GLRX5 Gene - Glutaredoxin 5
Iron-Sulfur Cluster Biogenesis and Erythropoietic Protoporphyria
Gene Information Card
| Symbol | GLRX5 |
|---|---|
| Full Name | Glutaredoxin 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q32.13 |
| NCBI Gene ID | 51218 ncbi.nlm.nih.gov/gene/51218 |
| Ensembl ID | ENSG00000182512 |
| UniProt ID | Q86SJ6 |
| OMIM ID | 609588 |
| HGNC ID | 29534 |
| Aliases | GRX5, FLB4739, PRO2653 |
Description
GLRX5 encodes a mitochondrial glutaredoxin that is essential for iron-sulfur (Fe-S) cluster biogenesis. The protein functions as a scaffold for Fe-S cluster assembly and transfer, playing a critical role in mitochondrial iron metabolism, heme synthesis, and cellular redox homeostasis. Mutations in GLRX5 cause a range of disorders including pyridoxine-refractory sideroblastic anemia and erythropoietic protoporphyria.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Erythropoietic protoporphyria (EPP) | Loss-of-function mutations impair Fe-S cluster assembly, leading to mitochondrial iron accumulation and protoporphyrin IX overload. | ClinVar, OMIM |
| Pyridoxine-refractory sideroblastic anemia | Defective Fe-S cluster biogenesis disrupts heme synthesis, causing ring sideroblasts and microcytic anemia. | ClinVar, OMIM |
| GLRX5-related mitochondrial dysfunction | Impaired Fe-S cluster transfer affects multiple mitochondrial enzymes, leading to oxidative stress and metabolic defects. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 15.2 | Medium |
| Liver | 12.8 | Medium |
| Spleen | 10.5 | Medium |
| Heart | 8.3 | Low |
| Skeletal muscle | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (erythroleukemia) | 18.4 | High expression |
| HepG2 (hepatocellular carcinoma) | 14.1 | Medium expression |
| HeLa (cervical carcinoma) | 9.7 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.294A>G (p.Ile98Met) | Missense | Rare | Reduced Fe-S cluster assembly; associated with EPP |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein; associated with sideroblastic anemia |
| c.358C>T (p.Arg120*) | Nonsense | Rare | Truncated protein; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations (missense, nonsense, start loss) lead to reduced or absent glutaredoxin activity, impairing Fe-S cluster biogenesis.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative effects documented; disease inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • iron-sulfur cluster assembly | • protein glutathionylation |
| • mitochondrion | • metal ion binding |
| • electron transfer activity |
Pathways
• Iron-sulfur cluster biogenesis (mitochondrial)
• Heme biosynthesis
• Cellular response to oxidative stress
Protein Summary
GLRX5 is a 157-amino acid mitochondrial glutaredoxin that contains a conserved CGFS active site motif. It acts as a monothiol glutaredoxin, binding Fe-S clusters and transferring them to target proteins. The protein is critical for erythroid differentiation and mitochondrial iron homeostasis. Defects lead to iron accumulation, protoporphyrin IX elevation, and anemia.
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