FDX1 Gene: Ferredoxin 1 - Function, Related Diseases, and Clinical Significance
Explore the FDX1 gene, its role in mitochondrial iron-sulfur cluster biosynthesis, steroid metabolism, and implications in lipoic acid metabolism and cancer research.
Gene Information Card
| Symbol | FDX1 |
|---|---|
| Full Name | Ferredoxin 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q22.3 |
| NCBI Gene ID | 2230 ncbi.nlm.nih.gov/gene/2230 |
| Ensembl ID | ENSG00000137710 |
| UniProt ID | P10109 |
| OMIM ID | 103260 |
| HGNC ID | 3638 |
| Aliases | ADX, FDX, LOH11CR1D |
Description
FDX1 encodes a mitochondrial ferredoxin that participates in electron transfer in various mitochondrial processes, including steroid hydroxylation and iron-sulfur cluster assembly. It also plays a critical role in lipoic acid synthesis and is implicated in cuproptosis, a form of copper-induced cell death.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial complex deficiency | FDX1 mutations impair iron-sulfur cluster biogenesis, leading to mitochondrial dysfunction. | ClinVar, OMIM |
| Steroid hormone deficiency | Reduced FDX1 activity affects adrenal steroidogenesis, potentially causing congenital lipoid adrenal hyperplasia-like phenotype. | OMIM, literature |
| Cancer (various) | FDX1 expression is associated with cuproptosis sensitivity; loss of FDX1 confers resistance to copper ionophores in cancer cells. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adrenal gland | High | High |
| Liver | Medium | Medium |
| Kidney | Medium | Medium |
| Heart | Medium | Medium |
| Brain | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | Medium | Liver cancer cell line |
| A549 | Medium | Lung cancer cell line |
| MCF7 | Low | Breast cancer cell line |
| K562 | Low | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.547C>T (p.Arg183Trp) | Missense | Rare | Impairs ferredoxin function, associated with mitochondrial disease |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of protein expression, likely pathogenic |
| c.IVS2+1G>A | Splice site | Rare | Splicing defect, reduced mRNA levels |
Mutation functional classification
Loss of Function (LOF)
FDX1 loss-of-function mutations reduce mitochondrial iron-sulfur cluster synthesis and lipoic acid production, leading to mitochondrial dysfunction and cuproptosis resistance.
Gain of Function (GOF)
No known gain-of-function mutations reported.
Dominant Negative (DN)
No evidence of dominant-negative effects; FDX1 mutations are typically recessive.
View complete mutation data：
Gene Ontology (GO)
| • iron ion binding (GO:0005506) | • electron transfer activity (GO:0009055) |
| • mitochondrion (GO:0005739) | • oxidoreductase activity (GO:0016491) |
| • iron-sulfur cluster assembly (GO:0015939) |
Pathways
• Steroid hormone biosynthesis
• Iron-sulfur cluster assembly
• Lipoic acid metabolism
• Cuproptosis pathway
Protein Summary
FDX1 is a mitochondrial ferredoxin that transfers electrons from NADPH-dependent ferredoxin reductase to cytochrome P450 enzymes involved in steroidogenesis and to iron-sulfur cluster assembly machinery. It also participates in the synthesis of lipoic acid, a cofactor for mitochondrial enzymes. Recent studies show FDX1 is a key regulator of cuproptosis, a copper-dependent cell death mechanism, making it a potential therapeutic target in cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FDX1 Knockout HEK293 Cell Line | EDJ-KQ3659 | Human | 2230 | Details Get a Quote |
| FDX1 Knockout A-549 Cell Line | EDJ-KQ25630 | Human | 2230 | Details Get a Quote |
| FDX1 Knockout HCT 116 Cell Line | EDJ-KQ25631 | Human | 2230 | Details Get a Quote |
| FDX1 Knockout HeLa Cell Line | EDJ-KQ25632 | Human | 2230 | Details Get a Quote |
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