ArticleEuropean journal of human genetics : EJHG2015
Linking genotypes database with locus-specific database and genotype-phenotype correlation in phenylketonuria.
Article in European journal of human genetics : EJHG, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- Italian national consensus statement on management and pharmacological treatment of phenylketonuria.Orphanet journal of rare diseases · 2021Pooled it
- Long-term comparative effectiveness of pegvaliase versus standard of care comparators in adults with phenylketonuria.Molecular genetics and metabolismTrial
- DNAJC12 Stabilizes Phenylalanine Hydroxylase and Facilitates Its Substrate-Dependent Activation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Analysis ofInternational journal of molecular sciences · 2026Article
- Integrating Functional Consequence Annotation With PAH Allelic Phenotype Values Refines Prediction of Tetrahydrobiopterin Responsiveness.Journal of inherited metabolic disease · 2026Observational
- Mapping the Severity of Phenylalanine Hydroxylase Deficiency.Journal of inherited metabolic disease · 2026Review
- Phenylalanine-tyrosine-catecholamine axis disorders: pathways, molecular diagnosis, therapeutics, and emerging translational monitoring technologies.Frontiers in molecular biosciences · 2026Review
- Current state of the treatment landscape of phenylketonuria.Orphanet journal of rare diseases · 2025Review
- Phenotypic study of humanized mice carrying the PAH deep intronic variant c.1199+502A>T.Orphanet journal of rare diseases · 2025Article
- The Influence of Phenylalanine Fluctuations and Intake on a 24 h Sapropterin Responsiveness Test in Patients with Phenylketonuria.Children (Basel, Switzerland) · 2025Article
- Assessment of Pathogenic Variants in the PAH Gene and Genotype-Phenotype Correlation in Phenylketonuria Patients from Turkey.Biochemical genetics · 2025Article
- Longitudinal Dietary Intake Data in Patients with Phenylketonuria from Europe: The Impact of Age and Phenylketonuria Severity.Nutrients · 2024Article
- Delays in Newborn Screening for Phenylketonuria from Birth to Diagnosis and Factors Affecting This.Children (Basel, Switzerland) · 2024Article
- Systems Biology and Inborn Error of Metabolism: Analytical Strategy in Investigating Different Biochemical/Genetic Parameters.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Pará.Molecular genetics & genomic medicine · 2023Article
- Article
- Allelic phenotype prediction of phenylketonuria based on the machine learning method.Human genomics · 2023Article
- Deubiquitinase USP19 extends the residual enzymatic activity of phenylalanine hydroxylase variants.Scientific reports · 2022Article
- Diagnosis of inborn errors of metabolism within the expanded newborn screening in the Madrid region.JIMD reports · 2022Article
- Personalized Medicine to Improve Treatment of Dopa-Responsive Dystonia-A Focus on Tyrosine Hydroxylase Deficiency.Journal of personalized medicine · 2021Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 5 countries.
Funding
Abstract
The wide range of metabolic phenotypes in phenylketonuria is due to a large number of variants causing variable impairment in phenylalanine hydroxylase function. A total of 834 phenylalanine hydroxylase gene variants from the locus-specific database PAHvdb and genotypes of 4181 phenylketonuria patients from the BIOPKU database were characterized using FoldX, SIFT Blink, Polyphen-2 and SNPs3D algorithms. Obtained data was correlated with residual enzyme activity, patients' phenotype and tetrahydrobiopterin responsiveness. A descriptive analysis of both databases was compiled and an interactive viewer in PAHvdb database was implemented for structure visualization of missense variants. We found a quantitative relationship between phenylalanine hydroxylase protein stability and enzyme activity (r(s) = 0.479), between protein stability and allelic phenotype (r(s) = -0.458), as well as between enzyme activity and allelic phenotype (r(s) = 0.799). Enzyme stability algorithms (FoldX and SNPs3D), allelic phenotype and enzyme activity were most powerful to predict patients' phenotype and tetrahydrobiopterin response. Phenotype prediction was most accurate in deleterious genotypes (≈ 100%), followed by homozygous (92.9%), hemizygous (94.8%), and compound heterozygous genotypes (77.9%), while tetrahydrobiopterin response was correctly predicted in 71.0% of all cases. To our knowledge this is the largest study using algorithms for the prediction of patients' phenotype and tetrahydrobiopterin responsiveness in phenylketonuria patients, using data from the locus-specific and genotypes database.
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