TFRC (Transferrin Receptor) Gene
Key regulator of cellular iron uptake and erythropoiesis
Gene Information Card
| Symbol | TFRC |
|---|---|
| Full Name | Transferrin Receptor |
| Gene Type | Protein coding |
| Chromosomal Location | 3q29 |
| NCBI Gene ID | 7037 ncbi.nlm.nih.gov/gene/7037 |
| Ensembl ID | ENSG00000072274 |
| UniProt ID | P02786 |
| OMIM ID | 190010 |
| HGNC ID | 11763 |
| Aliases | CD71, TFR, TFR1, p90, TRFR |
Description
The TFRC gene encodes the transferrin receptor (TfR1), a transmembrane glycoprotein essential for cellular iron uptake. It binds iron-loaded transferrin and mediates its internalization via clathrin-dependent endocytosis. TFRC is highly expressed on erythroid precursors, proliferating cells, and the blood-brain barrier. It plays a critical role in erythropoiesis, cell growth, and iron homeostasis. Mutations in TFRC cause combined immunodeficiency and iron-refractory anemia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Immunodeficiency 46 (IMD46) | Loss-of-function mutations impair iron uptake in lymphocytes, leading to defective T- and B-cell proliferation | OMIM #616740 |
| Iron-refractory iron deficiency anemia (IRIDA) | Reduced TFRC function limits erythroid iron supply, causing microcytic anemia unresponsive to oral iron | ClinVar, PMID: 27067056 |
| Hereditary hemochromatosis (modifier) | TFRC variants may influence iron overload severity by altering transferrin receptor expression | OMIM #235200 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 124.5 | High |
| Spleen | 68.3 | High |
| Liver | 42.1 | Medium |
| Placenta | 55.7 | High |
| Brain (cerebellum) | 12.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (erythroleukemia) | 156.2 | High expression due to erythroid lineage |
| HEK293 (embryonic kidney) | 45.8 | Moderate expression |
| HepG2 (hepatocellular carcinoma) | 38.5 | Moderate expression |
| Jurkat (T-cell leukemia) | 72.1 | High expression in proliferating lymphocytes |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.58C>T (p.Arg20*) | Nonsense | Rare | Loss of function; associated with IMD46 |
| c.1120G>A (p.Gly374Arg) | Missense | Rare | Impaired transferrin binding; causes IRIDA |
| c.1429C>T (p.Arg477Trp) | Missense | Rare | Reduced cell surface expression; immunodeficiency |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., p.Arg20*, p.Gly374Arg) reduce or abolish transferrin binding and internalization, leading to iron deficiency in erythroid and immune cells.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in TFRC.
Dominant Negative (DN)
No dominant-negative mutations described; TFRC mutations are typically recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Transferrin endocytosis and recycling (Reactome: R-HSA-917977)
• Iron uptake and transport (KEGG: hsa04978)
• Erythropoietin signaling (WikiPathways: WP2034)
Protein Summary
The transferrin receptor (TfR1) is a homodimeric type II transmembrane protein of 760 amino acids. Each monomer consists of a large C-terminal ectodomain that binds transferrin, a single transmembrane helix, and a short N-terminal cytoplasmic tail. The ectodomain contains a protease-like domain and an apical domain that coordinate iron-loaded transferrin. Upon binding, the complex is internalized via clathrin-coated pits; acidification in endosomes releases iron, and the receptor-transferrin complex recycles to the cell surface. TfR1 is essential for erythropoiesis and cellular proliferation. Its expression is regulated by iron regulatory proteins (IRPs) via iron-responsive elements (IREs) in the mRNA.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TFRC Knockout HEK293 Cell Line | EDC08077 | Human | 7037 | Details Get a Quote |
| TFRC (c.2041-100G>A )Point Mutation in HAP1 Cell Line | EDC03617 | Human | 7037 | Details Get a Quote |
| TFRC (c.1678-4G>A )Point Mutation in HAP1 Cell Line | EDC03618 | Human | 7037 | Details Get a Quote |
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