ArticleMolecular systems biology2014
Structure-energy-based predictions and network modelling of RASopathy and cancer missense mutations.
Article in Molecular systems biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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
40 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Personalized respiratory medicine: exploring the horizon, addressing the issues. Summary of a BRN-AJRCCM workshop held in Barcelona on June 12, 2014.American journal of respiratory and critical care medicine · 2015Pooled it
- A quantitative comparison of the deleteriousness of missense and nonsense mutations using the structurally resolved human protein interactome.Protein science : a publication of the Protein Society · 2025Article
- Sam-Sam Association Between EphA2 and SASH1: In Silico Studies of Cancer-Linked Mutations.Molecules (Basel, Switzerland) · 2025Article
- Exploring a Potential Optimization Route for Peptide Ligands of the Sam Domain from the Lipid Phosphatase Ship2.International journal of molecular sciences · 2024Article
- Understanding large scale sequencing datasets through changes to protein folding.Briefings in functional genomics · 2024Review
- Deciphering GB1's Single Mutational Landscape: Insights from MuMi Analysis.The journal of physical chemistry. B · 2024Article
- Genetic Testing in Patients with Autoimmune Lymphoproliferative Syndrome: Experience of 802 Patients at Cincinnati Children's Hospital Medical Center.Journal of clinical immunology · 2024Article
- Systems modeling of oncogenic G-protein and GPCR signaling reveals unexpected differences in downstream pathway activation.NPJ systems biology and applications · 2024Article
- Cancer-Related Mutations in the Sam Domains of EphA2 Receptor and Ship2 Lipid Phosphatase: A Computational Study.Molecules (Basel, Switzerland) · 2024Article
- Analysis of context-specific KRAS-effector (sub)complexes in Caco-2 cells.Life science alliance · 2023Article
- Computational Random Mutagenesis to Investigate RAS Mutant Signaling.Methods in molecular biology (Clifton, N.J.) · 2023Article
- How can same-gene mutations promote both cancer and developmental disorders?Science advances · 2022Article
- Enhanced interpretation of 935 hotspot and non-hotspot RAS variants using evidence-based structural bioinformatics.Computational and structural biotechnology journal · 2022Article
- Structural bioinformatics enhances mechanistic interpretation of genomic variation, demonstrated through the analyses of 935 distinct RAS family mutations.Bioinformatics (Oxford, England) · 2021Article
- The Ins and Outs of RAS Effector Complexes.Biomolecules · 2021Review
- PI3K Driver Mutations: A Biophysical Membrane-Centric Perspective.Cancer research · 2021Review
- PremPS: Predicting the impact of missense mutations on protein stability.PLoS computational biology · 2020Article
- RAS ubiquitylation modulates effector interactions.Small GTPases · 2020Article
- Drug Repositioning for Noonan and LEOPARD Syndromes by Integrating Transcriptomics With a Structure-Based Approach.Frontiers in pharmacology · 2020Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Ras/MAPK syndromes ('RASopathies') are a class of developmental disorders caused by germline mutations in 15 genes encoding proteins of the Ras/mitogen-activated protein kinase (MAPK) pathway frequently involved in cancer. Little is known about the molecular mechanisms underlying the differences in mutations of the same protein causing either cancer or RASopathies. Here, we shed light on 956 RASopathy and cancer missense mutations by combining protein network data with mutational analyses based on 3D structures. Using the protein design algorithm FoldX, we predict that most of the missense mutations with destabilising energies are in structural regions that control the activation of proteins, and only a few are predicted to compromise protein folding. We find a trend that energy changes are higher for cancer compared to RASopathy mutations. Through network modelling, we show that partly compensatory mutations in RASopathies result in only minor downstream pathway deregulation. In summary, we suggest that quantitative rather than qualitative network differences determine the phenotypic outcome of RASopathy compared to cancer mutations.
Indexed as
Identifiers
What OpenQuestion holds
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.