Affinage

FLNA

Filamin-A · UniProt P21333

Length
2647 aa
Mass
280.7 kDa
Annotated
2026-06-09
100 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FLNA encodes a large dimeric actin-crosslinking scaffold built from an N-terminal actin-binding domain and 24 immunoglobulin-like repeats, whose homodimerization is mediated by repeat 24 together with additional non-canonical contacts within repeats 16–24 (PMID:8088819, PMID:25686753). It is essential for the integrity of intercellular junctions and vascular/cardiac development, with complete loss in mice causing embryonic lethality and disrupted adherens junctions (PMID:17172441). The protein operates as a signaling hub that physically links transmembrane receptors to the actin cytoskeleton and the Rho-GTPase machinery: it binds the tyrosine kinase Syk at repeat 5 to drive ITAM-mediated platelet activation (PMID:20713593), stabilizes the GPIbα receptor against ADAM17/MMP9-mediated proteolysis during platelet biogenesis (PMID:21652675), and tethers the F-BAR protein PACSIN2 via repeat 20 to shape the megakaryocyte demarcation membrane system (PMID:25838348). Through differential coupling to RhoA and β1-integrin it acts antagonistically to FLNB in controlling stress fibers and cell spreading (PMID:28175289), and it directs cytoskeletal remodeling via PTPN12/Src/p190RhoGAP (PMID:26594644), Rap1 (PMID:29100390), and an ARHGAP24–RAC1–cofilin axis governing dendritogenesis (PMID:38852754). FLNA scaffolds somatostatin receptor SST2/SSTR2 signaling, restraining receptor diffusion and clustering at clathrin-coated pits to enable internalization and Gαi-coupled antitumoral signaling, a function gated by PKA phosphorylation at Ser2152 that uncouples Gαi recruitment (PMID:30098401, PMID:29931263). It additionally bridges ATG8-family proteins to the SNARE STX17 to promote autophagosome–lysosome fusion (PMID:37389864). FLNA mutations cause tissue-specific developmental disease, including isoform-specific congenital intestinal pseudo-obstruction (PMID:29024177), and elevated FLNA downstream of MEK–ERK drives dendritic pathology in Tsc1-null neurons (PMID:25277454).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1994 High

    Establishing the gene's domain architecture defined FLNA as a modular actin-binding protein, framing all later structure-function work.

    Evidence Genomic cloning and exon-intron sequencing of the 47-exon human gene

    PMID:8088819

    Open questions at the time
    • Does not address dimerization geometry
    • No functional assignment to individual repeats
  2. 2006 High

    Whether FLNA's essential role lay in cell migration or junction integrity was resolved by showing null embryos die with adherens junction and vascular defects, redefining its core developmental function.

    Evidence Complete and conditional knockout mouse with histology and adherens junction immunostaining

    PMID:17172441

    Open questions at the time
    • Molecular partners at the junction not identified
    • Tissue-specific contributions not dissected
  3. 2010 High

    Domain-resolved interaction mapping established FLNA as a direct signaling scaffold, linking Syk binding at repeat 5 to ITAM-driven platelet activation.

    Evidence Platelet-specific conditional KO with reciprocal Co-IP domain mapping and functional platelet assays

    PMID:20713593

    Open questions at the time
    • Whether other repeats bind additional kinases not addressed in this study
    • Structural basis of the repeat 5 interface unknown
  4. 2011 High

    The mechanism of FLNA-dependent platelet biogenesis was clarified by showing FLNA stabilizes surface GPIbα against metalloprotease cleavage, explaining the macrothrombocytopenia phenotype.

    Evidence Megakaryocyte-specific conditional KO with flow cytometry, macrophage ablation, and metalloproteinase westerns

    PMID:21652675

    Open questions at the time
    • Direct GPIbα-FLNA binding interface not mapped here
    • Link to premature platelet release not fully mechanistic
  5. 2015 High

    FLNA was shown to extend cytoskeletal scaffolding to membrane morphogenesis by tethering PACSIN2 at repeat 20 to drive demarcation membrane system formation.

    Evidence Co-IP domain mapping, in vitro membrane tubulation assay, and Flna-null megakaryocyte imaging

    PMID:25838348

    Open questions at the time
    • In vivo requirement for DMS in thrombopoiesis not quantified
    • Regulation of the interaction unknown
  6. 2015 High

    Dimerization studies revealed that repeat 24 alone is insufficient for stable homodimerization, implying non-canonical inter-repeat contacts beyond the canonical interface.

    Evidence Co-IP, in vitro cross-linking, and gel filtration of repeat 24 and repeat 16–24 constructs

    PMID:25686753

    Open questions at the time
    • Identity of the additional dimerization contacts not defined
    • No full-length structural model
  7. 2015 Medium

    A focal-adhesion-competent exon-40-skipping mutant defined an internal region dispensable for integrin binding, refining the structure-function map.

    Evidence Whole-exome sequencing, cDNA characterization, and integrin binding/focal adhesion assays

    PMID:26059841

    Open questions at the time
    • Functional consequences in tissue context untested
    • Other functions of the deleted region not assessed
  8. 2014 High

    FLNA was placed in receptor signaling pathways: as a scaffold required for SST2 receptor stabilization and Gαi-mediated antitumoral signaling, and as a MEK-ERK effector in TSC dendritic pathology.

    Evidence siRNA and dominant-negative FLNA in tumor cells; in utero electroporation with MEK inhibitor pharmacology in Tsc1-null neurons

    PMID:24828612 PMID:25277454

    Open questions at the time
    • Generality of receptor scaffolding beyond SST2 unclear
    • Transcriptional vs post-translational control of FLNA levels in neurons not fully separated
  9. 2015 Medium

    Yeast two-hybrid and signaling assays connected disease-associated repeat 1–8 mutations to loss of PTPN12 binding and dysregulated Src/p190RhoGAP, linking FLNA to focal adhesion signaling.

    Evidence Yeast two-hybrid, pull-down, Co-IP, and Src/p190RhoGAP phosphorylation assays

    PMID:26594644

    Open questions at the time
    • Single-lab interaction not reciprocally validated in vivo
    • Causality for MVP phenotype not established
  10. 2017 Medium

    FLNA was shown to act antagonistically to FLNB in RhoA activation and integrin expression, and tissue-specific isoforms were linked to organ-restricted disease.

    Evidence Co-IP and RhoA/integrin functional assays in chondrocytes; RNA-seq isoform analysis with CIPO genotype-phenotype correlation

    PMID:28175289 PMID:29024177

    Open questions at the time
    • Mechanism of differential RhoA coupling between filamins unknown
    • Functional difference between the two N-terminal isoforms not biochemically resolved
  11. 2018 High

    PKA phosphorylation of Ser2152 was established as a regulatory switch that uncouples FLNA-bound SST2 from Gαi, and single-molecule imaging defined FLNA's role in restraining receptor diffusion and enabling clathrin-mediated internalization.

    Evidence Phosphomimetic/phosphodeficient mutagenesis with functional readouts; fast multicolor single-molecule live imaging with dominant-negative perturbation

    PMID:29931263 PMID:30098401

    Open questions at the time
    • Generalizability of Ser2152 regulation to other receptors not tested here
    • Stoichiometry of FLNA-receptor interactions unknown
  12. 2021 Medium

    FLNA was implicated in nuclear DNA repair and cancer drug resistance through TRIM44-mediated stabilization and Wnt/ANXA2 signaling, expanding its roles beyond the cytoskeleton.

    Evidence TRIM44/p62 Co-IP and fractionation with irradiation DNA damage assays; FLNA-ANXA2 Co-IP, SP1 ChIP, and xenografts

    PMID:34018148 PMID:34211088

    Open questions at the time
    • Direct DNA repair function of nuclear FLNA not biochemically defined
    • Single-lab Co-IPs without reciprocal structural validation
  13. 2023 High

    FLNA was shown to function in autophagy by bridging ATG8 proteins to phosphorylated STX17, enabling autophagosome-lysosome fusion, with disease mutations disrupting these interactions.

    Evidence Phospho-site mapping, Co-IP interaction mapping, fusion assays, and disease-mutant constructs

    PMID:37389864

    Open questions at the time
    • Structural basis of ATG8 and STX17 binding regions not resolved
    • In vivo autophagy phenotype of these mutations not shown here
  14. 2024 Medium

    FLNA was assigned cell-cycle and neuronal morphogenesis roles via proteasomal control of Wee1 and an ARHGAP24-RAC1-cofilin axis governing dendritogenesis.

    Evidence FLNA knockdown/overexpression with proteasome inhibitor in carcinoma cells; conditional neuronal Flna depletion with RAC1/cofilin assays

    PMID:38852754 PMID:39528354

    Open questions at the time
    • Direct mechanism of FLNA-driven Wee1 phosphorylation unclear
    • ARHGAP24 binding interface on FLNA not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single scaffold coordinates its many partner-specific functions across cytoskeleton, receptor signaling, autophagy, nuclear repair, and cell cycle in a context-dependent manner remains unresolved.
  • No unified structural model of full-length dimeric FLNA with bound partners
  • Rules governing partner selection across tissues unknown
  • Quantitative interplay of phosphorylation and ubiquitination in regulating FLNA function undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 3
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-109582 Hemostasis 3 R-HSA-1266738 Developmental Biology 3 R-HSA-73894 DNA Repair 2 R-HSA-9612973 Autophagy 2
Partners
ANXA2ARHGAP24FLNBPACSIN2PTPN12STX17SYKTRIM44

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 The ABP-280 filamin gene (FLN/FLNA) was mapped to Xq28 by Southern blot analysis of somatic cell hybrid lines and fluorescence in situ hybridization, localizing it within a 200-kb region centromeric to G6PD and telomeric to the color vision locus. Southern blot of somatic cell hybrids, FISH Genomics High 8406501
1994 The human FLNA (FLN1) gene comprises 47 exons spanning ~26 kb; the actin-binding domain is encoded by exons 2–5; the 96-amino-acid rod repeats are encoded by the remaining 42 exons; and exon 29 encodes an alternatively spliced 8-amino-acid segment interrupting repeat 15. Genomic cloning and exon-intron sequencing Genomics High 8088819
2006 Complete loss of Flna in mice causes embryonic lethality with severe cardiac and vascular defects; Flna-null embryos display abnormal adherens junctions and aberrant endothelial/epithelial organization, demonstrating an essential role for FLNA in intercellular junctions and vascular development rather than in general cell migration. Conditional and complete knockout mouse model; histology; immunostaining of adherens junction markers Proceedings of the National Academy of Sciences of the United States of America High 17172441
2010 FlnA binds to the protein tyrosine kinase Syk at immunoglobulin-like repeat 5 of FlnA; loss of this interaction in FlnA-null platelets severely impairs ITAM- and ITAM-like-mediated signaling (Syk and PLCγ2 phosphorylation), platelet spreading, α-granule secretion, and integrin αIIbβ3 activation. Platelet-specific conditional KO (GATA1-Cre); Co-IP mapping of FlnA–Syk interaction to repeat 5; functional platelet assays (spreading, secretion, tyrosine phosphorylation) The Journal of experimental medicine High 20713593
2010 FLN-1/filamin in C. elegans is required to maintain actin filament organization in the spermatheca and uterus, and genetic epistasis with phospholipase PLC-1 places both proteins in the same pathway controlling embryo exit from the spermatheca. Deletion allele and RNAi depletion; double-mutant epistasis analysis; fluorescence colocalization Developmental biology Medium 20707996
2011 FlnA-null megakaryocytes prematurely release large, fragile platelets; FlnA stabilizes the platelet von Willebrand factor receptor GPIbα by providing cytoskeletal linkage, as shown by normal GPIbα surface expression on null megakaryocytes but decreased expression and increased ADAM17/MMP9-mediated degradation on null platelets. Megakaryocyte-specific conditional KO (PF4-Cre); flow cytometry; clodronate liposome macrophage ablation; surface receptor expression analysis; western blot for metalloproteinases Blood High 21652675
2014 FLNA overexpression in Tsc1-null neurons is driven by MEK1/2–ERK1/2 signaling (not mTOR), and elevated FLNA causes abnormal dendritic complexity; knockdown of FLNA in Tsc1-null neurons in vivo prevents dendritic abnormalities, placing FLNA downstream of MEK–ERK in the TSC dendritic pathology pathway. In utero electroporation (loss- and gain-of-function); conditional Tsc1-null mouse; MEK inhibitor pharmacology; in vivo FLNA knockdown with phenotypic rescue Neuron High 25277454
2014 FLNA is required for SST2 (somatostatin receptor 2) signaling and receptor stabilization in somatotroph tumor cells: FLNA silencing abolishes SST2-induced cyclin D1 reduction and caspase-3/7 activation; a FLNA dominant-negative mutant blocking SST2–FLNA binding reduces SST2 expression after prolonged agonist exposure; FLNA also scaffolds Gαi and partner proteins to SST2 to mediate ERK1/2 inhibition and apoptosis. siRNA silencing; dominant-negative FLNA mutant overexpression; caspase activity assay; ERK1/2 phosphorylation assay; cell proliferation assay in human GH-secreting tumor cells and GH3/GH4C1 rat cell lines Endocrinology High 24828612
2015 FlnA binds PACSIN2 via FlnA immunoglobulin-like repeat 20 interacting with the tip of PACSIN2's F-BAR domain; this interaction enhances PACSIN2 F-BAR-mediated membrane tubulation in vitro and is required for proper demarcation membrane system (DMS) formation and PACSIN2 localization in megakaryocytes and platelets. Co-IP (human platelets); domain-mapping of the FlnA–PACSIN2 interaction; in vitro membrane tubulation assay; Flna-null platelet/MK imaging; EGFP-PACSIN2 localization in wild-type vs Flna-null MKs Blood High 25838348
2015 MVP-associated FLNA missense mutations (G288R, P637Q, H743P) in repeats 1–8 abolish binding to the tyrosine phosphatase PTPN12 (PTP-PEST), identified by yeast two-hybrid screen, and impair activation of PTPN12 substrates Src and p190RhoGAP, linking FLNA to integrin/focal adhesion signaling via PTPN12. Yeast two-hybrid screen; pull-down; Co-IP; phosphorylation assays for Src and p190RhoGAP Journal of cardiovascular development and disease Medium 26594644
2017 FlnA physically interacts with FlnB in chondrocyte cytoplasm; FlnA more strongly binds and activates RhoA whereas FlnB indirectly inhibits RhoA; FlnA loss decreases β1-integrin expression while FlnB loss promotes it, demonstrating antagonistic roles of the two filamins in RhoA activation, integrin expression, actin stress fiber formation, and cell spreading. Co-IP (physical interaction); RhoA activation assay; integrin expression (western blot/flow cytometry); actin staining; fibronectin stimulation in null cells; cell spreading assay Human molecular genetics Medium 28175289
2017 Two FLNA transcripts differing by 28 N-terminal residues (initiated at ATG+1 and ATG+82) are expressed in a tissue-specific manner; the longer isoform (ATG+1) predominates in intestinal smooth muscle, and mutations that selectively eliminate this isoform cause congenital intestinal pseudo-obstruction (CIPO) without brain or cardiac involvement, mechanistically explaining tissue-specific phenotypes. RNA-seq; cDNA analysis; isoform-specific expression in patient fibroblasts and intestinal smooth muscle; identification of three transcription start sites Human mutation Medium 29024177
2018 PKA phosphorylates FLNA at S2152 (promoted by cAMP), and SST2 agonist stimulation decreases this phosphorylation; phosphomimetic S2152D FLNA abolishes SST2 antitumoral effects (inhibition of proliferation, apoptosis induction, migration inhibition via RhoA/cofilin), while S2152A FLNA is recruited to activated SST2 normally; S2152D FLNA constitutively binds SST2 but prevents Gαi recruitment, blocking signal transduction. Phosphomimetic/phosphodeficient FLNA mutant overexpression; Co-IP; immunofluorescence; proliferation, apoptosis, and migration assays; RhoA activation assay; cofilin phosphorylation assay in GH3/GH4C1 and primary somatotroph cells Cancer letters High 30098401
2018 Single-molecule microscopy shows SSTR2 and FLNA undergo transient interactions preferentially along actin fibers at the plasma membrane; these interactions restrain SSTR2 diffusion, promote agonist-induced SSTR2 clustering and recruitment to clathrin-coated pits, and are required for SSTR2 internalization; a dominant-negative FLNA fragment disrupting SSTR2–FLNA binding increases SSTR2 mobility and impairs clustering and internalization. Fast multicolor single-molecule microscopy in living cells; dominant-negative FLNA fragment; SSTR2 diffusion analysis; clathrin-coated pit recruitment assay Endocrinology High 29931263
2015 A missense mutation (p.Gly2593Glu) in the FLNA repeat 24 dimerization interface abolishes homodimerization of isolated repeat 24 in vitro, but extended repeat 16–24 constructs retain dimerization, implying additional non-canonical interactions contribute to FLNA homodimerization. Co-immunoprecipitation; in vitro cross-linking studies; gel filtration chromatography of repeat 24 and repeat 16–24 constructs Journal of molecular medicine (Berlin, Germany) High 25686753
2021 TRIM44 deubiquitinates p62 (sequestosome 1), promoting its oligomerization and cytoplasmic retention, which prevents p62-mediated nuclear degradation of FLNA and 53BP1, thereby increasing nuclear FLNA levels and DNA damage repair capacity. TRIM44 siRNA knockdown; western blot; subcellular fractionation; irradiation-induced DNA damage assay; co-IP for TRIM44–p62 interaction Oncogene Medium 34211088
2021 FLNA interacts with ANXA2 (annexin A2), and together they activate Wnt pathway signaling to promote gefitinib resistance in non-small-cell lung cancer; SP1 transcription factor promotes FLNA transcriptional activation; FLNA knockdown restores gefitinib sensitivity in vitro and in vivo. Co-IP (FLNA–ANXA2 interaction); ChIP (SP1 binding to FLNA promoter); CCK-8/flow cytometry; xenograft mouse model; western blot for Wnt pathway components Molecular and cellular biochemistry Medium 34018148
2022 TRIM44 interacts with FLNA and facilitates its stability through deubiquitination; FLNA is required for TRIM44-mediated upregulation of BRCA1 expression and homologous recombination repair, placing FLNA upstream of BRCA1 in a TRIM44/FLNA/BRCA1 axis that confers cisplatin resistance in lung adenocarcinoma. Co-IP (TRIM44–FLNA interaction); FLNA siRNA; BRCA1 depletion rescue experiment; immunofluorescence; xenograft model International journal of biological sciences Medium 35541909
2023 ULK kinase phosphorylates the autophagosomal SNARE STX17 at S289; FLNA acts as a linker between ATG8 family proteins and STX17, recruiting STX17 to autophagosomes; STX17 S289 phosphorylation promotes interaction with FLNA, enabling STX17 recruitment to autophagosomes and facilitating autophagosome–lysosome fusion; disease-causative FLNA mutations in the ATG8- and STX17-binding regions disrupt these interactions and impair fusion. Phospho-site mapping (ULK→STX17 S289); Co-IP (FLNA–ATG8, FLNA–STX17); autophagosome–lysosome fusion assay; disease-mutant FLNA constructs; subcellular localization studies The Journal of cell biology High 37389864
2023 WTAP-mediated N6-methyladenosine (m6A) modification of FLNA mRNA leads to post-transcriptional repression of FLNA expression, and the WTAP/FLNA axis inhibits autophagy in colon cancer cells. m6A dot blot hybridization; methylated RNA immunoprecipitation (MeRIP); dual-luciferase assay; RNA immunoprecipitation; western blot for FLNA and autophagy markers; rescue experiments Cell adhesion & migration Medium 36849408
2024 FLNA regulates Wee1 kinase protein levels by promoting its proteasomal degradation (via phosphorylation at Ser123); FLNA knockdown increases Wee1 and p-CDK1/cyclin B1 whereas FLNA overexpression increases p-Wee1(Ser123) and reduces Wee1 protein, reversed by lactacystin (proteasome inhibitor), placing FLNA as a negative regulator of Wee1 in adrenocortical carcinoma cells. FLNA knockdown and overexpression; western blot for Wee1, p-CDK1, cyclin B1, p-Wee1(Ser123); lactacystin proteasome inhibitor treatment; proliferation and apoptosis assays International journal of cancer Medium 39528354
2024 FLNA modulates RAC1 and cofilin activity through its interaction with the Rho-GTPase Activating Protein ARHGAP24, regulating dendritogenesis and spinogenesis in cortical pyramidal neurons; conditional Flna depletion from pyramidal neurons disrupts excitatory/inhibitory input balance. Conditional in utero electroporation of Cre in Flnaflox/flox mice; RAC1 activation assay; cofilin phosphorylation assay; Co-IP or interaction assay for FLNA–ARHGAP24; dendritic morphology quantification Neurobiology of disease Medium 38852754
2015 A loss-of-function FLNA mutation inducing in-frame exon 40 skipping produces a mutant FLNA missing 41 internal amino acids that retains binding affinity to integrin and capacity to induce focal adhesions comparable to wild-type protein, demonstrating that this internal region is dispensable for integrin binding and focal adhesion formation. Whole-exome sequencing; RT-PCR/cDNA characterization of exon skipping; functional assay of integrin binding and focal adhesion formation for mutant vs wild-type FLNA European journal of human genetics Medium 26059841
2017 FLNA colocalizes with Rap1-GTPase in cellular protrusions of pulmonary neuroendocrine tumor cells; FLNA silencing up-regulates Rap1 expression, and Rap1 silencing prevents the FLNA-silencing-induced increase in cell adhesion and decrease in cell migration, placing Rap1 downstream of FLNA in the regulation of these processes. siRNA silencing; immunofluorescence colocalization; Rap1 western blot; cell adhesion and migration assays; epistasis via double knockdown Oncotarget Medium 29100390
2020 FLNA directly interacts with Smad2, enhancing c-Met promoter activity; c-Met–AKT signaling phosphorylates FLNA at Ser2152, and this phosphorylation is correlated with EMT; co-immunoprecipitation confirmed FLNA–Smad2 interaction; FLNA knockdown reduces EMT and metastasis in colorectal cancer cells in vivo. Co-immunoprecipitation (FLNA–Smad2); luciferase reporter assay (c-Met promoter); orthotopic CRC mouse model; western blot for EMT markers and pFLNA(Ser2152) American journal of cancer research Medium 32195017

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Filamin A (FLNA) is required for cell-cell contact in vascular development and cardiac morphogenesis. Proceedings of the National Academy of Sciences of the United States of America 272 17172441
2004 Germline and mosaic mutations of FLN1 in men with periventricular heterotopia. Neurology 107 15249610
2010 A novel interaction between FlnA and Syk regulates platelet ITAM-mediated receptor signaling and function. The Journal of experimental medicine 95 20713593
2015 47 patients with FLNA associated periventricular nodular heterotopia. Orphanet journal of rare diseases 82 26471271
2011 FlnA-null megakaryocytes prematurely release large and fragile platelets that circulate poorly. Blood 82 21652675
2011 FLNA and PGK1 are two potential markers for progression in hepatocellular carcinoma. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 73 21471709
2002 Familial periventricular heterotopia: missense and distal truncating mutations of the FLN1 gene. Neurology 69 11914408
2006 Frontometaphyseal dysplasia: mutations in FLNA and phenotypic diversity. American journal of medical genetics. Part A 68 16835913
2004 A dual phenotype of periventricular nodular heterotopia and frontometaphyseal dysplasia in one patient caused by a single FLNA mutation leading to two functionally different aberrant transcripts. American journal of human genetics 56 14988809
2014 MEK-ERK1/2-dependent FLNA overexpression promotes abnormal dendritic patterning in tuberous sclerosis independent of mTOR. Neuron 54 25277454
2010 Diffuse abnormal layering of small intestinal smooth muscle is present in patients with FLNA mutations and x-linked intestinal pseudo-obstruction. The American journal of surgical pathology 50 20871226
2010 Lung disease associated with periventricular nodular heterotopia and an FLNA mutation. European journal of medical genetics 50 20888935
2015 FlnA binding to PACSIN2 F-BAR domain regulates membrane tubulation in megakaryocytes and platelets. Blood 49 25838348
2010 Terminal osseous dysplasia is caused by a single recurrent mutation in the FLNA gene. American journal of human genetics 49 20598277
2012 Cloning of a novel arylamidase gene from Paracoccus sp. strain FLN-7 that hydrolyzes amide pesticides. Applied and environmental microbiology 45 22544249
2010 FLN-1/filamin is required for maintenance of actin and exit of fertilized oocytes from the spermatheca in C. elegans. Developmental biology 43 20707996
2019 Upregulation of circFLNA contributes to laryngeal squamous cell carcinoma migration by circFLNA-miR-486-3p-FLNA axis. Cancer cell international 41 31384171
2014 Filamin A (FLNA) plays an essential role in somatostatin receptor 2 (SST2) signaling and stabilization after agonist stimulation in human and rat somatotroph tumor cells. Endocrinology 41 24828612
2009 Bilateral periventricular nodular heterotopia in France: frequency of mutations in FLNA, phenotypic heterogeneity and spectrum of mutations. Journal of neurology, neurosurgery, and psychiatry 41 19917821
2019 A fln-2 mutation affects lethal pathology and lifespan in C. elegans. Nature communications 39 31704915
2020 FLNA promotes chemoresistance of colorectal cancer through inducing epithelial-mesenchymal transition and smad2 signaling pathway. American journal of cancer research 38 32195017
2004 Mosaic mutations of the FLN1 gene cause a mild phenotype in patients with periventricular heterotopia. Neurogenetics 37 15459826
1993 Actin-binding protein (ABP-280) filamin gene (FLN) maps telomeric to the color vision locus (R/GCP) and centromeric to G6PD in Xq28. Genomics 37 8406501
2017 Filamin A (FLNA) mutation-A newcomer to the childhood interstitial lung disease (ChILD) classification. Pediatric pulmonology 36 28898549
2018 cAMP/PKA-induced filamin A (FLNA) phosphorylation inhibits SST2 signal transduction in GH-secreting pituitary tumor cells. Cancer letters 32 30098401
2012 Congenital short bowel syndrome as the presenting symptom in male patients with FLNA mutations. Genetics in medicine : official journal of the American College of Medical Genetics 32 23037936
2017 Opposing FlnA and FlnB interactions regulate RhoA activation in guiding dynamic actin stress fiber formation and cell spreading. Human molecular genetics 31 28175289
2013 Novel no-stop FLNA mutation causes multi-organ involvement in males. American journal of medical genetics. Part A 31 23873601
2005 Ehlers-Danlos syndrome and periventricular nodular heterotopia in a Spanish family with a single FLNA mutation. Journal of medical genetics 31 15994863
2010 Lung disease in FLNA mutation: confirmatory report. European journal of medical genetics 29 21194575
1994 The exon-intron organization of the human X-linked gene (FLN1) encoding actin-binding protein 280. Genomics 29 8088819
2015 Exon skipping causes atypical phenotypes associated with a loss-of-function mutation in FLNA by restoring its protein function. European journal of human genetics : EJHG 27 26059841
2013 An antiproliferative gene FLNA regulates migration and invasion of gastric carcinoma cell in vitro and its clinical significance. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 26 24241900
2021 TRIM44 mediated p62 deubiquitination enhances DNA damage repair by increasing nuclear FLNA and 53BP1 expression. Oncogene 25 34211088
2022 TRIM44 promotes BRCA1 functions in HR repair to induce Cisplatin Chemoresistance in Lung Adenocarcinoma by Deubiquitinating FLNA. International journal of biological sciences 24 35541909
2018 FLNA mutations in surviving males presenting with connective tissue findings: two new case reports and review of the literature. BMC medical genetics 24 30089473
2017 Differential regulation of two FLNA transcripts explains some of the phenotypic heterogeneity in the loss-of-function filaminopathies. Human mutation 24 29024177
2018 Single-Molecule Microscopy Reveals Dynamic FLNA Interactions Governing SSTR2 Clustering and Internalization. Endocrinology 23 29931263
2015 Filamin A (FLNA) modulates chemosensitivity to docetaxel in triple-negative breast cancer through the MAPK/ERK pathway. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 23 26546439
2015 MVP-Associated Filamin A Mutations Affect FlnA-PTPN12 (PTP-PEST) Interactions. Journal of cardiovascular development and disease 23 26594644
2012 Atypical male and female presentations of FLNA-related periventricular nodular heterotopia. European journal of medical genetics 23 22366253
2012 New insights into the versatile roles of platelet FlnA. Platelets 23 22372530
2019 Fucoidan affects oral squamous cell carcinoma cell functions in vitro by regulating FLNA-derived circular RNA. Annals of the New York Academy of Sciences 21 31495936
2010 Expansion of the Spectrum of FLNA Mutations Associated with Melnick-Needles Syndrome. Molecular syndromology 21 21031081
2023 WTAP regulates autophagy in colon cancer cells by inhibiting FLNA through N6-methyladenosine. Cell adhesion & migration 20 36849408
2021 Circular RNA FLNA acts as a sponge of miR-486-3p in promoting lung cancer progression via regulating XRCC1 and CYP1A1. Cancer gene therapy 20 33500536
2021 The expression of FLNA and CLU in PBMCs as a novel screening marker for hepatocellular carcinoma. Scientific reports 20 34290294
2012 FLNA genomic rearrangements cause periventricular nodular heterotopia. Neurology 20 22238415
2023 CSNK2 suppresses autophagy by activating FLN-NHL-containing TRIM proteins. Autophagy 18 37938186
2021 Interaction of FLNA and ANXA2 promotes gefitinib resistance by activating the Wnt pathway in non-small-cell lung cancer. Molecular and cellular biochemistry 18 34018148
2017 FLNA is implicated in pulmonary neuroendocrine tumors aggressiveness and progression. Oncotarget 18 29100390
2017 Filamin A (FLNA) regulates autophagy of bladder carcinoma cell and affects its proliferation, invasion and metastasis. International urology and nephrology 18 29288417
2015 Familial periventricular nodular heterotopia, epilepsy and Melnick-Needles Syndrome caused by a single FLNA mutation with combined gain-of-function and loss-of-function effects. Journal of medical genetics 18 25755106
2017 Clinical Validation of a Serum Protein Panel (FLNA, FLNB and KRT19) for Diagnosis of Prostate Cancer. Journal of molecular biomarkers & diagnosis 17 29682400
2017 Left main coronary artery compression by a dilated main pulmonary artery and left coronary sinus of Valsalva aneurysm in a patient with heritable pulmonary arterial hypertension and FLNA mutation. Pulmonary circulation 16 28660794
2017 Familial Ebstein Anomaly: Whole Exome Sequencing Identifies Novel Phenotype Associated With FLNA. Circulation. Cardiovascular genetics 16 29237676
2011 Structural and functional evaluation of C. elegans filamins FLN-1 and FLN-2. PloS one 16 21799850
2018 A novel truncating mutation in FLNA causes periventricular nodular heterotopia, Ehlers-Danlos-like collagenopathy and macrothrombocytopenia. Brain & development 15 29449050
2020 Role and mechanism of FLNa and UCP2 in the development of cervical cancer. Oncology reports 14 33125133
2019 Allogeneic mesenchymal stromal cells: Novel therapeutic option for mutated FLNA-associated respiratory failure in the pediatric setting. Pediatric pulmonology 14 31468740
2018 FLNa negatively regulated proliferation and metastasis in lung adenocarcinoma A549 cells via suppression of EGFR. Acta biochimica et biophysica Sinica 14 29272322
2011 In-frame deletion in FLNA causing familial periventricular heterotopia with skeletal dysplasia in males. American journal of medical genetics. Part A 14 21484998
2023 ULK phosphorylation of STX17 controls autophagosome maturation via FLNA. The Journal of cell biology 13 37389864
2021 Cardiovascular, Brain, and Lung Involvement in a Newborn With a Novel FLNA Mutation: A Case Report and Literature Review. Advances in neonatal care : official journal of the National Association of Neonatal Nurses 13 33852449
2021 Cardiovascular and connective tissue disorder features in FLNA-related PVNH patients: progress towards a refined delineation of this syndrome. Orphanet journal of rare diseases 13 34863227
2016 A distinct X-linked syndrome involving joint contractures, keloids, large optic cup-to-disc ratio, and renal stones results from a filamin A (FLNA) mutation. American journal of medical genetics. Part A 13 26804200
2015 Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy. Epilepsy & behavior : E&B 13 26340046
2010 Alteration of flagellar phenotype of Escherichia coli strain P12b, the standard type strain for flagellar antigen H17, possessing a new non-fliC flagellin gene flnA, and possible loss of original flagellar phenotype and genotype in the course of subculturing through semisolid media. Archives of microbiology 13 20174918
2015 Diverse phenotypic consequences of mutations affecting the C-terminus of FLNA. Journal of molecular medicine (Berlin, Germany) 12 25686753
2015 Association of mutations in FLNA with craniosynostosis. European journal of human genetics : EJHG 12 25873011
2022 Filamin FLN-2 promotes MVB biogenesis by mediating vesicle docking on the actin cytoskeleton. The Journal of cell biology 11 35575797
2020 FLN-1/filamin is required to anchor the actomyosin cytoskeleton and for global organization of sub-cellular organelles in a contractile tissue. Cytoskeleton (Hoboken, N.J.) 11 32969593
2016 Ehlers-Danlos syndrome with lethal cardiac valvular dystrophy in males carrying a novel splice mutation in FLNA. American journal of medical genetics. Part A 11 27739212
2015 A new variant of KMT2A(MLL)-FLNA fusion transcript in acute myeloid leukemia with ins(X;11)(q28;q23q23). Cancer genetics 11 25892123
2015 Expression of FLNa in human melanoma cells regulates the function of integrin α1β1 and phosphorylation and localisation of PKB/AKT/ERK1/2 kinases. European journal of cell biology 11 26572583
2020 Where the congenital heart disease meets the pulmonary arterial hypertension, FLNA matters: a case report and literature review. BMC pediatrics 10 33143682
2013 Screening of TGFBR1, TGFBR2, and FLNA in familial mitral valve prolapse. American journal of medical genetics. Part A 10 24243761
2010 FLNA p.V528M substitution is neither associated with bilateral periventricular nodular heterotopia nor with macrothrombocytopenia. Journal of human genetics 10 20844545
2022 Platelet function and filamin A expression in two families with novel FLNA gene mutations associated with periventricular nodular heterotopia and panlobular emphysema. American journal of medical genetics. Part A 9 35156755
2015 Frontometaphyseal dysplasia and keloid formation without FLNA mutations. American journal of medical genetics. Part A 9 25899317
2024 Therapeutic potential of targeting the FLNA-regulated Wee1 kinase in adrenocortical carcinomas. International journal of cancer 8 39528354
2022 TRIP13/FLNA Complex Promotes Tumor Progression and Is Associated with Unfavorable Outcomes in Melanoma. Journal of oncology 8 36268276
2019 Septo-optic dysplasia caused by a novel FLNA splice site mutation: a case report. BMC medical genetics 8 31234783
2025 FLNA, a disulfidptosis-related gene, modulates tumor immunity and progression in colorectal cancer. Cellular & molecular biology letters 7 40713509
2024 FLNA overexpression promotes papillary thyroid cancer aggression via the FAK/AKT signaling pathway. Endocrine connections 7 38614124
2023 Hypomethylation of DRD2 promotes breast cancer through the FLNA-ERK pathway. Cancer genetics 7 37729778
2021 The variants at FLNA and FLNB contribute to the susceptibility of hypertension and stroke with differentially expressed mRNA. The pharmacogenomics journal 7 33649519
2021 Chromium (VI) promotes EMT by regulating FLNA in BLCA. Environmental toxicology 7 33978285
2021 The clinical and imaging features of FLNA positive and negative periventricular nodular heterotopia. Biomedical journal 7 35660364
2017 Androgen receptor dysfunction as a prevalent manifestation in young male carriers of a FLNA gene mutation. American journal of medical genetics. Part A 7 28432720
1995 A comparative transcriptional map of a region of 250 kb on the human and mouse X chromosome between the G6PD and the FLN1 genes. Genomics 7 7490070
2024 FLNA regulates neuronal maturation by modulating RAC1-Cofilin activity in the developing cortex. Neurobiology of disease 6 38852754
2022 Phenotypic manifestations in FLNA-related periventricular nodular heterotopia: a case report and review of the literature. BMJ case reports 6 35414575
2022 Sema3d Restrained Hepatocellular Carcinoma Progression Through Inactivating Pi3k/Akt Signaling via Interaction With FLNA. Frontiers in oncology 6 35957887
2021 Whole-Exome Sequencing Reveals a Novel Mutation of FLNA Gene in an Iranian Family with Nonsyndromic Tetralogy of Fallot. Laboratory medicine 6 33942857
2019 Microdeletion in Xq28 with a polymorphic inversion in a patient with FLNA-associated progressive lung disease. Respiratory investigation 6 30987847
2025 Pulmonary hypertension in patients carrying FLNA loss-of-function variants. The European respiratory journal 5 39510553
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
2023 Mutation of FLNA attenuating the migration of abdominal muscles contributed to Melnick-Needles syndrome (MNS) in a family with recurrent miscarriage. Molecular genetics & genomic medicine 5 36734119
2021 Exon skip-inducing variants in FLNA in an attenuated form of frontometaphyseal dysplasia. American journal of medical genetics. Part A 5 34272929

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