ArticleNature communications2023
Saturation genome editing of DDX3X clarifies pathogenicity of germline and somatic variation.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 52 citations in OpenAlex.
- AlphaGenome Atlas:medRxiv : the preprint server for health sciences · 2026Article
- Minigene-based characterization and classification of splice-associated variants in succinate dehydrogenase B.NPJ precision oncology · 2026Article
- Why variant effect predictors and multiplexed assays agree and disagree.Nature communications · 2026Article
- Combining multiplexed functional data to improve variant classification.Genome medicine · 2026Article
- Article
- A multiplex, prime editing framework for identifying drug resistance variants at scale.Cell genomics · 2026Article
- Functional dissection ofProceedings of the National Academy of Sciences of the United States of America · 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
- Saturation Genome Editing TargetingCurrent issues in molecular biology · 2026Article
- Creating an atlas of variant effects to resolve variants of uncertain significance and guide cardiovascular medicine.Nature reviews. Cardiology · 2026Review
- Multiplexed assays of variant effect for clinical variant interpretation.Nature reviews. Genetics · 2026Review
- Clinical variant interpretation comparing two saturation genome editing-based functional studies forFrontiers in genetics · 2026Article
- Genomic stop codon scanning reveals quantitative principles of nonsense-mediated mRNA decay.bioRxiv : the preprint server for biology · 2025Article
- MaveMD: A functional data resource for genomic medicine.medRxiv : the preprint server for health sciences · 2025Article
- Editing stem cell genomes at scale to measure variant effects in diverse cell and genetic contexts.medRxiv : the preprint server for health sciences · 2025Article
- Saturation genome editing ofmedRxiv : the preprint server for health sciences · 2025Article
- Reassessment of variants of uncertain significance in tumor suppressor genes using new ClinGen PP1/PP4 criteria guidance.European journal of human genetics : EJHG · 2025Article
- Fueling chromosomal gene diversification and artificial evolution with CRISPR.Genome biology · 2025Review
- Saturation profiling of drug-resistant genetic variants using prime editing.Nature biotechnology · 2025Article
- DDX3X-related neurodevelopmental disorder in males - presenting a new cohort of 19 males and a literature review.European journal of human genetics : EJHG · 2025Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
Loss-of-function of DDX3X is a leading cause of neurodevelopmental disorders (NDD) in females. DDX3X is also a somatically mutated cancer driver gene proposed to have tumour promoting and suppressing effects. We perform saturation genome editing of DDX3X, testing in vitro the functional impact of 12,776 nucleotide variants. We identify 3432 functionally abnormal variants, in three distinct classes. We train a machine learning classifier to identify functionally abnormal variants of NDD-relevance. This classifier has at least 97% sensitivity and 99% specificity to detect variants pathogenic for NDD, substantially out-performing in silico predictors, and resolving up to 93% of variants of uncertain significance. Moreover, functionally-abnormal variants can account for almost all of the excess nonsynonymous DDX3X somatic mutations seen in DDX3X-driven cancers. Systematic maps of variant effects generated in experimentally tractable cell types have the potential to transform clinical interpretation of both germline and somatic disease-associated variation.
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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.