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FXN

frataxin

The FXN gene provides instructions for making the frataxin protein, which is primarily located in the mitochondria and plays a role in iron-sulphur cluster assembly. The FXN gene encodes frataxin, a protein crucial for mitochondrial function, particularly in forming iron-sulphur clusters essential for various cellular processes.

Chromosome 9q21.11 Various HGNC:3951 Tier C
FXN 9q21.11 p arm q arm 9

FXN is located on the long (q) arm of chromosome 9, at band 9q21.11. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 9 in the library →

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Clinical tests that include this

Carrier Screening panel
FXN is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The FXN gene is responsible for producing the frataxin protein, which is expressed in cells throughout the body, with notably high levels in the heart, spinal cord, liver, pancreas, and skeletal muscles. This protein is localised within the mitochondria, the energy-producing organelles of the cell. Frataxin's function is critical for cellular metabolism and its disruption can lead to severe health consequences.

The most well-characterised condition linked to FXN variants is Friedreich ataxia, an inherited neurodegenerative disorder. Understanding the FXN gene and its protein product is therefore important for comprehending the mechanisms underlying such conditions.

What the gene does

The frataxin protein, encoded by the FXN gene, is localised within the mitochondria, where it plays a key role in the assembly of iron-sulphur clusters. These clusters are vital components of many proteins involved in various cellular functions, including electron transport chain enzymes, which are critical for energy production. While its exact mechanism is not fully understood, frataxin appears to facilitate the formation and proper insertion of these iron-sulphur clusters into other proteins. This process is essential for maintaining mitochondrial health and overall cellular metabolism. Impaired frataxin function can lead to mitochondrial dysfunction, oxidative stress, and iron accumulation within the cell, particularly affecting tissues with high energy demands.

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Chromosome location

The FXN gene is situated on the long arm of chromosome 9 at position 9q21.11. The gene provides instructions for a protein that is 210 amino acids in length. Within the FXN gene, there is a specific region containing a GAA trinucleotide repeat sequence. The number of these repeats can vary among individuals and is particularly relevant to its associated conditions.

Protein structure

Domain architecture has not been experimentally characterised in detail for this protein.

Key variants

Variants within the FXN gene primarily involve expansions of a GAA trinucleotide repeat sequence. In most individuals, this repeat occurs fewer than 12 times. However, expansions of this repeat to an abnormally high number of copies can disrupt gene function. The length of these GAA repeat expansions is a significant factor influencing the severity and onset age of associated conditions. Other types of genetic variants, such as point mutations or deletions, may also occur but are less common.

The table below shows the top 9 pathogenic or likely-pathogenic variants currently classified in ClinVar for FXN.
View all on ClinVar →

Sample of pathogenic variants

9 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.317T>C
single nucleotide variant
 p.Leu106Ser Pathogenic ★★☆☆ not provided
c.169del
Deletion
 p.Ser57fs Pathogenic ★☆☆☆ not provided
c.211del
Deletion
 p.Gln71fs Pathogenic ★☆☆☆ Friedreich ataxia 1
c.285T>A
single nucleotide variant
 p.Tyr95Ter Pathogenic ★☆☆☆ not provided
c.460A>T
single nucleotide variant
 p.Ile154Phe Pathogenic ★☆☆☆ Friedreich ataxia 1
c.317T>G
single nucleotide variant
 p.Leu106Ter Pathogenic - Friedreich ataxia
c.371_376delinsTACACCTTGAGGACA
Indel
 p.Asp124_Ser126delinsValHisLeuGluAspThr Pathogenic - Friedreich ataxia 1
c.385-2A>G
single nucleotide variant
 - Pathogenic - Friedreich ataxia
c.438C>G
single nucleotide variant
 p.Asn146Lys Pathogenic - Friedreich ataxia 1

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Variants in the FXN gene are predominantly associated with Friedreich ataxia. This condition is characterised by progressive damage to the nervous system, leading to symptoms such as loss of coordination, muscle weakness, and speech difficulties. The number of GAA trinucleotide repeats in the FXN gene directly correlates with the presentation and progression of Friedreich ataxia. Other associated health issues can include heart problems and diabetes.

UK clinical status

The FXN gene is included in several UK NHS national genomic testing panels, indicating its clinical relevance in the UK. It is part of panels for conditions such as "Ataxia and cerebellar anomalies - childhood onset", "Hereditary ataxia", "Hereditary neuropathy or pain disorder", and "Hereditary spastic paraplegia, adult onset". These inclusions highlight its importance in diagnosing a range of neurological and metabolic disorders within the NHS Genomic Medicine Service.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Dystonia, chorea or related movement disorder, childhood onset · R57 NHS GMS → Hereditary neuropathy or pain disorder · R78 NHS GMS → Hereditary spastic paraplegia, childhood onset · R61 NHS GMS → Likely inborn error of metabolism · R98 NHS GMS → Ataxia and cerebellar anomalies - childhood onset NHS GMS → DDG2P NHS GMS → Hereditary ataxia, adult onset NHS GMS → Hereditary spastic paraplegia, adult onset NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the primary function of the FXN gene?

The FXN gene provides instructions for making the frataxin protein, which is crucial for assembling iron-sulphur clusters within the mitochondria. These clusters are essential for many proteins involved in cellular energy production.

Which genetic condition is most commonly associated with the FXN gene?

The FXN gene is most commonly associated with Friedreich ataxia, a progressive neurodegenerative disorder. This condition typically results from an abnormal expansion of a GAA trinucleotide repeat sequence within the gene.

Where is the frataxin protein found within the body?

The frataxin protein is found in cells throughout the body, with the highest concentrations in organs with high energy demands, such as the heart, spinal cord, liver, pancreas, and skeletal muscles. Within cells, it is located in the mitochondria.

References

  1. Pandolfo M, Pastore A. The pathogenesis of Friedreich ataxia and the structure and function of frataxin. Journal of neurology. 2009. PMID: 19283345
  2. Hebert MD. Targeting the gene in Friedreich ataxia. Biochimie. 2008. PMID: 18206656
  3. Castaldo I, Pinelli M, Monticelli A. DNA methylation in intron 1 of the frataxin gene is related to GAA repeat length and age of onset in Friedreich ataxia patients. Journal of medical genetics. 2008. PMID: 18697824
  4. Pandolfo M. Friedreich ataxia. Archives of neurology. 2008. PMID: 18852343
  5. Correia AR, Adinolfi S, Pastore A. Conformational stability of human frataxin and effect of Friedreich's ataxia-related mutations on protein folding. The Biochemical journal. 2006. PMID: 16787388
  6. Seznec H, Simon D, Bouton C. Friedreich ataxia: the oxidative stress paradox. Human molecular genetics. 2005. PMID: 15615771
  7. Stehling O, Elsässer HP, Brückel B. Iron-sulfur protein maturation in human cells: evidence for a function of frataxin. Human molecular genetics. 2004. PMID: 15509595
  8. Adinolfi S, Trifuoggi M, Politou AS. A structural approach to understanding the iron-binding properties of phylogenetically different frataxins. Human molecular genetics. 2002. PMID: 12140189
  9. Adam MP, Bick S, Mirzaa GM. Friedreich Ataxia. 1993. PMID: 20301458
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 27 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .