ArticleNature genetics2018
Multiplex assessment of protein variant abundance by massively parallel sequencing.
Article in Nature genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 297 papers.
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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
297 citing papers in PubMed, 514 citations in OpenAlex.
- Germ line genetic NBN variation and predisposition to B-cell acute lymphoblastic leukemia in children.Blood · 2024Trial
- Cardiomyocyte vulnerability to lamin polymer disruption revealed by saturation mutagenesis.bioRxiv : the preprint server for biology · 2026Article
- Interpretable biophysical neural networks of transcriptional activation domains separate roles of protein abundance and coactivator binding.Cell systems · 2026Article
- Systematic and proactive evaluation of AIRE missense variant effects.American journal of human genetics · 2026Article
- Validation structures for sequence variants of uncertain significance in hereditary cancer.European journal of human genetics : EJHG · 2026Review
- Autoinhibition of untimely DNA binding by structural disorder in the full-length peroxisome proliferator-activated receptors (PPARs).Nature communications · 2026Article
- A comprehensive map of missense trafficking variants in rhodopsin and their response to pharmacologic correction.Science advances · 2026Article
- Locus-Scale Massively Parallel Reporter Assays.bioRxiv : the preprint server for biology · 2026Article
- Kozak sequence libraries for systematically characterizing transgenes across expression levels.Nucleic acids research · 2026Article
- Combining multiplexed functional data to improve variant classification.Genome medicine · 2026Article
- An integrated, scaled approach to resolve TSC2 variants of uncertain significance.Nature communications · 2026Article
- Prevalence of TPMT and NUDT15 diplotypes in Mexican children with B-cell acute lymphoblastic leukemia.Pharmacogenetics and genomics · 2026Article
- Image-based, pooled phenotyping reveals multidimensional, disease-specific variant effects.Cell · 2026Article
- Allostery is a widespread cause of loss-of-function variant pathogenicity.Nature communications · 2026Article
- Deep mutational scanning reveals pharmacologically relevant insights into TYK2 signaling and disease.eLife · 2026Article
- Evidence for G6PD variant classification from multiplexed functional assays.Genome biology · 2026Article
- VEFill: accurate and generalizable deep mutational scanning score imputation across protein domains.Molecular systems biology · 2026Article
- Article
- Mapping the avoid-ome: a systematic open-science approach to predictive ADMET.Nature communications · 2026Review
- Functional dissection ofProceedings of the National Academy of Sciences of the United States of America · 2026Article
237 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
16 authors at 6 institutions in 2 countries.
Funding
Abstract
Determining the pathogenicity of genetic variants is a critical challenge, and functional assessment is often the only option. Experimentally characterizing millions of possible missense variants in thousands of clinically important genes requires generalizable, scalable assays. We describe variant abundance by massively parallel sequencing (VAMP-seq), which measures the effects of thousands of missense variants of a protein on intracellular abundance simultaneously. We apply VAMP-seq to quantify the abundance of 7,801 single-amino-acid variants of PTEN and TPMT, proteins in which functional variants are clinically actionable. We identify 1,138 PTEN and 777 TPMT variants that result in low protein abundance, and may be pathogenic or alter drug metabolism, respectively. We observe selection for low-abundance PTEN variants in cancer, and show that p.Pro38Ser, which accounts for ~10% of PTEN missense variants in melanoma, functions via a dominant-negative mechanism. Finally, we demonstrate that VAMP-seq is applicable to other genes, highlighting its generalizability.
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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.