TFR2 Gene - Transferrin Receptor 2
Key regulator of iron homeostasis and hereditary hemochromatosis
Gene Information Card
| Symbol | TFR2 |
|---|---|
| Full Name | Transferrin Receptor 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q22.1 |
| NCBI Gene ID | 7036 ncbi.nlm.nih.gov/gene/7036 |
| Ensembl ID | ENSG00000106327 |
| UniProt ID | Q9UP52 |
| OMIM ID | 604720 |
| HGNC ID | 11762 |
| Aliases | HFE3, TFRC2, TR2 |
Description
The TFR2 gene encodes transferrin receptor 2, a transmembrane protein that mediates cellular uptake of iron-bound transferrin. It is primarily expressed in the liver and plays a critical role in systemic iron homeostasis by regulating hepcidin expression. Mutations in TFR2 cause hereditary hemochromatosis type 3 (HFE3), an autosomal recessive disorder characterized by iron overload.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Hemochromatosis Type 3 | Loss-of-function mutations in TFR2 impair hepcidin regulation, leading to increased intestinal iron absorption and tissue iron deposition. | OMIM #604720; ClinVar; multiple case reports |
| Iron Overload (Secondary) | TFR2 variants may contribute to iron accumulation in chronic liver disease. | NCBI Gene; limited evidence |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Bone Marrow | 3.2 | Medium |
| Spleen | 2.1 | Low |
| Duodenum | 1.8 | Low |
| Heart | 0.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.3 | Hepatocellular carcinoma cell line |
| K562 | 4.7 | Erythroleukemia cell line |
| HEK293 | 1.2 | Embryonic kidney cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.750C>G (p.Tyr250Ter) | Nonsense | Rare | Loss of function; truncation of protein |
| c.1198G>A (p.Glu400Lys) | Missense | Rare | Loss of function; impaired transferrin binding |
| c.2074C>T (p.Arg692Ter) | Nonsense | Rare | Loss of function; premature stop codon |
Mutation functional classification
Loss of Function (LOF)
Most TFR2 mutations are loss-of-function, leading to reduced hepcidin expression and iron overload.
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)
| • transferrin receptor activity (GO:0004998) | • cellular iron ion homeostasis (GO:0006879) |
| • integral component of membrane (GO:0016021) | • iron ion transport (GO:0033572) |
| • intracellular organelle (GO:0043229) |
Pathways
• Iron metabolism (hepcidin-ferroportin axis)
• Transferrin/transferrin receptor recycling
Protein Summary
Transferrin receptor 2 (TFR2) is a 801-amino acid transmembrane glycoprotein that binds iron-loaded transferrin with lower affinity than TFR1. It is predominantly expressed in hepatocytes and erythroid precursors. TFR2 modulates hepcidin expression via the BMP/SMAD signaling pathway, thereby controlling systemic iron levels. Mutations in TFR2 disrupt this regulation, causing hereditary hemochromatosis type 3.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TFR2 Knockout HEK293 Cell Line | EDJ-KQ5925 | Human | 7036 | Details Get a Quote |
| TFR2 Knockout A-549 Cell Line | EDJ-KQ29466 | Human | 7036 | Details Get a Quote |
| TFR2 Knockout HCT 116 Cell Line | EDJ-KQ29467 | Human | 7036 | Details Get a Quote |
| TFR2 Knockout HeLa Cell Line | EDJ-KQ29468 | Human | 7036 | Details Get a Quote |
