FOXRED1

Chr 11AR

FAD dependent oxidoreductase domain containing 1

Also known as: FP634, H17, MC1DN19

FOXRED1 encodes a FAD-dependent oxidoreductase that serves as a chaperone protein required for the assembly of mitochondrial complex I (NADH dehydrogenase), particularly during mid-late assembly stages. Mutations cause mitochondrial complex I deficiency with autosomal recessive inheritance, typically presenting in infancy or early childhood with neurological symptoms, developmental delays, and multi-organ involvement. The gene shows extremely low constraint against loss-of-function variants (pLI near zero), consistent with its recessive disease mechanism.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.321 OMIM phenotype
Clinical SummaryFOXRED1
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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.
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ClinVar Variants
38 unique Pathogenic / Likely Pathogenic· 47 VUS of 200 total submissions
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GeneReview available — FOXRED1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.32LOEUF
pLI 0.000
Z-score 0.26
OE 0.95 (0.691.32)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.40Z-score
OE missense 1.07 (0.971.18)
291 obs / 272.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.95 (0.691.32)
00.351.4
Missense OE1.07 (0.971.18)
00.61.4
Synonymous OE1.19
01.21.6
LoF obs/exp: 25 / 26.4Missense obs/exp: 291 / 272.3Syn Z: -1.60
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFOXRED1-related mitochondrial complex I deficiencyLOFAR

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

DN
0.6649th %ile
GOF
0.5170th %ile
LOF
0.3841th %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

200 submitted variants in ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic13
VUS47
Likely Benign100
25
Pathogenic
13
Likely Pathogenic
47
VUS
100
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
0
9
0
25
Likely Pathogenic
13
0
0
0
13
VUS
0
44
3
0
47
Likely Benign
0
4
39
57
100
Benign
0
0
0
0
0
Total29485157185

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →