ArticleAmerican journal of human genetics2020
An Integrated Deep-Mutational-Scanning Approach Provides Clinical Insights on PTEN Genotype-Phenotype Relationships.
Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 58 citations in OpenAlex.
- Combining multiplexed functional data to improve variant classification.Genome medicine · 2026Article
- Image-based, pooled phenotyping reveals multidimensional, disease-specific variant effects.Cell · 2026Article
- MAVISp: A modular structure-based framework for protein variant effects.Protein science : a publication of the Protein Society · 2026Article
- Prime Editing Driven Functional Genomics: Bridging Genotype to Phenotype in the Post-Genomic Era.International journal of molecular sciences · 2026Review
- CodonMutator: a python-based automated oligonucleotide design framework for deep mutational scanning library construction.BMB reports · 2026Article
- A small molecule stabilizer rescues the surface expression of nearly all missense variants in a GPCR.Nature structural & molecular biology · 2025Article
- Elucidating PTEN conformational dynamics and phosphatase regulation via integrative modeling and mutation prediction.Structure (London, England : 1993) · 2025Article
- Neurobehavioral Signatures in Overgrowth Intellectual Disability Syndromes: Dissecting Genotype-Phenotype Relationships in the PI3K-AKT-MTOR Pathway.medRxiv : the preprint server for health sciences · 2025Article
- Deep mutational scanning of the multi-domain phosphatase SHP2 reveals mechanisms of regulation and pathogenicity.Nature communications · 2025Article
- Non-serous ovarian cancer in PTEN Hamartoma Tumor Syndrome: additional evidence for increased risk.Familial cancer · 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
- Germline PTEN genotype-dependent phenotypic divergence during the early neural developmental process of forebrain organoids.Molecular psychiatry · 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
- Source, co-occurrence, and prognostic value of PTEN mutations or loss in colorectal cancer.NPJ genomic medicine · 2023Article
- Machine Learning-Guided Protein Engineering.ACS catalysis · 2023Review
- An Atlas of Variant Effects to understand the genome at nucleotide resolution.Genome biology · 2023Article
- Pan-cancer genomic analysis shows hemizygous PTEN loss tumors are associated with immune evasion and poor outcome.Scientific reports · 2023Article
- Deep mutational scanning: A versatile tool in systematically mapping genotypes to phenotypes.Frontiers in genetics · 2023Review
- Gingival Overgrowths RevealingBiomedicines · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Germline variation in PTEN results in variable clinical presentations, including benign and malignant neoplasia and neurodevelopmental disorders. Despite decades of research, it remains unclear how the PTEN genotype is related to clinical outcomes. In this study, we combined two recent deep mutational scanning (DMS) datasets probing the effects of single amino acid variation on enzyme activity and steady-state cellular abundance with a large, well-curated clinical cohort of PTEN-variant carriers. We sought to connect variant-specific molecular phenotypes to the clinical outcomes of individuals with PTEN variants. We found that DMS data partially explain quantitative clinical traits, including head circumference and Cleveland Clinic (CC) score, which is a semiquantitative surrogate of disease burden. We built logistic regression models that use DMS and CADD scores to separate clinical PTEN variation from gnomAD control-only variation with high accuracy. By using a survival-like analysis, we identified molecular phenotype groups with differential risk of early cancer onset as well as lifetime risk of cancer. Finally, we identified classes of DMS-defined variants with significantly different risk levels for classical hamartoma-related features (odds ratio [OR] range of 4.1-102.9). In stark contrast, the risk for developing autism or developmental delay does not significantly change across variant classes (OR range of 5.4-12.4). Together, these findings highlight the potential impact of combining DMS datasets with rich clinical data and provide new insights that might guide personalized clinical decisions for PTEN-variant carriers.
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.