FXN

Chr 9

frataxin

Also known as: CyaY, FA, FARR, FRDA, X25

NCBI Gene: 2395 ENSG00000165060 UniProt: Q16595

The protein functions as an activator of iron-sulfur cluster assembly in mitochondria by facilitating persulfide transfer and binding ferrous iron during the synthesis of [2Fe-2S] clusters essential for cellular respiration. Autosomal recessive mutations involving GAA trinucleotide repeat expansions (>90 repeats) in an intron cause Friedreich ataxia and Friedreich ataxia with retained reflexes through reduced frataxin expression. The pathogenic mechanism involves impaired mitochondrial iron-sulfur cluster biogenesis leading to cellular energy deficiency and iron accumulation.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This nuclear gene encodes a mitochondrial protein which belongs to the FRATAXIN family. The protein functions in regulating mitochondrial iron transport and respiration. The expansion of intronic trinucleotide repeat GAA from 8-33 repeats to >90 repeats results in Friedreich ataxia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtFriedreich ataxia

Clinical highlights

Management implications

FXN has an approved disease-modifying therapy

Gene-disease validity (ClinGen)

Friedreich ataxia · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.72

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — FXN

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

omaveloxolone (Skyclarys)
small moleculeApproved · FDA 2023
Nrf2 activator improving mitochondrial function.
Delivery: Oral, once dailyEligibility: ≥16 yr
Not frataxin replacement
frataxin-delivery AAV programs (e.g. LX2006)
AAV gene therapyPhase 1/2
Deliver FXN to restore frataxin (cardiac-focused programs).
Delivery: One-time IV

Therapeutic landscape as of 2026-07. Educational only. Investigational ≠ available; not medical advice or eligibility. Approved entries are precise; investigational program names/phases are conservative and move fast. Curated from FDA/EMA approvals and the clinical-trial literature; verify against current labeling + ClinicalTrials.gov.

ClinicalTrials.gov

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.72LOEUF

pLI 0.345

Z-score 2.11

OE 0.23 (0.09–0.72)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.28Z-score

OE missense 0.92 (0.78–1.09)

94 obs / 102.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.23 (0.09–0.72)

0≤0.351.4

Missense OE?0.92 (0.78–1.09)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 2 / 8.7Missense obs/exp: 94 / 102.1Syn Z: -0.34

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

FXN · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — FXN

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Friedreich's Ataxia

Biomarkers in Friedreich's Ataxia

RECRUITING

NCT02497534University of FloridaStarted 2015-09

Friedreich AtaxiaCardiomyopathy, Secondary

Study of LX2006 Gene Therapy in Friedreich Ataxia Cardiomyopathy

RECRUITING

NCT07721025Phase PHASE2Lexeo TherapeuticsStarted 2026-06-25

LX2006Usual Care

Friedreich Ataxia

Characterisation of the Cognitive Profile of Patients Suffering From Friedreich's Ataxia

ACTIVE NOT RECRUITING

NCT05874388Institut National de la Santé Et de la Recherche Médicale, FranceStarted 2023-06-19

Spinocerebellar Ataxia Type 1Spinocerebellar Ataxia Type 2Spinocerebellar Ataxia Type 3

Natural History Study of and Genetic Modifiers in Spinocerebellar Ataxias

RECRUITING

NCT01060371Lauren MooreStarted 2010-04

Genetic TestingBlood CollectionMagnetic Resonance Imaging (MRI) Scan

Friedreich AtaxiaCardiomyopathiesCardiac Hypertrophy

Phase IA and IB Study of AAVrh.10hFXN Gene Therapy for the Cardiomyopathy of Friedreich's Ataxia

RECRUITING

NCT05302271Phase PHASE1Weill Medical College of Cornell UniversityStarted 2022-02-22

AAVrh.10hFXN, serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human FXNPrednisone

Hereditary Spastic ParaplegiaSpastic Ataxia

TreatHSP Platform: Adaptive Natural History Platform for Ataxias, HSPs, and Spastic Ataxias

RECRUITING

NCT07798674Heidelberg UniversityStarted 2024-07-16

Friedreich's Ataxia (FA)

A Study of SGT-212 Gene Therapy in Friedreich's Ataxia

RECRUITING

NCT07180355Phase PHASE1Solid Biosciences Inc.Started 2025-10-22

SGT-212

Rare DisordersUndiagnosed DisordersDisorders of Unknown Prevalence

Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

RECRUITING

NCT01793168Sanford HealthStarted 2010-07

Spinocerebellar Ataxia 27B (SCA27B)

A Randomized, Parallel-arm, Double Blind, Placebo-controlled Study to Assess the Efficacy of Fampridine for Patients With Spinocerebellar Ataxia SCA27B Caused by a GAA Expansion in the FGF14 Gene

RECRUITING

NCT07185347Phase PHASE3Assistance Publique - Hôpitaux de ParisStarted 2025-10-21

Fampridine 10 mg prolonged-release tablet (per os)Placebo (tablets per os)

Friedreich Ataxia

Friedreich Ataxia Nerve Ultrasund

RECRUITING

NCT07508631Centre Hospitalier Universitaire de NiceStarted 2025-12-01

Nerve ultrasound - routine exam

Friedreich AtaxiaCardiomyopathy, Secondary

Gene Therapy for Cardiomyopathy Associated With Friedreich's Ataxia

ACTIVE NOT RECRUITING

NCT05445323Phase PHASE1, PHASE2Lexeo TherapeuticsStarted 2022-08-24