Affinage

FLNC

Filamin-C · UniProt Q14315

Length
2725 aa
Mass
291.0 kDa
Annotated
2026-06-09
75 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FLNC encodes filamin C, a muscle-specific actin-binding and crosslinking protein built from an N-terminal actin-binding domain followed by 24 tandem immunoglobulin-like repeats, two hinge regions, and a paralog-unique insertion in repeat 20 (PMID:9791010). It is essential for striated muscle: loss of FLNc function blocks myoblast differentiation and fusion into elongated myotubes, and its deletion in mice causes perinatal lethality with deficient primary myogenesis and disrupted myotube integrity, partly through a TRIO-dependent pathway (PMID:16914736). At the Z-disk, filamin C anchors the dystrophin-glycoprotein complex via direct interaction with γ- and δ-sarcoglycan (PMID:10629222) and assembles a Z-band complex with IGFN1 and KY (PMID:20206623); its dimerized form is maintained at its proper location by the small heat-shock protein HSPB7, whose loss causes FLNC aggregation, mislocalization, and sarcoglycan dysregulation (PMID:26929074). Filamin C is required for adult cardiac function and sarcomere maintenance (PMID:36066120). FLNC variants produce cardiomyopathy through two distinct mechanisms: truncating and splice variants reduce protein levels, supporting a haploinsufficiency model for dilated cardiomyopathy (PMID:28008423), whereas missense variants in Ig-loop domains destabilize the protein, impair homo- and hetero-dimerization, and drive cytoplasmic aggregate formation that sequesters FLNC from the Z-disk, causing restrictive, hypertrophic, and arrhythmogenic phenotypes (PMID:26666891, PMID:29858533, PMID:34235269). These aggregates engage but overwhelm protein quality control, with dysregulation of chaperones, the ubiquitin-proteasome system, and autophagy/aggrephagy in affected muscle (PMID:23238331, PMID:38397924), and BAG3 recruitment to aggregates blocks alternative autophagic clearance (PMID:26969713). Variant-specific functional consequences extend to contractility and electrophysiology in patient iPSC-cardiomyocytes (PMID:29212899, PMID:39315490). Beyond muscle, FLNC is targeted for ubiquitination and proteasomal degradation by the MAGED2-TRIM28 E3 ligase complex (PMID:41310667) and participates in an S6K/FLNC/ITGβ3 signaling axis during osteoclastogenesis (PMID:39612888).

Mechanistic history

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

    Establishing the domain architecture defined how filamin C could function as an actin crosslinker and where muscle-specific features reside.

    Evidence cDNA cloning, RT-PCR, and sequence analysis identifying the actin-binding domain, 24 Ig-like repeats, two hinges, and a unique repeat-20 insertion

    PMID:9791010

    Open questions at the time
    • Does not assign function to the unique repeat-20 insertion
    • No structural data on dimerization or hinge flexibility
  2. 2000 Medium

    Identifying sarcoglycan partners placed filamin C within the dystrophin-glycoprotein complex and linked it to muscular dystrophy pathology.

    Evidence Yeast two-hybrid screen and immunofluorescence of patient and mouse muscle showing FLNC interaction with γ/δ-sarcoglycan and altered localization in dystrophy

    PMID:10629222

    Open questions at the time
    • Y2H interaction not biochemically reconstituted
    • Functional consequence of the interaction not tested
  3. 2006 High

    Loss-of-function in cells and mice showed filamin C is essential for myogenesis and myotube structure, not merely a passive crosslinker.

    Evidence Stable RNAi in C2C12 myoblasts and an exon-deletion knockout mouse, with epistasis comparison to TRIO-null cells

    PMID:16914736

    Open questions at the time
    • Molecular basis of the TRIO-FLNc pathway not defined
    • Mechanism linking FLNc to fusion machinery unresolved
  4. 2010 Medium

    Defining the IGFN1/KY/FLNC complex extended the Z-band interactome of filamin C beyond sarcoglycans.

    Evidence Yeast two-hybrid, co-purification, and immunofluorescence in skeletal muscle

    PMID:20206623

    Open questions at the time
    • Functional role of the complex not tested by loss-of-function
    • Stoichiometry and direct binding interfaces unknown
  5. 2016 Medium

    Multiple 2016 studies resolved the two-mechanism model of FLNC disease: haploinsufficiency from truncating/splice variants versus aggregation from missense variants.

    Evidence Patient cardiac Western blot plus zebrafish morpholino knockdown (haploinsufficiency); transfection of missense mutants in myoblasts/NIH3T3 plus patient IHC (aggregation)

    PMID:26666891 PMID:28008423

    Open questions at the time
    • Why some variants reduce protein while others aggregate not fully predictable
    • Threshold of FLNC level for cardiac dysfunction undefined
  6. 2016 High

    Reconstitution in zebrafish showed aggregate-driven Z-disk sequestration causes protein insufficiency and that BAG3 recruitment blocks autophagic clearance, identifying a tractable pathway node.

    Evidence Tagged FLNCW2710X overexpression, knockdown rescue, and BAG3 manipulation in zebrafish with immunofluorescence

    PMID:26969713

    Open questions at the time
    • Mechanism by which BAG3 blocks alternative autophagy not defined
    • Whether the same block applies to all aggregating variants untested
  7. 2016 High

    Demonstrating HSPB7 binds dimerized FLNC and is required for its localization established a chaperone safeguard against FLNC aggregation in vivo.

    Evidence Co-immunoprecipitation and muscle-specific HspB7 knockout mouse with immunofluorescence

    PMID:26929074

    Open questions at the time
    • Whether HSPB7 directly prevents aggregation or acts indirectly unclear
    • Binding interface on dimerized FLNC not mapped
  8. 2018 Medium

    Mapping Ig-loop missense variants to restrictive cardiomyopathy clarified a genotype-phenotype link distinct from haploinsufficiency.

    Evidence Transfection aggregation assays and zebrafish in vivo modeling of p.A1186V and p.A1183L

    PMID:29858533

    Open questions at the time
    • Why Ig-loop location dictates restrictive over dilated phenotype unresolved
    • No high-resolution structure of mutant Ig loops
  9. 2020 Medium

    Biochemical stability assays linked a specific missense variant to enhanced proteolytic susceptibility, grounding aggregation/insufficiency in measurable protein instability.

    Evidence Recombinant FLNC p.Pro442Arg proteolytic stability assay plus patient muscle proteomics

    PMID:32516863

    Open questions at the time
    • Single variant tested; generality across mutation classes unknown
    • Cellular degradation route not pinpointed
  10. 2021 High

    A dimerization-domain frameshift was shown to abolish homo- and hetero-dimerization, providing the molecular defect behind dominant-negative aggregation.

    Evidence Dimerization interaction and transfection assays with biophysical analysis plus proteomics of patient muscle aggregates

    PMID:34235269

    Open questions at the time
    • Whether the mutant titrates wild-type FLNC into aggregates not directly shown
    • Structural basis of dimerization failure not solved
  11. 2024 Medium

    iPSC-cardiomyocyte and structural studies refined variant-specific consequences, showing distinct electrophysiological and aggrephagy phenotypes across cardiomyopathy variants.

    Evidence Patient iPSC-cardiomyocyte calcium imaging, patch clamp, and transcriptomics (R1267Q vs V2264M); 3D modeling and patient muscle aggrephagy markers (A1186V)

    PMID:38397924 PMID:39315490

    Open questions at the time
    • Causal link from FLNC defect to Nav1.5/calcium changes not mechanistically traced
    • In vitro phenotypes not validated against patient cardiac function
  12. 2024 Medium

    Identifying non-muscle regulatory and signaling roles broadened FLNC biology to E3-ligase-controlled turnover and osteoclast signaling.

    Evidence Co-IP, ubiquitination, and degradation assays of the MAGED2-TRIM28-FLNC axis in breast cancer; transcriptomics, knockdown, S6K inhibition, and ovariectomized mouse model for the S6K/FLNC/ITGβ3 axis

    PMID:39612888 PMID:41310667

    Open questions at the time
    • Ubiquitination site and degron on FLNC not mapped
    • Whether MAGED2-TRIM28 regulates FLNC in muscle untested
    • Direct FLNC-ITGβ3 binding interface undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How distinct FLNC variant classes selectively produce dilated, restrictive, hypertrophic, or arrhythmogenic phenotypes, and how aggregate-induced quality-control failure could be therapeutically reversed, remain unresolved.
  • No unified structural model predicting phenotype from variant position
  • Mechanism converting FLNC aggregation into arrhythmic electrophysiology unknown
  • No validated intervention restoring FLNC clearance in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005856 cytoskeleton 3 GO:0005829 cytosol 2
Pathway
R-HSA-397014 Muscle contraction 3 R-HSA-9612973 Autophagy 2
Partners
BAG3HSPB7IGFN1ITGB3KYSGCDSGCGTRIM28
Complex memberships
IGFN1/KY/FLNC Z-band complexMAGED2-TRIM28 E3 ligase complexdystrophin-glycoprotein complex

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 FLNC (FLN2/filamin 2) was identified as a gamma- and delta-sarcoglycan interacting protein using yeast two-hybrid screening, establishing it as a component of the dystrophin-glycoprotein complex in skeletal muscle. FLN2 protein localization was found to be altered in limb-girdle muscular dystrophy and Duchenne muscular dystrophy patients and mice compared to unaffected individuals. Yeast two-hybrid screen, immunofluorescence localization in patient and mouse tissue The Journal of cell biology Medium 10629222
1998 Full-length FLNC (ABPL) was cloned and characterized as a 2,705 amino acid (~289 kDa) actin-binding protein containing an N-terminal actin-binding domain followed by 24 tandem immunoglobulin-like repeats, two hinge regions (Hinge I and Hinge II), and a unique 82-amino-acid insertion in repeat 20 absent in other filamin paralogues. An alternatively spliced isoform lacking Hinge I (~286 kDa) was identified by RT-PCR. cDNA cloning, RT-PCR, sequence analysis, comparison with genomic DNA Biochemical and biophysical research communications Medium 9791010
2000 The genomic structure of FLNC was determined: 48 exons and 47 introns spanning approximately 29.5 kb, with a unique exon 40A not present in FLNA or FLNB. FLNC was precisely mapped to chromosome 7q32. Genomic cloning, restriction mapping, sequence analysis Human genetics Medium 11153914
2006 Loss of FLNc function in C2C12 myoblasts (via stable RNAi knockdown) caused defects in myoblast differentiation and fusion, resulting in multinucleated 'myoballs' rather than elongated myotubes. FLNc-deficient mice (deletion of last 8 exons) died shortly after birth due to respiratory failure, with severely reduced birth weights, fewer muscle fibers and primary myotubes, variation in fiber size, and centrally located nuclei, indicating an essential role in primary myogenesis and myotube structural integrity. A TRIO-FLNc-dependent pathway was implicated in maintaining myotube structure, based on phenotypic similarity between FLNc-deficient and TRIO-deficient cells. Stable RNAi knockdown in C2C12 cells, knockout mouse model (exon deletion), phenotypic analysis, genetic epistasis comparison with TRIO-null cells Molecular and cellular biology High 16914736
2010 FLNC was identified as a binding partner of IGFN1 (Immunoglobulin-like and fibronectin type 3 domain-containing 1) by yeast two-hybrid screening, and KY, IGFN1, and FLNC were shown to form a Z-band associated protein complex in skeletal muscle by combined yeast two-hybrid, biochemical, and immunofluorescence data. Yeast two-hybrid screen, biochemical co-purification, immunofluorescence Experimental cell research Medium 20206623
2012 In FLNC mutation-associated myofibrillar myopathy, immunofluorescence studies of patient skeletal muscle revealed altered expression of chaperone proteins and components of proteasomal and autophagic degradation pathways specifically in muscle fibers with protein aggregates, suggesting dysfunction of protein quality control mechanisms as pathogenic driver. Immunofluorescence on patient muscle biopsy sections Autophagy Medium 23238331
2016 Expression of the FLNCW2710X mutant protein in zebrafish revealed that the mutant protein localizes correctly to the Z-disk and can rescue fiber disintegration caused by FLNC knockdown, demonstrating that functional domains required for muscle integrity are intact in the mutant. However, the mutant forms protein aggregates that sequester FLNC away from the Z-disk, causing myofibrillar disintegration through protein insufficiency. BAG3 is recruited to aggregates but does not degrade them via chaperone-assisted selective autophagy (CASA); instead, BAG3 recruitment blocks alternative autophagy pathways that would otherwise clear aggregates. Reducing BAG3 levels or stimulating autophagy could relieve this blockage. Fluorescently tagged overexpression in zebrafish, FLNC knockdown rescue assay, immunofluorescence, BAG3 manipulation Human molecular genetics High 26969713
2016 HSPB7 interacts with dimerized FLNC, as shown by co-immunoprecipitation. Skeletal-muscle-specific ablation of HspB7 caused FLNC aggregation and mislocalization in muscle, demonstrating that HSPB7 is required to maintain proper FLNC localization and prevent myopathy progression. Loss of HSPB7 also caused abnormal upregulation and mislocalization of γ- and δ-sarcoglycan (but not dystrophin) in muscle. Co-immunoprecipitation (HSPB7 with dimerized FLNC), conditional knockout mouse (muscle-specific HspB7 deletion), immunofluorescence Journal of cell science High 26929074
2016 Western blot analysis of cardiac tissue from a patient with FLNC splice variant showed decreased FLNC protein level, supporting haploinsufficiency as the mechanism of DCM pathogenesis. Morpholino knockdown of filamin Cb (ortholog) in zebrafish resulted in abnormal cardiac function and ultrastructure, providing in vivo evidence for the haploinsufficiency model. Western blot on patient cardiac tissue, zebrafish morpholino knockdown with cardiac phenotyping JACC. Basic to translational science Medium 28008423
2016 Cytoplasmic aggregates of filamin C were observed in transfected myoblast cell lines expressing the missense mutant FLNC (p.S1624L), and immunohistochemistry of heart tissue confirmed filamin C-specific cytoplasmic inclusions in patients, establishing that missense mutations in FLNC can cause protein aggregation distinct from the haploinsufficiency mechanism of truncating mutations. Transfection of myoblast cell lines with mutant FLNC, immunohistochemistry on patient cardiac tissue Human mutation Medium 26666891
2017 Immunohistochemical analysis of cardiac tissue from a patient with the FLNC p.V2297M variant showed diminished FLNC localization at the Z-disk while localization at the intercalated disk was preserved. Stem cell-derived cardiomyocytes carrying the p.V2297M variant had diminished contractile activity compared to controls, establishing that the variant disrupts Z-disk targeting and contractile function. Immunohistochemistry on patient cardiac tissue, stem cell-derived cardiomyocyte contractility assay Circulation. Cardiovascular genetics Medium 29212899
2016 Expression of the FLNC p.Tyr1216Asn mutant protein in NIH3T3 cells produced filamin C aggregates, while Western blot showed normal filamin C protein levels in patient muscle biopsies, demonstrating that this missense mutation causes aggregate formation without reducing total protein expression. Transfection of NIH3T3 cells, Western blot on patient muscle biopsies Revue neurologique Low 27633507
2018 FLNC missense variants localized in Ig-loop segments (p.A1186V and p.A1183L) were shown to be pathogenic by cellular studies (protein aggregation in transfected cells) and in vivo zebrafish modeling, which showed phenotypic abnormalities. This established that FLNC missense variants in Ig-loop segments predominantly cause restrictive cardiomyopathy via aggregate formation rather than haploinsufficiency. Transfection of cells with mutant FLNC, zebrafish in vivo modeling, morphological studies Human mutation Medium 29858533
2021 A frameshift mutation in the FLNC dimerization domain (p.K2676Pfs*3) produced a mutant FLNc protein that is misfolded, unstable, and incapable of forming homodimers or heterodimers with wild-type FLNc, as shown by interaction and transfection studies with biophysical analysis. Proteomic profiling of protein aggregates in patient muscle showed activation of the ubiquitin-proteasome system and autophagic pathways, indicating dysregulation of protein quality control. Interaction assays (dimerization), transfection studies, biophysical molecular analysis, proteomic profiling of muscle aggregates Neurology. Genetics High 34235269
2022 Adult-specific cardiac RNAi depletion of Drosophila Filamin (dFil, the FLNC ortholog) caused cardiac dilatation, impaired systolic function, and sarcomeric alterations, establishing that filamin is required for cardiac function and maintenance of sarcomere integrity in the adult stage. Deletion of the last four Ig-like domains of dFil was dispensable for cardiac function. Drosophila cardiac-specific RNAi knockdown, CRISPR/Cas9 domain deletion, cardiac functional assays Biology open Medium 36066120
2024 FLNC is ubiquitinated and subjected to proteasomal degradation by the MAGED2-TRIM28 E3 ubiquitin ligase complex. MAGED2 interacts with TRIM28 to enhance its ubiquitin ligase activity, and the complex targets FLNC for ubiquitination. Loss of FLNC downstream of this complex activates epithelial-to-mesenchymal transition (EMT), contributing to chemoresistance in triple-negative breast cancer. Biochemical assays (co-IP of MAGED2-TRIM28-FLNC complex), ubiquitination assay, proteasomal degradation assay, in vitro and in vivo functional experiments Cell communication and signaling : CCS Medium 41310667
2024 FLNC expression increases dramatically during osteoclast differentiation. Inhibition of FLNC suppressed markers of osteoclast differentiation (TRAP, NFATc1, c-Fos) and bone resorption activity. S6K kinase regulates FLNC expression, and FLNC interacts with integrin β3 (ITGβ3) in osteoclasts; inhibiting S6K with PF-4708671 reduced FLNC expression and the FLNC-ITGβ3 interaction. This established an S6K/FLNC/ITGβ3 signaling axis in osteoclastogenesis. Transcriptomics, RT-PCR, Western blot, adenoviral overexpression/knockdown, proteomics, S6K inhibitor treatment, ovariectomized mouse model Phytomedicine : international journal of phytotherapy and phytopharmacology Medium 39612888
2024 The FLNC p.Ala1186Val variant is located in the interstrand loop involved in intradomain stabilization and Ig-like domain interactions. 3D structural modeling showed local structural changes causing protein instability and aggregation in the form of cytoplasmic bodies. Myopathological studies showed prominent aggregation and upregulation of aggrephagy-associated proteins LC3B and p62 in patient muscle, demonstrating that protein aggregation with impaired aggrephagy underlies the disease mechanism. 3D protein structural modeling, immunohistochemistry/immunofluorescence on patient muscle, bioinformatics structural analysis Biomedicines Medium 38397924
2024 iPSC-derived cardiomyocytes from patients carrying FLNC R1267Q (arrhythmogenic cardiomyopathy-associated) versus V2264M (restrictive cardiomyopathy-associated) variants showed distinct molecular phenotypes: R1267Q caused greater disturbances in calcium dynamics, Nav1.5 kinetics, and action potentials compared to V2264M, accompanied by transcriptome changes in genes linked to action potential and sodium transport, establishing variant-specific effects on electrophysiology and calcium homeostasis. iPSC-derived cardiomyocytes from patients, calcium imaging, electrophysiology (patch clamp), transcriptomics Cytoskeleton (Hoboken, N.J.) Medium 39315490
2020 The recombinant FLNC p.Pro442Arg mutant protein (homozygous in a patient with congenital-onset myopathy) was shown to be less stable and more prone to degradation by proteolytic enzymes than wild-type FLNC in biochemical assays, establishing reduced protein stability as the molecular consequence of this mutation. Recombinant protein expression, proteolytic stability assay, proteomics of patient muscle Human mutation Medium 32516863

Source papers

Stage 0 corpus · 75 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies. Journal of the American College of Cardiology 366 27908349
2000 Filamin 2 (FLN2): A muscle-specific sarcoglycan interacting protein. The Journal of cell biology 233 10629222
2006 Loss of FilaminC (FLNc) results in severe defects in myogenesis and myotube structure. Molecular and cellular biology 141 16914736
2016 Mutations in FLNC are Associated with Familial Restrictive Cardiomyopathy. Human mutation 135 26666891
2020 A mutation update for the FLNC gene in myopathies and cardiomyopathies. Human mutation 132 32112656
2016 FLNC Gene Splice Mutations Cause Dilated Cardiomyopathy. JACC. Basic to translational science 88 28008423
1986 Structural organization and nucleotide sequence of mouse c-myb oncogene: activation in ABPL tumors is due to viral integration in an intron which results in the deletion of the 5' coding sequences. Nucleic acids research 72 3016644
1998 Molecular cloning of human ABPL, an actin-binding protein homologue. Biochemical and biophysical research communications 65 9791010
2017 Novel Mutation in FLNC (Filamin C) Causes Familial Restrictive Cardiomyopathy. Circulation. Cardiovascular genetics 63 29212899
2016 HSPB7 interacts with dimerized FLNC and its absence results in progressive myopathy in skeletal muscles. Journal of cell science 53 26929074
2019 A Novel Truncating Variant in FLNC-Encoded Filamin C May Serve as a Proarrhythmic Genetic Substrate for Arrhythmogenic Bileaflet Mitral Valve Prolapse Syndrome. Mayo Clinic proceedings 51 30935706
2020 FLNC truncations cause arrhythmogenic right ventricular cardiomyopathy. Journal of medical genetics 50 31924696
2018 De novo mutations in FLNC leading to early-onset restrictive cardiomyopathy and congenital myopathy. Human mutation 50 29858533
2016 FLNC myofibrillar myopathy results from impaired autophagy and protein insufficiency. Human molecular genetics 44 26969713
2019 A fln-2 mutation affects lethal pathology and lifespan in C. elegans. Nature communications 39 31704915
2017 A novel FLNC frameshift and an OBSCN variant in a family with distal muscular dystrophy. PloS one 35 29073160
2010 Identification of a Z-band associated protein complex involving KY, FLNC and IGFN1. Experimental cell research 30 20206623
2019 The Tolerance of Salinity in Rice Requires the Presence of a Functional Copy of FLN2. Biomolecules 28 31877655
2012 Novel FLNC mutation in a patient with myofibrillar myopathy in combination with late-onset cerebellar ataxia. Muscle & nerve 28 22806379
2012 Impairment of protein degradation in myofibrillar myopathy caused by FLNC/filamin C mutations. Autophagy 28 23238331
2000 Genomic structure and fine mapping of the two human filamin gene paralogues FLNB and FLNC and comparative analysis of the filamin gene family. Human genetics 28 11153914
2022 Loss-of-Function FLNC Variants Are Associated With Arrhythmogenic Cardiomyopathy Phenotypes When Identified Through Exome Sequencing of a General Clinical Population. Circulation. Genomic and precision medicine 26 35699965
2016 Quantitative proteomics reveals FLNC as a potential progression marker for the development of hepatocellular carcinoma. Oncotarget 25 27626164
2019 RNA sequencing-based transcriptome profiling of cardiac tissue implicates novel putative disease mechanisms in FLNC-associated arrhythmogenic cardiomyopathy. International journal of cardiology 23 31843279
2021 FLNC-Associated Myofibrillar Myopathy: New Clinical, Functional, and Proteomic Data. Neurology. Genetics 22 34235269
2016 Cardiac arrhythmia and late-onset muscle weakness caused by a myofibrillar myopathy with unusual histopathological features due to a novel missense mutation in FLNC. Revue neurologique 18 27633507
2016 Widening the spectrum of filamin-C myopathy: Predominantly proximal myopathy due to the p.A193T mutation in the actin-binding domain of FLNC. Neuromuscular disorders : NMD 16 27816332
2011 Structural and functional evaluation of C. elegans filamins FLN-1 and FLN-2. PloS one 16 21799850
2018 A novel splicing variant in FLNC gene responsible for a highly penetrant familial dilated cardiomyopathy in an extended Iranian family. Gene 14 29551499
2022 Filamin FLN-2 promotes MVB biogenesis by mediating vesicle docking on the actin cytoskeleton. The Journal of cell biology 11 35575797
2020 First clinical and myopathological description of a myofibrillar myopathy with congenital onset and homozygous mutation in FLNC. Human mutation 11 32516863
2023 Novel filamin C (FLNC) variant causes a severe form of familial mixed hypertrophic-restrictive cardiomyopathy. American journal of medical genetics. Part A 10 36864778
2025 Spatial transcriptomics and multi-omics reveal relapse and resistance mechanisms of EndMT-derived CAFs mediated by TNC and FLNC in glioblastoma. Journal of translational medicine 9 40598496
2020 Clinical exome sequencing revealed that FLNC variants contribute to the early diagnosis of cardiomyopathies in infant patients. Translational pediatrics 8 32154132
2017 Enrichment of putatively damaging rare variants in the DYX2 locus and the reading-related genes CCDC136 and FLNC. Human genetics 7 28866788
2022 Cardiovascular Involvement in Pediatric FLNC Variants: A Case Series of Fourteen Patients. Journal of cardiovascular development and disease 6 36286284
2021 FLNC and MYLK2 Gene Mutations in a Chinese Family with Different Phenotypes of Cardiomyopathy. International heart journal 6 33455984
2024 FLN-2 functions in parallel to linker of nucleoskeleton and cytoskeleton complexes and CDC-42/actin pathways during P-cell nuclear migration through constricted spaces in Caenorhabditis elegans. Genetics 5 38797871
2022 Case Report: A Chinese Family of Hypertrophic Cardiomyopathy Caused by a Novel Splicing Mutation in the FLNC Gene. Frontiers in genetics 5 35795207
2022 Flnc: Machine Learning Improves the Identification of Novel Long Noncoding RNAs from Stand-Alone RNA-Seq Data. Non-coding RNA 5 36287122
2021 Generation of CRISPR-Cas9 edited human induced pluripotent stem cell line carrying FLNC exon skipping variant. Stem cell research 5 34883448
2024 Distinct molecular features of FLNC mutations, associated with different clinical phenotypes. Cytoskeleton (Hoboken, N.J.) 4 39315490
2024 The FLNC Ala1186Val Variant Linked to Cytoplasmic Body Myopathy and Cardiomyopathy Causes Protein Instability. Biomedicines 3 38397924
2024 S6K/FLNC/ITGβ3 signaling pathway regulates osteoclastogenesis and the inhibition of osteoclastogenesis by columbianadin. Phytomedicine : international journal of phytotherapy and phytopharmacology 3 39612888
2022 A novel nonsense mutation in the dimerization domain of FLNC causing mild myofibrillar myopathy. Clinical neurology and neurosurgery 3 35961230
2022 Drosophila CRISPR/Cas9 mutants as tools to analyse cardiac filamin function and pathogenicity of human FLNC variants. Biology open 3 36066120
2021 A CRISPR/Cas9 strategy for the generation of a FLNC knockout hESC line (WAe009-A-70) to model dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. Stem cell research 3 34634758
2024 Generation of a pluripotent stem cell line (UMGi270-A) and a corresponding CRISPR/Cas9 modified isogenic control (UMGi270-A-1) from a patient with sudden onset dilated cardiomyopathy harboring a FLNC p.R2187P mutation. Stem cell research 2 38583294
2024 FLNC Associated Restrictive Cardiomyopathy and Hypertrabeculation, a Rare Association. Arquivos brasileiros de cardiologia 2 38922273
2024 Novel FLNC variants in pediatric cardiomyopathy: an insight into disease mechanisms. Human genomics 2 39472949
2023 A child with dilated cardiomyopathy and homozygous splice site variant in FLNC gene. Molecular genetics and metabolism reports 2 38077956
2022 Generation of two induced pluripotent stem cell lines from dilated cardiomyopathy patients carrying heterozygous FLNC mutations. Stem cell research 2 36194907
2021 Generation of a heterozygous FLNC mutation-carrying human iPSC line, USFi002-A, for modeling dilated cardiomyopathy. Stem cell research 2 34088019
2021 Generation of iPSC line FAMRCi010-A from patient with restrictive cardiomyopathy carrying genetic variant FLNC p.Gly2011Arg. Stem cell research 2 34971931
2024 Variable clinical expression of a novel FLNC truncating variant in a large family. International journal of cardiology 1 38360096
2024 Identification of a Missense Mutation in the FLNC Gene from a Chinese Family with Restrictive Cardiomyopathy. Journal of multidisciplinary healthcare 1 39582878
2023 FLN-2 functions in parallel to LINC complexes and Cdc42/actin pathways during P-cell nuclear migration through constricted spaces in Caenorhabditis elegans. bioRxiv : the preprint server for biology 1 37577634
2023 [Genetic testing and clinical analysis of a patient with Dilated cardiomyopathy due to variant of FLNC gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 37994141
2022 Novel combination of FLNC (c.5707G>A; p. Glu1903Lys) and BAG3 (c.610G>A; p.Gly204Arg) genetic variant expressing restrictive cardiomyopathy phenotype in an adolescent girl. Journal of genetics 1 36560844
2021 Generation of iPSC line (FAMRCi009-A) from patient with familial progressive cardiac conduction disorder carrying genetic variant FLNC p.Val2264Met. Stem cell research 1 34971933
2026 Recurrent Myocarditis After COVID Vaccination in a Patient With FLNC Mutation Undergoing Treatment for Lymphoma. JACC. Case reports 0 41532901
2026 fln-2 isoform-specifically regulates Caenorhabditis elegans health span by affecting pharyngeal function. Scientific reports 0 41667770
2026 Unveiling FLNC variants: iPSC-derived myogenic cells as a model to study disease mechanisms. Skeletal muscle 0 41680819
2026 Paediatric patient with FLNC and CTNNA3 variants presenting with frequent premature ventricular contractions and systolic dysfunction: a case report. Cardiology in the young 0 41891175
2026 [Clinical analysis of pediatric restrictive cardiomyopathy associated with FLNC gene variants in 5 children]. Zhonghua er ke za zhi = Chinese journal of pediatrics 0 41986269
2026 Case Report: Filamin-C (FLNC) as a cause of disease in a large South African family diagnosed with restrictive cardiomyopathy. Frontiers in medicine 0 42136867
2026 FLNC Complex Structural Variant Causing Distal Myopathy Identified by Family-Based Genome Sequencing. American journal of medical genetics. Part A 0 42244138
2025 Dilated Cardiomyopathy in a Young Patient With an FLNC Gene Mutation. Case reports in medicine 0 40524707
2025 A spurious fln-2 mutation in a wide variety of commonly used C. elegans strains. microPublication biology 0 40708994
2025 Novel FLNC and TGFB3 Mutations in Early Onset Familial Atrial Fibrillation With Diastolic Dysfunction. JACC. Case reports 0 41117735
2025 Targeting the MAGED2-TRIM28-FLNC axis overcomes chemoresistance in TNBC via EMT suppression. Cell communication and signaling : CCS 0 41310667
2025 Genetic and Clinical Characterization of FLNC Variants in Chinese Patients with Cardiomyopathy. Journal of cardiovascular development and disease 0 41440871
2025 Identification of a Novel FLNC Truncating Variant in Fetal Tetralogy of Fallot: A Case Report and Review of the Literature. Diagnostics (Basel, Switzerland) 0 41464097
2024 Filamin C (FLNC) truncating mutation in a fatal arrhythmogenic left ventricular cardiomyopathy (ALVC). Legal medicine (Tokyo, Japan) 0 38547641
2021 Cardiomyopathy, Proximal Myopathy, Camptocormia, and Novel Filamin C (FLNC) Variant: A Case Report. The American journal of case reports 0 34526477

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