ArticleComputational and structural biotechnology journal2021
Distinguishing between PTEN clinical phenotypes through mutation analysis.
Article in Computational and structural biotechnology journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Identification of high-risk non-synonymous SNPs (nsSNPs) in DNAH1 and DNAH17 genes associated with male infertility: a bioinformatics analysis.Journal of applied genetics · 2025Article
- Exploring the effects of missense mutations on protein thermodynamics through structure-based approaches: findings from the CAGI6 challenges.Human genetics · 2025Article
- Decoding Mechanisms of PTEN Missense Mutations in Cancer and Autism Spectrum Disorder using Interpretable Machine Learning Approaches.bioRxiv : the preprint server for biology · 2025Article
- AlzDiscovery: A computational tool to identify Alzheimer's disease-causing missense mutations using protein structure information.Protein science : a publication of the Protein Society · 2024Article
- Engineering G protein-coupled receptors for stabilization.Protein science : a publication of the Protein Society · 2024Article
- Characterizing and predicting ccRCC-causing missense mutations in Von Hippel-Lindau disease.Human molecular genetics · 2024Article
- AI-Driven Enhancements in Drug Screening and Optimization.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Cancer and Autism: How PTEN Mutations Degrade Function at the Membrane and Isoform Expression in the Human Brain.Journal of molecular biology · 2023Article
- Characterization on the oncogenic effect of the missense mutations of p53 via machine learning.Briefings in bioinformatics · 2023Article
- Neurodevelopmental disorders and cancer networks share pathways, but differ in mechanisms, signaling strength, and outcome.NPJ genomic medicine · 2023Article
- Article
- Identifying the Molecular Drivers of Pathogenic Aldehyde Dehydrogenase Missense Mutations in Cancer and Non-Cancer Diseases.International journal of molecular sciences · 2023Article
- On the linkage of thermodynamics and pathogenicity.Current opinion in structural biology · 2023Review
- Neurodevelopmental disorders and cancer networks share pathways; but differ in mechanisms, signaling strength, and outcome.bioRxiv : the preprint server for biology · 2023Article
- Nuclear PTEN's Functions in Suppressing Tumorigenesis: Implications for Rare Cancers.Biomolecules · 2023Review
- Compendium of proteins containing segments that exhibit zero-tolerance to amino acid variation in humans.Protein science : a publication of the Protein Society · 2022Article
- Systematic evaluation of computational tools to predict the effects of mutations on protein stability in the absence of experimental structures.Briefings in bioinformatics · 2022Article
- Dissecting mutational allosteric effects in alkaline phosphatases associated with different Hypophosphatasia phenotypes: An integrative computational investigation.PLoS computational biology · 2022Article
- Integrating thousands of PTEN variant activity and abundance measurements reveals variant subgroups and new dominant negatives in cancers.Genome medicine · 2021Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Phosphate and tensin homolog on chromosome ten (PTEN) germline mutations are associated with an overarching condition known as PTEN hamartoma tumor syndrome. Clinical phenotypes associated with this syndrome range from macrocephaly and autism spectrum disorder to Cowden syndrome, which manifests as multiple noncancerous tumor-like growths (hamartomas), and an increased predisposition to certain cancers. It is unclear, however, the basis by which mutations might lead to these very diverse phenotypic outcomes. Here we show that, by considering the molecular consequences of mutations in PTEN on protein structure and function, we can accurately distinguish PTEN mutations exhibiting different phenotypes. Changes in phosphatase activity, protein stability, and intramolecular interactions appeared to be major drivers of clinical phenotype, with cancer-associated variants leading to the most drastic changes, while ASD and non-pathogenic variants associated with more mild and neutral changes, respectively. Importantly, we show via saturation mutagenesis that more than half of variants of unknown significance could be associated with disease phenotypes, while over half of Cowden syndrome mutations likely lead to cancer. These insights can assist in exploring potentially important clinical outcomes delineated by PTEN variation.
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