Friedreich ataxia with retained reflexes

Summary

Friedreich ataxia with retained reflexes (MONDO:0800301) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Friedreich ataxia with retained reflexes
Mondo ID	MONDO:0800301
UMLS	C1847416
MedGen	376121
GARD	0026487
Is cancer (heuristic)	no

Also known as: FARR

Data availability: 1 ClinVar variant.

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 with retained reflexes

Related subtypes (2): Friedreich ataxia 2, Friedreich ataxia 1

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
561195	NG_008845.2:g.6725GAA[(200_900)]	FXN	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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	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: 0.