ArticleAmerican journal of human genetics2021
Identification of discriminative gene-level and protein-level features associated with pathogenic gain-of-function and loss-of-function variants.
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 31 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Individuals with JAK1 variants are affected by syndromic features encompassing autoimmunity, atopy, colitis, and dermatitis.The Journal of experimental medicine · 2024Pooled it
- Actually, what is a gain-of-function mutation?Genetics · 2026Article
- NEDAMSS syndrome-related truncating and missense mutations are associated with aberrant liquid-liquid phase separation of IRF2BPL.Nature communications · 2026Article
- An interpretable molecular framework for predicting cancer driver missense mutations.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Interpreting the functional impact of genetic variants: The need for context qualifiers.American journal of human genetics · 2026Review
- Mutation patterns and prognostic potentiality of homologous recombination repair genes in gliomas.BMC cancer · 2025Article
- Functional genomics for improving adoptive T-cell transfer therapies.Journal for immunotherapy of cancer · 2025Review
- Expanding the utility of variant effect predictions with phenotype-specific models.Nature communications · 2025Article
- Prevalence of loss-of-function, gain-of-function and dominant-negative mechanisms across genetic disease phenotypes.Nature communications · 2025Article
- Identification of a novelIntractable & rare diseases research · 2025Article
- PreMode predicts mode-of-action of missense variants by deep graph representation learning of protein sequence and structural context.Nature communications · 2025Article
- TARGET-SL: precision essential gene prediction using driver prioritisation and synthetic lethality.Briefings in bioinformatics · 2025Article
- Ligand distances as key predictors of pathogenicity and function in NMDA receptors.Human molecular genetics · 2025Article
- JAK/STAT in human diseases: a common axis in immunodeficiencies and hematological disorders.Frontiers in immunology · 2025Review
- Article
- Recurrent carotid paragangliomas in a syndromic patient with a heterozygous missense variant in DNA Methyltransferase 3 Alpha.American journal of medical genetics. Part A · 2025Article
- Insights into the ANKRD11 variants and short-stature phenotype through literature review and ClinVar database search.Orphanet journal of rare diseases · 2024Review
- Intrinsic endothelial hyperresponsiveness to inflammatory mediators drives acute episodes in models of Clarkson disease.The Journal of clinical investigation · 2024Article
- Rheostats, toggles, and neutrals, Oh my! A new framework for understanding how amino acid changes modulate protein function.The Journal of biological chemistry · 2024Review
- SIGMA leverages protein structural information to predict the pathogenicity of missense variants.Cell reports methods · 2024Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 4 countries.
Funding
Abstract
Identifying whether a given genetic mutation results in a gene product with increased (gain-of-function; GOF) or diminished (loss-of-function; LOF) activity is an important step toward understanding disease mechanisms because they may result in markedly different clinical phenotypes. Here, we generated an extensive database of documented germline GOF and LOF pathogenic variants by employing natural language processing (NLP) on the available abstracts in the Human Gene Mutation Database. We then investigated various gene- and protein-level features of GOF and LOF variants and applied machine learning and statistical analyses to identify discriminative features. We found that GOF variants were enriched in essential genes, for autosomal-dominant inheritance, and in protein binding and interaction domains, whereas LOF variants were enriched in singleton genes, for protein-truncating variants, and in protein core regions. We developed a user-friendly web-based interface that enables the extraction of selected subsets from the GOF/LOF database by a broad set of annotated features and downloading of up-to-date versions. These results improve our understanding of how variants affect gene/protein function and may ultimately guide future treatment options.
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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.