ArticleNPJ genomic medicine2021
Most myopathic lamin variants aggregate: a functional genomics approach for assessing variants of uncertain significance.
Article in NPJ genomic medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 25 citations in OpenAlex.
- An Unbiased Drug Screen in a Drosophila Model ofInternational journal of molecular sciences · 2026Article
- Cardiomyocyte vulnerability to lamin polymer disruption revealed by saturation mutagenesis.bioRxiv : the preprint server for biology · 2026Article
- Generation of two homozygous iPSC lines carrying variants of uncertain significance in LMNA associated with cardiomyopathy.Stem cell research · 2026Article
- Image-based, pooled phenotyping reveals multidimensional, disease-specific variant effects.Cell · 2026Article
- High-Throughput Methods for Variant Functional Assessment in Cardiac Disease.Circulation. Genomic and precision medicine · 2026Review
- Novel and Ultrarare Heterozygous Missense LMNA Variants Causing Familial Partial Lipodystrophy.The Journal of clinical endocrinology and metabolism · 2025Article
- LMNA-related cardiomyopathy: From molecular pathology to cardiac gene therapy.Journal of advanced research · 2025Review
- Rare Variation in LMNA Underlies Polycystic Ovary Syndrome Pathogenesis in 2 Independent Cohorts.The Journal of clinical endocrinology and metabolism · 2025Article
- A genetic variant inScience advances · 2025Article
- Genetics and Pharmacogenetics of Atrial Fibrillation: A Mechanistic Perspective.JACC. Basic to translational science · 2024Review
- Global Proteomic Analysis Reveals Alterations in Differentially Expressed Proteins between Cardiopathic Lamin A/C Mutations.Journal of proteome research · 2024Article
- The Influence of a Genetic Variant inInternational journal of molecular sciences · 2024Article
- Nuclear Abnormalities inGenes · 2024Article
- Tracking the uptake of labelled host-derived extracellular vesicles by the human fungal pathogenmicroLife · 2024Article
- Case Report: ConcurrentFrontiers in genetics · 2024Article
- Long lifetime and tissue-specific accumulation of lamin A/C in Hutchinson-Gilford progeria syndrome.The Journal of cell biology · 2024Article
- Intermediate, but not average: The unusual lives of the nuclear lamin proteins.Current opinion in cell biology · 2023Review
- Caenorhabditis elegans models for striated muscle disorders caused by missense variants of human LMNA.PLoS genetics · 2023Article
- Drosophila Models Reveal Properties of Mutant Lamins That Give Rise to Distinct Diseases.Cells · 2023Article
- Effects of mutant lamins on nucleo-cytoskeletal coupling inFrontiers in cell and developmental biology · 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
7 authors at 1 institution in 1 country.
Funding
Abstract
Hundreds of LMNA variants have been associated with several distinct disease phenotypes. However, genotype-phenotype relationships remain largely undefined and the impact for most variants remains unknown. We performed a functional analysis for 178 variants across five structural domains using two different overexpression models. We found that lamin A aggregation is a major determinant for skeletal and cardiac laminopathies. An in vitro solubility assay shows that aggregation-prone variants in the immunoglobulin-like domain correlate with domain destabilization. Finally, we demonstrate that myopathic-associated LMNA variants show aggregation patterns in induced pluripotent stem cell derived-cardiomyocytes (iPSC-CMs) in contrast to non-myopathic LMNA variants. Our data-driven approach (1) reveals that striated muscle laminopathies are predominantly protein misfolding diseases, (2) demonstrates an iPSC-CM experimental platform for characterizing laminopathic variants in human cardiomyocytes, and (3) supports a functional assay to aid in assessing pathogenicity for myopathic variants of uncertain significance.
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.