion. Is active in mitochondrial matrix. Is expressed in several structures, including alimentary system; genitourinary system; nervous system; respiratory system; and sensory organ. Human ortholog(s) of this gene implicated in fumarase deficiency and lung non-small cell carcinoma. Orthologous to human FH (fumarate hydratase). [provided by Alliance of Genome Resources, Apr 2025]
Expression: Ubiquitous expression in heart adult (RPKM 118.0), placenta adult (RPKM 84.7) and 28 other tissues See more
Orthologs: all
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Genomic context

Location:: 1 H3; 1 81.58 cM

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	1	NC_000067.7 (175428944..175453201, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	1	NC_000067.6 (175601378..175625635, complement)

Chromosome 1 - NC_000067.7 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: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Hepatic Klf10-Fh1 axis promotes exercise-mediated amelioration of NASH in mice.
Title: Hepatic Klf10-Fh1 axis promotes exercise-mediated amelioration of NASH in mice.
roles for fumarate metabolism in hematopoietic stem cell (HSC) maintenance and hematopoietic differentiation and reveal a differential requirement for mitochondrial Fh1 in normal hematopoiesis and leukemia propagation.
Title: Fumarate hydratase is a critical metabolic regulator of hematopoietic stem cell functions.
Adipose-Specific Deficiency of Fumarate Hydratase in Mice Protects Against Obesity, Hepatic Steatosis, and Insulin Resistance.
Title: Adipose-Specific Deficiency of Fumarate Hydratase in Mice Protects Against Obesity, Hepatic Steatosis, and Insulin Resistance.
Reexpression of cytosolic FH in FH1-deficient mice is critical for the suppression of renal cyst development and restoration of defects in the arginine biosynthesis pathway.
Title: A role for cytosolic fumarate hydratase in urea cycle metabolism and renal neoplasia.
study found that loss of FH activity conferred protection from apoptosis in normal human renal cells and fibroblasts
Title: Cells lacking the fumarase tumor suppressor are protected from apoptosis through a hypoxia-inducible factor-independent, AMPK-dependent mechanism.
Tumor-derived FH and SDH mutations accumulate fumarate and succinate, leading to enzymatic inhibition of multiple alpha-KG-dependent dioxygenases and consequent alterations of genome-wide histone and DNA methylation.
Title: Inhibition of α-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors.
identification of a metabolic pathway that is induced in Fh1-deficient cells to demonstrate that inhibition of haem oxygenation is synthetically lethal when combined with Fh1 deficiency, providing a new potential target for treating HLRCC patients
Title: Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase.
Data suggest that FH deficiency compels cells to adopt an early, reversible, and progressive protumorigenic metabolic milieu that is reminiscent of that driving the Warburg effect.
Title: Expression profiling in progressive stages of fumarate-hydratase deficiency: the contribution of metabolic changes to tumorigenesis.
These experiments demonstrated that upregulation of HIF-1alpha occurs as a direct consequence of FH inactivation.
Title: Dysregulation of hypoxia pathways in fumarate hydratase-deficient cells is independent of defective mitochondrial metabolism.
progression of tumors where FH is lost might be boosted by activation of the MET oncogene, which is able to drive cell-autonomous tumor progression
Title: Fumarase tumor suppressor gene and MET oncogene cooperate in upholding transformation and tumorigenesis.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (4)
Targeted (2) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Fh1 (e-PCR), detects polymorphism
- UniSTS:525485

Fh1 (e-PCR), detects polymorphism
- UniSTS:546770

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables catalytic activity	IEA Inferred from Electronic Annotation more info
enables fumarate hydratase activity	IBA Inferred from Biological aspect of Ancestor more info
enables fumarate hydratase activity	IEA Inferred from Electronic Annotation more info
enables fumarate hydratase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables fumarate hydratase activity	ISS Inferred from Sequence or Structural Similarity more info
enables lyase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in DNA damage response	IEA Inferred from Electronic Annotation more info
involved_in DNA damage response	ISS Inferred from Sequence or Structural Similarity more info
involved_in DNA repair	IEA Inferred from Electronic Annotation more info
involved_in arginine metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in fumarate metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in fumarate metabolic process	IEA Inferred from Electronic Annotation more info
involved_in fumarate metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in fumarate metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in malate metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in malate metabolic process	IEA Inferred from Electronic Annotation more info
involved_in malate metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cold-induced thermogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of double-strand break repair via nonhomologous end joining	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	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in urea cycle	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in chromosome	IEA Inferred from Electronic Annotation more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IEA Inferred from Electronic Annotation more info
located_in nucleus	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: fumarate hydratase, mitochondrial

Names: EF-3; fumarase

NP_034339.2

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.