ArticleNature communications2019
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 76 citations in OpenAlex.
- Deep phenotyping of EHMT1 ankyrin repeat domain missense variants in Kleefstra syndrome by multi-tiered structural genomics analyses at atomic resolution.Human molecular genetics · 2026Article
- Evolution-guided yeast complementation reveals functional differences in human PSPH variants.FEBS open bio · 2026Article
- eSIG-Net: an interaction language model that decodes the protein code of single mutations.Nature methods · 2026Article
- Selective chr21 homolog silencing reveals polymorphisms influence the epigenetic silencing and functional dosage of RWDD2B.American journal of human genetics · 2026Article
- eSIG-Net: Accurate prediction of single-mutation induced perturbations on protein interactions using a language model.bioRxiv : the preprint server for biology · 2026Article
- The impact of low-frequency genetic variants on serum protein levels.bioRxiv : the preprint server for biology · 2026Article
- A scalable approach to resolving variants of uncertain significance.bioRxiv : the preprint server for biology · 2026Article
- Predicting interaction-specific protein-protein interaction perturbations by missense variants with MutPred-PPI.bioRxiv : the preprint server for biology · 2026Article
- Learning the language of protein-protein interactions.Nature communications · 2026Article
- Comprehensive analysis of molecular immunological characteristics and potential biomarkers in brucellosis.Frontiers in immunology · 2026Article
- Selective chr21 homolog silencing reveals polymorphisms influence the epigenetic silencing and functional dosage of RWDD2B.bioRxiv : the preprint server for biology · 2025Article
- Sliding Window Interaction Grammar (SWING): a generalized interaction language model for peptide and protein interactions.Nature methods · 2025Article
- Impact of a Heterozygous C1RCells · 2025Article
- Learning the language of protein-protein interactions.bioRxiv : the preprint server for biology · 2025Article
- Article
- Decoding the functional impact of the cancer genome through protein-protein interactions.Nature reviews. Cancer · 2025Review
- Translating pharmacogenomic sequencing data into drug response predictions-How to interpret variants of unknown significance.British journal of clinical pharmacology · 2025Review
- Uncovering cell-type-specific immunomodulatory variants and molecular phenotypes in COVID-19 using structurally resolved protein networks.Cell reports · 2024Article
- Article
- SAAMBE-MEM: a sequence-based method for predicting binding free energy change upon mutation in membrane protein-protein complexes.Bioinformatics (Oxford, England) · 2024Article
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
Each human genome carries tens of thousands of coding variants. The extent to which this variation is functional and the mechanisms by which they exert their influence remains largely unexplored. To address this gap, we leverage the ExAC database of 60,706 human exomes to investigate experimentally the impact of 2009 missense single nucleotide variants (SNVs) across 2185 protein-protein interactions, generating interaction profiles for 4797 SNV-interaction pairs, of which 421 SNVs segregate at > 1% allele frequency in human populations. We find that interaction-disruptive SNVs are prevalent at both rare and common allele frequencies. Furthermore, these results suggest that 10.5% of missense variants carried per individual are disruptive, a higher proportion than previously reported; this indicates that each individual's genetic makeup may be significantly more complex than expected. Finally, we demonstrate that candidate disease-associated mutations can be identified through shared interaction perturbations between variants of interest and known disease mutations.
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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.