History and Nomenclature: The TFRC gene was assigned to chromosome 3 in 1982. It was located in 3q22 - qter the following year. It precisely maps to 3q29. Transferrin receptor was first detected as the proliferation-associated receptor for transferrin on leukemia cells. Transferrin receptor 2 is a distinct protein belonging to transferrin receptor-like family and its gene TFR maps to chromosome 7q22.

13 alternative splicing variants have been described. The full-length transcript contains 19 exons encoding 760 amino acids.

There is no known pseudogene derived from TFRC.

A plasma membrane transport glycoprotein composed of disulfide-linked polypeptide chains, each 84.8-kDa molecular weight. Belongs to the peptidase m28 family.

Expressed in a wide range of cell types and tissues. Expression level is highest in lymphocytes, placenta and neoplastic cells.

TFRC is a cell surface membrane protein.

TFRC is primarily involved in iron homeostasis by regulating cellular iron uptake in interaction with the HFE protein. It is also crucial in iron transportation from mother to fetus.
Transferrin receptor is the main receptor for transferrin and allows transferrin-bound iron uptake by the cell. Its expression is regulated by cellular iron requirements. Conserved iron-response elements in the 3-untranslated region of transferrin receptor mRNA enhance binding of iron regulatory proteins 1 and 2. The hereditary hemochromatosis protein HFE competes for binding with transferrin for an overlapping binding site. It is also involved in materno-fetal iron transport via the placenta.

There are no disease-causing mutations in the TFRC gene. However, there are missense coding region variants that may have functional effects. The only one with appreciable frequency (rs3817672) is in exon 4 and encodes S142G amino acid substitution. This polymorphism does not have a homogeneous global distribution. Its minor allele in Caucasians is the major allele in Asians and Africans. There is no nonsense mutation described in TFRC. TFRC is not involved in any known translocations. Tfrc knockout mice are not viable and die during embryonic development due to erythropoietic and neuronal development problems.
The short arm of chromosome 3 also harbors other iron-related genes: transferrin (3q22.1), lactotransferrin (3q21-q23), melanotransferrin (3q28-q29) and ceruloplasmin (3q23-q25). Trisomy of chromosome 3, gain of the whole 3q arm and gain of 3q27-qter have been noted in various malignancies including both solid tumors and hematopoietic ones.