TFR2 R455Q - GET-Evidence

Curation:
Currentness:

TFR2 R455Q

(TFR2 Arg455Gln)


Short summary

Hypothesized to be increase risk or severity of hemochromatosis, but only speculations based on a couple sporadic observations (no statistical significance).

Variant evidence
Computational 2

Other variants in this gene implicated in causing hemochromatosis, Polyphen 2 predicts damaging effect

Functional

No functional data

Case/Control

No statistically significant observations

See Hofmann WK et al. 2002 (12150153), Lee PL et al. 2006 (16424658).

Familial -
 
Clinical importance
Severity 4

Hemochromatosis

Treatability 4
Penetrance 2

Not thought to be strongly causal, may increase risk with low penetrance

 

Impact

Low clinical importance, Uncertain pathogenic

(The "low clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

undefined

Summary of published research, and additional commentary

 

Allele frequency

  • T @ chr7:100226902: 0.2% (25/10758) in EVS
  • Frequency shown in summary reports: 0.2% (25/10758)

Publications
 

Hofmann WK, Tong XJ, Ajioka RS, Kushner JP, Koeffler HP. Mutation analysis of transferrin-receptor 2 in patients with atypical hemochromatosis. Blood. 2002 Aug 1;100(3):1099-100. PubMed PMID: 12150153.

This variant is characterized as novel and is seen in the brother of a proband with hemochromatosis, one of a cohort of 11 sibling cases where both were homozygous for HFE-C282Y but had discordant phenotypes. The brother carrying this variant had a more severe phenotype (with liver fibrosis), and so the authors speculate that it may be a modulator that increases severity of hemochromatosis. However, the observation lacks statistical significance.

Lee PL, Barton JC. Hemochromatosis and severe iron overload associated with compound heterozygosity for TFR2 R455Q and two novel mutations TFR2 R396X and G792R. Acta Haematol. 2006;115(1-2):102-5. PubMed PMID: 16424658.

(Based only on information in the abstract) A report of a single case, with a patient carrying a couple different variants in this gene (in addition to this, he had a nonsense mutation, R396X, and G792R). The authors concluded the variants in this gene were causal.

Genomes
 

huBAAC98 - CGI sample GS01173-DNA_F02 from PGP sample 70008981
het T @ chr7:100226902

 

Other external references
 

    dbSNP
  • rs41303501
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.982 (probably damaging)
    Web search results (32 hits -- see all)
  • Hemochromatosis and severe iron overload associated with ...
    Hemochromatosis and severe iron overload associated with compound heterozygosity for TFR2 R455Q and two novel mutations TFR2 R396X and G792R. ...
    www.ncbi.nlm.nih.gov/pubmed/16424658
  • Hemochromatosis and Severe Iron Overload Associated with ...
    Hemochromatosis and Severe Iron Overload Associated with Compound Heterozygosity for TFR2 R455Q and Two Novel Mutations TFR2 R396X and G792R ...
    content.karger.com/ProdukteDB/produkte.asp?...
  • Acta Haematologica 2006, Vol. 115, No. 1-2
    High-Dose Idarubicin, Busulphan and Melphalan for Autologous Stem Cell Transplantation in ... Heterozygosity for TFR2 R455Q and Two Novel Mutations TFR2 R396X and G792R ...
    content.karger.com/ProdukteDB/produkte.asp?...
  • Homozygous p.M172K mutation of the TFR2 gene in an Italian ...
    The p.M172K TFR2 mutation was identified in. two Italian siblings aged 32 and 40 years old ... associated with compound heterozygosity for TFR2 R455Q ...
    www.haematologica.org/cgi/reprint/91/8_Suppl/ECR33.pdf
  • The Scripps Research Institute - Scientific Report 2006
    Hemochromatosis and severe iron overload associated with compound heterozygosity for TFR2 R455Q and two novel mutations TFR2 R396X and G792R. Acta Haematol. ...
    www.scripps.edu/news/sr/sr2006/mem06beutler.html
  • SpringerProtocols: Abstract: In Silico Analysis of SNPs and ...
    Springer Protocols is the largest subscription-based electronic database of reproducible laboratory protocols in the Life and Biomedical Sciences.
    springerprotocols.com/Abstract/doi/10.1007/...
  • Identification of New Mutations of the HFE, Hepcidin, and ...
    TfR2 has 48% identity to transferrin receptor (TfR1) in the extracellular ... and Hofmann et al. (11) found the TfR2 R455Q mutation in a family with the HFE ...
    www.clinchem.org/cgi/content/full/49/12/1981
  • James Barton - research profile on BiomedExperts
    Hemochromatosis and severe iron overload associated with compound heterozygosity for TFR2 R455Q and two novel mutations TFR2 R396X and G792R. ...
    www.biomedexperts.com/Profile.bme/86645/James_C_Barton
  • TFR2-Related Hereditary Hemochromatosis
    The diagnosis of TFR2-HHC in individuals with clinical symptoms and/or ... for TFR2 R455Q and two novel mutations TFR2 R396X and G792R. Acta Haematol 2006;115:102 ...
    ncbi.nlm.nih.gov/bookshelf/picrender.fcgi?...&blobtype=pdf
  • ELSEVIER.ES - REVISTAS
    Nuevos conceptos patogénicos sobre la hemocromatosis hereditaria ... Los TfR2 se expresan principalmente en hepatocitos, aunque también en las criptas duodenales y las células ...
    elsevier.es/revistas/ctl_servlet?_f=7064&articuloid=13089718

Other in silico analyses
 

  • NBLOSUM100 score = 0
  • GET-Evidence autoscore = 6

Edit history
 

Gene search

"GENE" or "GENE A123C":

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