The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

FXN  -  frataxin

Homo sapiens

Synonyms: CyaY, FA, FARR, FRDA, Frataxin, mitochondrial, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of FXN


Psychiatry related information on FXN


High impact information on FXN

  • Friedreich ataxia (FRDA), the most common autosomal recessive neurodegenerative disease among Europeans and people of European descent, is characterized by an early onset (usually before the age of 25), progressive ataxia, sensory loss, absence of tendon reflexes and pyramidal weakness of the legs [10].
  • Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits [11].
  • We have recently identified a unique group of patients whose clinical presentations are characterized by autosomal recessive inheritance, early age of onset, FRDA-like clinical presentations and hypoalbuminemia [10].
  • Friedreich's ataxia (FRDA) is an autosomal recessive degenerative disorder that primarily affects the nervous system and heart [12].
  • FRDA is caused primarily by a GAA repeat expansion within the first intron of the frataxin gene, which accounts for 98% of mutant alleles [4].

Chemical compound and disease context of FXN


Biological context of FXN


Anatomical context of FXN


Associations of FXN with chemical compounds

  • The iron-loaded homopolymer can be detected on non-denaturing gels by either protein or iron staining demonstrating a stable association between frataxin and iron [1].
  • Given the shared clinical features between Friedreich ataxia, vitamin E deficiency and some mitochondriopathies, our data suggest that a reduction in frataxin results in oxidative damage [21].
  • Iron-sulfur protein maturation in human cells: evidence for a function of frataxin [22].
  • Upon frataxin depletion by RNAi, the enzyme activities of the mitochondrial Fe/S proteins, aconitase and succinate dehydrogenase, were decreased, while the activities of non-Fe/S proteins remained constant [22].
  • Iron-sulfur cluster biosynthesis. Characterization of frataxin as an iron donor for assembly of [2Fe-2S] clusters in ISU-type proteins [23].

Physical interactions of FXN

  • These data suggest that frataxin binds the iron-sulfur biogenesis Nfs1/ISCU complex through ISD11, that the interaction is nickel-dependent, and that multiple consequences of frataxin deficiency are duplicated by ISD11 deficiency [24].

Other interactions of FXN

  • In this study, we report the co-existence, in a 5-year old boy with FA, of a double mutation in two distinct genes [X25 (A allele: 850 triplets; B allele: 1000 triplets), and cardiac troponin T (TNNT2) (287G>A)] [2].
  • Hypertrophic cardiomyopathy is a common finding in FA, and it is widely recognised as specific for the diagnosis of disease status [2].
  • In order to investigate whether retained tendon reflexes are characteristic of FRDA caused by the second locus, FRDA2, we studied an unrelated FRDA patient with retained tendon reflexes [25].
  • Using RT-PCR, northern and sequence analyses, we now demonstrate that X25 comprises part of the STM7 gene, contributing to at least four splice variants, and report the identification of new coding sequences [26].
  • METHODS: Small-pool polymerase chain reaction analysis, a sensitive technique that allows the measurement of repeat length in individual FXN genes, was used to analyze somatic instability of the expanded GAA triplet-repeat sequence in multiple tissues obtained from six autopsies of Friedreich's ataxia patients [3].

Analytical, diagnostic and therapeutic context of FXN

  • In radiolabeled yeast cells, human frataxin is recovered by immunoprecipitation with approximately five atoms of (55)Fe bound per molecule [1].
  • When the human frataxin precursor is expressed in S.cerevisiae, the mitochondrially generated mature form is separated by gel filtration into monomer and a high molecular weight pool of >600 kDa [1].
  • In situ hybridization analyses revealed that mouse frataxin expression correlates well with the main site of neurodegeneration, but the expression pattern is broader than expected from the pathology of the disease [27].
  • Here, we developed a cell culture model in which the RNA interference (RNAi) technology was used to deplete a potential component of Fe/S protein maturation, frataxin, in human HeLa cells [22].
  • We identified the mitochondrial processing peptidase beta (MPPbeta) as a frataxin protein partner using the yeast two-hybrid assay [28].


  1. Assembly and iron-binding properties of human frataxin, the protein deficient in Friedreich ataxia. Cavadini, P., O'Neill, H.A., Benada, O., Isaya, G. Hum. Mol. Genet. (2002) [Pubmed]
  2. Co-existence of frataxin and cardiac troponin T gene mutations in a child with Friedreich Ataxia and familial hypertrophic cardiomyopathy. Cuda, G., Mussari, A., Concolino, D., Costanzo, F.S., Strisciuglio, P. Hum. Mutat. (2002) [Pubmed]
  3. Progressive gaa expansions in dorsal root ganglia of Friedreich's ataxia patients. De Biase, I., Rasmussen, A., Endres, D., Al-Mahdawi, S., Monticelli, A., Cocozza, S., Pook, M., Bidichandani, S.I. Ann. Neurol. (2007) [Pubmed]
  4. Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia. Rötig, A., de Lonlay, P., Chretien, D., Foury, F., Koenig, M., Sidi, D., Munnich, A., Rustin, P. Nat. Genet. (1997) [Pubmed]
  5. The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin. Moreira, M.C., Barbot, C., Tachi, N., Kozuka, N., Uchida, E., Gibson, T., Mendonça, P., Costa, M., Barros, J., Yanagisawa, T., Watanabe, M., Ikeda, Y., Aoki, M., Nagata, T., Coutinho, P., Sequeiros, J., Koenig, M. Nat. Genet. (2001) [Pubmed]
  6. Secondary abnormalities of mitochondrial DNA associated with neurodegeneration. Tabrizi, S.J., Schapira, A.H. Biochem. Soc. Symp. (1999) [Pubmed]
  7. Quantitative analyses of dynamic strain sensitivity in human skin mechanoreceptors. Edin, B.B. J. Neurophysiol. (2004) [Pubmed]
  8. International Cooperative Ataxia Rating Scale (ICARS): appropriate for studies of Friedreich's ataxia? Cano, S.J., Hobart, J.C., Hart, P.E., Korlipara, L.V., Schapira, A.H., Cooper, J.M. Mov. Disord. (2005) [Pubmed]
  9. Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich's ataxia. Calabrese, V., Lodi, R., Tonon, C., D'Agata, V., Sapienza, M., Scapagnini, G., Mangiameli, A., Pennisi, G., Stella, A.M., Butterfield, D.A. J. Neurol. Sci. (2005) [Pubmed]
  10. Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene. Date, H., Onodera, O., Tanaka, H., Iwabuchi, K., Uekawa, K., Igarashi, S., Koike, R., Hiroi, T., Yuasa, T., Awaya, Y., Sakai, T., Takahashi, T., Nagatomo, H., Sekijima, Y., Kawachi, I., Takiyama, Y., Nishizawa, M., Fukuhara, N., Saito, K., Sugano, S., Tsuji, S. Nat. Genet. (2001) [Pubmed]
  11. Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits. Puccio, H., Simon, D., Cossée, M., Criqui-Filipe, P., Tiziano, F., Melki, J., Hindelang, C., Matyas, R., Rustin, P., Koenig, M. Nat. Genet. (2001) [Pubmed]
  12. Respiratory deficiency due to loss of mitochondrial DNA in yeast lacking the frataxin homologue. Wilson, R.B., Roof, D.M. Nat. Genet. (1997) [Pubmed]
  13. Friedreich's ataxia protein: phylogenetic evidence for mitochondrial dysfunction. Gibson, T.J., Koonin, E.V., Musco, G., Pastore, A., Bork, P. Trends Neurosci. (1996) [Pubmed]
  14. Manganese Is the Link between Frataxin and Iron-Sulfur Deficiency in the Yeast Model of Friedreich Ataxia. Irazusta, V., Cabiscol, E., Reverter-Branchat, G., Ros, J., Tamarit, J. J. Biol. Chem. (2006) [Pubmed]
  15. Lipoamide dehydrogenase: rapid heat inactivation in platelets of patients with recessively inherited ataxia. Kark, R.A., Budelli, M.M., Becker, D.M., Weiner, L.P., Forsythe, A.B. Neurology (1981) [Pubmed]
  16. Lack of efficacy of phosphatidylcholine in ataxias. Sorbi, S., Piacentini, S., Marini, P., De Scisciolo, G., Amantini, A., Amaducci, L. Neurology (1988) [Pubmed]
  17. Structural and functional brain imaging in Friedreich's ataxia. Junck, L., Gilman, S., Gebarski, S.S., Koeppe, R.A., Kluin, K.J., Markel, D.S. Arch. Neurol. (1994) [Pubmed]
  18. Atypical Friedreich ataxia caused by compound heterozygosity for a novel missense mutation and the GAA triplet-repeat expansion. Bidichandani, S.I., Ashizawa, T., Patel, P.I. Am. J. Hum. Genet. (1997) [Pubmed]
  19. The Friedreich ataxia critical region spans a 150-kb interval on chromosome 9q13. Montermini, L., Rodius, F., Pianese, L., Moltò, M.D., Cossée, M., Campuzano, V., Cavalcanti, F., Monticelli, A., Palau, F., Gyapay, G. Am. J. Hum. Genet. (1995) [Pubmed]
  20. Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Campuzano, V., Montermini, L., Moltò, M.D., Pianese, L., Cossée, M., Cavalcanti, F., Monros, E., Rodius, F., Duclos, F., Monticelli, A., Zara, F., Cañizares, J., Koutnikova, H., Bidichandani, S.I., Gellera, C., Brice, A., Trouillas, P., De Michele, G., Filla, A., De Frutos, R., Palau, F., Patel, P.I., Di Donato, S., Mandel, J.L., Cocozza, S., Koenig, M., Pandolfo, M. Science (1996) [Pubmed]
  21. Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes. Campuzano, V., Montermini, L., Lutz, Y., Cova, L., Hindelang, C., Jiralerspong, S., Trottier, Y., Kish, S.J., Faucheux, B., Trouillas, P., Authier, F.J., Dürr, A., Mandel, J.L., Vescovi, A., Pandolfo, M., Koenig, M. Hum. Mol. Genet. (1997) [Pubmed]
  22. Iron-sulfur protein maturation in human cells: evidence for a function of frataxin. Stehling, O., Elsässer, H.P., Brückel, B., Mühlenhoff, U., Lill, R. Hum. Mol. Genet. (2004) [Pubmed]
  23. Iron-sulfur cluster biosynthesis. Characterization of frataxin as an iron donor for assembly of [2Fe-2S] clusters in ISU-type proteins. Yoon, T., Cowan, J.A. J. Am. Chem. Soc. (2003) [Pubmed]
  24. Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex and multiple mitochondrial chaperones. Shan, Y., Napoli, E., Cortopassi, G. Hum. Mol. Genet. (2007) [Pubmed]
  25. Locus heterogeneity in Friedreich ataxia. Kostrzewa, M., Klockgether, T., Damian, M.S., Müller, U. Neurogenetics (1997) [Pubmed]
  26. The Friedreich's ataxia gene encodes a novel phosphatidylinositol-4- phosphate 5-kinase. Carvajal, J.J., Pook, M.A., dos Santos, M., Doudney, K., Hillermann, R., Minogue, S., Williamson, R., Hsuan, J.J., Chamberlain, S. Nat. Genet. (1996) [Pubmed]
  27. Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin. Koutnikova, H., Campuzano, V., Foury, F., Dollé, P., Cazzalini, O., Koenig, M. Nat. Genet. (1997) [Pubmed]
  28. Maturation of wild-type and mutated frataxin by the mitochondrial processing peptidase. Koutnikova, H., Campuzano, V., Koenig, M. Hum. Mol. Genet. (1998) [Pubmed]
WikiGenes - Universities