Affinage

ACTA2

Actin, aortic smooth muscle · UniProt P62736

Length
377 aa
Mass
42.0 kDa
Annotated
2026-06-09
100 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACTA2 encodes smooth muscle α-actin, the dominant actin isoform of vascular smooth muscle cells and myofibroblasts, where it provides the structural filament that supports myosin-driven contraction and cell motility (PMID:26153420, PMID:24204762). Pathogenic missense variants act largely through allosteric and dominant-negative effects on filament behavior: R258C destabilizes filaments, sensitizes them to cofilin severing, expands the G-actin pool by tighter profilin binding, and slows myosin-driven motility (PMID:26153420); R149C is additionally retained by the CCT chaperonin folding complex, lowering mutant monomer levels and reducing penetrance while enhancing aberrant formin-driven nucleation (PMID:34600884); and modeling of R179 places it at the inter-strand filament interface, consistent with its severe phenotype (PMID:26637293). Functionally, these variants drive a contractile-to-synthetic phenotypic switch in SMCs, increasing proliferation and migration while reducing contractility — a switch that is reversible by base-editing correction of R179H in iPSC-SMCs and humanized mice, and by metabolic rescue (boosting oxidative respiration with nicotinamide riboside) in R179C SMCs (PMID:40378078, PMID:40603847, PMID:34244757). Beyond its structural role, ACTA2 loss perturbs cytoskeletal signaling, reducing ERK1/2 phosphorylation in myofibroblasts and altering RhoA/Rac1 balance (PMID:24204762). ACTA2 transcription is repressed by the purine-rich element binding protein Purβ, which binds the purine-rich strand of the promoter MCAT cis-element as a homodimer through electrostatic and hydrophobic ssDNA interactions and recruits the corepressor YBX1 (PMID:23724822, PMID:27064749), and is epigenetically tuned by histone H4 acetylation at its promoter and by H3K27 trimethylation that mediates sustained angiotensin II-induced silencing (PMID:25853442, PMID:35360022). In some cell types Acta2 is functionally dispensable, as cardiac fibroblast-specific deletion is compensated by upregulation of other actin isoforms (PMID:36007455).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1990 High

    Established the genomic location of the vascular smooth muscle actin gene, providing the foundation for linking ACTA2 to human disease loci.

    Evidence Southern blot of somatic cell hybrids and chromosomal in situ hybridization

    PMID:2398629

    Open questions at the time
    • No functional or mechanistic characterization
    • Does not address protein-level activity
  2. 2013 High

    Resolved how ACTA2 transcription is held in check, showing Purβ homodimers cooperatively bind the purine-rich strand of the MCAT promoter element and recruit YBX1 to repress expression.

    Evidence shRNA knockdown, promoter-reporter assays, recombinant truncation mutants, and biophysical ssDNA binding in fibroblasts

    PMID:23724822

    Open questions at the time
    • Repression characterized in fibroblasts, not vascular SMCs
    • Physiological signals controlling Purβ occupancy not defined
  3. 2013 Medium

    Demonstrated that ACTA2 is functionally required for myofibroblast motility and contraction independent of other actin isoforms, and unexpectedly modulates MAPK signaling.

    Evidence Multiple knockdown approaches with motility/contraction assays and ERK1/2 Western blot in hepatic stellate cells plus liver injury model

    PMID:24204762

    Open questions at the time
    • Mechanism linking ACTA2 to ERK1/2 phosphorylation unresolved
    • Single lab
  4. 2013 Medium

    Extended ACTA2's role beyond contraction to cancer cell metastasis, showing it is required for migration, invasion, and transendothelial penetration in lung adenocarcinoma.

    Evidence shRNA/siRNA knockdown with in vitro invasion assays and in vivo metastasis model, c-MET/FAK Western blot

    PMID:23995859

    Open questions at the time
    • Whether c-MET/FAK changes are direct or downstream of motility loss unclear
    • Single lab
  5. 2015 High

    Defined the molecular pathophysiology of a TAAD-causing variant, showing R258C destabilizes filaments and impairs myosin force generation through allosteric effects rather than direct contacts at the mutated residue.

    Evidence TIRF single-filament assays, in vitro motility, cofilin severing and profilin binding with baculovirus-expressed recombinant protein

    PMID:26153420

    Open questions at the time
    • Allosteric structural basis not resolved atomically
    • Single variant studied in reconstitution
  6. 2015 Medium

    Connected histone acetylation to ACTA2 induction, showing TGF-β2 increases H4 acetylation at the promoter and HDAC inhibition blocks ACTA2 upregulation and EMT.

    Evidence ChIP for H4 acetylation at the ACTA2 promoter with TSA treatment and migration assays in lens epithelial cells

    PMID:25853442

    Open questions at the time
    • Specific HAT/HDAC enzymes not identified
    • Limited follow-up, single lab
  7. 2016 High

    Resolved the chemical basis of Purβ repression to specific basic residues mediating ssDNA contacts and YBX1 corepressor binding.

    Evidence Site-directed mutagenesis of R267/K82/R159 with quantitative ssDNA binding titrations and promoter-reporter assays

    PMID:27064749

    Open questions at the time
    • In vivo relevance of individual residues not tested
    • Single lab
  8. 2016 Medium

    Placed ACTA2 downstream of a receptor signaling cascade, showing EGFR/HER2 dimerization induces ACTA2 via JAK2/STAT1 to drive breast cancer cell motility and metastasis.

    Evidence HER2 overexpression, JAK2/STAT1 pharmacological inhibition, STAT1 overexpression, ACTA2 shRNA and in vivo metastasis model

    PMID:28881584

    Open questions at the time
    • Direct STAT1 binding at ACTA2 promoter not demonstrated
    • Single lab
  9. 2018 Medium

    Tested the in vivo consequence of ACTA2 loss under hemodynamic stress, showing knockout mice develop AngII-induced aortic dilation with VSMC apoptosis and phenotypic modulation.

    Evidence ACTA2 knockout mice with AngII infusion, ultrasound, TUNEL apoptosis and OPN/Bax-Bcl2 analysis

    PMID:30233845

    Open questions at the time
    • No baseline phenotype, mechanism of stress sensitivity unclear
    • Limited mechanistic depth
  10. 2020 Low

    Linked ACTA2 to RhoA/Rac1 GTPase balance in neural stem cell migration.

    Evidence siRNA knockdown in primary NSCs with migration assay and RhoA/Rac1 expression analysis

    PMID:32508931

    Open questions at the time
    • Signaling inferred from expression changes rather than epistasis
    • Single knockdown approach
  11. 2021 High

    Explained reduced penetrance of a common variant by showing R149C is retained in the CCT chaperonin, lowering functional mutant levels while still perturbing filament organization.

    Evidence CRISPR knock-in mouse, CCT-binding retention assay, in vitro motility, TIRF nucleation assay and aortic contraction

    PMID:34600884

    Open questions at the time
    • How CCT retention varies across variants not generalized
    • Quantitative threshold for pathogenicity undefined
  12. 2021 Medium

    Provided patient-derived functional evidence that ACTA2 mutations directly impair SMC contractility and migration and reduce SMAD2 phosphorylation.

    Evidence Fibroblast transdifferentiation to SMC-like cells with cytoskeletal, TGFβ/SMAD2 and migration/contraction assays

    PMID:34244757

    Open questions at the time
    • Link between actin defect and SMAD2 signaling unresolved
    • Single lab
  13. 2022 High

    Revealed cell-type-specific dispensability, showing cardiac fibroblast-specific Acta2 deletion is tolerated through compensatory upregulation of other actin isoforms.

    Evidence Tamoxifen-inducible cardiac fibroblast-specific knockout with post-MI functional readouts and RT-qPCR for actin isoforms

    PMID:36007455

    Open questions at the time
    • Whether vascular SMCs mount similar compensation untested
    • Trigger of isoform compensation unknown
  14. 2022 Medium

    Identified an epigenetic 'vascular memory' mechanism in which transient AngII causes sustained ACTA2 silencing via H3K27me3 and reduced myocardin.

    Evidence Mouse AngII infusion with post-infusion follow-up, RNAseq, H3K27me3 immunostaining, replicated in human aortic VSMCs

    PMID:35360022

    Open questions at the time
    • Methyltransferase responsible not identified
    • Causal role of H3K27me3 correlative
  15. 2023 Medium

    Showed that abnormally elevated ACTA2, not only its loss, is pathogenic, driving hyperactive contraction in aganglionic Hirschsprung bowel.

    Evidence Immunohistochemistry in HSCR patients and Ednrb−/− mice with siRNA knockdown and contraction assay in intestinal SMCs

    PMID:37278766

    Open questions at the time
    • Upstream cause of ACTA2 elevation undefined
    • Single lab
  16. 2024 Medium

    Established a dominant-negative mechanism for TAAD-associated missense variants using a heterologous system, showing heterozygous mutant ACTA2 disrupts actin organization and mitochondrial distribution.

    Evidence S. cerevisiae heterozygous expression with spot growth and fluorescence microscopy of actin and mitochondria

    PMID:38486025

    Open questions at the time
    • Yeast system may not capture mammalian SMC context
    • Mechanism of mitochondrial mispositioning unclear
  17. 2025 High

    Demonstrated reversibility of the disease phenotype, showing base-editing correction of R179H prevents the contractile-to-synthetic switch in iPSC-SMCs and rescues multi-organ pathology in humanized mice.

    Evidence iPSC-derived SMC differentiation, CRISPR adenine base editing, AAV9 in vivo delivery and humanized knock-in mouse rescue

    PMID:40378078

    Open questions at the time
    • Durability and off-target profile of in vivo editing not fully defined
    • Single variant corrected
  18. 2025 High

    Linked the ACTA2-mutant phenotype to metabolic state, showing R179C SMCs fail to differentiate and rely on glycolysis, with oxidative-respiration boosting (nicotinamide riboside) restoring differentiation and preventing occlusive lesions.

    Evidence SMC-specific knock-in mouse with carotid injury, metabolic flux assays and nicotinamide riboside rescue

    PMID:40603847

    Open questions at the time
    • Mechanism coupling actin mutation to glycolytic shift unresolved
    • Single variant studied

Open questions

Synthesis pass · forward-looking unresolved questions
  • How specific ACTA2 variants are mechanistically partitioned between loss-of-function, dominant-negative filament interference, and chaperonin-mediated reduction — and how these map onto the divergent vascular, cerebrovascular, gut, and bladder phenotypes — remains unresolved.
  • No unifying genotype-mechanism-phenotype framework across variants
  • Structural basis of allosteric defects not resolved atomically
  • Coupling between cytoskeletal defects and metabolic/signaling reprogramming undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005856 cytoskeleton 3 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-397014 Muscle contraction 3 R-HSA-1266738 Developmental Biology 2
Partners
CCTCFL (COFILIN)MYH11PFN (PROFILIN)TPM (SMOOTH MUSCLE TROPOMYOSIN)
Complex memberships
CCT/TCP1 chaperonin (transient client)

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 The R258C mutation in smooth muscle α-actin (SM α-actin, ACTA2) disrupts actin filament stability: R258C filaments are less stable than WT, more susceptible to severing by cofilin, and smooth muscle tropomyosin provides little protection from cofilin cleavage of mutant filaments. Profilin binds tighter to the R258C monomer, increasing the pool of G-actin. In an in vitro motility assay, smooth muscle myosin moves R258C filaments more slowly than WT, and under loaded conditions small ensembles of myosin are unable to produce force on R258C actin-tropomyosin filaments, suggesting tropomyosin occupies an inhibitory position on mutant actin. These defects are allosteric—many cannot be explained by direct interaction with the mutated residue. TIRF microscopy (single-filament growth assay), in vitro motility assay, baculovirus-expressed recombinant protein, cofilin severing assay, profilin-binding assay Proceedings of the National Academy of Sciences of the United States of America High 26153420
2021 The common ACTA2 variant p.Arg149Cys (R149C) causes increased retention of mutant SM α-actin in the chaperonin-containing TCP1 (CCT) folding complex, reducing the amount of mutant protein that reaches functional levels in smooth muscle cells. This explains reduced penetrance: enhanced CCT binding lowers mutant monomer levels, minimizing its effect on SMC function. In vitro motility assays confirmed decreased interaction of R149C mutant filaments with SM myosin. TIRF microscopy showed enhanced nucleation of R149C SM α-actin by formin, correlating with disorganized and reduced actin filaments in Acta2R149C/+ SMCs. CRISPR/Cas9 knock-in mouse model, in vitro motility assay, TIRF microscopy, chaperonin-binding retention assay, aortic contraction assay The Journal of biological chemistry High 34600884
2025 The ACTA2 R179H pathogenic variant causes a dramatic phenotypic switch in human iPSC-derived smooth muscle cells from a contractile to a synthetic state, associated with increased proliferation and migration and reduced contractility. CRISPR adenine base editing (ABE8e-SpCas9-VRQR) correcting R179H prevented this phenotypic switch and restored normal SMC function in vitro. In humanized R179H mice, in vivo AAV9-delivered base editing rescued aortic dilation/dissection, bladder enlargement, gut dilation, and hydronephrosis. iPSC-derived SMC differentiation, CRISPR adenine base editing, AAV9 in vivo delivery, functional contractility/migration/proliferation assays, humanized knock-in mouse model Circulation High 40378078
2025 SMCs carrying the Acta2 R179C mutation fail to fully differentiate and maintain stem cell-like features including increased migration and elevated glycolytic flux compared to WT SMCs. Boosting mitochondrial oxidative respiration with nicotinamide riboside (NR) drives differentiation and decreases migration of mutant SMCs. In an Acta2SMC-R179C/+ mouse carotid injury model, mutant mice develop intraluminal SMC accumulation causing moyamoya-like occlusive lesions, neurological symptoms, and neuron loss; NR treatment prevents all of these phenotypes. SMC-specific knock-in mouse model, carotid artery injury, nicotinamide riboside treatment, migration/differentiation/metabolic flux assays, histology, neurological scoring Nature communications High 40603847
2013 Purine-rich element binding protein B (Purβ) represses ACTA2 transcription by cooperatively binding the sense (purine-rich) strand of the ACTA2 5′ promoter-enhancer MCAT cis-element as a homodimer with three separate ssDNA-binding modules formed by inter- and intramolecular subdomain interactions. Purβ knockdown in mouse embryo fibroblasts promoted myofibroblast-like morphology, increased ACTA2 expression (confirmed by promoter-reporter assay), and increased cell migration. Discrete Purβ subdomains mediating ssDNA binding, protein-protein interaction with corepressor YBX1, and ACTA2 enhancer inhibition were mapped. shRNA stable knockdown, promoter-reporter assay, recombinant truncation mutants, biochemical/biophysical ssDNA binding assays, computational structural modeling Biochemistry High 23724822
2016 Purβ represses ACTA2 transcription through electrostatic and hydrophobic interactions with the purine-rich ssDNA of the MCAT element in the Acta2 promoter. Site-directed mutagenesis of basic residues R267 (intermolecular subdomain) and K82/R159 (intramolecular subdomains) reduced both ssDNA binding affinity and Acta2 repressor activity in fibroblast promoter-reporter assays. R267A mutation additionally impaired binding to the Acta2 corepressor YBX1. Site-directed mutagenesis, quantitative ssDNA binding assays (salt/pH/detergent titration), promoter-reporter assay in fibroblasts, purified recombinant Purβ variants Biochemistry High 27064749
2013 ACTA2 is required for myofibroblast cell motility and contraction in hepatic stellate cells. Inhibition of Acta2 by multiple knockdown techniques reduced cellular motility and contraction without affecting other cytoplasmic actin isoforms. Acta2 knockdown was also associated with a significant reduction in ERK1/2 phosphorylation, indicating ACTA2 regulates signaling (MAPK pathway) in addition to its structural role. In vitro wound healing and contraction assays, siRNA/shRNA knockdown, ERK1/2 phosphorylation (Western blot), in vivo liver injury model PloS one Medium 24204762
2022 Cardiac fibroblast-specific deletion of Acta2 does not prevent myofibroblast differentiation or impair post-MI cardiac repair. Acta2-null cardiac myofibroblasts show normal proliferation, migration, and contractility and a normal total filamentous actin level because deletion triggers compensatory transcriptional upregulation of non-Acta2 actin isoforms (particularly Actg2 and Acta1). MRTF-A is critical for myofibroblast differentiation but is not required for this compensatory response. Tamoxifen-inducible cardiac fibroblast-specific Acta2 knockout mouse, post-MI survival/histology/function, proliferation/migration/contractility assays, RT-qPCR for actin isoforms Journal of molecular and cellular cardiology High 36007455
2015 TGF-β2 treatment of lens epithelial cells increases histone H4 acetylation specifically at the ACTA2 promoter region (assessed by ChIP), correlating with increased ACTA2 mRNA and protein expression and EMT. The HDAC inhibitor trichostatin-A (TSA) suppresses TGF-β2-induced ACTA2 upregulation and EMT while globally elevating acetylated H4 (but reducing H4 acetylation at the ACTA2 promoter under TGF-β2 stimulation). Chromatin immunoprecipitation (ChIP) for H4 acetylation at ACTA2 promoter, RT-qPCR/Western blot for ACTA2, TSA treatment, cell migration assay Eye (London, England) Medium 25853442
2016 EGFR/HER2 dimerization induces ACTA2 expression through a JAK2/STAT1 signaling pathway in breast cancer cells. HER2 overexpression increases both STAT1 and ACTA2 protein levels; STAT1 inhibition (fludarabine) or JAK2 inhibition (AG490) decreases basal ACTA2 expression, and STAT1 overexpression increases ACTA2. ACTA2 knockdown suppresses cell motility in vitro and reduces lung metastatic nodules in vivo. HER2 transient/stable overexpression, siRNA knockdown, JAK2/STAT1 inhibitors, ACTA2 shRNA, in vivo mouse lung metastasis model Oncotarget Medium 28881584
2013 ACTA2 expression in lung adenocarcinoma cells is required for metastatic potential: ACTA2 knockdown impairs in vitro migration, invasion, clonogenicity, and transendothelial penetration without affecting proliferation, and reduces in vivo metastatic potential. ACTA2 downregulation reduces c-MET and FAK expression in lung adenocarcinoma cells and is accompanied by loss of mesenchymal characteristics. shRNA/siRNA knockdown of ACTA2, in vitro migration/invasion/transendothelial assays, in vivo metastasis model (PC14PE6 cells), Western blot for c-MET and FAK Clinical cancer research Medium 23995859
2018 Deletion of ACTA2 in mice promotes angiotensin II-induced aortic lumen dilation, with increased expression of osteopontin (OPN), elevated Bax/Bcl-2 ratio, increased VSMC apoptosis, and phenotypic modulation of VSMCs compared to WT mice receiving AngII. Baseline ACTA2 knockout mice had no severe vascular phenotype. ACTA2 knockout mouse model, AngII osmotic minipump infusion, ultrasound lumen measurement, RT-qPCR/Western blot, TUNEL apoptosis assay, immunohistochemistry Journal of thoracic disease Medium 30233845
2020 ACTA2 downregulation in neural stem cells (NSCs) inhibits migration by impeding actin filament polymerization via increased RhoA expression and decreased Rac1 expression, placing ACTA2 upstream of RhoA/Rac1 GTPase balance in NSC cytoskeletal regulation. siRNA knockdown of ACTA2 in primary NSCs, migration assay, RT-PCR/immunostaining for ACTA2, RhoA/Rac1 expression analysis Stem cells international Low 32508931
2021 ACTA2 pathogenic variants (ACTA2, MYH11) in transdifferentiated VSMC-like cells show impaired migration velocity and reduced contractility (ACTA2) and decreased SMAD2 phosphorylation in ACTA2 cells, providing functional evidence that ACTA2 mutations directly impair SMC contractile and migratory function. Fibroblast transdifferentiation to SMC-like cells, cytoskeletal integrity assessment, TGFβ signaling (SMAD2 phosphorylation) assay, migration velocity assay, contraction assay Human molecular genetics Medium 34244757
2024 Novel ACTA2 missense variants associated with TAAD act through a dominant-negative mechanism on yeast actin, disrupting actin cytoskeletal organization and mitochondrial distribution. Wild-type yeast expressing heterozygous mutant ACTA2 alleles showed significant increases in cells with abnormal mitochondrial distribution and abnormal actin cytoskeleton organization, consistent with dominant-negative interference with WT actin function. S. cerevisiae heterozygous expression assay, spot growth test, fluorescence microscopy of actin cytoskeleton and mitochondrial morphology European journal of human genetics Medium 38486025
2015 3D molecular modeling of the actin filament structure revealed that the R179 residue is positioned at the interface between the two strands of filamentous actin, and the R179H mutation destabilizes inter-strand bundling, providing a structural explanation for the severe vascular phenotype associated with this mutation. Actin three-dimensional molecular modeling (computational structural analysis), correlated with histopathological findings in patient tissue Acta neuropathologica communications Low 26637293
1990 The vascular smooth muscle actin gene (ACTSA/ACTA2) was assigned to human chromosome 10, specifically the long arm at q22-q24, by Southern blot analysis of rodent-human somatic cell hybrids and in situ hybridization. Southern blot of somatic cell hybrids, chromosomal in situ hybridization Jinrui idengaku zasshi. The Japanese journal of human genetics High 2398629
2022 Transient angiotensin II infusion causes sustained downregulation of ACTA2 (α-smooth muscle actin) in aortic tissue beyond AngII withdrawal, associated with increased H3K27me3 at aortic nuclei and decreased myocardin (MYOCD) expression, indicating epigenetic silencing of ACTA2 as a 'vascular memory' mechanism. This was reproduced in cultured human aortic VSMCs. Mouse AngII infusion model with post-infusion follow-up, RNAseq aortic profiling, RT-qPCR/immunohistochemistry validation, H3K27me3 immunostaining, human VSMC cell culture Frontiers in cardiovascular medicine Medium 35360022
2023 In Hirschsprung disease (HSCR) aganglionic segments, ACTA2 expression is abnormally elevated specifically in circular smooth muscle beginning at embryonic day E15.5 in Ednrb−/− mice. siRNA knockdown of Acta2 in intestinal smooth muscle cells (iSMCs) weakens their contraction ability, demonstrating that elevated ACTA2 directly drives hyperactive contraction in aganglionic bowel. Immunohistochemistry in HSCR patients and Ednrb−/− mice, siRNA knockdown of Acta2 in iSMCs, contraction functional assay Pediatric surgery international Medium 37278766
2014 RHOA knockdown significantly downregulates ACTA2 gene expression in both osteoblast-like and osteoclast-like cells, placing RHOA upstream of ACTA2 in a bone cell regulatory pathway. siRNA knockdown of RHOA, microarray analysis, qRT-PCR validation in multiple human bone cell lines PloS one Low 24840563

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease. American journal of human genetics 425 19409525
2010 De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction. American journal of medical genetics. Part A 210 20734336
2013 Smooth muscle α actin (Acta2) and myofibroblast function during hepatic wound healing. PloS one 152 24204762
2011 Novel MYH11 and ACTA2 mutations reveal a role for enhanced TGFβ signaling in FTAAD. International journal of cardiology 130 21937134
2015 Aortic Disease Presentation and Outcome Associated With ACTA2 Mutations. Circulation. Cardiovascular genetics 117 25759435
2017 Human lung branching morphogenesis is orchestrated by the spatiotemporal distribution of ACTA2, SOX2, and SOX9. American journal of physiology. Lung cellular and molecular physiology 114 28971977
2013 Alpha-smooth muscle actin (ACTA2) is required for metastatic potential of human lung adenocarcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 110 23995859
2012 A novel distinctive cerebrovascular phenotype is associated with heterozygous Arg179 ACTA2 mutations. Brain : a journal of neurology 104 22831780
2014 An α-smooth muscle actin (acta2/αsma) zebrafish transgenic line marking vascular mural cells and visceral smooth muscle cells. PloS one 83 24594685
2009 Mutation of ACTA2 gene as an important cause of familial and nonfamilial nonsyndromatic thoracic aortic aneurysm and/or dissection (TAAD). Human mutation 80 19639654
2019 The estrogen-regulated lncRNA H19/miR-216a-5p axis alters stromal cell invasion and migration via ACTA2 in endometriosis. Molecular human reproduction 70 31323679
2011 Risk of dissection in thoracic aneurysms associated with mutations of smooth muscle alpha-actin 2 (ACTA2). Heart (British Cardiac Society) 63 21212136
2015 Vascular disease-causing mutation R258C in ACTA2 disrupts actin dynamics and interaction with myosin. Proceedings of the National Academy of Sciences of the United States of America 55 26153420
2012 R179H mutation in ACTA2 expanding the phenotype to include prune-belly sequence and skin manifestations. American journal of medical genetics. Part A 51 22302747
2021 Long non-coding RNA ACTA2-AS1 promotes ductular reaction by interacting with the p300/ELK1 complex. Journal of hepatology 45 34953958
2016 Dimerization of EGFR and HER2 induces breast cancer cell motility through STAT1-dependent ACTA2 induction. Oncotarget 42 28881584
2015 The defining pathology of the new clinical and histopathologic entity ACTA2-related cerebrovascular disease. Acta neuropathologica communications 39 26637293
2010 Analysis of ACTA2 in European Moyamoya disease patients. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 37 20970362
2011 Three novel mutations in the ACTA2 gene in German patients with thoracic aortic aneurysms and dissections. European journal of human genetics : EJHG 31 21248741
2013 ACTA2 mutation with childhood cardiovascular, autonomic and brain anomalies and severe outcome. American journal of medical genetics. Part A 30 23613326
2023 ACTA2 Expression Predicts Survival and Is Associated with Response to Immune Checkpoint Inhibitors in Gastric Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 29 36508166
2020 A novel mechanism by which ACTA2-AS1 promotes cervical cancer progression: acting as a ceRNA of miR-143-3p to regulate SMAD3 expression. Cancer cell international 28 32774166
2020 Cerebrovascular Disease Progression in Patients With ACTA2 Arg179 Pathogenic Variants. Neurology 28 33199432
2023 USP51/ZEB1/ACTA2 axis promotes mesenchymal phenotype in gastric cancer and is associated with low cohesion characteristics. Pharmacological research 26 36603607
2020 ACTA2-AS1 suppresses lung adenocarcinoma progression via sequestering miR-378a-3p and miR-4428 to elevate SOX7 expression. Cell biology international 25 32808728
2022 Loss of Acta2 in cardiac fibroblasts does not prevent the myofibroblast differentiation or affect the cardiac repair after myocardial infarction. Journal of molecular and cellular cardiology 24 36007455
2019 European reference network for rare vascular diseases (VASCERN) consensus statement for the screening and management of patients with pathogenic ACTA2 variants. Orphanet journal of rare diseases 24 31752940
2014 Congenital fixed dilated pupils due to ACTA2- multisystemic smooth muscle dysfunction syndrome. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society 24 24621862
2018 Deletion of ACTA2 in mice promotes angiotensin II induced pathogenesis of thoracic aortic aneurysms and dissections. Journal of thoracic disease 23 30233845
2018 Expanding the Distinctive Neuroimaging Phenotype of ACTA2 Mutations. AJNR. American journal of neuroradiology 23 30262641
2018 ACTA2 Cerebral Arteriopathy: Not Just a Puff of Smoke. Cerebrovascular diseases (Basel, Switzerland) 23 30300893
2012 Neonatal stroke and progressive leukoencephalopathy in a child with an ACTA2 mutation. Journal of child neurology 23 22752479
2022 Knockdown of lncRNA ACTA2-AS1 reverses cisplatin resistance of ovarian cancer cells via inhibition of miR-378a-3p-regulated Wnt5a. Bioengineered 21 35412951
2014 Influence of ARHGEF3 and RHOA knockdown on ACTA2 and other genes in osteoblasts and osteoclasts. PloS one 21 24840563
2020 Actin Alpha 2 (ACTA2) Downregulation Inhibits Neural Stem Cell Migration through Rho GTPase Activation. Stem cells international 20 32508931
2022 Long non-coding RNA ACTA2-AS1 inhibits the cisplatin resistance of non-small cell lung cancer cells through inhibiting autophagy by suppressing TSC2. Cell cycle (Georgetown, Tex.) 19 34985374
2019 Knockdown of ACTA2‑AS1 promotes liver cancer cell proliferation, migration and invasion. Molecular medicine reports 19 30664183
2017 Transdifferentiation of Human Dermal Fibroblasts to Smooth Muscle-Like Cells to Study the Effect of MYH11 and ACTA2 Mutations in Aortic Aneurysms. Human mutation 19 28074631
2013 Cerebral arteriopathy associated with Arg179His ACTA2 mutation. Journal of neurointerventional surgery 19 24353327
2015 Progressive Aortic Dilation Associated With ACTA2 Mutations Presenting in Infancy. Pediatrics 18 26034244
2016 Indirect and direct revascularization of ACTA2 cerebral arteriopathy: feasibility of the superficial temporal artery to anterior cerebral artery bypass with posterior auricular artery interposition graft: case report. Journal of neurosurgery. Pediatrics 17 27176728
2015 Association of histone acetylation at the ACTA2 promoter region with epithelial mesenchymal transition of lens epithelial cells. Eye (London, England) 17 25853442
2014 Congenital mydriasis and prune belly syndrome in a child with an ACTA2 mutation. Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus 17 24998021
1990 Assignment of the vascular smooth muscle actin gene ACTSA to human chromosome 10. Jinrui idengaku zasshi. The Japanese journal of human genetics 16 2398629
2021 LncRNA ACTA2-AS1 suppress colon adenocarcinoma progression by sponging miR-4428 upregulation BCL2L11. Cancer cell international 15 33845844
2014 Twins with progressive thoracic aortic aneurysm, recurrent dissection and ACTA2 mutation. Pediatrics 15 25225139
2013 Structural basis of multisite single-stranded DNA recognition and ACTA2 repression by purine-rich element binding protein B (Purβ). Biochemistry 15 23724822
2016 Cerebral arteriopathy associated with heterozygous Arg179Cys mutation in the ACTA2 gene: Report in 2 newborn siblings. Brain & development 14 27567161
2013 Cerebral arteriopathy associated with Arg179His ACTA2 mutation. BMJ case reports 14 24293535
2021 Tmem100- and Acta2-Lineage Cells Contribute to Implant Osseointegration in a Mouse Model. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 13 33528844
2013 Iris Flocculi as an ocular marker of ACTA2 mutation in familial thoracic aortic aneurysms and dissections. Ophthalmic genetics 13 24020716
2020 High-resolution iris and retinal imaging in multisystemic smooth muscle dysfunction syndrome due to a novel Asn117Lys substitution in ACTA2: a case report. BMC ophthalmology 12 32093627
2018 Iris anomalies and the incidence of ACTA2 mutation. The British journal of ophthalmology 12 29875232
2024 Long non-coding RNA ACTA2-AS1 suppresses metastasis of papillary thyroid cancer via regulation of miR-4428/KLF9 axis. Clinical epigenetics 11 38195623
2021 Mechanism underlying the regulation of lncRNA ACTA2-AS1 on CXCL2 by absorbing miRNA-532-5p as ceRNA in the development of ovarian cancer. International journal of clinical and experimental pathology 11 34093945
2021 Identification of ACTA2 as a Key Contributor to Venous Malformation. Frontiers in cell and developmental biology 11 34858981
2020 A Potential Theragnostic Regulatory Axis for Arthrofibrosis Involving Adiponectin (ADIPOQ) Receptor 1 and 2 (ADIPOR1 and ADIPOR2), TGFβ1, and Smooth Muscle α-Actin (ACTA2). Journal of clinical medicine 11 33213041
2012 Brachial artery occlusion in a young adult with an ACTA2 thoracic aortic aneurysm. Vascular medicine (London, England) 11 22946110
2022 Colonic healing requires Wnt produced by epithelium as well as Tagln+ and Acta2+ stromal cells. Development (Cambridge, England) 10 34910127
2017 Two patients with the heterozygous R189H mutation in ACTA2 and Complex congenital heart defects expands the cardiac phenotype of multisystemic smooth muscle dysfunction syndrome. American journal of medical genetics. Part A 10 28328125
2011 Renal FMD may not confer a familial hypertensive risk nor is it caused by ACTA2 mutations. Pediatric nephrology (Berlin, Germany) 10 21553326
2021 Molecular phenotyping and functional assessment of smooth muscle-like cells with pathogenic variants in aneurysm genes ACTA2, MYH11, SMAD3 and FBN1. Human molecular genetics 9 34244757
2021 Resistance of Acta2R149C/+ mice to aortic disease is associated with defective release of mutant smooth muscle α-actin from the chaperonin-containing TCP1 folding complex. The Journal of biological chemistry 9 34600884
2018 Novel variants in the ACTA2 and MYH11 genes in a Cypriot family with thoracic aortic aneurysms: a case report. BMC medical genetics 9 30526509
2022 lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells. Open medicine (Warsaw, Poland) 8 35274046
2014 Correlation between single nucleotide polymorphisms of the ACTA2 gene and coronary artery stenosis in patients with type 2 diabetes mellitus. Experimental and therapeutic medicine 8 24669260
2021 ACTA2 mutation is responsible for multisystemic smooth muscle dysfunction syndrome with seizures: A case report and review of literature. World journal of clinical cases 7 34734057
2021 ACTA2-Related Dysgyria: An Under-Recognized Malformation of Cortical Development. AJNR. American journal of neuroradiology 7 34857515
2020 Dysregulated epidermal growth factor and tumor growth factor-beta receptor signaling through GFAP-ACTA2 protein interaction in liver fibrosis. Pakistan journal of medical sciences 7 32494274
2017 ACTA2 mutation and postpartum hemorrhage: a case report. BMC medical genetics 7 29202781
2024 Cardiac manifestations of human ACTA2 variants recapitulated in a zebrafish model. Journal of human genetics 6 38316882
2022 Overexpression of long non-coding RNA ACTA2-AS1 inhibits the viability, proliferation, migration and invasion of colorectal cancer cells. Tissue & cell 6 35325674
2022 Sustained Downregulation of Vascular Smooth Muscle Acta2 After Transient Angiotensin II Infusion: A New Model of "Vascular Memory". Frontiers in cardiovascular medicine 6 35360022
2021 Cerebral arteriopathy in ACTA2 mutations: a spectrum of disease highlighted by a case of variable penetrance in two siblings. Journal of neurosurgery. Pediatrics 6 33513575
2017 Search for genetic factors in bicuspid aortic valve disease: ACTA2 mutations do not play a major role. Interactive cardiovascular and thoracic surgery 6 29049801
2016 Electrostatic and Hydrophobic Interactions Mediate Single-Stranded DNA Recognition and Acta2 Repression by Purine-Rich Element-Binding Protein B. Biochemistry 6 27064749
2023 Long Noncoding RNA ACTA2-AS1 Inhibits Cell Growth and Facilitates Apoptosis in Gastric Cancer by Binding with miR-6720-5p to Regulate ESRRB. Biochemical genetics 5 37222961
2023 Abnormally elevated expression of ACTA2 of circular smooth muscle leads to hyperactive contraction in aganglionic segments of HSCR. Pediatric surgery international 5 37278766
2022 Familial acute aortic dissection associated with a novel ACTA2 germline variant. Virchows Archiv : an international journal of pathology 5 35896809
2019 Characteristic Cerebrovascular Findings Associated with ACTA2 Gene Mutations. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 5 30975232
2025 Genomic Editing of a Pathogenic Sequence Variant in ACTA2 Rescues Multisystemic Smooth Muscle Dysfunction Syndrome in Mice. Circulation 4 40378078
2025 Human Amniotic Epithelial Stem Cell Exosomes Regulate Chondrocyte Ferroptosis through ACTA2-AS1-Targeted Binding to ACSL4 for Osteoarthritis Intervention. Research (Washington, D.C.) 4 40785968
2023 A highly penetrant ACTA2 mutation of thoracic aortic disease. Journal of cardiothoracic surgery 4 38044429
2022 Expanding the genetic and phenotypic spectrum of ACTA2-related vasculopathies in a Dutch cohort. Genetics in medicine : official journal of the American College of Medical Genetics 4 36053285
2021 The natural history of a family with aortic dissection associated with a novel ACTA2 variant. Annals of vascular surgery 4 34437965
2020 ACTA2 leukovasculopathy: A rare pediatric white matter disorder. Radiology case reports 4 32595813
2020 Refractory cerebral infarction in a child with an ACTA2 mutation. Brain & development 4 33342581
2023 Neonatal diagnosis of ACTA2-related disease: A case report and review of literature. American journal of medical genetics. Part A 3 36607831
2020 Aneurysmal Dilatation of Ductus Arteriosus and Pulmonary Artery in Association With ACTA2 Mutation. World journal for pediatric & congenital heart surgery 3 32452246
2025 Immature Acta2R179C/+ smooth muscle cells cause moyamoya-like cerebrovascular lesions in mice prevented by boosting OXPHOS. Nature communications 2 40603847
2023 Augmenting Mitochondrial Respiration in Immature Smooth Muscle Cells with an ACTA2 Pathogenic Variant Mitigates Moyamoya-like Cerebrovascular Disease. Research square 2 37886459
2022 Triple bypass for multisystem smooth muscle dysfunction syndrome due to Arg179His ACTA2 mutation. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 2 35248443
2022 Clinical and neuroimaging features of a familial pathogenic ACTA2 variant as a model of a vascular neurocristopathy. Neuroradiology 2 35420309
2020 Expanding the cerebrovascular phenotype of the p.R258H variant in ACTA2 related hereditary thoracic aortic disease (HTAD). Journal of the neurological sciences 2 32464348
2017 Management of Bilateral Axillary Aneurysms, Threatened Limb, and Diffuse Vasculopathy in a Patient With ACTA2 Mutation. The Canadian journal of cardiology 2 28343608
2009 [Cloning and expression analysis of porcine ACTA2 gene and its association with production traits]. Yi chuan = Hereditas 2 19586843
2024 A yeast based assay establishes the pathogenicity of novel missense ACTA2 variants associated with aortic aneurysms. European journal of human genetics : EJHG 1 38486025
2023 Aortic Dissection and a Previously Unreported ACTA2 Missense Variant Mutation in a Young Patient: A Case Report. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 1 37672683
2021 Nonsurgical treatment of cerebral ischemia associated with ACTA2 cerebral arteriopathy: a case report and literature review. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 1 34546411
2020 ACTA2 Mutation: Microsurgeon Beware! Plastic and reconstructive surgery. Global open 1 33299681

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