ArticleCell2015
Widespread macromolecular interaction perturbations in human genetic disorders.
Open access · bronzeAbstract read
In one paragraph
Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 347 papers.
0numbers the graph read from it
0cells of the map it votes in
347citing papers in PubMed
29.1field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
347 citing papers in PubMed, 629 citations in OpenAlex.
- Graph-based representations in modern protein science.The Biochemical journal · 2026Review
- Genetic landscape of an in vivo protein interactome.Nature genetics · 2026Article
- 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
- Revisiting retinal and macular degeneration in the genomics era.Nature reviews. Genetics · 2026Review
- Cellular Consequences, Citrullination Substrates, and Antigenicity of Targeting PAD4 to Cell Surfaces.ACS central science · 2026Article
- Large-scale quaternary structural transitions underlie gain of function of SPOP cancer mutations.Molecular cell · 2026Article
- Variant characterization in the intrinsically disordered human proteome.Nature structural & molecular biology · 2026Article
- Human genetics across levels of biological organization.Nature reviews. Genetics · 2026Review
- Addressing multiple facets of ligand-receptor network inference including single-cell proteomics.Nucleic acids research · 2026Article
- Isotope Decluttering Reduces Spectral Complexity while Maintaining Protein Structure.Analytical chemistry · 2026Article
- Structural insights into predicted protein-protein interactions and protein complexes in the human proteome.Scientific reports · 2026Article
- A Novel BIRC6 Variant Impairs Apoptotic Regulation in Familial Premature Ovarian Insufficiency: Functional Validation in a CRISPR/Cas9 Zebrafish Model.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- eSIG-Net: an interaction language model that decodes the protein code of single mutations.Nature methods · 2026Article
- Artificial intelligence in the assessment of epilepsy-related genetic mutations: Learned from GABAEpilepsia open · 2026Review
- Protein Stability, Turnover Kinetics, and Abundance Constrain the Scaling of Protein Interaction Networks.bioRxiv : the preprint server for biology · 2026Article
- Early Clinical, Imaging, and Pathological Characteristics of SRPK3/TTN-Digenic Myopathy.Annals of clinical and translational neurology · 2026Article
- Strategies for constructing context-specific protein-protein interaction networks.Briefings in bioinformatics · 2026Review
- Phenotypic prediction of missense variants via deep contrastive learning.Nature biomedical engineering · 2026Article
- Targeting protein protein interactions and their modulators to enable new therapeutic strategies for human diseases.NPJ systems biology and applications · 2026Review
- A gene interaction network-based molecular taxonomy of dilated cardiomyopathy highlighting immune and inflammatory heterogeneity.Clinical and experimental medicine · 2026Article
287 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
48 authors at 10 institutions in 3 countries.
Nidhi SahniGenomic Analysis of Network Perturbations Center of Excellence in Genomic Science (CEGS), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Song YiGenomic Analysis of Network Perturbations Center of Excellence in Genomic Science (CEGS), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Mikko TaipaleWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Juan I Fuxman BassProgram in Systems Biology, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Jasmin Coulombe-HuntingtonDepartment of Bioengineering, Faculty of Engineering, McGill University, Montreal, QC H3A 0C3, Canada.
Fan YangGenomic Analysis of Network Perturbations Center of Excellence in Genomic Science (CEGS), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Departments of Molecular Genetics and Computer Science, University of Toronto, Toronto, ON M5S 3E1, Canada; Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON M5G 1X5, Canada.
Jian PengComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Jochen WeileGenomic Analysis of Network Perturbations Center of Excellence in Genomic Science (CEGS), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Departments of Molecular Genetics and Computer Science, University of Toronto, Toronto, ON M5S 3E1, Canada; Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON M5G 1X5, Canada.
Georgios I KarrasWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Yang WangGenomic Analysis of Network Perturbations Center of Excellence in Genomic Science (CEGS), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
István A KovácsGenomic Analysis of Network Perturbations Center of Excellence in Genomic Science (CEGS), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Complex Network Research (CCNR) and Departments of Physics, Biology and Computer Science, Northeastern University, Boston, MA 02115, USA.
Atanas KamburovCenter for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Irina KrykbaevaWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Mandy H LamDonnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
George TuckerComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Vikram KhuranaWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Amitabh SharmaGenomic Analysis of Network Perturbations Center of Excellence in Genomic Science (CEGS), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Complex Network Research (CCNR) and Departments of Physics, Biology and Computer Science, Northeastern University, Boston, MA 02115, USA.
Yang-Yu LiuCenter for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Complex Network Research (CCNR) and Departments of Physics, Biology and Computer Science, Northeastern University, Boston, MA 02115, USA.
Nozomu YachieGenomic Analysis of Network Perturbations Center of Excellence in Genomic Science (CEGS), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Departments of Molecular Genetics and Computer Science, University of Toronto, Toronto, ON M5S 3E1, Canada; Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON M5G 1X5, Canada.
Quan ZhongCenter for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Yun ShenGenomic Analysis of Network Perturbations Center of Excellence in Genomic Science (CEGS), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Alexandre PalagiCenter for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Adriana San-MiguelCenter for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Changyu FanGenomic Analysis of Network Perturbations Center of Excellence in Genomic Science (CEGS), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Dawit BalchaGenomic Analysis of Network Perturbations Center of Excellence in Genomic Science (CEGS), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Amelie DricotGenomic Analysis of Network Perturbations Center of Excellence in Genomic Science (CEGS), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Daniel M JordanDivision of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Program in Biophysics, Harvard University, Cambridge, MA 02139, USA.
Jennifer M WalshCenter for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Akash A ShahCenter for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Xinping YangCenter for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Ani K StoyanovaCenter for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Alex LeightonComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Michael A CalderwoodGenomic Analysis of Network Perturbations Center of Excellence in Genomic Science (CEGS), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Yves JacobCenter for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Département de Virologie, Unité de Génétique Moléculaire des Virus ARN (GMVR), Institut Pasteur, UMR3569, Centre National de la Recherche Scientifique, and Université Paris Diderot, Paris, France.
Michael E CusickGenomic Analysis of Network Perturbations Center of Excellence in Genomic Science (CEGS), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Kourosh Salehi-AshtianiCenter for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Luke J WhitesellWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Shamil SunyaevDivision of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Bonnie BergerComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Mathematics and Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Albert-László BarabásiGenomic Analysis of Network Perturbations Center of Excellence in Genomic Science (CEGS), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Complex Network Research (CCNR) and Departments of Physics, Biology and Computer Science, Northeastern University, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Benoit CharloteauxGenomic Analysis of Network Perturbations Center of Excellence in Genomic Science (CEGS), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
David E HillGenomic Analysis of Network Perturbations Center of Excellence in Genomic Science (CEGS), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Tong HaoGenomic Analysis of Network Perturbations Center of Excellence in Genomic Science (CEGS), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Frederick P RothGenomic Analysis of Network Perturbations Center of Excellence in Genomic Science (CEGS), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Departments of Molecular Genetics and Computer Science, University of Toronto, Toronto, ON M5S 3E1, Canada; Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON M5G 1X5, Canada; Canadian Institute for Advanced Research, Toronto, ON M5G 1Z8, Canada.
Yu XiaCenter for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Bioengineering, Faculty of Engineering, McGill University, Montreal, QC H3A 0C3, Canada.
Albertha J M WalhoutCenter for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Program in Systems Biology, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Susan LindquistWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Cambridge, MA 02139, USA. Electronic address: lindquist@wi.mit.edu.
Marc VidalGenomic Analysis of Network Perturbations Center of Excellence in Genomic Science (CEGS), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: marc_vidal@dfci.harvard.edu.
Dana-Farber Cancer Institute · USHarvard University · USMassachusetts Institute of Technology · USWhitehead Institute for Biomedical Research · USNortheastern University · USBroad Institute · USLunenfeld-Tanenbaum Research Institute · CAMcGill University · CAUniversity of Massachusetts Chan Medical School · USUniversity of Toronto · CA
Funding
Genomic Analysis of Network Perturbations in Human DiseaseP50HG004233 · NHGRI · DANA-FARBER CANCER INST · PI VIDAL, MARC · 2007 to 2017
$31.6MThe C. elegans Interactome ProjectR01HG001715 · NHGRI · MASSACHUSETTS GENERAL HOSPITAL · PI HILL, DAVID E., ROTH, FREDERICK P · 1998 to 2010
$16.5MIdentifying transcription factor binding sites in the C. elegans genomeR01GM082971 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI WALHOUT, A. J. MARIAN · 2008 to 2016
$5.8MResource ProjectU41HG001715 · NHGRI · DANA-FARBER CANCER INST · PI HILL, DAVID E. · 2015 to 2017
$4.7MGeneration and validation of a comprehensive human disease mutant ORF resourceRC4HG006066 · NHGRI · DANA-FARBER CANCER INST · PI HAO, TONG, HILL, DAVID E. · 2010 to 2010
$4.6MStructure-Based Prediction of the InteractomeR01GM081871 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BERGER, BONNIE · 2008 to 2020
$4.3MHoward Hughes Medical InstituteNHGRI NIH HHS P50 HG004233NHGRI NIH HHS P50HG004233NHGRI NIH HHS R01 HG001715NHGRI NIH HHS R01HG001715NHGRI NIH HHS RC4 HG006066NHGRI NIH HHS RC4HG006066NHGRI NIH HHS U41 HG001715NIGMS NIH HHS GM082971NIGMS NIH HHS R01 GM081871
Abstract
How disease-associated mutations impair protein activities in the context of biological networks remains mostly undetermined. Although a few renowned alleles are well characterized, functional information is missing for over 100,000 disease-associated variants. Here we functionally profile several thousand missense mutations across a spectrum of Mendelian disorders using various interaction assays. The majority of disease-associated alleles exhibit wild-type chaperone binding profiles, suggesting they preserve protein folding or stability. While common variants from healthy individuals rarely affect interactions, two-thirds of disease-associated alleles perturb protein-protein interactions, with half corresponding to "edgetic" alleles affecting only a subset of interactions while leaving most other interactions unperturbed. With transcription factors, many alleles that leave protein-protein interactions intact affect DNA binding. Different mutations in the same gene leading to different interaction profiles often result in distinct disease phenotypes. Thus disease-associated alleles that perturb distinct protein activities rather than grossly affecting folding and stability are relatively widespread.
Indexed as
Mutation, MissenseProtein Interaction MapsDiseaseDNA-Binding ProteinsGenome-Wide Association StudyHumansOpen Reading FramesProtein FoldingProteinsProtein StabilityDNA-Binding ProteinsProteins
Identifiers
What Socratic holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
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 Socratic graph.