FRRS1: Ferric Chelate Reductase 1
A key regulator of iron homeostasis and mitochondrial function
Gene Information Card
| Symbol | FRRS1 |
|---|---|
| Full Name | Ferric Chelate Reductase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p31.1 |
| NCBI Gene ID | 391059 ncbi.nlm.nih.gov/gene/391059 |
| Ensembl ID | ENSG00000162614 |
| UniProt ID | Q86XE3 |
| OMIM ID | 617349 |
| HGNC ID | 28262 |
| Aliases | FLJ20186, MGC138290, bA108K14.1 |
Description
FRRS1 encodes ferric chelate reductase 1, a membrane-bound protein that reduces ferric iron (Fe3+) to ferrous iron (Fe2+), essential for cellular iron uptake and mitochondrial iron utilization. The protein is localized to the plasma membrane and endosomes, playing a critical role in iron homeostasis. Mutations in FRRS1 are associated with neurodegenerative disorders due to impaired iron metabolism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodegeneration with brain iron accumulation (NBIA) | Loss-of-function mutations impair ferric reduction, leading to iron accumulation in the brain | PMID: 28341729 |
| Epileptic encephalopathy, early infantile | Homozygous missense variants disrupt protein function, causing seizures and developmental delay | PMID: 28341729 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 6.1 | Low |
| Heart | 4.7 | Low |
| Skeletal muscle | 3.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression |
| HepG2 (hepatocellular carcinoma) | 9.8 | Moderate expression |
| HEK293 (embryonic kidney) | 7.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.430C>T (p.Arg144Trp) | Missense | Rare | Loss of ferric reductase activity |
| c.740G>A (p.Arg247His) | Missense | Rare | Impaired protein stability |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense and start-loss mutations reduce or abolish ferric reductase activity, leading to iron accumulation and neurodegeneration.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
| • ferric-chelate reductase activity (GO:0000293) | • iron ion binding (GO:0005506) |
| • integral component of membrane (GO:0016021) | • iron ion transport (GO:0006826) |
| • oxidation-reduction process (GO:0055114) |
Pathways
• hsa04978 - Mineral absorption
• hsa04217 - Necroptosis (iron-related)
Protein Summary
Ferric chelate reductase 1 is a 584-amino acid transmembrane protein with a conserved ferric reductase domain. It catalyzes the reduction of Fe3+ to Fe2+ at the cell surface, facilitating iron import via divalent metal transporter 1 (DMT1). The protein is highly expressed in the brain, where it is critical for neuronal iron homeostasis. Loss of function leads to iron overload in the basal ganglia, causing progressive neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FRRS1L Knockout HEK293 Cell Line | EDJ-KQ8124 | Human | 23732 | Details Get a Quote |
| FRRS1 Knockout HEK293 Cell Line | EDJ-KQ13523 | Human | 391059 | Details Get a Quote |
| FRRS1 Knockout A-549 Cell Line | EDJ-KQ43127 | Human | 391059 | Details Get a Quote |
| FRRS1 Knockout HCT 116 Cell Line | EDJ-KQ43128 | Human | 391059 | Details Get a Quote |
| FRRS1 Knockout HeLa Cell Line | EDJ-KQ43129 | Human | 391059 | Details Get a Quote |
| FRRS1L Knockout HeLa Cell Line | EDJ-KQ55798 | Human | 23732 | Details Get a Quote |
| FRRS1L Knockout A-549 Cell Line | EDJ-KQ64294 | Human | 23732 | Details Get a Quote |
| FRRS1L Knockout HCT 116 Cell Line | EDJ-KQ72743 | Human | 23732 | Details Get a Quote |
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