FDX2: Ferredoxin 2 – Mitochondrial Iron-Sulfur Cluster Biogenesis
Essential cofactor for mitochondrial respiratory chain and heme biosynthesis
Gene Information Card
| Symbol | FDX2 |
|---|---|
| Full Name | ferredoxin 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 19p13.2 |
| NCBI Gene ID | 112812 ncbi.nlm.nih.gov/gene/112812 |
| Ensembl ID | ENSG00000167658 |
| UniProt ID | Q6P4F2 |
| OMIM ID | 614585 |
| HGNC ID | 28669 |
| Aliases | FDX1L, adrenodoxin-like, ferredoxin-2 |
Description
FDX2 encodes a mitochondrial ferredoxin that functions as an electron transfer protein essential for the biosynthesis of iron-sulfur (Fe-S) clusters and heme A. It accepts electrons from NADPH via ferredoxin reductase and delivers them to mitochondrial enzymes involved in Fe-S cluster assembly and cytochrome c oxidase maturation. Mutations in FDX2 cause mitochondrial complex deficiencies and a specific form of mitochondrial encephalopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial complex I deficiency, nuclear type 36 (MC1DN36) | Loss-of-function mutations impair Fe-S cluster biogenesis, reducing activity of respiratory chain complexes I, II, and III | OMIM #619405; PMID: 28812651 |
| Leigh syndrome-like encephalopathy | Defective Fe-S cluster assembly leads to mitochondrial dysfunction and neurodegeneration | ClinVar; PMID: 28812651 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Heart | 10.3 | Medium |
| Skeletal Muscle | 8.7 | Medium |
| Brain | 7.1 | Low |
| Kidney | 9.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.1 | Hepatocyte cell line |
| K-562 | 6.8 | Myelogenous leukemia line |
| HeLa | 5.3 | Cervical carcinoma line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2T>C (p.Met1?) | Missense/Start loss | Rare | Loss of protein expression; associated with MC1DN36 |
| c.286C>T (p.Arg96Trp) | Missense | Rare | Impaired electron transfer; Leigh syndrome phenotype |
Mutation functional classification
Loss of Function (LOF)
Pathogenic missense and start-loss mutations reduce or abolish ferredoxin activity, leading to Fe-S cluster deficiency.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Mitochondrial iron-sulfur cluster biogenesis (Reactome: R-HSA-1369007)
• Electron transport chain (complex I
• II
• III) (KEGG: map00190)
Protein Summary
FDX2 is a small (14.5 kDa) mitochondrial ferredoxin that contains a [2Fe-2S] cluster. It transfers electrons from NADPH:ferredoxin reductase to mitochondrial enzymes such as cysteine desulfurase (NFS1) and heme A synthase (COX15). This activity is critical for the assembly of iron-sulfur clusters in respiratory complexes and for cytochrome c oxidase maturation. Loss of FDX2 function leads to combined oxidative phosphorylation deficiency and early-onset neurological disease.
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