PAH R261Q - GET-Evidence

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

To be considered sufficiently evaluated a variant must have both "variant evidence" and "clinical importance" scores filled in.

Please help improve GET-Evidence by evaluating evidence for this variant!

Curation:
Currentness:

PAH R261Q

(PAH Arg261Gln)


Short summary

Expression analysis in mammalian cells shows the PAH-R261Q allele to have no effect on the enzymatic function of PAH. Deficiency of this enzyme is associated with phenylketonuria (PKU).

Variant evidence
Computational 1

PolyPhen-2 predicts PAH-R261Q to be PROBABLY DAMAGING with a score of 1.000 (sensitivity: 0.00; specificity: 1.00).

Functional 1

“Expression analysis in heterozygous mammalian cells after site-directed mutagenesis demonstrated that the Arg158-to-Gln158 mutation is a PKU mutation, whereas the Arg261-to-Gln261 mutation is apparently silent in the assay system.”

See Okano Y et al. 1990 (1967207).

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 @ chr12:103246653: 0.0% (4/10758) in EVS
  • Frequency shown in summary reports: 0.0% (4/10758)

Publications
 

Okano Y, Wang T, Eisensmith RC, Steinmann B, Gitzelmann R, Woo SL. Missense mutations associated with RFLP haplotypes 1 and 4 of the human phenylalanine hydroxylase gene. Am J Hum Genet. 1990 Jan;46(1):18-25. PubMed PMID: 1967207; PubMed Central PMCID: PMC1683547.

“Expression analysis in heterozygous mammalian cells after site-directed mutagenesis demonstrated that the Arg158-to-Gln158 mutation is a PKU mutation, whereas the Arg261-to-Gln261 mutation is apparently silent in the assay system.”

Genomes
 

Other external references
 

    PolyPhen-2
  • Score: 1.0 (probably damaging)

Other in silico analyses
 

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

Edit history
 

Gene search

"GENE" or "GENE A123C":

Log in