ArticleAmerican journal of human genetics2021
Massively parallel characterization of CYP2C9 variant enzyme activity and abundance.
Article in American journal of human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 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.
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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.
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Who cites it
79 citing papers in PubMed, 114 citations in OpenAlex.
- Homology-Based Variant-Effect Predictors Break Down on Cytochrome P450 Pharmacogenes.bioRxiv : the preprint server for biology · 2026Article
- The shape of fitness functions and the distribution of mutational effect sizes jointly limit adaptation by regulatory mutations.Nature ecology & evolution · 2026Article
- The power of many: when genetics met yeasts and high-throughput.Biological reviews of the Cambridge Philosophical Society · 2026Review
- The Nematicide Tioxazafen Disrupts Proteasome Function via Cytochrome P450 Bioactivation.bioRxiv : the preprint server for biology · 2026Article
- An integrated, scaled approach to resolve TSC2 variants of uncertain significance.Nature communications · 2026Article
- Overestimating zero-shot fitness prediction: Broad benchmarks mask local failures and practical limitations.bioRxiv : the preprint server for biology · 2026Article
- Allostery is a widespread cause of loss-of-function variant pathogenicity.Nature communications · 2026Article
- Evidence for G6PD variant classification from multiplexed functional assays.Genome biology · 2026Article
- Article
- SynFit: Synergistic Contrastive Learning for Multi-Objective Protein Fitness Prediction and Optimization.bioRxiv : the preprint server for biology · 2026Article
- Generative Artificial Intelligence-Empowered Virtual Evolution of Enzyme with the VERnet Model.ACS catalysis · 2026Article
- Supervised learning of protein variant effects across large-scale mutagenesis datasets.Protein science : a publication of the Protein Society · 2026Article
- Computational variant predictors for pharmacogenomics: from evaluation of single alleles to assessment of adverse drug reactions to antidepressants.The pharmacogenomics journal · 2026Article
- The evolving landscape of pharmacogenomics: Current achievements and future directions.Pharmacological reviews · 2026Review
- Creating an atlas of variant effects to resolve variants of uncertain significance and guide cardiovascular medicine.Nature reviews. Cardiology · 2026Review
- Decoding the substrate specificity landscape of a promiscuous enzyme through multi-substrate mutational scanning.Nature communications · 2026Article
- Deconvolving mutation effects on protein stability and function with disentangled protein language models.bioRxiv : the preprint server for biology · 2026Article
- A near-complete map of human cytosolic degrons and their relevance for disease.Science advances · 2026Article
- Multiplexed assays of variant effect for clinical variant interpretation.Nature reviews. Genetics · 2026Review
- An integrated, scaled approach to resolve TSC2 variants of uncertain significance.bioRxiv : the preprint server for biology · 2026Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
CYP2C9 encodes a cytochrome P450 enzyme responsible for metabolizing up to 15% of small molecule drugs, and CYP2C9 variants can alter the safety and efficacy of these therapeutics. In particular, the anti-coagulant warfarin is prescribed to over 15 million people annually and polymorphisms in CYP2C9 can affect individual drug response and lead to an increased risk of hemorrhage. We developed click-seq, a pooled yeast-based activity assay, to test thousands of variants. Using click-seq, we measured the activity of 6,142 missense variants in yeast. We also measured the steady-state cellular abundance of 6,370 missense variants in a human cell line by using variant abundance by massively parallel sequencing (VAMP-seq). These data revealed that almost two-thirds of CYP2C9 variants showed decreased activity and that protein abundance accounted for half of the variation in CYP2C9 function. We also measured activity scores for 319 previously unannotated human variants, many of which may have clinical relevance.
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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.