Locus FRDA FXN
Disease ID
FRDA
Gene ID
FXN
Updated
Jul 15, 2026
v2.24.0
v2.24.0
Other gene loci
–
Clinical Links
Bioinformatical Links
Disease
Name Friedreich ataxia
Inheritance
Description Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder characterized by progressive gait and limb ataxia with associated limb muscle weakness, absent lower limb reflexes, extensor plantar responses, dysarthria, and decreased vibratory sense and proprioception. Onset is usually in the first or second decade, before the end of puberty1 .
Prevalence
1 50,000
Age of Onset Typical: 10-15; Range: 2-803 .
HPO Terms
–
Association
Mendelian
Locus
Details 96% of FA patients have biallelic GAA expansions in intron 1 (compared to compound heterozygous with another mutation type), in which the reference allele is conventionally 5-33 repeats3 . Intermediate alleles (34-55) are associated with premutations, but may lead to disease as exact pathogenicity/penetrance thresholds have not been demarcated. Dysphagia is highly prevalent and progressive4,3 . The expanded repeats can be interrupted with GAAGAG, GAAGGA, or GAAGAAAA sequences, leading to differential phenotypes5 . Allele size is correlated with disease severity and inversely correlated to age of onset6 . ~20% of patients carry an expanded composite (GAA-GGA) allele with large tracts of tandem GGA triplets near the 5' end of the repeat (median ~44, range 22-342), with further minor interruptions occurring in ~10% of cases7 .
Detection
RP-PCR and long-range PCR have been used to detect expansions [@pmid:35595154]. Standard long-range PCR and RP-PCR poorly amplify GC rich expanded composite (GAA-GGA) alleles and fail to detect proximal FXN deletions, so affected individuals may be misclassified as homozygous for expansions, though composite alleles are recovered through the addition of 7-deaza-dGTP [@pmid:41432640]. Long-read sequencing has sized large alleles and resolved sequence organization, including proximal deletions [@pmid:35595154; @pmid:41432640].
Alleles
Ref. Motif Reference motif, reference orientation
GAA
Ranges
Benign (ref.) Benign motif, reference orientation
–
Benign (gene) Benign motif, gene orientation
–
Pathogenic (ref.) Pathogenic motif, reference orientation
AAG
Pathogenic (gene) Pathogenic motif, gene orientation
AAG
Unknown (ref.) Unknown motif, reference orientation
–
Unknown (gene) Unknown motif, gene orientation
–
Interruption (ref.) Interruption motif, reference orientation
–
Interruption (gene) Interruption motif, gene orientation
–
gnomAD
References
Direct supporting references for info on this page.
2
Profiling of Short-Tandem-Repeat Disease Alleles in 12,632 Human Whole Genomes.
Haibao,Tang, Ewen F,Kirkness, Christoph,Lippert, William H,Biggs, Martin,Fabani, Ernesto,Guzman, Smriti,Ramakrishnan, Victor,Lavrenko, Boyko,Kakaradov, Claire,Hou, Barry,Hicks, David,Heckerman, Franz J,Och, C Thomas,Caskey, J Craig,Venter, Amalio,Telenti
American journal of human genetics · 2017-11-02
pmid:291000845
Sequence variation in GAA repeat expansions may cause differential phenotype display in Friedreich's ataxia.
D O,McDaniel, B,Keats, V V,Vedanarayanan, S H,Subramony
Movement disorders : official journal of the Movement Disorder Society · 2001-11-01
pmid:117487526
Clinical and genetic abnormalities in patients with Friedreich's ataxia.
A,Dürr, M,Cossee, Y,Agid, V,Campuzano, C,Mignard, C,Penet, J L,Mandel, A,Brice, M,Koenig
The New England journal of medicine · 1996-10-17
pmid:88159387
Unrecognized high prevalence of expanded composite repeats in Friedreich ataxia.
Morgan C,Devore, Christina,Lam, Graham,Wiley, Courtney C,Park, David R,Lynch, Sanjay I,Bidichandani
Human molecular genetics · 2026-02-10
pmid:414326408
Diseases of unstable repeat expansion: mechanisms and common principles.
Jennifer R,Gatchel, Huda Y,Zoghbi
Nature reviews. Genetics · 2005-10-01
pmid:162057149
Clinical and neuroimaging review of triplet repeat diseases.
Ryo,Kurokawa, Mariko,Kurokawa, Akihiko,Mitsutake, Moto,Nakaya, Akira,Baba, Yasuhiro,Nakata, Toshio,Moritani, Osamu,Abe
Japanese journal of radiology · 2022-09-28
pmid:3616976810
Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion.
V,Campuzano, L,Montermini, M D,Moltò, L,Pianese, M,Cossée, F,Cavalcanti, E,Monros, F,Rodius, F,Duclos, A,Monticelli, F,Zara, J,Cañizares, H,Koutnikova, S I,Bidichandani, C,Gellera, A,Brice, P,Trouillas, G,De Michele, A,Filla, R,De Frutos, F,Palau, P I,Patel, S,Di Donato, J L,Mandel, S,Cocozza, M,Koenig, M,Pandolfo
Science (New York, N.Y.) · 1996-03-08
pmid:8596916Additional Literature
Additional literature related to this locus.
Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem
repeats, and disease, in medline format)
Dysregulation of sphingolipid-metabolizing enzymes in Friedreich's ataxia:
Zenouska,Ramchunder, Ester,Kalef-Ezra, Saqlain,Suleman, Fred Jonathan,Edzeamey, Sandor,Szunyogh, Owen,Gittins, Natalia,Castro Mena, Richard,Wade-Martins, Adamo,Valle, Charareh,Pourzand, Sara,Anjomani Virmouni
iScience · 2026-06-22
pmid:42383006Frataxin deficiency drives cardiac dysfunction and transcriptional dysregulation in Friedreich ataxia iPSC model.
Jarmon G,Lees, Haoxiang,Zhang, Lebei,Jiao, Anne M,Kong, Ren Jie,Phang, Li,Li, Nan,Su, Sebastian,Bass-Stringer, Hei-Yi H,Woo, Anthony S,Mukhtar, Alice,Pébay, Mirella,Dottori, Louise,Corben, Martin,Delatycki, Roger,Peverill, Stephen,Wilcox, Jarny,Choi, Jeffrey M,Pullin, Davis,McCarthy, Jill S,Napierala, Marek,Napierala, Shiang Y,Lim
Cell death & disease · 2026-06-23
pmid:42331777Assessing airway clearance dysfunction in Friedreich's ataxia: A focus on peak cough flow.
Barbara K,Smith, Mackenzi A,Coker, Cristina,Liberati, Blake P,Meyer, Samantha,Norman, Jessica,Ehrbar, Carmen,Leon-Astudillo, Sub,Subramony, Manuela,Corti
Journal of neuromuscular diseases · 2026-06-08
pmid:42253100Compound Heterozygote Friedreich Ataxia Patients With Covert Proximal FXN Gene Deletions.
Michael P,Lazaropoulos, Morgan C,Devore, Christina,Lam, Courtney,Park, Sanjay,Bidichandani, David R,Lynch
Annals of clinical and translational neurology · 2026-06-02
pmid:42227166Therapeutic activity of a hematopoietic stem cell-delivered cell-penetrating frataxin in Friedreich's ataxia models.
Jeffrey,Pido-Lopez, Shefta E,Moula, Enas,Shaban, Konstantinos,Stamatiou, Bethan J,Critchley, Thomas E,Whittaker, Stina,Svensson, Sara,Anjomani-Virmouni, Ester,Kalef-Ezra, Lucinda,Carr, Jane,Hassel, Adrian J,Thrasher, Manju A,Kurian, Ian A,Blair, Teerapat,Rojsajjakul, Giorgia,Santilli, Arturo,Sala
Cell reports. Medicine · 2026-05-13
pmid:42134333Genome-wide detection and clinical prioritization of tandem repeat outliers using long-read sequencing.
Sophia B,Gibson, Nikhita,Damaraju, J Gus,Gustafson, Elsa V,Balton, Sirisak,Chanprasert, Ian A,Glass, Martha,Horike-Pyne, Runjun D,Kumar, Kathleen A,Leppig, Chris,Lundberg, Jane,Ranchalis, Elisabeth A,Rosenthal, Andrew K,Solomon, Andrew B,Stergachis, Mark,Wener, Gail P,Jarvik, Elizabeth E,Blue, Katrina M,Dipple, Harriet,Dashnow, Lea M,Starita, Danny E,Miller
medRxiv : the preprint server for health sciences · 2026-05-01
pmid:42094143The TRKB Agonist 7,8-dihydroxyflavone Alleviates DNA Damage and Apoptosis in a Neuronal Cell Model of Friedreich's Ataxia.
Jorge,Galán-Cruz, Andrés,Vicente-Acosta, Frida,Loría, Javier,Díaz-Nido, Saúl,Herranz-Martín
Molecular neurobiology · 2026-04-22
pmid:42018061Longitudinal analysis shows GAA1 length and baseline clinical status as robust predictors of progression in Friedreich ataxia.
Leire,Manrique, Francisco,Martínez-Dubarbie, Ana L,Pelayo-Negro, Natalia,Benitez-Calle, María Victoria,Sanchez-Pelaez, Daniel,Cota-Gonzalez, Ruben,Loza, Raquel,Martinez-Díaz, Juan,Irure-Ventura, Coro,Sanchez-Quintana, Ivelisse,Sanchez, Antoni,Matilla-Dueñas, Jon,Infante
Journal of neurology · 2026-04-09
pmid:41954755Peripheral frataxin levels govern long-term clinical progression in Friedreich ataxia.
Christian,Rummey, Ian A,Blair, Clementina,Mesaros, Teerapat,Rojsajjakul, Yina,Dong, George,Wilmot, Theresa,Zesiewicz, Kathy,Mathews, Joseph C,Hoyle, Lauren,Seeberger, Louise A,Corben, Martin Bruce,Delatycki, Richard S,Finkel, Richard H,Roxburgh, Antoine,Duquette, Grace,Yoon, Christopher M,Gomez, S H,Subramony, Susan,Perlman, Shana,Mccormack, David R,Lynch
BMJ neurology open · 2026-03-23
pmid:41919005