FDXR

Chr 17AR

ferredoxin reductase

Also known as: ADR, ADXR, ANOA, MMDS9B

NCBI Gene: 2232ENSG00000161513UniProt: P22570

This gene encodes a mitochondrial flavoprotein that initiates electron transport for cytochromes P450 receiving electrons from NADPH. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2012]

Primary Disease Associations & Inheritance

Auditory neuropathy and optic atrophyMIM #617717
AR
Multiple mitochondrial dysfunctions syndrome 9BMIM #620887
AR
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— FDXR
🧬
Gene-Disease Validity (ClinGen)
FDXR-related optic atrophy mitochondrial dysfunction syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.82LOEUF
pLI 0.000
Z-score 2.28
OE 0.52 (0.34–0.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.91Z-score
OE missense 0.86 (0.78–0.95)
294 obs / 341.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.52 (0.34–0.82)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.78–0.95)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 14 / 26.7Missense obs/exp: 294 / 341.1Syn Z: 0.74

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

FDXR · protein map & ClinVar variants

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

Gene2Phenotype Curations

FDXR-related optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome

strong
ARLoss Of FunctionAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantframeshift variant NMD triggering

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Auditory neuropathy and optic atrophy

MIM #617717

Molecular basis of disorder known

Autosomal recessive

Multiple mitochondrial dysfunctions syndrome 9B

MIM #620887

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical and genetic landscape of optic atrophy in 826 families: insights from 50 nuclear genes.
Zheng Y et al.·Brain
2025
FDXR-associated disease: a challenging differential diagnosis with inflammatory peripheral neuropathy.
Masnada S et al.·Neurol Sci
2023
Ocular and neurological manifestations of the FDXR-related disorder.
Kaler A et al.·J AAPOS
2025Review
FDXR variants cause adrenal insufficiency and atypical sexual development.
Pignatti E et al.·JCI Insight
2024Case report
The top 10 most frequently involved genes in hereditary optic neuropathies in 2186 probands.
Rocatcher A et al.·Brain
2023
Biallelic FDXR mutations induce ferroptosis in a rare mitochondrial disease with ataxia.
Wang J et al.·Free Radic Biol Med
2025Case report
FDXR-associated disease in a Chinese cohort: Unraveling expanded ocular phenotypes and genetic spectrum.
Wei X et al.·Exp Eye Res
2023Cohort
FDXR-Associated Oculopathy: Congenital Amaurosis and Early-Onset Severe Retinal Dystrophy as Common Presenting Features in a Chinese Population.
Yi S et al.·Genes (Basel)
2023
Expanding the clinical and genetic spectrum of FDXR deficiency by functional validation of variants of uncertain significance.
Stenton SL et al.·Hum Mutat
2021Functional
[Analysis of clinical phenotype and genetic variants in a child with mitochondrial F-S disease due to variants of FDXR gene].
Hu W et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2023Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools