PDB rendering based on 1ekg.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols  ; CyaY; FA; FARR; FRDA; X25
External IDs GeneCards:
EC number
RNA expression pattern
Species Human Mouse
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

Frataxin is a protein that in humans is encoded by the FXN gene.[1][2]

Frataxin is localized to the mitochondrion. The function of frataxin is not entirely clear, but it seems to be involved in assembly of iron-sulfur clusters. It has been proposed to act as either an iron chaperone or an iron storage protein.[3]

Frataxin mRNA is predominantly expressed in tissues with a high metabolic rate (including liver, kidney, brown fat and heart). Mouse and yeast frataxin homologues contain a potential N-terminal mitochondrial targeting sequence, and human frataxin has been observed to co-localise with a mitochondrial protein. Furthermore, disruption of the yeast gene has been shown to result in mitochondrial dysfunction. Friedreich's ataxia is thus believed to be a mitochondrial disease caused by a mutation in the nuclear genome (specifically, expansion of an intronic GAA triplet repeat in the FXN gene, which encodes the protein frataxin.).[1][4][5]


  • Clinical significance 1
  • Interactions 2
  • References 3
  • Further reading 4
  • External links 5

Clinical significance

Reduced expression of frataxin is the cause of Friedreich's ataxia (FRDA), a lethal neurodegenerative disease. The reduction in frataxin gene expression may be attributable from either the silencing of transcription of the frataxin gene because of epigenetic modifciations in the chromosomal entity[6] or from the inability of splicing the expanded GAA repeats in the first intron of the pre-mRNA as seen in Bacteria[7] and Human cells[8] or both. The expansion of intronic trinucleotide repeat GAA results in Friedreich's ataxia.[9]

An overexpression of frataxin in Drosophila has shown an increase in antioxidant capability, resistance to oxidative stress insults and longevity.[10]


Frataxin has been shown to biologically interact with PMPCB.[11]


  1. ^ a b Campuzano V, Montermini L, Moltò MD, Pianese L, Cossée M, Cavalcanti F, Monros E, Rodius F, Duclos F, Monticelli A, Zara F, Cañizares J, Koutnikova H, Bidichandani SI, Gellera C, Brice A, Trouillas P, De Michele G, Filla A, De Frutos R, Palau F, Patel PI, Di Donato S, Mandel JL, Cocozza S, Koenig M, Pandolfo M (March 1996). "Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion". Science 271 (5254): 1423–7.  
  2. ^ Carvajal JJ, Pook MA, dos Santos M, Doudney K, Hillermann R, Minogue S, Williamson R, Hsuan JJ, Chamberlain S (October 1996). "The Friedreich's ataxia gene encodes a novel phosphatidylinositol-4- phosphate 5-kinase". Nat. Genet. 14 (2): 157–62.  
  3. ^ Adinolfi S, Iannuzzi C, Prischi F, Pastore C, Iametti S, Martin SR, Bonomi F, Pastore A (April 2009). "Bacterial frataxin CyaY is the gatekeeper of iron-sulfur cluster formation catalyzed by IscS". Nat. Struct. Mol. Biol. 16 (4): 390–6.  
  4. ^ Durr A, Cossee M, Agid Y, Campuzano V, Mignard C, Penet C, Mandel JL, Brice A, Koenig M (October 1996). "Clinical and genetic abnormalities in patients with Friedreich's ataxia". N. Engl. J. Med. 335 (16): 1169–75.  
  5. ^ Koutnikova H, Campuzano V, Foury F, Dollé P, Cazzalini O, Koenig M (August 1997). "Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin". Nat. Genet. 16 (4): 345–51.  
  6. ^ Kim E, Napierala M, Dent SY (July 2011). "Hyperexpansion of GAA repeats affects post-initiation steps of FXN transcription in Friedreich's ataxia". Nucleic Acids Res. 39 (4): 1–12.  
  7. ^ Pan X, Ding Y, Shi L (November 2009). "The roles of SbcCD and RNaseE in the transcription of GAA · TTC repeats in Escherichia coli". DNA Repair (Amst). 8 (11): 1321–7.  
  8. ^ Baralle M, Pastor T, Bussani E, Pagani F (July 2008). "Influence of Friedreich Ataxia GAA Noncoding Repeat Expansions on Pre-mRNA Processing". Am J Hum Genet. 83 (1): 77–88.  
  9. ^ "Entrez Gene: FXN frataxin". 
  10. ^ Runko AP, Griswold AJ, Min KT (March 2008). "Overexpression of frataxin in the mitochondria increases resistance to oxidative stress and extends lifespan in Drosophila". FEBS Lett. 582 (5): 715–9.  
  11. ^ Koutnikova, H; Campuzano V; Koenig M (Sep 1998). "Maturation of wild-type and mutated frataxin by the mitochondrial processing peptidase". Hum. Mol. Genet. (ENGLAND) 7 (9): 1485–9.  

Further reading

  • Thierbach, R.; Drewes, G.; Fusser, M.; Voigt, A.; Kuhlow, D.; Blume, U.; Schulz, T. J.; Reiche, C.; Glatt, H.; Epe, B.; Steinberg, P.; Ristow, M. (2010). "The Friedreich's ataxia protein frataxin modulates DNA base excision repair in prokaryotes and mammals". Biochemical Journal 432 (1): 165–172.  
  • Montermini L, Rodius F, Pianese L, et al. (1995). "The Friedreich Ataxia Critical Region Spans A 150-kb Interval on Chromosome 9q13". Am. J. Hum. Genet. 57 (5): 1061–7.  
  • Bidichandani SI, Ashizawa T, Patel PI (1997). "Atypical Friedreich ataxia caused by compound heterozygosity for a novel missense mutation and the GAA triplet-repeat expansion". Am. J. Hum. Genet. 60 (5): 1251–6.  
  • Babcock M, de Silva D, Oaks R, et al. (1997). "Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin". Science 276 (5319): 1709–12.  
  • Koutnikova H, Campuzano V, Foury F, et al. (1997). "Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin". Nat. Genet. 16 (4): 345–51.  
  • Wilson RB, Roof DM (1997). "Respiratory deficiency due to loss of mitochondrial DNA in yeast lacking the frataxin homologue". Nat. Genet. 16 (4): 352–7.  
  • Campuzano V, Montermini L, Lutz Y, et al. (1998). "Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes". Hum. Mol. Genet. 6 (11): 1771–80.  
  • Rötig A, de Lonlay P, Chretien D, et al. (1997). "Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia". Nat. Genet. 17 (2): 215–7.  
  • Jiralerspong S, Liu Y, Montermini L, et al. (1997). "Frataxin shows developmentally regulated tissue-specific expression in the mouse embryo". Neurobiol. Dis. 4 (2): 103–13.  
  • Koutnikova H, Campuzano V, Koenig M (1998). "Maturation of wild-type and mutated frataxin by the mitochondrial processing peptidase". Hum. Mol. Genet. 7 (9): 1485–9.  
  • Zühlke C, Laccone F, Cossée M, et al. (1998). "Mutation of the start codon in the FRDA1 gene: linkage analysis of three pedigrees with the ATG to ATT transversion points to a unique common ancestor". Hum. Genet. 103 (1): 102–5.  
  • Bartolo C, Mendell JR, Prior TW (1999). "Identification of a missense mutation in a Friedreich's ataxia patient: implications for diagnosis and carrier studies". Am. J. Med. Genet. 79 (5): 396–9.  
  • Cossée M, Dürr A, Schmitt M, et al. (1999). "Friedreich's ataxia: point mutations and clinical presentation of compound heterozygotes". Ann. Neurol. 45 (2): 200–6.  
  • Coppola G, De Michele G, Cavalcanti F, et al. (1999). "Why do some Friedreich's ataxia patients retain tendon reflexes? A clinical, neurophysiological and molecular study". J. Neurol. 246 (5): 353–7.  
  • Branda SS, Cavadini P, Adamec J, et al. (1999). "Yeast and human frataxin are processed to mature form in two sequential steps by the mitochondrial processing peptidase". J. Biol. Chem. 274 (32): 22763–9.  
  • Gordon DM, Shi Q, Dancis A, Pain D (1999). "Maturation of frataxin within mammalian and yeast mitochondria: one-step processing by matrix processing peptidase". Hum. Mol. Genet. 8 (12): 2255–62.  
  • Forrest SM, Knight M, Delatycki MB, et al. (2000). "The correlation of clinical phenotype in Friedreich ataxia with the site of point mutations in the FRDA gene". Neurogenetics 1 (4): 253–7.  
  • Al-Mahdawi S, Pook M, Chamberlain S (2000). "A novel missense mutation (L198R) in the Friedreich's ataxia gene". Hum. Mutat. 16 (1): 95.  
  • Dhe-Paganon S, Shigeta R, Chi YI, et al. (2000). "Crystal structure of human frataxin". J. Biol. Chem. 275 (40): 30753–6.  

External links

  • GeneReviews/NCBI/NIH/UW entry on Friedreich Ataxia
  • frataxin at the US National Library of Medicine Medical Subject Headings (MeSH)