TFRC (transferrin receptor (p90, CD71))

2008-04-01   M Tevfik Dorak 

Genomic Immunoepidemiology Laboratory, HUMIGEN LLC, The Institute for Genetic Immunology, Hamilton, NJ 08690-3303, USA





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.

Implicated in

Entity name
Cancer Susceptibility
Overexpression of TFRC in malignant cells mediates higher iron uptake required for cell division. Expression is activated by c-Myc.
No mutation or variation in TFRC causes cancer and TFRC is not involved in cancer-associated translocations.
TFRC variant S142G modifies the associations of HFE C282Y mutation in cancer susceptibility for hepatocellular carcinoma, breast cancer, leukemia, colorectal cancer and multiple myeloma. Biological plausibility of these associations has been supported by the successful use of monoclonal antibodies against transferrin receptor in cancer treatment in vitro and in vivo.


Pubmed IDLast YearTitleAuthors
153134612004Transferrin receptor 1.Aisen P et al
110963442000Interaction between haemochromatosis and transferrin receptor genes in hepatocellular carcinoma.Beckman LE et al
62853431982Human transferrin receptor: expression of the receptor is assigned to chromosome 3.Enns CA et al
125518242003Cytogenetic and molecular delineation of a region of chromosome 3q commonly gained in marginal zone B-cell lymphoma.Gazzo S et al
97327491982Expression of human transferrin receptor is controlled by a gene on chromosome 3: assignment using species specificity of a monoclonal antibody.Goodfellow PN et al
94286301997NotI linking/jumping clones of human chromosome 3: mapping of the TFRC, RAB7 and HAUSP genes to regions rearranged in leukemia and deleted in solid tumors.Kashuba VI et al
27472891989Translocation (3;21) in Philadelphia positive chronic myeloid leukemia: high resolution chromosomal analysis and immunological study on five new cases.Lafage-Pochitaloff-Huvalé M et al
101923901999Transferrin receptor is necessary for development of erythrocytes and the nervous system.Levy JE et al
60940091984The human transferrin receptor gene: genomic organization, and the complete primary structure of the receptor deduced from a cDNA sequence.McClelland A et al
63090001983Chromosome 3q (22-ter) encodes the human transferrin receptor.Miller YE et al
165080122006Activation of transferrin receptor 1 by c-Myc enhances cellular proliferation and tumorigenesis.O'Donnell KA et al
30021711985Regional localization of the human transferrin receptor gene to 3q26.2----qter.Rabin M et al
104926401999Expression analysis of genes at 3q26-q27 involved in frequent amplification in squamous cell lung carcinoma.Rácz A et al
172877272007Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses.Radoshitzky SR et al
122181822002Mouse transferrin receptor 1 is the cell entry receptor for mouse mammary tumor virus.Ross SR et al
62706801981Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin.Sutherland R et al
30047041986Mechanisms of growth inhibition by anti-transferrin receptor monoclonal antibodies.Taetle R et al
29842531985Role of transferrin, Fe, and transferrin receptors in myeloid leukemia cell growth. Studies with an antitransferrin receptor monoclonal antibody.Taetle R et al
35452111986Structure and function of transferrin receptors and their relationship to cell growth.Trowbridge IS et al
85477121994The blockage of the human transferrin receptor by a monoclonal antibody, EA.3, induces growth inhibition in leukemia cell lines.Valentini M et al
97884681998Interaction between haemochromatosis and transferrin receptor genes in multiple myeloma.Van Landeghem GF et al
167887582006PIK3CA and TFRC located in 3q are new prognostic factors in esophageal squamous cell carcinoma.Wada S et al
24009931990Combinations of anti-transferrin receptor monoclonal antibodies inhibit human tumor cell growth in vitro and in vivo: evidence for synergistic antiproliferative effects.White S et al

Other Information

Locus ID:

NCBI: 7037
MIM: 190010
HGNC: 11763
Ensembl: ENSG00000072274


dbSNP: 7037
ClinVar: 7037
TCGA: ENSG00000072274


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Hematopoietic cell lineageKEGGko04640
Hematopoietic cell lineageKEGGhsa04640
HIF-1 signaling pathwayKEGGhsa04066
Vesicle-mediated transportREACTOMER-HSA-5653656
Membrane TraffickingREACTOMER-HSA-199991
trans-Golgi Network Vesicle BuddingREACTOMER-HSA-199992
Clathrin derived vesicle buddingREACTOMER-HSA-421837
Golgi Associated Vesicle BiogenesisREACTOMER-HSA-432722
Transmembrane transport of small moleculesREACTOMER-HSA-382551
Iron uptake and transportREACTOMER-HSA-917937
Transferrin endocytosis and recyclingREACTOMER-HSA-917977
Clathrin-mediated endocytosisREACTOMER-HSA-8856828
Cargo recognition for clathrin-mediated endocytosisREACTOMER-HSA-8856825

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
172877272007Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses.188
149802232004Structure of the human transferrin receptor-transferrin complex.135
168938962006Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing.105
179940112007SNX4 coordinates endosomal sorting of TfnR with dynein-mediated transport into the endocytic recycling compartment.102
237544142013Identification of transferrin receptor 1 as a hepatitis C virus entry factor.92
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
198644582009MICAL-L1 links EHD1 to tubular recycling endosomes and regulates receptor recycling.82
201336742010Binding and uptake of H-ferritin are mediated by human transferrin receptor-1.82
165080122006Activation of transferrin receptor 1 by c-Myc enhances cellular proliferation and tumorigenesis.81
171730372007Dynein is required for receptor sorting and the morphogenesis of early endosomes.80


M Tevfik Dorak

TFRC (transferrin receptor (p90, CD71))

Atlas Genet Cytogenet Oncol Haematol. 2008-04-01

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