ArticleJournal of biomolecular structure & dynamics2019
Dynamics and structural stability effects of germline PTEN mutations associated with cancer versus autism phenotypes.
Article in Journal of biomolecular structure & dynamics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer.Molecular autism · 2019Pooled it
- Recognizing genetic association between Lhermitte-Duclos Disease and Autism Spectrum Disorder in PTEN-related patients: a case report and literature comprehension.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Elucidating PTEN conformational dynamics and phosphatase regulation via integrative modeling and mutation prediction.Structure (London, England : 1993) · 2025Article
- Computational studies on the functional and structural impact of pathogenic mutations in enzymes.Protein science : a publication of the Protein Society · 2025Review
- Decoding Mechanisms of PTEN Missense Mutations in Cancer and Autism Spectrum Disorder using Interpretable Machine Learning Approaches.bioRxiv : the preprint server for biology · 2025Article
- Review
- Preliminary insights on the mutational spectrum of BRCA1 and BRCA2 genes in Pakhtun ethnicity breast cancer patients from Khyber Pakhtunkhwa (KP), Pakistan.Neoplasia (New York, N.Y.) · 2024Article
- A Bi-Institutional Study of Gastrointestinal and Hepatic Manifestations in Children WithGastro hep advances · 2024Article
- Cancer and Autism: How PTEN Mutations Degrade Function at the Membrane and Isoform Expression in the Human Brain.Journal of molecular biology · 2023Article
- Article
- Mutational Landscape and In-Silico Analysis ofACS omega · 2023Article
- Comparative Protein Structural Network Analysis Reveals C-Terminal Tail Phosphorylation Structural Communication Fingerprint inThe journal of physical chemistry. B · 2023Article
- Allostery: Allosteric Cancer Drivers and Innovative Allosteric Drugs.Journal of molecular biology · 2022Review
- Structural and Dynamic Effects of PTEN C-Terminal Tail Phosphorylation.Journal of chemical information and modeling · 2022Article
- Comprehensive characterization of PTEN mutational profile in a series of 34,129 colorectal cancers.Nature communications · 2022Article
- Prevalence and clinical/molecular characteristics of PTEN mutations in Turkish children with autism spectrum disorders and macrocephaly.Molecular genetics & genomic medicine · 2021Article
- The mechanism of full activation of tumor suppressor PTEN at the phosphoinositide-enriched membrane.iScience · 2021Article
- Autism-associatedeLife · 2021Article
- Phosphorylation and Driver Mutations in PI3Kα and PTEN Autoinhibition.Molecular cancer research : MCR · 2021Review
- PremPS: Predicting the impact of missense mutations on protein stability.PLoS computational biology · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Individuals with germline mutations in the tumor suppressor gene phosphatase and tensin homolog (PTEN), irrespective of clinical presentation, are diagnosed with PTEN hamartoma tumor syndrome (PHTS). PHTS confers a high risk of breast, thyroid, and other cancers or autism spectrum disorder (ASD) with macrocephaly. It remains unclear why mutations in one gene can lead to seemingly disparate phenotypes. Thus, we sought to identify differences in ASD vs. cancer-associated germline PTEN missense mutations by investigating putative structural effects induced by each mutation. We utilized a theoretical computational approach combining in silico structural analysis and molecular dynamics (MD) to interrogate 17 selected mutations from our patient population: six mutations were observed in patients with ASD (only), six mutations in patients with PHTS-associated cancer (only), four mutations shared across both phenotypes, and one mutation with both ASD and cancer. We demonstrate structural stability changes where all six cancer-associated mutations showed a global decrease in structural stability and increased dynamics across the domain interface with a proclivity to unfold, mediating a closed (inactive) active site. In contrast, five of the six ASD-associated mutations showed localized destabilization that contribute to the partial opening of the active site. Our results lend insight into distinctive structural effects of germline PTEN mutations associated with PTEN-ASD vs. those associated with PTEN-cancer, potentially aiding in identification of the shared and separate molecular features that contribute to autism or cancer, thus, providing a deeper understanding of genotype-phenotype relationships for germline PTEN mutations.
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