PAH E280K - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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Curation:
Currentness:

PAH E280K

(PAH Glu280Lys)


Short summary

 

Variant evidence
Computational -
Functional -
Case/Control -
Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pathogenic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • T @ chr12:103246597: 0.0% (3/10758) in EVS
  • Frequency shown in summary reports: 0.0% (3/10758)

Publications
 

Genomes
 

Other external references
 

    PolyPhen-2
  • Score: 1.0 (probably damaging)
    Web search results (115 hits -- see all)
  • Prediction of multiple hypermutable codons in the human PAH ...
    The E280K mutation in exon 7 of the PAH gene is a cause of phenylketonuria. ... The PAH mutation database shows that the allele accounts for 1.5% of ...
    www.ncbi.nlm.nih.gov/pubmed/9101291
  • Structural Studies on Phenylalanine Hydroxylase and ...
    Several 3-dimensional structures of truncated forms of PAH have been determined in our laboratory and by ... expected, expression of E280K human PAH in Escherichia coli results ...
    pediatrics.aappublications.org/cgi/content/full/112/.../1557
  • Mutations Detected in Patients with BH4-responsive PAH Deficiency
    BH4-responsive PAH Deficiency. blue = mutations with residual activity (measured or ... K320N. P314S. A313T. S310Y. A300S. P281S. P281L. P281A. E280K. P278I. P275L ...
    www.bh4.org/biopkudocs/PAH_domains.pdf
  • PubMed: 9101291
    The E280K mutation in exon 7 of the PAH gene is a cause of phenylketonuria. ... The PAH mutation database shows that the allele accounts for 1.5% of ...
    www.genome.jp/dbget-bin/www_bget?pubmed+9101291
  • DOI: 10.1542/peds.112.6.S1.1557 2003;112;1557-1565 Pediatrics ...
    PAH mutations. Also, with the aid of recent crystal struc- ture ... sion of E280K human PAH in Escherichia coli results. in an enzyme with only approximately ...
    pediatrics.aappublications.org/cgi/reprint/112/6/S1/1557.pdf
  • PAH : Phenylalanine Hydroxylase Locus Knowledgebase web site
    PAH Phenylalanine Hydroxylase Locus Specific Database,Medical Genetics, McGill University Health Centre
    www.pahdb.mcgill.ca/?Topic=About&Section=CuratorsPage&Page=0
  • Mutation at the phenylalanine hydroxylase gene (PAH) and its ...
    Mutation at the phenylalanine hydroxylase gene (PAH) and its use to document population ... descent because they were recurrent mutations (E280K and R408W); and ...
    www.nature.com/ejhg/journal/v6/n1/abs/5200153a.html
  • Correction of kinetic and stability defects by ...
    when compared with the WT PAH structures, consistent with the mild. effects the mutant has ... E280K, were found to display a decoupled oxidation of the cofactor ...
    www.bh4.org/pdf/erlandsenPNAS.pdf
  • Genotype/Phenotype
    PAHdb Advanced Search ... Y356X. R408W. EX3del4765. Y343D. Y343D [p.E56E;IVS2+1G>A] p.E280K. Go to Top. Copyright 2007 Debelle Laboratory. All right reserved. Best viewed in 1024x768 ...
    pahdb.mcgill.ca/PahdbSearch.php?.../Phenotype
  • 13 1 2 3 4 5 6 7 8 9 10 11 12 Introns Exons
    E280K. T278I. P275L. K274fsdel11bp. G272X. R270K. I269L. R261Q. R261X. R252W ... Mutations with residual PAH activity (potentially BH4-responsive) Mutations associated ...
    www.biopku.org/biopkudocs/biopku_pah_map.pdf

Other in silico analyses
 

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

Edit history
 

Gene search

"GENE" or "GENE A123C":

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