FOXRED1

Chr 11AR

FAD dependent oxidoreductase domain containing 1

NCBI Gene: 55572ENSG00000110074UniProt: Q96CU9

Required for the assembly of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) (PubMed:20858599, PubMed:25678554). Involved in mid-late stages of complex I assembly (PubMed:25678554)

Primary Disease Associations & Inheritance

Mitochondrial complex I deficiency, nuclear type 19MIM #618241
AR
500
ClinVar variants
94
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— FOXRED1
🧬
Gene-Disease Validity (ClinGen)
Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
94 Pathogenic / Likely Pathogenic· 124 VUS of 500 total submissions

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.
1.32LOEUF
pLI 0.000
Z-score 0.26
OE 0.95 (0.69–1.32)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.40Z-score
OE missense 1.07 (0.97–1.18)
291 obs / 272.3 exp
Tolerant

Tolerant to missense variation

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.0.95 (0.69–1.32)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.07 (0.97–1.18)
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.1.19
0≤1.21.6
LoF obs/exp: 25 / 26.4Missense obs/exp: 291 / 272.3Syn Z: -1.60

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic66
Likely Pathogenic28
VUS124
Likely Benign257
Benign11
Conflicting14
66
Pathogenic
28
Likely Pathogenic
124
VUS
257
Likely Benign
11
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
1
50
0
66
Likely Pathogenic
18
4
6
0
28
VUS
0
102
19
3
124
Likely Benign
0
6
106
145
257
Benign
0
1
10
0
11
Conflicting
—14
Total33114191148500

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

View in ClinVar →

Protein Context — Lollipop Plot

FOXRED1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

FOXRED1-related mitochondrial complex I deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Mitochondrial complex I deficiency, nuclear type 19

MIM #618241

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — FOXRED1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Animal Model for Leigh Syndrome.
El-Desouky S et al.·Methods Mol Biol
2019Functional
Clinical and molecular characterization of pediatric mitochondrial disorders in south of China.
Hu C et al.·Eur J Med Genet
2020
Biallelic FOXRED1 mutations cause infantile mitochondrial encephalopathy with complex I disassembly and basal ganglia degeneration.
Pan C et al.·Mitochondrion
2026Case report
Skeletal Muscle Gene Expression Signatures of Obese High and Low Responders to Endurance Exercise Training.
Kovac L et al.·J Clin Endocrinol Metab
2024
Investigating the dual role of mitochondrial and nuclear genome variants in pediatric cardiomyopathies.
Temena MA et al.·Sci Rep
2025
[Clinical and genetic characteristics analysis of 18 children with infantile epileptic spasms syndrome associated with mitochondrial gene variants].
Wu TH et al.·Zhonghua Er Ke Za Zhi
2025
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