Friedreich ataxia 1

Summary

Friedreich ataxia 1 (MONDO:0100340) is a disease caused by FXN (GenCC Definitive), with 1 cohort gene and 71 clinical trials. Top therapeutic interventions include omaveloxolone, bupropion, and citalopram.

At a glance

• Causal gene: FXN (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 19
• Clinical trials: 71

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Friedreich ataxia 1
Mondo ID	MONDO:0100340
MeSH	C565561
OMIM	229300
DOID	DOID:0111218
UMLS	C1856689
MedGen	383962
GARD	0026147
Is cancer (heuristic)	no

Also known as: FRDA1 · Friedreich ataxia · Friedreich ataxia 1 · Friedreich ataxia type 1

Data availability: 19 ClinVar variants · 2 GenCC gene-disease records · 85 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive cerebellar ataxia › autosomal recessive degenerative and progressive cerebellar ataxia › Friedreich ataxia › Friedreich ataxia 1

Related subtypes (2): Friedreich ataxia 2, Friedreich ataxia with retained reflexes

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

19 retrieved; paginated sample, class counts are floors:

7 pathogenic, 4 likely pathogenic, 3 uncertain significance, 2 conflicting classifications of pathogenicity, 1 benign, 1 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1065563	NM_000144.5(FXN):c.165+1338AAG[180]	FXN	Pathogenic	criteria provided, single submitter
263606	NM_000144.5(FXN):c.11_12del (p.Leu4fs)	FXN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
35514	NM_000144.5(FXN):c.371_376delinsTACACCTTGAGGACA (p.Asp124_Ser126delinsValHisLeuGluAspThr)	FXN	Pathogenic	no assertion criteria provided
3981	NM_000144.5(FXN):c.460A>T (p.Ile154Phe)	FXN	Pathogenic	criteria provided, single submitter
3983	NM_000144.5(FXN):c.3G>T (p.Met1Ile)	FXN	Pathogenic	criteria provided, multiple submitters, no conflicts
4072409	NC_000009.12:g.69037287_69037304GAA[120]	FXN	Pathogenic	no assertion criteria provided
4685500	NM_000144.5(FXN):c.211del (p.Gln71fs)	FXN	Pathogenic	criteria provided, single submitter
549677	NM_000144.5(FXN):c.438C>G (p.Asn146Lys)	FXN	Pathogenic	no assertion criteria provided
1064596	NM_000144.5(FXN):c.166-5T>G	FXN	Likely pathogenic	criteria provided, single submitter
3233904	NM_000144.5(FXN):c.483-12_483del	FXN	Likely pathogenic	criteria provided, single submitter
3340519	NM_000144.5(FXN):c.482+1G>T	FXN	Likely pathogenic	criteria provided, single submitter
3902437	NM_000144.5(FXN):c.410G>T (p.Gly137Val)	FXN	Likely pathogenic	criteria provided, single submitter
264451	NM_000144.5(FXN):c.118C>T (p.Arg40Cys)	FXN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3982	NM_000144.5(FXN):c.389G>T (p.Gly130Val)	FXN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1032212	NM_000144.5(FXN):c.146C>A (p.Thr49Asn)	FXN	Uncertain significance	criteria provided, multiple submitters, no conflicts
3779680	NM_000144.5(FXN):c.212del (p.Gln71fs)	FXN	Uncertain significance	criteria provided, single submitter
4532127	NM_000144.5(FXN):c.367T>C (p.Tyr123His)	FXN	Uncertain significance	criteria provided, single submitter
129120	NM_000144.5(FXN):c.54A>G (p.Pro18=)	FXN	Benign	criteria provided, multiple submitters, no conflicts
804267	NG_008845.2:g.6743_6746delinsGAAGGA[66]GAAG	FXN	Likely benign	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
FXN	Definitive	Autosomal recessive	Friedreich ataxia 1	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FXN	Orphanet:95	Friedreich ataxia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FXN	HGNC:3951	ENSG00000165060	Q16595	Frataxin, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FXN	Frataxin, mitochondrial	Functions as an activator of persulfide transfer to the scaffoding protein ISCU as component of the core iron-sulfur cluster (ISC) assembly complex and participates to the [2Fe-2S] cluster assembly.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FXN	Other/Unknown	no		Frataxin/CyaY, Frataxin, Frataxin_CS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
heart left ventricle	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FXN	251	ubiquitous	marker	right lobe of liver, apex of heart, heart left ventricle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FXN	2,291

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FXN	Q16595	19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Mitochondrial iron-sulfur cluster biogenesis	1	815.7×	0.003	FXN
Maturation of TCA enzymes and regulation of TCA cycle	1	571.0×	0.003	FXN
Complex III assembly	1	439.2×	0.003	FXN
Mitochondrial protein import	1	167.9×	0.006	FXN

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of lyase activity	1	16852.0×	0.001	FXN
proprioception	1	4213.0×	0.002	FXN
[4Fe-4S] cluster assembly	1	3370.4×	0.002	FXN
oxidative phosphorylation	1	1404.3×	0.002	FXN
[2Fe-2S] cluster assembly	1	1404.3×	0.002	FXN
negative regulation of organ growth	1	1404.3×	0.002	FXN
mitochondrial respiratory chain complex III assembly	1	1203.7×	0.002	FXN
negative regulation of multicellular organism growth	1	1123.5×	0.002	FXN
response to iron ion	1	936.2×	0.002	FXN
iron ion transport	1	887.0×	0.002	FXN
negative regulation of release of cytochrome c from mitochondria	1	802.5×	0.002	FXN
embryo development ending in birth or egg hatching	1	732.7×	0.002	FXN
organ growth	1	732.7×	0.002	FXN
protein autoprocessing	1	648.1×	0.002	FXN
muscle cell cellular homeostasis	1	648.1×	0.002	FXN
heme biosynthetic process	1	601.9×	0.002	FXN
iron-sulfur cluster assembly	1	601.9×	0.002	FXN
adult walking behavior	1	495.6×	0.002	FXN
intracellular iron ion homeostasis	1	244.2×	0.005	FXN
cellular response to hydrogen peroxide	1	234.1×	0.005	FXN
protein maturation	1	163.6×	0.006	FXN
negative regulation of apoptotic process	1	34.8×	0.029	FXN

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FXN	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
FXN	7	Binding:7

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	FXN

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
FXN	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 71.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	31
PHASE2	16
PHASE1	11
PHASE1/PHASE2	6
PHASE4	2
PHASE3	2
EARLY_PHASE1	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01716221	PHASE4	COMPLETED	An Objective Double-blind Evaluation of Bupropion and Citalopram in an Individual With Friedreich Ataxia
NCT04801303	PHASE4	COMPLETED	Evaluation of the Effects of Calcitriol’s in the Neurological Symptoms of Friedreich’s Ataxia Patients
NCT05515536	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Assess the Safety and Efficacy of Vatiquinone in Participants With Friedreich Ataxia
NCT06953583	PHASE3	RECRUITING	A Study to Learn More About the Effects and Long-Term Safety of BIIB141 (Omaveloxolone) in Participants With Friedreich’s Ataxia Aged 2 to 15 Years Old (BRAVE)
NCT04577352	PHASE2/PHASE3	COMPLETED	A Study to Assess the Efficacy and Safety of Vatiquinone for the Treatment of Participants With Friedreich Ataxia
NCT05445323	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Gene Therapy for Cardiomyopathy Associated With Friedreich’s Ataxia
NCT06447025	PHASE2	RECRUITING	An Open-Label Study of CTI-1601 in Subjects With Friedreich’s Ataxia
NCT06874010	PHASE1/PHASE2	RECRUITING	A Multiple Ascending Dose Study of DT-216P2 in Patients With Friedreich’s Ataxia
NCT00224640	PHASE1/PHASE2	COMPLETED	Iron-Chelating Therapy and Friedreich Ataxia
NCT00229632	PHASE2	COMPLETED	Idebenone to Treat Friedreich’s Ataxia
NCT00824512	PHASE2	COMPLETED	Efficacy of EGb761 in Patients Suffering From Friedreich Ataxia
NCT01339884	PHASE1/PHASE2	COMPLETED	A Study of Resveratrol as Treatment for Friedreich Ataxia
NCT01493973	PHASE2	COMPLETED	Efficacy Study of Epoetin Alfa in Friedreich Ataxia
NCT01965327	PHASE2	COMPLETED	Interferon Gamma-1b in Friedreich Ataxia (FRDA)
NCT02035020	PHASE2	COMPLETED	A Phase IIa Trial to Test Safety and Efficacy Interferon Gamma Treatment in Elevating Frataxin Levels in FRDA Patients
NCT02255435	PHASE2	COMPLETED	A Study to Learn About the Effects and Safety of RTA 408 (Omaveloxolone) in People Aged 16 to 40 With Friedreich’s Ataxia
NCT03214588	PHASE2	COMPLETED	Efficacy, Tolerability, and Pharmacokinetics of Multiple Doses of Oral TAK-831 in Adults With Friedreich Ataxia
NCT03761511	PHASE2	WITHDRAWN	Study of the Efficacy and Safety of Nicotinamide in Patients With Friedreich Ataxia
NCT03888664	PHASE2	COMPLETED	Open Trail of γIFN for Friedreich Ataxia
NCT03917225	PHASE2	COMPLETED	A Clinical Study to Evaluate the Effect of MIN-102 on the Progression of Friedreich’s Ataxia in Male and Female Patients
NCT03933163	PHASE2	COMPLETED	Micronised Resveratrol as a Treatment for Friedreich Ataxia
NCT04273165	PHASE2	COMPLETED	Safety and Efficacy of Etravirine in Friedreich Ataxia Patients
NCT04817111	PHASE2	COMPLETED	NAD+ Precursor Supplementation in Friedreich’s Ataxia
NCT04921930	PHASE1/PHASE2	COMPLETED	Evaluation of the Effect of Artesunate in Friedreich Ataxia (FA)
NCT05168774	PHASE1/PHASE2	COMPLETED	FRDA Investigator Initiated Study (IIS) With Elamipretide
NCT05485987	PHASE2	COMPLETED	A Study of Vatiquinone for the Treatment of Participants With Friedreich Ataxia
NCT05579691	PHASE2	COMPLETED	A Double-Blind, Placebo-Controlled, Dose Exploration Study of CTI-1601 in Adult Subjects With Friedreich’s Ataxia
NCT05302271	PHASE1	RECRUITING	Phase IA and IB Study of AAVrh.10hFXN Gene Therapy for the Cardiomyopathy of Friedreich’s Ataxia
NCT06054893	PHASE1	ACTIVE_NOT_RECRUITING	A Study to Find Out How BIIB141 (Omaveloxolone) is Processed in the Body and to Learn More About Its Safety in Participants With Friedreich’s Ataxia Aged 2 to 15 Years Old
NCT06772870	PHASE1	NOT_YET_RECRUITING	A Single Ascending Dose Study of DT-216P2 in Normal Healthy Participants
NCT00015808	PHASE1	COMPLETED	Safety Study of Idebenone to Treat Friedreich’s Ataxia
NCT00078481	PHASE1	COMPLETED	Phase 1 Trial of Idebenone to Treat Patients With Friedreich’s Ataxia
NCT04176991	PHASE1	COMPLETED	Single Ascending Dose Study of CTI-1601 Versus Placebo in Subjects With Friedreich’s Ataxia
NCT04519567	PHASE1	COMPLETED	Multiple Ascending Dose Study of CTI-1601 Versus Placebo in Subjects With Friedreich’s Ataxia
NCT05285540	PHASE1	COMPLETED	Study to Evaluate DT-216 in Adult Patients With Friedreich Ataxia
NCT05573698	PHASE1	COMPLETED	Study to Evaluate Multiple Ascending Dose and Multi-Dose of DT-216 in Adult Patients With Friedreich Ataxia
NCT06483802	PHASE1	WITHDRAWN	A Study of ASP2016 in Adults Who Have Heart Disease Associated With Friedreich Ataxia
NCT06681766	PHASE1	TERMINATED	A Study to Assess Nomlabofusp in Adolescents and Children With Friedreich’s Ataxia
NCT02424435	EARLY_PHASE1	COMPLETED	Methylprednisolone Treatment of Friedreich Ataxia
NCT02705547	EARLY_PHASE1	COMPLETED	Rosuvastatin (Crestor) in Friedreich Ataxia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
OMAVELOXOLONE	4	6
BUPROPION	4	3
CITALOPRAM	4	3
IDEBENONE	4	3
ARTESUNATE	4	1
CALCITRIOL	4	1
ETRAVIRINE	4	1
INTERFERON GAMMA-1B	4	1
NIACINAMIDE	4	1
VATIQUINONE	3	3
INTERFERON	3	2
RESVERATROL	3	2
ELAMIPRETIDE	3	1
LERIGLITAZONE	3	1
NICOTINAMIDE RIBOSIDE	3	1
NOMLABOFUSP	2	5
LUVADAXISTAT	2	1
CHEMBL498563	0	1