FXN

Chr 9AR

frataxin

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

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]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 0.722 OMIM phenotypes
Clinical SummaryFXN
🧬
Gene-Disease Validity (ClinGen)
Friedreich ataxia · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
26 unique Pathogenic / Likely Pathogenic· 57 VUS of 148 total submissions
💊
Clinical Trials
9 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — FXN
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.72LOEUF
pLI 0.345
Z-score 2.11
OE 0.23 (0.090.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.28Z-score
OE missense 0.92 (0.781.09)
94 obs / 102.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.23 (0.090.72)
00.351.4
Missense OE?0.92 (0.781.09)
00.61.4
Synonymous OE?1.06
01.21.6
LoF obs/exp: 2 / 8.7Missense obs/exp: 94 / 102.1Syn Z: -0.34
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFXN-related Friedreich ataxiaLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6551th %ile
GOF
0.4579th %ile
LOF
0.3842th %ile

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

148 submitted variants in ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic10
VUS57
Likely Benign19
Benign25
Conflicting9
16
Pathogenic
10
Likely Pathogenic
57
VUS
19
Likely Benign
25
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
5
4
0
16
Likely Pathogenic
7
2
1
0
10
VUS
1
50
3
3
57
Likely Benign
0
7
3
9
19
Benign
0
3
18
4
25
Conflicting
9
Total15672916136

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

41 pathogenic / likely-pathogenic (of 57) ClinVar copy-number / structural variants overlap FXN — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

FXN · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

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
Friedreich Ataxia

A Natural History Study to TRACK Brain and Spinal Cord Changes in Individuals with Friedreich Ataxia (TRACK-FA)

ACTIVE NOT RECRUITING
NCT04349514Monash UniversityStarted 2021-02-10
Natural history
Rare DisordersUndiagnosed DisordersDisorders of Unknown Prevalence

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

RECRUITING
NCT01793168Sanford HealthStarted 2010-07
Friedreich Ataxia

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

RECRUITING
NCT05874388Institut National de la Santé Et de la Recherche Médicale, FranceStarted 2023-06-19
Friedreich's Ataxia

Biomarkers in Friedreich's Ataxia

RECRUITING
NCT02497534University of FloridaStarted 2015-09
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 AtaxiaCardiomyopathy, Secondary

Gene Therapy for Cardiomyopathy Associated With Friedreich's Ataxia

ACTIVE NOT RECRUITING
NCT05445323Phase PHASE1, PHASE2Lexeo TherapeuticsStarted 2022-08-24
Low dose LX2006Mid Dose LX2006High Dose LX2006
Friedreich Ataxia

Friedreich Ataxia Nerve Ultrasund

RECRUITING
NCT07508631Centre Hospitalier Universitaire de NiceStarted 2025-12-01
Nerve ultrasound - routine exam
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