ArticleGenome medicine2020
A proactive genotype-to-patient-phenotype map for cystathionine beta-synthase.
Article in Genome medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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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.
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Who cites it
46 citing papers in PubMed, 79 citations in OpenAlex.
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- Molecular dynamics simulations of intrinsically disordered protein regions enable biophysical interpretation of variant-effect predictors.HGG advances · 2026Article
- Determining the intra-residue correlation of missense variant impact using MAVE scores: implications for the ACMG/AMP PM5 criterion for DNA variant classification.Genome medicine · 2026Article
- The functional landscape of coding variation in the familial hypercholesterolemia geneScience (New York, N.Y.) · 2026Article
- Multiplexed assays of variant effect for clinical variant interpretation.Nature reviews. Genetics · 2026Review
- Protein structure shapes natural genetic variation andbioRxiv : the preprint server for biology · 2025Article
- MaveMD: A functional data resource for genomic medicine.medRxiv : the preprint server for health sciences · 2025Article
- Systematic and proactive evaluation of AIRE missense variant effects.bioRxiv : the preprint server for biology · 2025Article
- Variant scoring tools for deep mutational scanning.Molecular systems biology · 2025Review
- Mapping MAVE data for use in human genomics applications.Genome biology · 2025Article
- A probabilistic graphical model for estimating selection coefficients of nonsynonymous variants from human population sequence data.Nature communications · 2025Article
- Article
- A missense variant effect map for the human tumor-suppressor protein CHK2.American journal of human genetics · 2024Article
- Sequence modeling and design from molecular to genome scale with Evo.Science (New York, N.Y.) · 2024Article
- Article
- Comprehensive analysis of the functional impact of single nucleotide variants of human CHEK2.PLoS genetics · 2024Article
- Scalable approaches for generating, validating and incorporating data from high-throughput functional assays to improve clinical variant classification.Human genetics · 2024Article
- Deep Mutational Scanning in Disease-related Genes with Saturation Mutagenesis-Reinforced Functional Assays (SMuRF).bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundFor the majority of rare clinical missense variants, pathogenicity status cannot currently be classified. Classical homocystinuria, characterized by elevated homocysteine in plasma and urine, is caused by variants in the cystathionine beta-synthase (CBS) gene, most of which are rare. With early detection, existing therapies are highly effective.
methodsDamaging CBS variants can be detected based on their failure to restore growth in yeast cells lacking the yeast ortholog CYS4. This assay has only been applied reactively, after first observing a variant in patients. Using saturation codon-mutagenesis, en masse growth selection, and sequencing, we generated a comprehensive, proactive map of CBS missense variant function.
resultsOur CBS variant effect map far exceeds the performance of computational predictors of disease variants. Map scores correlated strongly with both disease severity (Spearman's ϱ = 0.9) and human clinical response to vitamin B
conclusionsWe demonstrate that highly multiplexed cell-based assays can yield proactive maps of variant function and patient response to therapy, even for rare variants not previously seen in the clinic.
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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.