FXN
Chr 9ARfrataxin
Also known as: CyaY, FA, FARR, FRDA, X25
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.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
205 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 7 | 5 | 37 | 0 | 49 |
Likely Pathogenic | 7 | 2 | 9 | 0 | 18 |
VUS | 1 | 50 | 18 | 3 | 72 |
Likely Benign | 0 | 7 | 4 | 9 | 20 |
Benign | 0 | 3 | 18 | 4 | 25 |
Conflicting | — | 9 | |||
| Total | 15 | 67 | 86 | 16 | 193 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in 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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Natural History Study to TRACK Brain and Spinal Cord Changes in Individuals with Friedreich Ataxia (TRACK-FA)
ACTIVE NOT RECRUITINGBiomarkers in Friedreich's Ataxia
RECRUITINGA 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
RECRUITINGPhase IA and IB Study of AAVrh.10hFXN Gene Therapy for the Cardiomyopathy of Friedreich's Ataxia
RECRUITINGRare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
RECRUITINGCharacterisation of the Cognitive Profile of Patients Suffering From Friedreich's Ataxia
RECRUITINGGene Therapy for Cardiomyopathy Associated With Friedreich's Ataxia
ACTIVE NOT RECRUITINGA Study of SGT-212 Gene Therapy in Friedreich's Ataxia
RECRUITINGFriedreich Ataxia Nerve Ultrasund
RECRUITINGExternal Resources
Links to major genomics databases and tools