ArticleAmerican journal of human genetics2017
Proteome-Scale Investigation of Protein Allosteric Regulation Perturbed by Somatic Mutations in 7,000 Cancer Genomes.
Article in American journal of human genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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
46 citing papers in PubMed, 91 citations in OpenAlex.
- Allostery is a widespread cause of loss-of-function variant pathogenicity.Nature communications · 2026Article
- Seven complete comparative maps of allosteric mutations in a protein family.Nature communications · 2026Article
- Computational approaches to druggable site identification: Current status and future perspective.Acta pharmaceutica Sinica. B · 2026Review
- The Evolving Landscape of Protein Allostery: From Computational and Experimental Perspectives.Journal of molecular biology · 2025Review
- A Comprehensive Review of Deep Learning Applications with Multi-Omics Data in Cancer Research.Genes · 2025Review
- Depletion-dependent activity-based protein profiling using SWATH/DIA-MS detects serine hydrolase lipid remodeling in lung adenocarcinoma progression.Nature communications · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Article
- PDE10A as a novel diagnostic and therapeutic target in cancer: insights and challenges.Frontiers in oncology · 2025Review
- CDMPred: a tool for predicting cancer driver missense mutations with high-quality passenger mutations.PeerJ · 2024Article
- PDE10A Inactivation Prevents Doxorubicin-Induced Cardiotoxicity and Tumor Growth.Circulation research · 2023Article
- DeepAlloDriver: a deep learning-based strategy to predict cancer driver mutations.Nucleic acids research · 2023Article
- On the linkage of thermodynamics and pathogenicity.Current opinion in structural biology · 2023Review
- Aiding Cancer's "Sweet Tooth": Role of Hexokinases in Metabolic Reprogramming.Life (Basel, Switzerland) · 2023Review
- Coevolution-based prediction of key allosteric residues for protein function regulation.eLife · 2023Article
- The protein architecture and allosteric landscape of HNF4α.Frontiers in endocrinology · 2023Review
- A Structure-Based Allosteric Modulator Design Paradigm.Health data science · 2023Review
- A multilayer dynamic perturbation analysis method for predicting ligand-protein interactions.BMC bioinformatics · 2022Article
- Known allosteric proteins have central roles in genetic disease.PLoS computational biology · 2022Article
- Targeting RAS phosphorylation in cancer therapy: Mechanisms and modulators.Acta pharmaceutica Sinica. B · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
The allosteric regulation triggering the protein's functional activity via conformational changes is an intrinsic function of protein under many physiological and pathological conditions, including cancer. Identification of the biological effects of specific somatic variants on allosteric proteins and the phenotypes that they alter during tumor initiation and progression is a central challenge for cancer genomes in the post-genomic era. Here, we mapped more than 47,000 somatic missense mutations observed in approximately 7,000 tumor-normal matched samples across 33 cancer types into protein allosteric sites to prioritize the mutated allosteric proteins and we tested our prediction in cancer cell lines. We found that the deleterious mutations identified in cancer genomes were more significantly enriched at protein allosteric sites than tolerated mutations, suggesting a critical role for protein allosteric variants in cancer. Next, we developed a statistical approach, namely AlloDriver, and further identified 15 potential mutated allosteric proteins during pan-cancer and individual cancer-type analyses. More importantly, we experimentally confirmed that p.Pro360Ala on PDE10A played a potential oncogenic role in mediating tumorigenesis in non-small cell lung cancer (NSCLC). In summary, these findings shed light on the role of allosteric regulation during tumorigenesis and provide a useful tool for the timely development of targeted cancer therapies.
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.