TFR2 transferrin receptor 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TFR2provided by HGNC
Official Full Name: transferrin receptor 2provided by HGNC
Primary source: HGNC:HGNC:11762
See related: Ensembl:ENSG00000106327 MIM:604720; AllianceGenome:HGNC:11762
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HFE3; TFRC2
Summary: This gene encodes a single-pass type II membrane protein, which is a member of the transferrin receptor-like family. This protein mediates cellular uptake of transferrin-bound iron, and may be involved in iron metabolism, hepatocyte function and erythrocyte differentiation. Mutations in this gene have been associated with hereditary hemochromatosis type III. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, May 2011]
Expression: Restricted expression toward liver (RPKM 143.5) See more
Orthologs: mouse all
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Genomic context

Location:: 7q22.1

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (100620420..100641552, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (101860501..101881634, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (100218043..100239175, complement)

Chromosome 7 - NC_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Circ-STC2 promotes the ferroptosis of nucleus pulposus cells via targeting miR-486-3p/TFR2 axis.
Title: Circ-STC2 promotes the ferroptosis of nucleus pulposus cells via targeting miR-486-3p/TFR2 axis.
TFR2 regulates ferroptosis and enhances temozolomide chemo-sensitization in gliomas.
Title: TFR2 regulates ferroptosis and enhances temozolomide chemo-sensitization in gliomas.
Assessment of iron overload in a cohort of Sri Lankan patients with transfusion dependent beta thalassaemia and its correlation with pathogenic variants in HBB, HFE, SLC40A1, and TFR2 genes.
Title: Assessment of iron overload in a cohort of Sri Lankan patients with transfusion dependent beta thalassaemia and its correlation with pathogenic variants in HBB, HFE, SLC40A1, and TFR2 genes.
New Mutations in HFE2 and TFR2 Genes Causing Non HFE-Related Hereditary Hemochromatosis.
Title: New Mutations in HFE2 and TFR2 Genes Causing Non HFE-Related Hereditary Hemochromatosis.
Evaluation of the Association of Transferrin Receptor Type 2 Gene Mutation (Y250X) with Iron Overload in Major beta- Thalassemia.
Title: Evaluation of the Association of Transferrin Receptor Type 2 Gene Mutation (Y250X) with Iron Overload in Major β- Thalassemia.
Estimates of West African Ancestry in African Americans Using Alleles of Iron-Related Genes HJV, SLC40A1, and TFR2.
Title: Estimates of West African Ancestry in African Americans Using Alleles of Iron-Related Genes HJV, SLC40A1, and TFR2.
Iron-loaded transferrin potentiates erythropoietin effects on erythroblast proliferation and survival: a novel role through transferrin receptors.
Title: Iron-loaded transferrin potentiates erythropoietin effects on erythroblast proliferation and survival: a novel role through transferrin receptors.
Low expression of transferrin receptor 2 predict poor prognosis in gastric cancer patients.
Title: Low expression of transferrin receptor 2 predict poor prognosis in gastric cancer patients.
Orphan Nuclear Receptor ERRgamma Is a Transcriptional Regulator of CB1 Receptor-Mediated TFR2 Gene Expression in Hepatocytes.
Title: Orphan Nuclear Receptor ERRγ Is a Transcriptional Regulator of CB1 Receptor-Mediated TFR2 Gene Expression in Hepatocytes.
Transferrin receptor 1 (TfR1) mediates cellular uptake of holo-Tf and H-ferritin; New World arenaviruses and Plasmodium vivax use TfR1 for entry into host cells. In hepatocytes, TfR2 forms a complex with HFE and serves as an iron sensor. In erythroblasts, TfR2 forms a complex with EPO receptor and regulates erythropoiesis.
Title: Transferrin and transferrin receptors update.

Submit: New GeneRIF Correction See all GeneRIFs (71)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Hemochromatosis type 3 MedGen: C1858664 OMIM: 604250 GeneReviews: TFR2-Related Hemochromatosis	Compare labs

EBI GWAS Catalog

Description
A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Seventy-five genetic loci influencing the human red blood cell. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of transferrin receptor 2 (TFR2) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:1317244 (e-PCR)
- UniSTS:66075

RH45450 (e-PCR)
- UniSTS:70758

RH80164 (e-PCR)
- UniSTS:89706

D7S2897 (e-PCR)
- UniSTS:35455

RH47495 (e-PCR)
- UniSTS:81553

TFR2__5247 (e-PCR)
- UniSTS:463320

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables co-receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transferrin receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables transferrin receptor activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in acute-phase response	IEA Inferred from Electronic Annotation more info
involved_in cellular response to iron ion	IGI Inferred from Genetic Interaction more info	PubMed
involved_in endocytic iron import into cell	IBA Inferred from Biological aspect of Ancestor more info
involved_in endocytic iron import into cell	IGI Inferred from Genetic Interaction more info	PubMed
involved_in intracellular iron ion homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in intracellular iron ion homeostasis	TAS Traceable Author Statement more info	PubMed
involved_in iron ion transport	NAS Non-traceable Author Statement more info	PubMed
involved_in multicellular organismal-level iron ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of endocytosis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of peptide hormone secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein maturation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
involved_in receptor-mediated endocytosis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in response to iron ion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in transferrin transport	IGI Inferred from Genetic Interaction more info	PubMed

Component	Evidence Code	Pubs
part_of HFE-transferrin receptor complex	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in external side of plasma membrane	IGI Inferred from Genetic Interaction more info	PubMed
located_in plasma membrane	IGI Inferred from Genetic Interaction more info	PubMed
located_in plasma membrane	NAS Non-traceable Author Statement more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: transferrin receptor protein 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007989.1 RefSeqGene

Range

4999..26131

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001206855.3 → NP_001193784.1 transferrin receptor protein 2 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs at the 5' end compared to variant 1, and initiates translation from an in-frame downstream AUG, resulting in an isoform (2, also known as beta) with a shorter N-terminus (lacking the transmembrane domain) compared to isoform 1. While there is transcript support for this variant (PMID:10409623), the protein is predicted.

Source sequence(s)

AC099394

UniProtKB/Swiss-Prot

Q9UP52

Related

ENST00000476304.5

Conserved Domains (3) summary

cd09848
Location:238 → 471

M28_TfR; M28 Zn-peptidase Transferrin Receptor family

cd02128
Location:40 → 230

PA_TfR; PA_TfR: Protease-associated domain containing proteins like transferrin receptor (TfR). This group contains various PA domain-containing proteins similar to human TfR1 and TfR2. TfR1 and TfR2 are type II membrane proteins, belonging to the peptidase M28 ...

pfam04253
Location:503 → 620

TFR_dimer; Transferrin receptor-like dimerization domain
NM_003227.4 → NP_003218.2 transferrin receptor protein 2 isoform 1

See identical proteins and their annotated locations for NP_003218.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1, also known as alpha).

Source sequence(s)

AC099394, AF067864, BI917390, DR004213

Consensus CDS

CCDS34707.1

UniProtKB/Swiss-Prot

A6NGM7, O75422, Q1HE13, Q9HA99, Q9NX67, Q9UP52

Related

ENSP00000223051.3, ENST00000223051.8

Conserved Domains (3) summary

cd09848
Location:409 → 642

M28_TfR; M28 Zn-peptidase Transferrin Receptor family

cd02128
Location:211 → 401

PA_TfR; PA_TfR: Protease-associated domain containing proteins like transferrin receptor (TfR). This group contains various PA domain-containing proteins similar to human TfR1 and TfR2. TfR1 and TfR2 are type II membrane proteins, belonging to the peptidase M28 ...

pfam04253
Location:674 → 787

TFR_dimer; Transferrin receptor-like dimerisation domain