ArticleGenetics2012
Surrogate genetics and metabolic profiling for characterization of human disease alleles.
Article in Genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 50 citations in OpenAlex.
- Classical Homocystinuria Incidentally Diagnosed Following a Normal Newborn Screening Result.International journal of neonatal screening · 2026Article
- Meta-EA: a gene-specific combination of available computational tools for predicting missense variant effects.Nature communications · 2025Article
- Mycobacteria that cause tuberculosis have retained ancestrally acquired genes for the biosynthesis of chemically diverse terpene nucleosides.PLoS biology · 2024Article
- The functional impact of 1,570 individual amino acid substitutions in human OTC.American journal of human genetics · 2023Article
- Integrating deep mutational scanning and low-throughput mutagenesis data to predict the impact of amino acid variants.GigaScience · 2022Article
- Article
- Integrative Functional Genomic Analysis in Multiplex Autism Families from Kazakhstan.Disease markers · 2022Article
- Congenital cataract: An ocular manifestation of classical homocystinuria.Molecular genetics & genomic medicine · 2021Article
- Yeast as a Tool to Understand the Significance of Human Disease-Associated Gene Variants.Genes · 2021Review
- Precise Replacement ofG3 (Bethesda, Md.) · 2020Article
- A yeast-based complementation assay elucidates the functional impact of 200 missense variants in human PSAT1.Journal of inherited metabolic disease · 2020Article
- Cross-Species Complementation of Nonessential Yeast Genes Establishes Platforms for Testing Inhibitors of Human Proteins.Genetics · 2020Article
- A proactive genotype-to-patient-phenotype map for cystathionine beta-synthase.Genome medicine · 2020Article
- Assessing computational predictions of the phenotypic effect of cystathionine-beta-synthase variants.Human mutation · 2019Article
- Osmoregulation in Barnacles: An Evolutionary Perspective of Potential Mechanisms and Future Research Directions.Frontiers in physiology · 2019Review
- Saccharomyces genome database informs human biology.Nucleic acids research · 2018Article
- CRISPR-UnLOCK: Multipurpose Cas9-Based Strategies for Conversion of Yeast Libraries and Strains.Frontiers in microbiology · 2017Article
- Polymorphisms of cystathionine beta-synthase gene are associated with susceptibility to sepsis.European journal of human genetics : EJHG · 2016Article
- An extended set of yeast-based functional assays accurately identifies human disease mutations.Genome research · 2016Article
- Efforts to make and apply humanized yeast.Briefings in functional genomics · 2016Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Cystathionine-β-synthase (CBS) deficiency is a human genetic disease causing homocystinuria, thrombosis, mental retardation, and a suite of other devastating manifestations. Early detection coupled with dietary modification greatly reduces pathology, but the response to treatment differs with the allele of CBS. A better understanding of the relationship between allelic variants and protein function will improve both diagnosis and treatment. To this end, we tested the function of 84 CBS alleles previously sequenced from patients with homocystinuria by ortholog replacement in Saccharomyces cerevisiae. Within this clinically associated set, 15% of variant alleles were indistinguishable from the predominant CBS allele in function, suggesting enzymatic activity was retained. An additional 37% of the alleles were partially functional or could be rescued by cofactor supplementation in the growth medium. This large class included alleles rescued by elevated levels of the cofactor vitamin B6, but also alleles rescued by elevated heme, a second CBS cofactor. Measurement of the metabolite levels in CBS-substituted yeast grown with different B6 levels using LC-MS revealed changes in metabolism that propagated beyond the substrate and product of CBS. Production of the critical antioxidant glutathione through the CBS pathway was greatly decreased when CBS function was restricted through genetic, cofactor, or substrate restriction, a metabolic consequence with implications for treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.