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FLASH GENE

Symbol

FXN

contributors: mct/shn - updated : 29-01-2016

HGNC name	frataxin
HGNC id	3951

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

ASSOCIATED DISORDERS

corresponding disease(s)

FRDA

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional         detrimental effect of frataxin silencing, not only for astrocytes, but also for neuron-glia interactions, underlining the need to take into account the role of non-cell autonomous processes in FRDA constitutional     --low   induced mitochondrial dysfunction due to a bioenergetic deficit and abnormal Ca(2+) homeostasis in the mitochondria that were associated with oxidative and endoplasmic reticulum stresses tumoral     --over   in several tumor cell lines in response to hypoxic stress, a condition often associated with tumor progression

Susceptibility

diabetes (insulin resistance)

Variant & Polymorphism

Candidate gene
Marker
Therapy target	extramitochondrial frataxin can fully replace mitochondrial frataxin in promoting survival of frataxin cells
	effects of frataxin knockdown in HeLa cells are rescued by expression mitochondrial ferritin
	monitoring the methylation status may be a useful biomarker for tracking therapeutic benefit following administration of epigenetic drugs
	System Type Disorder Pubmed neurology ataxia   therapeutic efforts should focus on an approach that combines iron removal from mitochondria with a treatment that increases cytosolic iron levels to maximize residual frataxin expression in FRDA patients neurology ataxia   the antioxidant Idebenone delays the cardiac disease onset, progression and death of frataxin deficient animals by 1 week, but does not correct the Fe-S enzyme deficiency suuporting its utilization for the treatment of FRDA neurology ataxia   ectopic expression of enzymes that scavenge H2O2 in Drosophila FRDA model suppresses the deleterious phenotypes associated with frataxin deficiency neurology ataxia   genetic modulation of the PPARgamma pathway affects frataxin levels in vitro, supporting PPARgamma as a novel therapeutic target in FRDA neurology ataxia   possibility of modulating frataxin stability through the use of small molecules designed to directly target K147, the single lysine residue responsible for its ubiquitination and degradation

ANIMAL & CELL MODELS

	deletion of exon 4 of the mouse Frda gene lead to embryonic lethality a few days after implantation whith no iron accumulation
	striated muscle frataxin-deficient line and a neuron/cardiac muscle frataxin-deficient line display cardiac hypertrophy without skeletal muscle involvement, large sensory neuron dysfunction without alteration of the small sensory and motor neurons, and deficient activities of complexes I-III of the respiratory chain and of the aconitases
	Mice carrying a hepatocyte-specific disruption of the frataxin gene develop multiple liver tumours
	in mouse FRDA model the Fe-S enzyme deficiency occurs at 4 weeks of age prior to cardiac dilatation and concomitant development of left ventricular hypertrophy and the mitochondrial iron accumulation occurs at a terminal stage
	suppression of the Drosophila frataxin confers distinct phenotypes in larvae and adults, leading to giant long-lived larvae and to conditional short-lived adults resulting to diminished activities of numerous heme- and iron-sulfur-containing enzymes, loss of intracellular iron homeostasis and increased susceptibility to iron toxicity
	disruption of Fxn protein frataxin specifically in murine hepatocytes leads to reduced life span and development of multiple hepatic tumors, increased oxidative stress, impaired respiration and reduced ATP levels and reduced activity of iron-sulfur cluster
	frataxin-deficient cells are more prone to undergo stress-induced mitochondrial damage and apoptosis, while the overexpression of frataxin confers protection to a variety of cell types
	frataxin silencing in HeLa cells caused a reduction of growth, inhibition of the activity of aconitase and superoxide dismutase-2 and reduction of cytosolic ferritins without alteration of mitochondrial iron content
	frataxin deficiency in murine liver is associated with increased basal levels of oxidative DNA base damage