Affinage

ACTC1

Actin, alpha cardiac muscle 1 · UniProt P68032

Round 2 corrected
Length
377 aa
Mass
42.0 kDa
Annotated
2026-04-28
59 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACTC1 encodes the principal thin-filament actin of the cardiac sarcomere, where its polymerization and interaction with myosin, troponin, and Z-band/intercalated-disc scaffolds govern contraction, relaxation, and force transmission. Disease-causing missense mutations alter distinct functional surfaces: mutations affecting the actin–myosin interface (e.g., M84T, E101K) cause congenital heart defects including atrial septal defect, whereas mutations at force-transmission domains cause dilated cardiomyopathy, and mutations that increase myofibrillar Ca²⁺ sensitivity (e.g., E99K) produce hypertrophic cardiomyopathy with hypercontractility, impaired lusitropy, aberrant Ca²⁺ release, and arrhythmogenesis (PMID:9563954, PMID:10330430, PMID:21622575, PMID:25418306, PMID:23604709). Heterozygous ACTC1 variants also cause distal arthrogryposis with cardiac defects, establishing a shared requirement in cardiac and skeletal muscle (PMID:37457373). Polymerization-defective mutations (e.g., G247D) impair Rho-GTPase/SRF signalling and promote cardiomyocyte apoptosis, while reduced ACTC1 expression—whether through promoter variants, 3′UTR miRNA gain-of-function, or epigenetic silencing—is linked to congenital heart disease and septal defects (PMID:31434612, PMID:20962418, PMID:27139165, PMID:40848833).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1998 High

    Establishing that ACTC1 mutations cause dilated cardiomyopathy answered whether sarcomeric actin itself—not just myosin or regulatory proteins—could drive heart failure through defective force transmission.

    Evidence Genetic linkage and sequencing in two familial DCM pedigrees identifying missense mutations at Z-band/intercalated-disc attachment domains

    PMID:9563954

    Open questions at the time
    • No direct measurement of force transmission deficit
    • Biochemical mechanism of each mutation unresolved
  2. 1999 High

    Discovery that a different ACTC1 mutation causes HCM established that the same gene could underlie two opposing cardiomyopathies, generating the hypothesis that mutation location—contraction-affecting versus force-transmission-affecting—determines phenotype.

    Evidence Linkage analysis and candidate gene sequencing with significant lod score in an HCM family

    PMID:10330430

    Open questions at the time
    • Functional consequence of Ala295Ser on contractile parameters not yet measured
    • No direct structural mapping to actin–myosin interface
  3. 2003 Medium

    Identification of a physical ACTC1–band 3 (AE1) interaction at intercalated discs revealed a non-myosin binding partner, suggesting ACTC1 participates in membrane-cytoskeletal coupling beyond pure force generation.

    Evidence Yeast two-hybrid screen with reciprocal co-immunoprecipitation from rat heart and confocal colocalization

    PMID:12898519

    Open questions at the time
    • Functional consequence of disrupting the ACTC1–band 3 interaction unknown
    • Not tested with DCM-causing mutations mapping to the intercalated disc domain
  4. 2010 Medium

    Demonstration that ACTC1 knockdown increases cardiomyocyte apoptosis established a pro-survival role beyond contractile function, linking reduced ACTC1 expression to congenital heart disease pathogenesis.

    Evidence siRNA knockdown in H9C2 cells with TUNEL, caspase-3 and Bcl-2 readouts, correlated with reduced ACTC1 in human CHD tissue

    PMID:20962418

    Open questions at the time
    • Signalling pathway from ACTC1 loss to apoptosis not delineated
    • Single cell line (H9C2) used
  5. 2011 High

    Quantitative measurement of the E99K mutation's effect on Ca²⁺ sensitivity and troponin I phosphorylation-dependent regulation in reconstituted thin filaments and transgenic mice provided the first direct mechanistic explanation for HCM-associated hypercontractility.

    Evidence In vitro motility assay on reconstituted thin filaments, skinned papillary muscle mechanics, MRI and ECG in transgenic mice, human carrier samples

    PMID:21622575

    Open questions at the time
    • Structural basis of E99K's effect on troponin I phosphorylation coupling unresolved
    • Mechanism of transition from hypertrophy to dilation not addressed
  6. 2013 High

    Calorimetric measurement of the E99K muscle showed that hypercontractility is accompanied by reduced contractile efficiency, establishing energetic maladaptation as a feature of ACTC1-driven HCM.

    Evidence Intact papillary muscle mechanics, myofibril Ca²⁺-jump protocol, heat+work calorimetry in transgenic mice

    PMID:23604709

    Open questions at the time
    • Whether energy inefficiency is a universal feature of ACTC1 HCM mutations or specific to E99K
    • Mitochondrial compensation mechanisms not examined
  7. 2014 High

    Demonstration that the DCM-causing E361G mutation specifically uncouples PKA/troponin I phosphorylation-dependent lusitropy without altering sarcomere-length sensitivity distinguished the DCM mechanism from the HCM mechanism at the same molecular level—thin-filament regulation.

    Evidence Ca²⁺-jump protocol in single transgenic mouse myofibrils with propranolol-modulated troponin I phosphorylation

    PMID:25418306

    Open questions at the time
    • Whether this uncoupling is generalizable to other DCM-causing ACTC1 mutations
    • Structural basis for selective loss of phosphorylation sensitivity not resolved
  8. 2016 Medium

    A 3′UTR variant creating a miR-139-5p binding site demonstrated that ACTC1 haploinsufficiency via post-transcriptional regulation can cause atrial septal defect, expanding the mutational mechanism beyond coding-region changes.

    Evidence Luciferase reporter assay with miR-139-5p mimic/inhibitor in transfected cells, whole-genome sequencing of ASD family

    PMID:27139165

    Open questions at the time
    • In vivo miR-139-5p levels in developing septum not measured
    • No animal model confirming ASD from 3′UTR-mediated ACTC1 reduction
  9. 2017 High

    Age-dependent aberrant Ca²⁺ release (sparks, waves) in young E99K mice during a vulnerable window linked the elevated myofibrillar Ca²⁺ sensitivity to arrhythmogenesis and sudden cardiac death, with genetic background modifying penetrance.

    Evidence Confocal Ca²⁺ imaging in isolated ventricular myocytes, Ca²⁺ spark analysis, histological fibrosis quantification across two inbred backgrounds

    PMID:28887330

    Open questions at the time
    • Molecular basis for age-dependent normalization of Ca²⁺ transients in survivors unknown
    • Modifier genes underlying background-dependent penetrance not identified
  10. 2019 Medium

    Showing that the G247D mutation inhibits actin polymerization and abolishes Rho-GTPase/SRF signalling established a non-contractile signalling axis disrupted in ACTC1-linked DCM and congenital heart defects.

    Evidence In vitro actin polymerization assay, SRF luciferase reporter, Rho-GTPase pull-down, nuclear G-actin fractionation in NRVCMs

    PMID:31430208 PMID:31434612

    Open questions at the time
    • Whether SRF pathway disruption is a common mechanism in other ACTC1 DCM mutations
    • In vivo rescue by restoring SRF signalling not attempted
  11. 2023 Medium

    Identification of ACTC1 variants causing distal arthrogryposis with congenital heart defects in five families demonstrated that ACTC1 is required in skeletal as well as cardiac muscle, broadening its disease spectrum beyond cardiomyopathy.

    Evidence Exome/genome sequencing with co-segregation analysis across five independent families

    PMID:37457373

    Open questions at the time
    • Functional consequence of DA-causing variants on actin polymerization or myosin interaction not tested
    • Skeletal muscle biopsy data not available for most families
  12. 2025 Medium

    Promoter variants reducing ACTC1 transcription were directly validated, and LMOD2 was identified as a physical ACTC1 interactor regulating myogenic differentiation, while an ACTC1–BMP4 axis was established in prostate cancer, extending ACTC1 functions beyond sarcomeric contraction.

    Evidence Luciferase promoter assay and EMSA in HL-1 cardiomyocytes; Co-IP of LMOD2–ACTC1 with LMOD2 KO in C2C12; overexpression/knockdown with BMP4 rescue in prostate cancer xenografts

    PMID:40745266 PMID:40848833 PMID:41286808

    Open questions at the time
    • LMOD2–ACTC1 interaction awaits reciprocal Co-IP and domain mapping
    • BMP4 mechanism downstream of ACTC1 not delineated
    • Relevance of ACTC1 in non-muscle tissues in vivo remains preliminary

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the high-resolution structural basis for mutation-specific phenotype determination (HCM versus DCM versus congenital defect), the signalling pathways linking ACTC1 loss to apoptosis, the in vivo relevance of ACTC1 in non-muscle contexts, and whether therapeutic restoration of Ca²⁺ sensitivity or SRF signalling can prevent disease progression.
  • No cryo-EM or crystal structure of mutant ACTC1 in thin filament context
  • No gene therapy or allele-specific silencing study for ACTC1 cardiomyopathy
  • Mechanism linking ACTC1 to septal morphogenesis not established beyond expression correlation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 5 GO:0008092 cytoskeletal protein binding 3
Localization
GO:0005856 cytoskeleton 6 GO:0005886 plasma membrane 1
Pathway
R-HSA-1643685 Disease 6 R-HSA-397014 Muscle contraction 6 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 2 R-HSA-5357801 Programmed Cell Death 2
Partners
LMOD2MYH7SLC4A1TNNC1TNNI3
Complex memberships
cardiac sarcomeric thin filament

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Missense mutations in the cardiac actin gene (ACTC) that affect universally conserved amino acids in domains attaching to Z bands and intercalated discs co-segregate with hereditary dilated cardiomyopathy (IDC), suggesting that defective force transmission from cardiac myocytes is a mechanism underlying heart failure. Genetic linkage analysis and direct sequencing in two unrelated familial IDC pedigrees Science High 9563954
1999 The ACTC gene (alpha-cardiac actin) is identified as a novel disease gene for familial hypertrophic cardiomyopathy (HCM), with an Ala295Ser mutation in exon 5; ACTC is the first sarcomeric gene in which mutations cause two distinct cardiomyopathies (HCM and dilated), leading to the hypothesis that HCM-causing mutations affect sarcomere contraction while DCM-causing mutations affect force transmission. Linkage analysis, candidate gene sequencing, lod score analysis in a family pedigree The Journal of Clinical Investigation High 10330430
2003 Alpha-cardiac actin (ACTC) physically binds to the cardiac isoform of band 3 (AE1 anion exchanger); the interaction was identified by yeast two-hybrid and confirmed by reciprocal co-immunoprecipitation from rat heart; confocal microscopy localised band 3 to the intercalated disc, suggesting the interaction occurs at the site of sarcomere attachment to the plasma membrane. Yeast two-hybrid, co-immunoprecipitation (reciprocal), confocal microscopy Journal of Cellular Biochemistry Medium 12898519
2011 The HCM-causing ACTC E99K mutation increases myofibrillar Ca²⁺ sensitivity ~2.3-fold in transgenic mouse reconstituted thin filaments (in vitro motility assay) and ~1.3-fold in human carrier samples; it also abolishes the normal change in Ca²⁺ sensitivity linked to troponin I phosphorylation. Transgenic mice exhibit apical hypertrophy, sudden cardiac death, atrial flutter, reduced β-adrenergic contractile response, and eventual dilated cardiomyopathy. In vitro motility assay on reconstituted thin filaments, skinned papillary muscle mechanics, cardiac MRI, ECG, transgenic mouse model The Journal of Biological Chemistry High 21622575
2013 ACTC E99K papillary muscles produce 3–4-fold greater force than non-transgenic controls under isometric conditions, relax ~1.4-fold slower, and show ~2-fold higher myofibrillar Ca²⁺ sensitivity (EC₅₀ 0.39 vs 0.80 μmol/l); energy turnover is disproportionately elevated relative to work produced (efficiency 11–16% vs 15–18%), establishing hypercontractility driven by elevated myofibrillar Ca²⁺ sensitivity as the primary deficit. Intact papillary muscle mechanics, myofibril Ca²⁺-jump protocol, heat+work calorimetry, Ca²⁺ imaging in isolated myocytes American Journal of Physiology. Heart and Circulatory Physiology High 23604709
2014 The DCM-causing mutation ACTC E361G specifically abolishes troponin I phosphorylation-dependent modulation of Ca²⁺ sensitivity and relaxation kinetics in intact cardiac myofibrils, without affecting sarcomere-length-dependent activation or response to EMD57033; this demonstrates uncoupling of PKA-mediated lusitropy in an intact contractile system. Ca²⁺-jump protocol in single transgenic mouse cardiac myofibrils, propranolol treatment to vary troponin I phosphorylation levels Biophysical Journal High 25418306
2016 A mutation in the 3'UTR of ACTC1 (c.*1784T>C) creates a novel target site for miR-139-5p, reducing ACTC1 gene expression; luciferase reporter assays confirm the mutation specifically downregulates expression, and miR-139-5p mimic/inhibitor modulate this effect, suggesting haploinsufficiency via a gain-of-function miRNA regulatory mechanism as a cause of familial ASD. Whole genome sequencing, luciferase reporter assay, miR-139-5p mimic and inhibitor transfection Scientific Reports Medium 27139165
2017 Young ACTC E99K transgenic mice in their vulnerable period (28–40 days) exhibit elevated Ca²⁺ transients, increased Ca²⁺ spark mass, and greater propensity for spontaneous Ca²⁺ waves compared to non-transgenic littermates, despite similar sarcoplasmic reticulum Ca²⁺ content; these aberrant Ca²⁺ release events are associated with sudden cardiac death and increased myocardial fibrosis. Adult survivors normalize Ca²⁺ transients. Penetrance of sudden death depends on genetic background (CBA/Ca vs C57Bl6). Isolated ventricular myocyte Ca²⁺ imaging (confocal), Ca²⁺ spark analysis, histology (collagen quantification), transgenic mouse model with two genetic backgrounds American Journal of Physiology. Heart and Circulatory Physiology High 28887330
2017 Variable expression of cardiac α-actin (Actc1) in early adult skeletal muscle across Collaborative Cross strains (up to 24-fold) is negatively correlated with promoter methylation at the Actc1 transcriptional start site in a strain-dependent manner, while histone modifications and chromatin accessibility are unaltered; eQTL mapping confirms a cis-acting regulatory locus at the Actc1 locus in both heart and skeletal muscle. Expression QTL mapping, bisulfite sequencing (methylation), ATAC-seq/chromatin accessibility, histone ChIP across Collaborative Cross mouse strains Biochimica et Biophysica Acta. Gene Regulatory Mechanisms Medium 28847732
2018 hiPSC-derived cardiomyocytes carrying the E99K-ACTC1 mutation exhibit arrhythmogenesis in both 3D engineered heart tissues and 2D monolayers; Ca²⁺ handling expression studies informed pharmacological rescue, wherein dual dantrolene/ranolazine treatment was most effective, establishing E99K mutant ACTC1 protein as a primary driver of arrhythmia with Ca²⁺ handling as a central mechanism. Isogenic hiPSC-CM pairs, 3D engineered heart tissue, 2D monolayer Ca²⁺ imaging, pharmacological rescue (dantrolene/ranolazine) Stem Cell Reports Medium 30392975
2018 Knockdown of ACTC1 by siRNA in the U87MG glioblastoma cell line significantly inhibits cell migration (distance travelled reduced from ~3600 μm to ~1265 μm over 72 h), demonstrating a functional role for ACTC1 in tumour cell motility. siRNA knockdown, time-lapse cell migration tracking assay, droplet digital PCR, immunocytochemistry Journal of the Neurological Sciences Medium 30055382
2019 The ACTC1 p.Gly247Asp (G247D) mutation inhibits actin polymerization (confirmed by in vitro polymerization assay) and impairs Rho-GTPase/SRF signalling: overexpression of native ACTC1 strongly activates SRF-driven luciferase in NRVCMs whereas G247D abolishes this; mutant ACTC1 shows reduced GTP-bound Rho-GTPase and increased nuclear accumulation of globular actin, establishing defective actin polymerization as the mechanism linking G247D to impaired SRF signalling and DCM. In vitro actin polymerization assay, luciferase reporter assay (SRF/SM22-RE), Rho-GTPase pull-down (active Rho), nuclear fractionation and G-actin immunoblot, overexpression in NRVCMs Biochemical and Biophysical Research Communications Medium 31434612
2019 A heterozygous ACTC1 p.Gly247Asp mutation causes ultrastructural sarcomeric disarray, myofibrillar degeneration, and increased apoptosis in human myocardial tissue; in neonatal rat ventricular cardiomyocytes, overexpression of the mutant (but not wild-type) ACTC1 causes structural defects and apoptosis; molecular dynamics and polymerization assays confirm actin polymerization/turnover defects, implicating defective actin signalling in both cardiac developmental defects (ASD) and contractile dysfunction (DCM). Ultrastructural electron microscopy, cardiac proteomics, NRVCM overexpression, molecular dynamics simulation, actin polymerization assay, TUNEL apoptosis assay Circulation. Genomic and Precision Medicine Medium 31430208
2010 Reduced ACTC1 expression in sporadic congenital heart disease samples correlates with increased cardiomyocyte apoptosis; siRNA-mediated knockdown of Actc1 in H9C2 cardiomyocyte cell line increases apoptosis with increased Caspase-3 and decreased Bcl-2 expression, indicating ACTC1 promotes cardiomyocyte survival. RT-PCR, Western blot, immunohistochemistry, TUNEL assay, siRNA knockdown in H9C2 cells Circulation Journal Medium 20962418
2015 ACTC1 mutations causing congenital heart defects (p.Met84Thr, p.Glu101Lys, p.Met125Val) cluster in a region of actin in close apposition to the myosin heavy chain head domain, whereas mutations causing cardiomyopathies (p.Ala297Ser, p.Asp313His, p.Arg314His) map to a distinct interaction surface; this spatial distinction suggests that the clinical phenotypic consequence of an ACTC1 mutation is partly determined by which actin–myosin interaction surface is disrupted. Linkage analysis, Sanger sequencing, structural mapping of mutations onto actin–myosin complex structure PLoS One Low 26061005
2023 Heterozygous missense variants in ACTC1 cause distal arthrogryposis (DA) with congenital heart defects in five families, demonstrating that ACTC1 function is shared in both cardiac and skeletal muscle; the finding establishes ACTC1 as the first gene underlying DA that also causes cardiac abnormalities. Exome/genome sequencing, familial co-segregation analysis across five independent families HGG Advances Medium 37457373
2025 LMOD2 (leiomodin-2) physically interacts with ACTC1 as confirmed by Co-IP; LMOD2 knockout in C2C12 myoblasts alters muscle fiber type composition and inhibits myoblast proliferation, placing the LMOD2–ACTC1 interaction in the regulation of myogenic differentiation. Co-immunoprecipitation, RNA-seq, LMOD2 knockout in C2C12 cells, lentiviral knockdown in vivo BMC Genomics Medium 40745266
2025 ACTC1 overexpression in prostate cancer cells promotes proliferation and migration, while knockdown suppresses these behaviors; transcriptomic analysis identifies BMP4 as a key downstream effector, and BMP4 overexpression rescues the inhibitory effects of ACTC1 knockdown, establishing an ACTC1–BMP4 signalling axis in prostate cancer progression. Overexpression and siRNA knockdown in prostate cancer cell lines, xenograft mouse model, RNA-seq, BMP4 rescue experiment BMC Cancer Medium 41286808
2025 The zebrafish Acta1b p.T126I mutation (orthologous to human ACTC1 T126I) causes progressive dilated cardiomyopathy with sex-specific differences: female mutants show earlier diastolic dysfunction, more severe cardiac remodeling, and lower survival than males; molecular profiling reveals sex-specific alterations in calcium handling genes (serca2, pln1, slc8a1a) and proteostasis regulators (hsf1, bag3), with upregulation of the stress marker nppb and downregulation of gata4/mef2ca. CRISPR-generated zebrafish knock-in model, longitudinal echocardiography, histology, sex-stratified gene expression profiling bioRxivpreprint Medium bio_10.1101_2025.08.26.672352
2025 Variants in ACTC1 promoter region alter ACTC1 transcriptional activity as measured by luciferase assay in mouse cardiomyocytes (HL-1); EMSA and JASPAR analysis indicate the variants affect transcription factor binding, linking promoter variants to reduced ACTC1 expression and ventricular septal defect pathogenesis. Sanger sequencing, luciferase promoter activity assay in HL-1 cells, electrophoretic mobility shift assay (EMSA) Gene Medium 40848833

Source papers

Stage 0 corpus · 59 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genetics in medicine : official journal of the American College of Medical Genetics 1945 23788249
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2016 An improved smaller biotin ligase for BioID proximity labeling. Molecular biology of the cell 665 26912792
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1998 Actin mutations in dilated cardiomyopathy, a heritable form of heart failure. Science (New York, N.Y.) 560 9563954
2011 Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation. Nature cell biology 490 21423176
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2007 Functional specialization of beta-arrestin interactions revealed by proteomic analysis. Proceedings of the National Academy of Sciences of the United States of America 360 17620599
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2008 Mutations in sarcomere protein genes in left ventricular noncompaction. Circulation 328 18506004
2008 Shared genetic causes of cardiac hypertrophy in children and adults. The New England journal of medicine 309 18403758
2005 Compound and double mutations in patients with hypertrophic cardiomyopathy: implications for genetic testing and counselling. Journal of medical genetics 291 16199542
1999 Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy. The Journal of clinical investigation 274 10330430
2012 The cellular EJC interactome reveals higher-order mRNP structure and an EJC-SR protein nexus. Cell 272 23084401
2011 A directed protein interaction network for investigating intracellular signal transduction. Science signaling 258 21900206
2022 Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration. Cell 256 35063084
2002 NUANCE, a giant protein connecting the nucleus and actin cytoskeleton. Journal of cell science 245 12118075
1994 Nuclear translocation of angiogenin in proliferating endothelial cells is essential to its angiogenic activity. Proceedings of the National Academy of Sciences of the United States of America 243 8127865
2008 HIV envelope-CXCR4 signaling activates cofilin to overcome cortical actin restriction in resting CD4 T cells. Cell 240 18775311
2017 Optimized fragmentation schemes and data analysis strategies for proteome-wide cross-link identification. Nature communications 221 28524877
1998 Establishment of a functional human immunodeficiency virus type 1 (HIV-1) reverse transcription complex involves the cytoskeleton. The Journal of experimental medicine 217 9841925
2016 A High-Density Map for Navigating the Human Polycomb Complexome. Cell reports 216 27705803
2010 Clinical features and outcome of hypertrophic cardiomyopathy associated with triple sarcomere protein gene mutations. Journal of the American College of Cardiology 216 20359594
2018 Isogenic Pairs of hiPSC-CMs with Hypertrophic Cardiomyopathy/LVNC-Associated ACTC1 E99K Mutation Unveil Differential Functional Deficits. Stem cell reports 55 30392975
2011 Molecular mechanism of the E99K mutation in cardiac actin (ACTC Gene) that causes apical hypertrophy in man and mouse. The Journal of biological chemistry 54 21622575
2019 Cardiac α-Actin (ACTC1) Gene Mutation Causes Atrial-Septal Defects Associated With Late-Onset Dilated Cardiomyopathy. Circulation. Genomic and precision medicine 53 31430208
2020 Use of a human embryonic stem cell model to discover GABRP, WFDC2, VTCN1 and ACTC1 as markers of early first trimester human trophoblast. Molecular human reproduction 37 32359161
2010 Reduced ACTC1 expression might play a role in the onset of congenital heart disease by inducing cardiomyocyte apoptosis. Circulation journal : official journal of the Japanese Circulation Society 34 20962418
2013 Exome sequencing identifies a novel variant in ACTC1 associated with familial atrial septal defect. The Canadian journal of cardiology 28 24461919
2014 The dilated cardiomyopathy-causing mutation ACTC E361G in cardiac muscle myofibrils specifically abolishes modulation of Ca(2+) regulation by phosphorylation of troponin I. Biophysical journal 25 25418306
2013 Mechanical and energetic properties of papillary muscle from ACTC E99K transgenic mouse models of hypertrophic cardiomyopathy. American journal of physiology. Heart and circulatory physiology 25 23604709
2017 Variable cardiac α-actin (Actc1) expression in early adult skeletal muscle correlates with promoter methylation. Biochimica et biophysica acta. Gene regulatory mechanisms 24 28847732
1989 The cardiac actin locus (Actc-1) is not on mouse chromosome 17 but is linked to beta 2-microglobulin on chromosome 2. Genomics 23 2570027
2016 Impact of apoptotic circulating tumor cells (aCTC) in metastatic breast cancer. Breast cancer research and treatment 20 27696083
2016 A gain-of-function ACTC1 3'UTR mutation that introduces a miR-139-5p target site may be associated with a dominant familial atrial septal defect. Scientific reports 18 27139165
2018 Actin, alpha, cardiac muscle 1 (ACTC1) knockdown inhibits the migration of glioblastoma cells in vitro. Journal of the neurological sciences 17 30055382
2015 A Novel Alpha Cardiac Actin (ACTC1) Mutation Mapping to a Domain in Close Contact with Myosin Heavy Chain Leads to a Variety of Congenital Heart Defects, Arrhythmia and Possibly Midline Defects. PloS one 17 26061005
2013 Evaluating the association between pathological myopia and SNPs in RASGRF1. ACTC1 and GJD2 genes at chromosome 15q14 and 15q25 in a Chinese population. Ophthalmic genetics 14 23834555
2023 Variants in ACTC1 underlie distal arthrogryposis accompanied by congenital heart defects. HGG advances 12 37457373
2017 Age- and strain-related aberrant Ca2+ release is associated with sudden cardiac death in the ACTC E99K mouse model of hypertrophic cardiomyopathy. American journal of physiology. Heart and circulatory physiology 10 28887330
2020 Data on the role of cardiac α-actin (ACTC1) gene mutations on SRF-signaling. Data in brief 8 31921954
2003 alpha-cardiac actin (ACTC) binds to the band 3 (AE1) cardiac isoform. Journal of cellular biochemistry 7 12898519
2019 A cardiac α-actin (ACTC1) p. Gly247Asp mutation inhibits SRF-signaling in vitro in neonatal rat cardiomyocytes. Biochemical and biophysical research communications 5 31434612
2022 Mutational Assessment in NKX2-5 and ACTC1 Genes in Patients with Congenital Cardiac Septal Defect (CCSD) from Ethnic Kashmiri Population. International journal of environmental research and public health 4 36011517
2025 LMOD2 interaction with ACTC1 regulates myogenic differentiation. BMC genomics 3 40745266
2025 ACTC1 Variants Result in Isolated and Syndromic Cardiac Phenotypes. Clinical genetics 1 40421724
2025 ACTC1 promotes tumor progression by upregulating BMP4 expression in prostate cancer. BMC cancer 1 41286808
2023 Prinzmetal angina in a child with actin gene ACTC1 mutation. Cardiology in the young 1 37489518
2025 Identification and pathological significance of variants in the promoter region of ACTC1 gene in congenital ventricular septal defect. Gene 0 40848833
2025 2-Ethylhexyl Diphenyl Phosphate Inhibited C2C12 Myoblast Differentiation by Regulating ACTC1. Journal of biochemical and molecular toxicology 0 40878268
2024 A De Novo Mutation in ACTC1 and a TTN Variant Linked to a Severe Sporadic Infant Dilated Cardiomyopathy Case. Case reports in genetics 0 39759977
2023 Variants in ACTC1 underlie distal arthrogryposis accompanied by congenital heart defects. medRxiv : the preprint server for health sciences 0 36945405