Affinage

LMNA

Prelamin-A/C · UniProt P02545

Length
664 aa
Mass
74.1 kDa
Annotated
2026-06-10
100 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Lamin A/C is a nuclear lamina component that organizes the nuclear envelope and safeguards cell identity, and whose mutation drives cardiomyopathy through a convergent network of stress and signaling pathways (PMID:14644157, PMID:33529599). At the nuclear envelope, lamin A/C is required and sufficient to anchor emerin and nesprin-1alpha, and its loss or mutation mislocalizes these partners to the ER (PMID:14644157, PMID:12673789, PMID:15053843). The lamina tethers chromatin through lamin-associated domains (LADs) that hold non-lineage genes in a transcriptionally repressed state; pathogenic mutations selectively disrupt peripheral chromatin contacts in cardiomyocytes and aberrantly upregulate non-myocyte lineage genes, eroding cardiomyocyte identity (PMID:33529599, PMID:38577741). Lamin A/C additionally interacts with matrin-3 through its tail domain and with c-Myc, restraining c-Myc-driven transcription of tRNA-processing genes (PMID:25948554, PMID:38769668), and a nucleoplasmic pool is recruited by BAF to sites of nuclear envelope rupture, a repair function blocked by progeria-associated farnesylation (PMID:35269487). Mutations confer mechanical fragility, reducing nuclear stiffness and altering nuclear shape (PMID:37585285). LMNA cardiomyopathy proceeds through aberrant activation of ERK1/2-JNK and Dusp4-AKT-mTOR signaling with impaired autophagy (PMID:20388542, PMID:23044536, PMID:23048029), E2F/DNA-damage/TP53 induction (PMID:30696354, PMID:35891706), PDGF pathway activation (PMID:31316208), disrupted actin-microtubule crosstalk via cofilin-1/MRTF-A/SRF/ATAT1 (PMID:36550158), Nesprin-1 LINC-mediated mechanical stress transmission (PMID:35925868), and Golgi/ER stress (PMID:38718107); pharmacological or genetic interruption of each pathway rescues cardiac function in mouse and iPSC models. Aberrant LMNA splicing controlled by SRSF1/SRSF2/SRSF6 governs production of the farnesylated progerin isoform (PMID:26999604, PMID:21875900).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2003 High

    Established that lamin A/C is the obligate nuclear-envelope anchor for emerin and nesprin-1alpha, defining its structural role at the lamina.

    Evidence Immunofluorescence of LMNA-null patient fibroblasts with wild-type cDNA rescue; transfection of R377H mutant

    PMID:12673789 PMID:14644157

    Open questions at the time
    • Does not define the binding interface on lamin A/C for each partner
    • Mechanism linking mislocalization to tissue-specific disease not addressed
  2. 2004 Medium

    Showed disease mutations destabilize lamin A and perturb additional envelope and transcription machinery in muscle, hinting at tissue-selective consequences.

    Evidence Immunocytochemistry, EM and cell synchronization in R377H AD-EDMD patient cells

    PMID:15053843

    Open questions at the time
    • Single mutation in one patient lineage
    • Causal link between LBR/RNA Pol II changes and muscle phenotype not established
  3. 2009 Medium

    Demonstrated a mutation can directly alter lamin A/C biochemistry, changing DNA-binding via aberrant disulfide oligomerization and raising oxidative stress.

    Evidence Gel retardation, ESR spectroscopy, immunofluorescence in R439C patient fibroblasts

    PMID:19220582

    Open questions at the time
    • In vitro DNA-binding change not connected to specific gene-regulatory outcome in vivo
    • Single lab
  4. 2010 High

    Identified JNK and FAS/mitochondrial apoptosis activation as causal contributors to LMNA cardiomyopathy, converting correlative pathway changes into therapeutic targets.

    Evidence SP600125 JNK inhibition in Lmna(H222P/H222P) mice; E82K cardiac transgenic mice with TUNEL/caspase analysis

    PMID:20388542 PMID:21151901

    Open questions at the time
    • How nuclear lamina defects activate cytoplasmic JNK signaling is unresolved
    • Apoptosis findings rely on a single transgenic model
  5. 2011 High

    Defined the AKT-mTOR/autophagy axis and its driver Dusp4 as a pathogenic mechanism, linking aberrant signaling to defective protein quality control.

    Evidence mTOR inhibitor rescue and autophagy flux assays in Lmna(H222P/H222P) mice; Dusp4-overexpressing transgenic mice

    PMID:23044536 PMID:23048029

    Open questions at the time
    • Upstream coupling of lamin defect to ERK1/2-Dusp4 induction not mechanistically resolved
    • Restricted to one Lmna mouse allele
  6. 2011 High

    Identified SR proteins (SRSF1, SRSF2, SRSF6) as regulators of LMNA exon 11 splicing that control lamin A versus progerin production, enabling antisense correction strategies.

    Evidence RNAi knockdown, RNA structure analysis, RT-PCR and in vivo ASO administration in HGPS mouse models and MEFs

    PMID:21875900 PMID:26999604

    Open questions at the time
    • How splice-factor activity is regulated in different tissues not defined
    • Relevance to non-progeria LMNA isoform balance unclear
  7. 2013 High

    Connected prelamin A accumulation and farnesylation to endothelial dysfunction in lipodystrophy, with statin/antioxidant rescue implicating maturation defects.

    Evidence Lentiviral R482W expression in endothelial cells, NO/ROS/adhesion assays, pravastatin treatment

    PMID:23846499

    Open questions at the time
    • Cell-type specificity of prelamin A maturation defect not explained
    • Link to systemic lipodystrophy phenotype indirect
  8. 2015 Medium

    Mapped a direct lamin A tail interaction with matrin-3, adding a nucleoplasmic binding partner disrupted by truncating mutations.

    Evidence Reciprocal Co-IP, mass spectrometry pulldown, domain mapping, 3D microscopy in LMNA mutant cells

    PMID:25948554

    Open questions at the time
    • Functional consequence of the interaction not established
    • Single lab
  9. 2019 High

    Established PDGF signaling and the E2F/DNA-damage/TP53 pathway as causal, druggable drivers of LMNA cardiac dysfunction using isogenic and genetic-epistasis approaches.

    Evidence Isogenic iPSC-CMs with PDGFRb inhibition/knockdown; conditional Tp53 deletion in LMNA D300N mice

    PMID:30696354 PMID:31316208

    Open questions at the time
    • How lamina disruption activates PDGF and E2F/TP53 pathways mechanistically unresolved
    • Tp53 deletion provides only partial rescue
  10. 2021 High

    Showed the lamina safeguards cardiomyocyte identity via LAD-mediated chromatin tethering and genome stability, linking lamina-chromatin contacts to lineage gene silencing and DSB localization.

    Evidence Isogenic hiPSC-derived cell types with DamID/CUT&RUN, END-seq and RNA-seq

    PMID:33529599 PMID:38577741

    Open questions at the time
    • Molecular basis of cell-type-selective LAD disruption not defined
    • Causal order between chromatin detachment and gene misregulation unresolved
  11. 2022 High

    Resolved cytoskeletal and mechanotransduction mechanisms — cofilin-1/MRTF-A/SRF/ATAT1 tubulin acetylation and Nesprin-1 LINC microtubule anchoring — and BAF-dependent nuclear rupture repair, broadening the pathogenic network.

    Evidence Co-IP, Atat1 KO and tubastatin A rescue; CRISPR Nesprin-1 KASH disruption in Lmna mice; live-cell nuclear rupture imaging with farnesylation inhibition

    PMID:35269487 PMID:35891706 PMID:35925868 PMID:36550158

    Open questions at the time
    • Integration of these parallel pathways into a single hierarchy not established
    • BAF-rupture repair findings from a single lab
  12. 2024 High

    Extended the mechanism to Golgi/ER stress and CREB3/MED25 signaling in acute cardiac Lmna loss, and revealed a tumor-suppressive lamin A-c-Myc transcriptional axis outside the heart.

    Evidence Conditional cardiomyocyte Lmna deletion with translatome profiling and autophagy/ER-stress modulators; Co-IP/MS, ChIP and organoid assays for c-Myc interaction

    PMID:38718107 PMID:38769668

    Open questions at the time
    • Whether Golgi stress is primary or downstream of other pathways unclear
    • c-Myc axis characterized in neuroblastoma, generalizability untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single lamina defect is funneled into the many distinct downstream pathways (JNK/mTOR, PDGF, TP53, cytoskeletal, Golgi stress) and which are primary versus secondary remains unresolved.
  • No unified hierarchy linking nuclear-envelope perturbation to the divergent effector pathways
  • Tissue specificity of LMNA disease mechanisms not mechanistically explained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 3 GO:0005198 structural molecule activity 2 GO:0060090 molecular adaptor activity 2 GO:0003677 DNA binding 1
Localization
GO:0005635 nuclear envelope 3 GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2 GO:0005654 nucleoplasm 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-397014 Muscle contraction 2 R-HSA-4839726 Chromatin organization 2 R-HSA-73894 DNA Repair 2 R-HSA-8953854 Metabolism of RNA 2 R-HSA-9612973 Autophagy 2
Partners
BANF1EMDLBRMATR3MYCSYNE1
Complex memberships
LINC complexnuclear lamina

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Complete absence of lamins A and C (homozygous Y259X mutation) causes mislocalization of emerin and nesprin-1alpha to the endoplasmic reticulum, and transfection of wild-type lamin A or C cDNA restores correct nuclear envelope anchorage of both proteins, demonstrating that lamin A or C is sufficient and required for proper localization of emerin and nesprin-1alpha at the nuclear envelope. Immunofluorescence microscopy of patient fibroblasts (homozygous and heterozygous LMNA null), cDNA rescue transfection Experimental cell research High 14644157
2003 The LMNA R377H missense mutation causes mislocalization of both lamin A/C and emerin in transfected muscle (C2C12) and non-muscle (COS-7) cells, indicating that this mutation disrupts lamina organization and emerin anchoring. Cell transfection experiments with immunofluorescence Human mutation Medium 12673789
2004 The LMNA R377H mutation in AD-EDMD patient cells leads to instability (accelerated degradation) of lamin A protein, aberrant cytoplasmic localization of the lamin B receptor (LBR) in association with the ER, and altered intranuclear distribution of active RNA polymerase II specifically in muscle cells. Cell synchronization experiments, immunocytochemistry, electron microscopy in patient lymphoblastoid cells, fibroblasts, myoblasts and muscle tissue BMC cell biology Medium 15053843
2009 The LMNA R439C mutation introduces an extra cysteine enabling disulfide-mediated lamin A/C oligomerization, which alters the DNA-binding properties of the C-terminal domain (gel retardation assay shows increased DNA-binding affinity compared to wild-type), and R439C patient fibroblasts show significantly elevated reactive oxygen species upon induction of oxidative stress. Gel retardation assays, electron spin resonance spectroscopy, immunofluorescence of patient fibroblasts Journal of cellular and molecular medicine Medium 19220582
2010 Pharmacological inhibition of JNK signaling with SP600125 in Lmna(H222P/H222P) mice (which show abnormally activated JNK in the heart) significantly delays left ventricular dilatation, prevents decreases in ejection fraction and fibrosis, and blocks upregulation of natriuretic peptide precursors and sarcomere architecture proteins, demonstrating a causal role for JNK pathway activation in LMNA cardiomyopathy. In vivo pharmacological treatment of Lmna(H222P/H222P) mouse model, echocardiography, Western blot, qPCR Biochimica et biophysica acta High 20388542
2010 The LMNA E82K mutation causes mislocalization of lamin A/C in the nucleus, induces swollen mitochondria with loss of cristae, and activates both FAS and mitochondrial apoptosis pathways (increased FAS expression, cytochrome c release, caspase-8/-9/-3 activation) in heart-specific transgenic mice, resulting in an 8.5-fold increase in apoptosis. Heart tissue-specific transgenic mouse model, immunofluorescence, electron microscopy, Western blot, echocardiography, TUNEL PloS one Medium 21151901
2011 AKT-mTOR signaling is hyperactivated in hearts of Lmna(H222P/H222P) mice; pharmacological reduction of mTOR activity ameliorates cardiomyopathy and this improvement correlates with restored autophagy, demonstrating that impaired autophagy downstream of hyperactivated AKT-mTOR contributes to LMNA cardiomyopathy pathogenesis. Western blot, mTOR inhibitor treatment, autophagy flux assays, echocardiography in Lmna(H222P/H222P) mice Autophagy High 23044536
2012 Dual specificity phosphatase 4 (Dusp4) is transcriptionally induced by ERK1/2 and is highly expressed in hearts of Lmna(H222P/H222P) mice; cardiac-selective Dusp4 overexpression in transgenic mice causes cardiomyopathy similar to LMNA cardiomyopathy by positively regulating AKT-mTOR signaling and impairing autophagy. Transgenic mouse overexpression, Western blot, AKT-mTOR pathway analysis, autophagy assays, echocardiography The Journal of biological chemistry High 23048029
2011 SRSF2 binds to exon 11 sequences of the LMNA pre-mRNA and promotes splicing toward lamin A (versus lamin C); an antisense oligonucleotide targeting exon 11 increases lamin C production at the expense of prelamin A and reduces progerin expression in HGPS fibroblasts and in vivo in mice. ASO transfection, RNAi knockdown of SRSF2, RT-PCR, in vivo ASO administration in wild-type and HGPS mouse models The Journal of clinical investigation High 26999604
2011 SR proteins SRSF1 and SRSF6 regulate utilization of the exon 11 5' splice site in LMNA pre-mRNA controlling lamin A vs. progerin production; SRSF1 depletion reduces progerin and rescues dysmorphic nuclei in HGPS-like MEFs, while SRSF6 depletion aggravates the phenotype. The HGPS c.1824C>T mutation changes RNA secondary structure accessibility of the 5' splice site. RNAi knockdown in HGPS mouse model MEFs, RNA structure analysis, RT-PCR, immunofluorescence, mutant mouse model Human molecular genetics High 21875900
2013 The lipodystrophy-associated LMNA p.R482W mutation causes abnormal accumulation of prelamin A at the nuclear envelope in endothelial cells (due to decreased prelamin A maturation), induces endothelial dysfunction with decreased NO production, increased leukocyte adhesion, cellular senescence, oxidative stress, and DNA damage; these effects are prevented by pravastatin (which inhibits prelamin A farnesylation) or antioxidants. Lentiviral transduction of human coronary artery endothelial cells, patient fibroblast analysis, immunofluorescence, NO measurement, leukocyte adhesion assay, ROS measurement, pravastatin treatment Arteriosclerosis, thrombosis, and vascular biology High 23846499
2015 Lamin A interacts with matrin-3 through the lamin A tail domain; anti-matrin-3 antibodies co-immunoprecipitate lamin A, the lamin-A binding domain maps to the carboxy-terminal half of matrin-3, and the LMNA truncating mutation Δ303 (lacking the matrin-3 binding domain) increases the 3D distance between lamin A and matrin-3 in cells. Co-immunoprecipitation, mass spectrometry pulldown of lamin A tail, domain mapping, 3D fluorescence microscopy in LMNA mutant cells Human molecular genetics Medium 25948554
2019 PDGF signaling pathway is aberrantly activated in LMNA-mutant iPSC-derived cardiomyocytes compared to isogenic controls; pharmacological and molecular inhibition of PDGF signaling (targeting PDGFRβ) ameliorates arrhythmic phenotypes and aberrant calcium homeostasis in mutant iPSC-CMs. Patient-specific iPSC-CMs with isogenic controls, electrophysiology, calcium imaging, pharmacological inhibition and molecular knockdown of PDGF pathway Nature High 31316208
2019 Cardiac myocyte-specific expression of the LMNA D300N mutation activates the E2F/DNA damage response/TP53 pathway; conditional deletion of Tp53 in cardiac myocytes of LMNA D300N mice partially rescues myocardial fibrosis, apoptosis, left ventricular dilatation and dysfunction, demonstrating a causal pathogenic role for this pathway. Tet-off bigenic mouse model, conditional Tp53 knockout, RNA-seq, Western blot, immunofluorescence, echocardiography, survival analysis Circulation research High 30696354
2020 Sarcolipin, an inhibitor of SERCA (SR Ca2+ ATPase), is abnormally elevated early in the disease course of Lmna(H222P/H222P) mice (before left ventricular functional changes), altering calcium handling; AAV9-mediated RNAi knockdown of sarcolipin delays cardiac dysfunction in this mouse model. Western blot and qPCR in mouse hearts, AAV9-RNAi knockdown, calcium handling assays, echocardiography Biochemistry and biophysics reports Medium 32490213
2021 Pathogenic LMNA mutations from DCM patients introduced into hiPSCs cause specific disruptions of peripheral chromatin interactions in cardiomyocytes (but not hepatocytes or adipocytes), enriched for transcriptionally active genes with lower LAMIN B1 contact frequency; disrupted lamina-chromatin regions are enriched for non-myocyte lineage genes whose expression is aberrantly upregulated, suggesting the lamina network safeguards cardiomyocyte identity. Isogenic hiPSC-derived cardiomyocytes, hepatocytes, adipocytes; DamID lamina-chromatin interaction profiling, RNA-seq, nuclear morphology analysis, patient myocardium analysis Cell stem cell High 33529599
2022 In LMNA-mutant cardiomyopathy, ERK1/2-phosphorylated cofilin-1 (phospho-T25) binds MRTF-A in the cytoplasm, preventing SRF nuclear activation and reducing ATAT1 (α-tubulin acetyltransferase 1) expression, thereby decreasing α-tubulin acetylation; tubastatin A treatment to increase α-tubulin acetylation restores Connexin 43 localization and improves cardiac function in Lmna(H222P/H222P) mice. Co-immunoprecipitation (phospho-cofilin-1/MRTF-A), Atat1 knockout mice, tubastatin A pharmacological treatment, immunofluorescence, echocardiography, patient-derived iPSC-CMs Nature communications High 36550158
2022 Nesprin-1 LINC complexes are the predominant nuclear envelope anchor for microtubule cytoskeleton components (nucleation activities and motor complexes) in cardiomyocytes; CRISPR-mediated disruption of the Nesprin-1 KASH domain suppresses Lmna-linked cardiac pathology, likely by reducing microtubule cytoskeleton activities at the nucleus. CRISPR disruption of Nesprin-1 KASH domain in Lmna-mutant mice, immunofluorescence for microtubule components at the nucleus, cardiac phenotype assessment Human molecular genetics High 35925868
2022 BAF (Barrier-to-Autointegration Factor) recruits a mobile, nucleoplasmic population of A-type lamins to sites of nuclear rupture via its association with the Ig-like β-fold domain of A-type lamins; farnesylated prelamin A and lamin B1 fail to localize to nuclear ruptures (unless farnesylation is inhibited); progeria-associated LMNA mutations inhibit recruitment of A-type lamins to ruptures due to permanent farnesylation or inhibition of BAF binding. Live-cell imaging of nuclear rupture/repair, domain mapping, farnesylation inhibitor treatment, FRAP-like analysis, progeria mutant cell lines Cells Medium 35269487
2022 Lmna deletion in cardiac fibroblasts (Pdgfra-Cre) induces double-stranded DNA breaks, activates the DNA damage response (phospho-H2AFX, ATM, phospho-TP53, CDKN1A), and induces senescence-associated secretory phenotype (SASP: TGFβ1, CTGF, LGALS3), partially recapitulating the DCM phenotype and demonstrating that LMNA deficiency in fibroblasts contributes to DCM through DDR/SASP mechanisms. Conditional Lmna knockout in fibroblasts (Pdgfra-Cre:Lmna F/F), RNA-seq, Western blot for DDR markers, beta-galactosidase senescence assay, echocardiography The journal of cardiovascular aging High 35891706
2023 LMNA mutant iPSC-CMs show altered nuclear shape/size and reduced nuclear stiffness and fragility (especially R249Q mutation); the degree of nuclear abnormalities correlates with mislocalization of Lamin A/C and Lamin B1 from the nuclear envelope, with mislocalization likely due to altered lamin assembly. Patient-specific iPSC-CMs, atomic force microscopy (nuclear stiffness), immunofluorescence quantification of lamin localization, nuclear morphometry Molecular biology of the cell Medium 37585285
2024 Lamin A physically interacts with c-Myc, inhibiting c-Myc transactivation of tRNA processing genes (EPRS, LARS), thereby suppressing the malate-aspartate shuttle (MAS), aerobic glycolysis, and neuroblastoma tumorigenesis; co-immunoprecipitation and mass spectrometry confirmed the lamin A–c-Myc interaction, and the LMNA-binding compound lobeline facilitates this interaction to suppress tumor progression. Co-immunoprecipitation, mass spectrometry, dual-luciferase reporter, chromatin immunoprecipitation, Western blot, RT-PCR, organoid models from c-Myc knock-in mice Clinical and translational medicine Medium 38769668
2024 Cardiomyocyte-specific Lmna deletion in adult mice causes rapid cardiomyopathy preceded by nuclear abnormalities, Golgi dilation/fragmentation, and CREB3-mediated stress activation; MED25 (a transcriptional cofactor regulating Golgi stress) is activated; autophagy is disrupted. Modulators of autophagy or ER stress significantly delayed cardiac dysfunction and prolonged survival. Conditional cardiomyocyte-specific Lmna deletion, translatome profiling, immunofluorescence for Golgi markers, pharmacological modulators of autophagy/ER stress, echocardiography, survival analysis Science advances High 38718107
2021 LMNA regulates transcription through lamin-associated domains (LADs) in cardiac myocytes; LAD-associated genes have ~16-fold lower transcript levels than non-LAD genes; in Lmna-deficient cardiomyocytes, double-stranded DNA breaks are enriched in non-LAD and loss-of-LAD regions associated with transcription. END-Sequencing for genome-wide DSBs, CUT&RUN for LAD definition in cardiac myocytes (Myh6-Cre:LmnaF/F mice), RNA-seq Cardiovascular research Medium 38577741

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Nature genetics 555 10655060
2000 Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B). Human molecular genetics 466 10814726
2016 Hutchinson-Gilford Progeria Syndrome: A premature aging disease caused by LMNA gene mutations. Ageing research reviews 236 27374873
2019 Activation of PDGF pathway links LMNA mutation to dilated cardiomyopathy. Nature 183 31316208
2011 Targeted gene correction of laminopathy-associated LMNA mutations in patient-specific iPSCs. Cell stem cell 183 21596650
2003 Nuclear envelope alterations in fibroblasts from LGMD1B patients carrying nonsense Y259X heterozygous or homozygous mutation in lamin A/C gene. Experimental cell research 158 14644157
2019 DNA Damage Response/TP53 Pathway Is Activated and Contributes to the Pathogenesis of Dilated Cardiomyopathy Associated With LMNA (Lamin A/C) Mutations. Circulation research 134 30696354
2021 Pathogenic LMNA variants disrupt cardiac lamina-chromatin interactions and de-repress alternative fate genes. Cell stem cell 106 33529599
2020 The Broad Spectrum of LMNA Cardiac Diseases: From Molecular Mechanisms to Clinical Phenotype. Frontiers in physiology 95 32719615
1996 Chromosomal assignment of human nuclear envelope protein genes LMNA, LMNB1, and LBR by fluorescence in situ hybridization. Genomics 90 8838815
2008 Extreme phenotypic diversity and nonpenetrance in families with the LMNA gene mutation R644C. American journal of medical genetics. Part A 88 18478590
2016 Modulation of LMNA splicing as a strategy to treat prelamin A diseases. The Journal of clinical investigation 87 26999604
2011 LMNA cardiomyopathy: cell biology and genetics meet clinical medicine. Disease models & mechanisms 82 21810905
2017 Identification of pathogenic gene mutations in LMNA and MYBPC3 that alter RNA splicing. Proceedings of the National Academy of Sciences of the United States of America 80 28679633
2005 LMNA mutation position predicts organ system involvement in laminopathies. Clinical genetics 80 15952983
2000 Mutations in the LMNA gene encoding lamin A/C. Human mutation 78 11102973
2017 Gene-Based Risk Stratification for Cardiac Disorders in LMNA Mutation Carriers. Circulation. Cardiovascular genetics 75 29237675
2013 Lipodystrophy-linked LMNA p.R482W mutation induces clinical early atherosclerosis and in vitro endothelial dysfunction. Arteriosclerosis, thrombosis, and vascular biology 74 23846499
2011 A conserved splicing mechanism of the LMNA gene controls premature aging. Human molecular genetics 64 21875900
2003 Functional consequences of an LMNA mutation associated with a new cardiac and non-cardiac phenotype. Human mutation 61 12673789
2014 LMNA-associated myopathies: the Italian experience in a large cohort of patients. Neurology 60 25274841
2017 Current insights into LMNA cardiomyopathies: Existing models and missing LINCs. Nucleus (Austin, Tex.) 59 28125396
2013 Generation and characterization of a conditional deletion allele for Lmna in mice. Biochemical and biophysical research communications 56 23998933
2005 A novel homozygous Ala529Val LMNA mutation in Turkish patients with mandibuloacral dysplasia. The Journal of clinical endocrinology and metabolism 56 15998779
2002 Characterization of adiposity and metabolism in Lmna-deficient mice. Biochemical and biophysical research communications 56 11855819
2019 Modeling of LMNA-Related Dilated Cardiomyopathy Using Human Induced Pluripotent Stem Cells. Cells 52 31208058
2010 Pharmacological inhibition of c-Jun N-terminal kinase signaling prevents cardiomyopathy caused by mutation in LMNA gene. Biochimica et biophysica acta 52 20388542
2022 Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations. Nature communications 51 36550158
2012 Dual specificity phosphatase 4 mediates cardiomyopathy caused by lamin A/C (LMNA) gene mutation. The Journal of biological chemistry 51 23048029
2000 LMNA R482Q mutation in partial lipodystrophy associated with reduced plasma leptin concentration. The Journal of clinical endocrinology and metabolism 51 10999791
2014 Antagonistic functions of LMNA isoforms in energy expenditure and lifespan. EMBO reports 50 24639560
2012 LMNA knock-down affects differentiation and progression of human neuroblastoma cells. PloS one 43 23049808
2010 LMNA E82K mutation activates FAS and mitochondrial pathways of apoptosis in heart tissue specific transgenic mice. PloS one 43 21151901
2019 Cardiac and Neuromuscular Features of Patients With LMNA-Related Cardiomyopathy. Annals of internal medicine 42 31476771
2012 Reactivation of autophagy ameliorates LMNA cardiomyopathy. Autophagy 41 23044536
2017 Clinical disease presentation and ECG characteristics of LMNA mutation carriers. Open heart 40 28123761
2004 Expression and localization of nuclear proteins in autosomal-dominant Emery-Dreifuss muscular dystrophy with LMNA R377H mutation. BMC cell biology 40 15053843
2009 The R439C mutation in LMNA causes lamin oligomerization and susceptibility to oxidative stress. Journal of cellular and molecular medicine 39 19220582
2012 An inherited LMNA gene mutation in atypical Progeria syndrome. American journal of medical genetics. Part A 37 22991222
2006 Werner syndrome and mutations of the WRN and LMNA genes in France. Human mutation 37 16786514
2023 Clinical Spectrum of LMNA-Associated Type 2 Familial Partial Lipodystrophy: A Systematic Review. Cells 32 36899861
2022 Deletion of the Lmna gene in fibroblasts causes senescence-associated dilated cardiomyopathy by activating the double-stranded DNA damage response and induction of senescence-associated secretory phenotype. The journal of cardiovascular aging 32 35891706
2006 Mutations of the LMNA gene can mimic autosomal dominant proximal spinal muscular atrophy. Neurogenetics 32 17136397
2004 LMNA mutations in cardiac transplant recipients. Cardiology 32 15539782
2002 Identification of lamin A/C ( LMNA) gene mutations in Korean patients with autosomal dominant Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy 1B. Journal of human genetics 31 12032588
2023 Epigenetics in LMNA-Related Cardiomyopathy. Cells 30 36899919
2018 Lipodystrophic syndromes due to LMNA mutations: recent developments on biomolecular aspects, pathophysiological hypotheses and therapeutic perspectives. Nucleus (Austin, Tex.) 30 29578370
2015 Disruption of the lamin A and matrin-3 interaction by myopathic LMNA mutations. Human molecular genetics 30 25948554
2013 DNA damage accumulation and TRF2 degradation in atypical Werner syndrome fibroblasts with LMNA mutations. Frontiers in genetics 30 23847654
2012 Human longevity and common variations in the LMNA gene: a meta-analysis. Aging cell 30 22340368
2023 Nesprin-1 LINC complexes recruit microtubule cytoskeleton proteins and drive pathology in Lmna-mutant striated muscle. Human molecular genetics 29 35925868
2020 LMNA functions as an oncogene in hepatocellular carcinoma by regulating the proliferation and migration ability. Journal of cellular and molecular medicine 29 32896989
2018 Exploring the Crosstalk Between LMNA and Splicing Machinery Gene Mutations in Dilated Cardiomyopathy. Frontiers in genetics 29 30050558
2011 LMNA-linked lipodystrophies: from altered fat distribution to cellular alterations. Biochemical Society transactions 29 22103520
2007 Hutchinson-Gilford progeria syndrome: clinical findings in three patients carrying the G608G mutation in LMNA and review of the literature. The British journal of dermatology 29 17459035
2008 The R527H mutation in LMNA gene causes an increased sensitivity to ionizing radiation. Cell cycle (Georgetown, Tex.) 28 18604166
2024 From gene to mechanics: a comprehensive insight into the mechanobiology of LMNA mutations in cardiomyopathy. Cell communication and signaling : CCS 27 38539233
2017 Gene Therapy via Trans-Splicing for LMNA-Related Congenital Muscular Dystrophy. Molecular therapy. Nucleic acids 27 29499949
2020 Genotype-phenotype analysis of LMNA-related diseases predicts phenotype-selective alterations in lamin phosphorylation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26 32413188
2014 Normal and aberrant splicing of LMNA. Journal of medical genetics 26 24459210
2021 International retrospective natural history study of LMNA-related congenital muscular dystrophy. Brain communications 24 34240052
2020 LMNA Missense Mutation Causes Nonsense-Mediated mRNA Decay and Severe Dilated Cardiomyopathy. Circulation. Genomic and precision medicine 23 32818388
2018 Upregulation of the aging related LMNA splice variant progerin in dilated cardiomyopathy. PloS one 23 29702688
2015 LMNA cardiomyopathy detected in Japanese arrhythmogenic right ventricular cardiomyopathy cohort. Journal of cardiology 23 26620845
2015 Novel mutations in LMNA A/C gene and associated phenotypes. Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology 22 27199538
2010 Cell-extrinsic defective lymphocyte development in Lmna(-/-) mice. PloS one 22 20405040
2009 Novel LMNA gene mutation in a patient with Atypical Werner's Syndrome. The Korean journal of internal medicine 22 19270485
2017 FPLD2 LMNA mutation R482W dysregulates iPSC-derived adipocyte function and lipid metabolism. Biochemical and biophysical research communications 21 29108996
2008 LMNA mRNA expression is altered in human obesity and type 2 diabetes. Obesity (Silver Spring, Md.) 21 18497734
2023 Nuclear damage in LMNA mutant iPSC-derived cardiomyocytes is associated with impaired lamin localization to the nuclear envelope. Molecular biology of the cell 20 37585285
2023 LMNA Cardiomyopathy: Important Considerations for the Heart Failure Clinician. Journal of cardiac failure 20 37659618
2020 Unraveling LMNA Mutations in Metabolic Syndrome: Cellular Phenotype and Clinical Pitfalls. Cells 20 32012908
2020 Clinical spectrum and genetic variations of LMNA-related muscular dystrophies in a large cohort of Chinese patients. Journal of medical genetics 20 32571898
2010 Disheveled hair and ear (Dhe), a spontaneous mouse Lmna mutation modeling human laminopathies. PloS one 20 20376364
2022 Mechanisms of A-Type Lamin Targeting to Nuclear Ruptures Are Disrupted in LMNA- and BANF1-Associated Progerias. Cells 19 35269487
2005 [Autosomal dominant limb-girdle muscular dystrophy associated with conduction defects (LGMD1B): a description of 8 new families with the LMNA gene mutations]. Revue neurologique 19 15678000
2020 Activation of sarcolipin expression and altered calcium cycling in LMNA cardiomyopathy. Biochemistry and biophysics reports 18 32490213
2023 Accelerated Aging in LMNA Mutations Detected by Artificial Intelligence ECG-Derived Age. Mayo Clinic proceedings 17 36775737
2021 Integrated analysis reveals the alterations that LMNA interacts with euchromatin in LMNA mutation-associated dilated cardiomyopathy. Clinical epigenetics 17 33407844
2021 Phenotypic Variability in iPSC-Induced Cardiomyocytes and Cardiac Fibroblasts Carrying Diverse LMNA Mutations. Frontiers in physiology 17 34975533
2011 Low and high expressing alleles of the LMNA gene: implications for laminopathy disease development. PloS one 17 21980471
2019 Expression of Lmna-R225X nonsense mutation results in dilated cardiomyopathy and conduction disorders (DCM-CD) in mice: Impact of exercise training. International journal of cardiology 16 31668660
2022 The LMNA p.R541C mutation causes dilated cardiomyopathy in human and mice. International journal of cardiology 15 35714719
2024 Targeting c-Myc transactivation by LMNA inhibits tRNA processing essential for malate-aspartate shuttle and tumour progression. Clinical and translational medicine 14 38769668
2023 Modulation of cytoskeleton in cardiomyopathy caused by mutations in LMNA gene. American journal of physiology. Cell physiology 14 37125775
2020 Atypical Progeroid Syndrome and Partial Lipodystrophy Due to LMNA Gene p.R349W Mutation. Journal of the Endocrine Society 14 32913962
2013 Investigation of age-related changes in LMNA splicing and expression of progerin in human skeletal muscles. International journal of clinical and experimental pathology 14 24294364
2006 Myofiber degeneration in autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD) (LGMD1B). Brain pathology (Zurich, Switzerland) 14 17107595
2024 Perinuclear damage from nuclear envelope deterioration elicits stress responses that contribute to LMNA cardiomyopathy. Science advances 13 38718107
2022 Efficacy and Safety of ARRY-371797 in LMNA-Related Dilated Cardiomyopathy: A Phase 2 Study. Circulation. Genomic and precision medicine 13 36515663
2016 A novel nonsense mutation in LMNA gene identified by Exome Sequencing in an atrial fibrillation family. European journal of medical genetics 13 27373676
2025 DNA double-stranded breaks, a hallmark of aging, defined at the nucleotide resolution, are increased and associated with transcription in the cardiac myocytes in LMNA-cardiomyopathy. Cardiovascular research 12 38577741
2023 Systematic in vivo candidate evaluation uncovers therapeutic targets for LMNA dilated cardiomyopathy and risk of Lamin A toxicity. Journal of translational medicine 12 37840136
2014 Congenital fiber type disproportion myopathy caused by LMNA mutations. Journal of the neurological sciences 12 24642510
2025 LMNA-related cardiomyopathy: From molecular pathology to cardiac gene therapy. Journal of advanced research 11 39827909
2025 Location of LMNA Variants and Clinical Outcomes in Cardiomyopathy. JAMA cardiology 11 40601341
2017 Identification of novel RNA isoforms of LMNA. Nucleus (Austin, Tex.) 11 28857661
2014 Mandibuloacral Dysplasia Caused by LMNA Mutations and Uniparental Disomy. Case reports in genetics 11 24639906
2014 LMNA-related dilated cardiomyopathy. Oxford medical case reports 11 25988045
2010 LMNA rs4641 and the muscle lamin A and C isoforms in twins--metabolic implications and transcriptional regulation. The Journal of clinical endocrinology and metabolism 11 20501691

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