FDXR

Chr 17AR

ferredoxin reductase

Also known as: ADR, ADXR, ANOA, MMDS9B

NCBI Gene: 2232 ENSG00000161513 UniProt: P22570 OMIM: 103270

The protein initiates electron transport for mitochondrial cytochromes P450 by transferring electrons from NADPH, functioning as a mitochondrial flavoprotein essential for cellular metabolism. Autosomal recessive mutations cause auditory neuropathy with optic atrophy and multiple mitochondrial dysfunctions syndrome 9B through loss of function. The pathogenic mechanism involves disrupted mitochondrial electron transport leading to impaired cellular energy production.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.822 OMIM phenotypes

Clinical Summary— FDXR

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Gene-Disease Validity (ClinGen)

FDXR-related optic atrophy mitochondrial dysfunction syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

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

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ClinVar Variants

26 unique Pathogenic / Likely Pathogenic· 106 VUS of 217 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.82LOEUF

pLI 0.000

Z-score 2.28

OE 0.52 (0.34–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.91Z-score

OE missense 0.86 (0.78–0.95)

294 obs / 341.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.52 (0.34–0.82)

0≤0.351.4

Missense OE?0.86 (0.78–0.95)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 14 / 26.7Missense obs/exp: 294 / 341.1Syn Z: 0.74

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongFDXR-related optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndromeLOFAR

This gene — mechanism propensity

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

0.6938th %ile

GOF

0.5563th %ile

LOF

0.3162th %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

217 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8

Likely Pathogenic18

VUS106

Likely Benign30

Benign31

Conflicting9

Pathogenic

Likely Pathogenic

106

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	4	1	0	8
Likely Pathogenic	9	9	0	0	18
VUS	4	99	1	2	106
Likely Benign	1	13	1	15	30
Benign	0	6	21	4	31
Conflicting	—				9
Total	17	131	24	21	202

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap FDXR — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →