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9 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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FOXRED2
FAD dependent oxidoreductase domain containing 2
Chromosome 22 · 22q12.3
NCBI Gene: 80020Ensembl: ENSG00000100350.16HGNC: HGNC:26264UniProt: A0A8I5KV30
34PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingflavin adenine dinucleotide bindingERAD pathwayendoplasmic reticulum lumenAlzheimer diseaseParkinson diseaselysosomal storage diseasemultiple sclerosis
✦AI Summary

FOXRED2 is a FAD-dependent oxidoreductase with emerging roles in cancer metabolism and disease pathogenesis. The protein likely functions as a flavoprotein capable of reductive activation of hypoxia-targeting prodrugs 1, demonstrating enzymatic activity toward xenobiotic metabolism previously uncharacterized for this protein. In melanoma, FOXRED2 expression is significantly elevated compared to normal skin, and knockdown inhibits proliferation, invasion, and migration while promoting apoptosis 2, suggesting oncogenic function in cutaneous malignancy. Beyond cancer, FOXRED2 has been identified through machine learning as a key gene associated with diabetic vascular aging and altered immune cell infiltration in vascular smooth muscle 3. Genetic variation in FOXRED2 (SNP rs144281) correlates with differential sensitivity to the anesthetic sevoflurane 4, indicating pharmacogenetic relevance. Additionally, FOXRED2 variants appear associated with COVID-19 severity outcomes 5 and malignant progression of neuroepithelial tumors 6. The gene is also part of a KRAS-driven transcriptomic signature with prognostic power in non-small cell lung cancer 7. These findings collectively suggest FOXRED2's multifaceted involvement in redox metabolism, cancer biology, vascular disease, and immune regulation, though its precise molecular mechanisms in most contexts remain incompletely characterized.

Sources cited
1
FOXRED2 expression is elevated in cutaneous malignant melanoma; knockdown inhibits proliferation, invasion, migration, and promotes apoptosis
PMID: 38076169
2
FOXRED2 is a flavoreductase capable of reductively activating hypoxia-targeting prodrugs including SN29428, PR-104A, tirapazamine, and SN30000
PMID: 24632291
3
FOXRED2 identified as key gene associated with diabetic vascular aging and correlated with immune cell infiltration changes in vascular smooth muscle
PMID: 38809515
4
FOXRED2 SNP rs144281 associated with differential sensitivity to sevoflurane anesthesia
PMID: 35202912
5
FOXRED2 identified among top significant genes associated with COVID-19 severity outcomes
PMID: 39557769
6
FOXRED2 carries somatic mutations in neuroepithelial tumor progression from PLNTY-like tumor to epithelioid glioblastoma
PMID: 41508055
7
FOXRED2 is part of KRAS-driven transcriptomic signature with prognostic power in non-small cell lung cancer
PMID: 27859136
Disease Associationsⓘ20
Alzheimer diseaseOpen Targets
0.27Weak
lysosomal storage diseaseOpen Targets
0.27Weak
multiple sclerosisOpen Targets
0.27Weak
neurodegenerative diseaseOpen Targets
0.27Weak
Parkinson diseaseOpen Targets
0.27Weak
melanomaOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.02Suggestive
frozen shoulderOpen Targets
0.02Suggestive
susceptibility to familial cutaneous melanomaOpen Targets
0.02Suggestive
cutaneous melanomaOpen Targets
0.02Suggestive
nevusOpen Targets
0.01Suggestive
cervical cancerOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
metastatic melanomaOpen Targets
0.01Suggestive
ulcer diseaseOpen Targets
0.01Suggestive
ulcerative colitisOpen Targets
0.01Suggestive
vulvar intraepithelial neoplasiaOpen Targets
0.01Suggestive
non-small cell lung carcinomaOpen Targets
0.00Suggestive
breast cancerOpen Targets
0.00Suggestive
adult T-cell leukemia/lymphomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
UBXN4Shared pathway100%FAM8A1Shared pathway100%RNF121Shared pathway100%TMUB2Shared pathway100%RNF175Shared pathway100%TMUB1Shared pathway100%
Tissue Expression6 tissues
Brain
100%
Ovary
32%
Bone Marrow
22%
Liver
18%
Heart
18%
Lung
9%
Gene Interaction Network
Click a node to explore
FOXRED2UBXN4FAM8A1RNF121TMUB2RNF175TMUB1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8IWF2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.80LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.59 [0.45–0.80]
RankingsWhere FOXRED2 stands among ~20K protein-coding genes
  • #11,155of 20,598
    Most Researched34
  • #6,635of 17,882
    Most Constrained (LOEUF)0.80
Genes detectedFOXRED2
Sources retrieved9 papers
Response time—
📄 Sources
9▼
1
Knockdown of FOXRED2 restrains proliferation, invasion and migration of human melanoma cells.
PMID: 38076169
Heliyon · 2023
1.00
2
The flavoprotein FOXRED2 reductively activates nitro-chloromethylbenzindolines and other hypoxia-targeting prodrugs.
PMID: 24632291
Biochem Pharmacol · 2014
0.89
3
Identification of key genes and biological pathways associated with vascular aging in diabetes based on bioinformatics and machine learning.
PMID: 38809515
Aging (Albany NY) · 2024
0.78
4
Potential miRNA-gene interactions determining progression of various ATLL cancer subtypes after infection by HTLV-1 oncovirus.
PMID: 36978083
BMC Med Genomics · 2023
0.67
5
Whole-exome sequencing reveals genetic variations in humans with differential sensitivity to sevoflurane:A prospective observational study.
PMID: 35202912
Biomed Pharmacother · 2022
0.56