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    FLNA filamin A [ Homo sapiens (human) ]

    Gene ID: 2316, updated on 21-Mar-2023

    Summary

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    Official Symbol
    FLNAprovided by HGNC
    Official Full Name
    filamin Aprovided by HGNC
    Primary source
    HGNC:HGNC:3754
    See related
    Ensembl:ENSG00000196924 MIM:300017; AllianceGenome:HGNC:3754
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    FLN; FMD; MNS; OPD; ABPX; CSBS; CVD1; FGS2; FLN1; NHBP; OPD1; OPD2; XLVD; XMVD; FLN-A; ABP-280
    Summary
    The protein encoded by this gene is an actin-binding protein that crosslinks actin filaments and links actin filaments to membrane glycoproteins. The encoded protein is involved in remodeling the cytoskeleton to effect changes in cell shape and migration. This protein interacts with integrins, transmembrane receptor complexes, and second messengers. Defects in this gene are a cause of several syndromes, including periventricular nodular heterotopias (PVNH1, PVNH4), otopalatodigital syndromes (OPD1, OPD2), frontometaphyseal dysplasia (FMD), Melnick-Needles syndrome (MNS), and X-linked congenital idiopathic intestinal pseudoobstruction (CIIPX). Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2009]
    Expression
    Broad expression in endometrium (RPKM 345.6), esophagus (RPKM 285.0) and 22 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See FLNA in Genome Data Viewer
    Location:
    Xq28
    Exon count:
    48
    Annotation release Status Assembly Chr Location
    RS_2023_03 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (154348531..154374634, complement)
    RS_2023_03 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (152585064..152611166, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (153576899..153603002, complement)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene transketolase like 1 Neighboring gene uncharacterized LOC105373386 Neighboring gene Xq28 proximal FLNA-EMD recombination region Neighboring gene Xq28 distal FLNA-EMD recombination region Neighboring gene uncharacterized LOC124905228 Neighboring gene emerin

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. The long Filamin-A isoform is required for intestinal development and motility: implications for chronic intestinal pseudo-obstruction. Zada A, et al. Hum Mol Genet, 2023 Jan 1. PMID 35981053, Free PMC Article
    2. Heterogenous Disease Course and Long-Term Outcome of Children's Interstitial Lung Disease Related to Filamin A Gene Variants. Carlens J, et al. Ann Am Thorac Soc, 2022 Dec. PMID 35767027
    3. Computational analysis of missense filamin-A variants, including the novel p.Arg484Gln variant of two brothers with periventricular nodular heterotopia. Gerlevik U, et al. PLoS One, 2022. PMID 35613087, Free PMC Article
    4. Exon skip-inducing variants in FLNA in an attenuated form of frontometaphyseal dysplasia. Wade EM, et al. Am J Med Genet A, 2021 Dec. PMID 34272929
    5. Terminal osseous dysplasia with pigmentary defects and cardiomyopathy caused by a novel FLNA variant. Rumping L, et al. Am J Med Genet A, 2021 Dec. PMID 34254723, Free PMC Article

    See all (597) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The long Filamin-A isoform is required for intestinal development and motility: implications for chronic intestinal pseudo-obstruction.
      Title: The long Filamin-A isoform is required for intestinal development and motility: implications for chronic intestinal pseudo-obstruction.
    2. Heterogenous Disease Course and Long-Term Outcome of Children's Interstitial Lung Disease Related to Filamin A Gene Variants.
      Title: Heterogenous Disease Course and Long-Term Outcome of Children's Interstitial Lung Disease Related to Filamin A Gene Variants.
    3. A gain-of-function filamin A mutation in mouse platelets induces thrombus instability.
      Title: A gain-of-function filamin A mutation in mouse platelets induces thrombus instability.
    4. A-to-I RNA editing of Filamin A regulates cellular adhesion, migration and mechanical properties.
      Title: A-to-I RNA editing of Filamin A regulates cellular adhesion, migration and mechanical properties.
    5. Computational analysis of missense filamin-A variants, including the novel p.Arg484Gln variant of two brothers with periventricular nodular heterotopia.
      Title: Computational analysis of missense filamin-A variants, including the novel p.Arg484Gln variant of two brothers with periventricular nodular heterotopia.
    6. TRIM44 promotes BRCA1 functions in HR repair to induce Cisplatin Chemoresistance in Lung Adenocarcinoma by Deubiquitinating FLNA.
      Title: TRIM44 promotes BRCA1 functions in HR repair to induce Cisplatin Chemoresistance in Lung Adenocarcinoma by Deubiquitinating FLNA.
    7. Filamin A Is Required for NK Cell Cytotoxicity at the Expense of Cytokine Production via Synaptic Filamentous Actin Modulation.
      Title: Filamin A Is Required for NK Cell Cytotoxicity at the Expense of Cytokine Production via Synaptic Filamentous Actin Modulation.
    8. Exon skip-inducing variants in FLNA in an attenuated form of frontometaphyseal dysplasia.
      Title: Exon skip-inducing variants in FLNA in an attenuated form of frontometaphyseal dysplasia.
    9. Terminal osseous dysplasia with pigmentary defects and cardiomyopathy caused by a novel FLNA variant.
      Title: Terminal osseous dysplasia with pigmentary defects and cardiomyopathy caused by a novel FLNA variant.
    10. Whole-Exome Sequencing Reveals a Novel Mutation of FLNA Gene in an Iranian Family with Nonsyndromic Tetralogy of Fallot.
      Title: Whole-Exome Sequencing Reveals a Novel Mutation of FLNA Gene in an Iranian Family with Nonsyndromic Tetralogy of Fallot.
    Submit: New GeneRIF Correction See all GeneRIFs (246)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Cardiac valvular dysplasia, X-linked
    MedGen: C0262436 OMIM: 314400 GeneReviews: FLNA Deficiency
    		Compare labs
    FG syndrome 2
    MedGen: C1845902 OMIM: 300321 GeneReviews: Not available
    		Compare labs
    Frontometaphyseal dysplasia 1
    MedGen: C4281559 OMIM: 305620 GeneReviews: X-Linked Otopalatodigital Spectrum Disorders
    		Compare labs
    Heterotopia, periventricular, X-linked dominant
    MedGen: C1848213 OMIM: 300049 GeneReviews: FLNA Deficiency
    		Compare labs
    Intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked
    MedGen: C2746068 OMIM: 300048 GeneReviews: FLNA Deficiency
    		Compare labs
    Melnick-Needles syndrome
    MedGen: C0025237 OMIM: 309350 GeneReviews: X-Linked Otopalatodigital Spectrum Disorders
    		Compare labs
    Oto-palato-digital syndrome, type I
    MedGen: C0265251 OMIM: 311300 GeneReviews: X-Linked Otopalatodigital Spectrum Disorders
    		Compare labs
    Oto-palato-digital syndrome, type II
    MedGen: C1844696 OMIM: 304120 GeneReviews: X-Linked Otopalatodigital Spectrum Disorders
    		Compare labs
    Terminal osseous dysplasia-pigmentary defects syndrome
    MedGen: C1846129 OMIM: 300244 GeneReviews: Not available
    		Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2020-12-02)

    ClinGen Genome Curation PagePubMed
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2020-12-02)

    ClinGen Genome Curation PagePubMed

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Tandem affinity purification and mass spectrometry analysis identify filamin A (FLNA), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    env Filamin-A-dependent activation of the RhoA-ROCK-LIMK-cofilin pathway is a major event in HIV-1 gp120-induced receptor clustering PubMed
    env HIV-1 gp120 promotes filamin binding to both CD4 and CXCR4 PubMed
    Gag-Pol gag-pol Tandem affinity purification and mass spectrometry analysis identify filamin A (FLNA), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Nef nef Tandem affinity purification and mass spectrometry analysis identify filamin A (FLNA), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Pr55(Gag) gag Cellular biotinylated filamin A, alpha (FLNA) protein is incorporated into HIV-1 Gag virus-like particles PubMed
    gag Tandem affinity purification and mass spectrometry analysis identify filamin A (FLNA), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    gag HIV-1 Gag binds to filamin A through the CA domain, which leads to facilitate Gag trafficking to the plasma membrane PubMed
    gag HIV-1 Gag co-localizes with filamin A in mammalian cells. Depletion of filamin A inhibits HIV-1 particle release and induces Gag accumulation at the LE/MVB compartment PubMed
    Tat tat Filamin A, alpha (FLNA) is identified to interact with HIV-1 Tat mutant Nullbasic in HeLa cells by LC MS/MS PubMed
    tat Expression of HIV-1 Tat upregulates the abundance of filamin A, alpha (FLNA) in the nucleoli of Jurkat T-cells PubMed
    Vpr vpr HIV-1 Vpr upregulates FLNA in HeLa cells within 12 hours of exposure PubMed
    retropepsin gag-pol A number of focal adhesion plaque proteins are specifically cleaved by HIV-1 protease, including fimbrin, focal adhesion plaque kinase (FAK), talin, and, to a lesser extent, filamin, spectrin and fibronectin PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ43642, DKFZp434P031

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA-binding transcription factor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables Fc-gamma receptor I complex binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables G protein-coupled receptor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables GTPase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables RNA binding HDA PubMed 
    enables actin filament binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables cadherin binding HDA PubMed 
    enables kinase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables potassium channel regulator activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein kinase C binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables small GTPase binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables transmembrane transporter binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in actin crosslink formation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in actin cytoskeleton reorganization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in adenylate cyclase-inhibiting dopamine receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in angiogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in blood coagulation, intrinsic pathway NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in blood vessel remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cell-cell junction organization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cilium assembly IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cytoplasmic sequestering of protein IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in early endosome to late endosome transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in epithelial to mesenchymal transition IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in establishment of protein localization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in heart morphogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in megakaryocyte development NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    acts_upstream_of_or_within mitotic spindle assembly IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of DNA-binding transcription factor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of neuron projection development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of transcription by RNA polymerase I IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in platelet aggregation HMP PubMed 
    involved_in positive regulation of I-kappaB kinase/NF-kappaB signaling HMP PubMed 
    involved_in positive regulation of axon regeneration IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of integrin-mediated signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of platelet activation NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of potassium ion transmembrane transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of protein import into nucleus IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of substrate adhesion-dependent cell spreading IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein localization to cell surface IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein localization to plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein stabilization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in receptor clustering IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of actin filament bundle assembly IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of cell migration IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of membrane repolarization during atrial cardiac muscle cell action potential IC
    Inferred by Curator
    more info
    		  
    involved_in regulation of membrane repolarization during cardiac muscle cell action potential ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in release of sequestered calcium ion into cytosol NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in semaphorin-plexin signaling pathway IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in synapse organization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in tubulin deacetylation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in wound healing, spreading of cells IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of Myb complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in Z disc ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    located_in actin cytoskeleton IC
    Inferred by Curator
    more info
    		 PubMed 
    located_in actin cytoskeleton IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in actin filament bundle IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in axonal growth cone IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in brush border IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cell cortex IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cell-cell junction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    located_in focal adhesion HDA PubMed 
    part_of glycoprotein Ib-IX-V complex NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in membrane HDA PubMed 
    located_in nucleolus IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in perikaryon IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in trans-Golgi network IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    filamin-A
    Names
    actin binding protein 280
    alpha-filamin
    endothelial actin-binding protein
    epididymis secretory sperm binding protein
    filamin A, alpha
    filamin-1
    non-muscle filamin

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_011506.2 RefSeqGene

      Range
      5005..31108
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1340

    mRNA and Protein(s)

    1. NM_001110556.2 → NP_001104026.1  filamin-A isoform 2

      See identical proteins and their annotated locations for NP_001104026.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) includes an alternate in-frame exon and encodes a slightly longer protein isoform (2).
      Source sequence(s)
      AB191260, AL050396, BP235228, X53416
      Consensus CDS
      CCDS48194.1
      UniProtKB/Swiss-Prot
      P21333, Q8NF52
      UniProtKB/TrEMBL
      Q60FE5, Q6NXF2
      Related
      ENSP00000358866.3, ENST00000369850.10
      Conserved Domains (4) summary
      smart00033
      Location:172 → 264
      CH; Calponin homology domain
      smart00557
      Location:1448 → 1542
      IG_FLMN; Filamin-type immunoglobulin domains
      cd00014
      Location:44 → 148
      CH; Calponin homology domain; actin-binding domain which may be present as a single copy or in tandem repeats (which increases binding affinity). The CH domain is found in cytoskeletal and signal transduction proteins, including actin-binding proteins like ...
      pfam00630
      Location:1445 → 1536
      Filamin; Filamin/ABP280 repeat

    2. NM_001456.4 → NP_001447.2  filamin-A isoform 1

      See identical proteins and their annotated locations for NP_001447.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) is the predominant transcript and encodes a slightly shorter protein isoform (1).
      Source sequence(s)
      AB191260, AC245140, BC067111, BP235228, X53416
      Consensus CDS
      CCDS44021.1
      UniProtKB/Swiss-Prot
      P21333
      UniProtKB/TrEMBL
      Q60FE5, Q6NXF2
      Related
      ENSP00000353467.4, ENST00000360319.9
      Conserved Domains (4) summary
      smart00033
      Location:172 → 264
      CH; Calponin homology domain
      smart00557
      Location:1448 → 1542
      IG_FLMN; Filamin-type immunoglobulin domains
      cd00014
      Location:44 → 148
      CH; Calponin homology domain; actin-binding domain which may be present as a single copy or in tandem repeats (which increases binding affinity). The CH domain is found in cytoskeletal and signal transduction proteins, including actin-binding proteins like ...
      pfam00630
      Location:1445 → 1536
      Filamin; Filamin/ABP280 repeat

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_03

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      154348531..154374634 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      152585064..152611166 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P21333.4 GenPept UniProtKB/Swiss-Prot:P21333

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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