SLC25A28: Mitochondrial Iron Transporter and Key Regulator of Iron Homeostasis
Comprehensive genomic, functional, and clinical overview of the SLC25A28 gene encoding mitoferrin-2
Gene Information Card
| Symbol | SLC25A28 |
|---|---|
| Full Name | Solute Carrier Family 25 Member 28 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q24.2 |
| NCBI Gene ID | 81894 ncbi.nlm.nih.gov/gene/81894 |
| Ensembl ID | ENSG00000119950 |
| UniProt ID | Q96A46 |
| OMIM ID | 610819 |
| HGNC ID | 23418 |
| Aliases | MFRN2, MRS3/4, FLJ20443 |
Description
SLC25A28 encodes mitoferrin-2 (MFRN2), a mitochondrial inner membrane protein that functions as an iron importer essential for heme biosynthesis and iron-sulfur cluster assembly. It is ubiquitously expressed and plays a critical role in cellular iron homeostasis. Mutations in SLC25A28 are associated with inherited disorders of iron metabolism and have been implicated in cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Anemia, sideroblastic, with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) | Loss-of-function mutations impair mitochondrial iron import, leading to defective heme synthesis and mitochondrial dysfunction | OMIM #616084; ClinVar |
| Hereditary hemochromatosis (modifier) | Altered iron transport may exacerbate iron overload | OMIM #235200; literature |
| Cancer (various types) | Dysregulated iron metabolism promotes tumor growth; overexpression observed in some malignancies | COSMIC; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Liver | 9.8 | Medium |
| Heart | 7.2 | Low |
| Brain | 5.1 | Low |
| Kidney | 6.4 | Low |
| Testis | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (erythroleukemia) | 15.2 | High expression; relevant for erythropoiesis |
| HepG2 (hepatocellular carcinoma) | 10.1 | Moderate expression |
| HeLa (cervical carcinoma) | 8.5 | Moderate expression |
| HEK293 (embryonic kidney) | 6.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.335C>T (p.Pro112Leu) | Missense | Rare | Impaired iron transport; associated with SIFD |
| c.430G>A (p.Gly144Arg) | Missense | Rare | Reduced protein stability; SIFD |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of translation initiation; SIFD |
| c.682C>T (p.Arg228*) | Nonsense | Rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense and nonsense mutations (e.g., p.Pro112Leu, p.Arg228*) reduce or abolish mitochondrial iron import, leading to sideroblastic anemia and immunodeficiency.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in SLC25A28.
Dominant Negative (DN)
Not established; SLC25A28 mutations are typically recessive.
View complete mutation data：
Gene Ontology (GO)
| • mitochondrion (GO:0005739) | • integral component of membrane (GO:0016021) |
| • iron ion transmembrane transporter activity (GO:0005381) | • iron ion transport (GO:0006826) |
| • cellular iron ion homeostasis (GO:0006879) | • heme biosynthetic process (GO:0006783) |
| • iron-sulfur cluster assembly (GO:0016226) |
Pathways
• Iron metabolism (Reactome: R-HSA-917937)
• Heme biosynthesis (Reactome: R-HSA-189451)
• Mitochondrial iron-sulfur cluster biogenesis (Reactome: R-HSA-1369007)
Protein Summary
Mitoferrin-2 (MFRN2) is a 364-amino acid mitochondrial inner membrane protein with six transmembrane domains. It mediates the import of ferrous iron (Fe2+) into the mitochondrial matrix, a rate-limiting step for heme and iron-sulfur cluster synthesis. MFRN2 is ubiquitously expressed, with highest levels in erythroid tissues. Its function is essential for erythropoiesis and cellular energy metabolism.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID |
|---|
