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ACTN4 Gene

protein-coding   GIFtS: 69
GCID: GC19P039138

Actinin, Alpha 4

(Previous name: focal segmental glomerulosclerosis 1)
(Previous symbol: FSGS1)
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Actinin, Alpha 41 2     FSGS2 5
FSGS11 2 5     ACTININ-42
Focal Segmental Glomerulosclerosis 11 2     Actinin Alpha4 Isoform2
Non-Muscle Alpha-Actinin 42 3     alpha-actinin-42
F-Actin Cross-Linking Protein2 3     

External Ids:    HGNC: 1661   Entrez Gene: 812   Ensembl: ENSG000001304027   OMIM: 6046385   UniProtKB: O437073   

Export aliases for ACTN4 gene to outside databases

Previous GC identifers: GC19P039725 GC19P039529 GC19P043814 GC19P043830 GC19P035584


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for ACTN4 Gene:
Alpha actinins belong to the spectrin gene superfamily which represents a diverse group of cytoskeletal proteins,
including the alpha and beta spectrins and dystrophins. Alpha actinin is an actin-binding protein with multiple
roles in different cell types. In nonmuscle cells, the cytoskeletal isoform is found along microfilament bundles
and adherens-type junctions, where it is involved in binding actin to the membrane. In contrast, skeletal,
cardiac, and smooth muscle isoforms are localized to the Z-disc and analogous dense bodies, where they help
anchor the myofibrillar actin filaments. This gene encodes a nonmuscle, alpha actinin isoform which is
concentrated in the cytoplasm, and thought to be involved in metastatic processes. Mutations in this gene have
been associated with focal and segmental glomerulosclerosis. (provided by RefSeq, Jul 2008)

GeneCards Summary for ACTN4 Gene:
ACTN4 (actinin, alpha 4) is a protein-coding gene. Diseases associated with ACTN4 include focal segmental glomerulosclerosis, and clear cell adenocarcinoma. GO annotations related to this gene include actin binding and calcium ion binding. An important paralog of this gene is SPTBN2.

UniProtKB/Swiss-Prot: ACTN4_HUMAN, O43707
Function: F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures.
This is a bundling protein. Probably involved in vesicular trafficking via its association with the CART complex.
The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation. Involved
in tight junction assembly in epithelial cells probably through interaction with MICALL2. Links MICALL2 to the
actin cytoskeleton and recruits it to the tight junctions

Gene Wiki entry for ACTN4 (Actinin alpha 4) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000019.10  NT_011109.17  NC_018930.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the ACTN4 gene promoter:
         Oct-B1   oct-B3   oct-B2   ATF-2   CUTL1   YY1   POU2F1   POU2F1a   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): ACTN4 promoter sequence
   Search Chromatin IP Primers for ACTN4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat ACTN4


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 19q13   Ensembl cytogenetic band:  19q13.2   HGNC cytogenetic band: 19q13

ACTN4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ACTN4 gene location

GeneLoc information about chromosome 19         GeneLoc Exon Structure

GeneLoc location for GC19P039138:  view genomic region     (about GC identifiers)

Start:
39,138,267 bp from pter      End:
39,222,223 bp from pter
Size:
83,957 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: ACTN4_HUMAN, O43707 (See protein sequence)
Recommended Name: Alpha-actinin-4  
Size: 911 amino acids; 104854 Da
Subunit: Homodimer; antiparallel (By similarity). Binds TRIM3 at the N-terminus (By similarity). Interacts with
MICALL2 (preferentially in opened conformation); stimulated by RAB13 activation (By similarity). Identified in a
complex with CASK, IQGAP1, MAGI2, NPHS1, SPTAN1 and SPTBN1 (By similarity). Identified in a IGF2BP1-dependent
mRNP granule complex containing untranslated mRNAs. Component of the CART complex, at least composed of ACTN4,
HGS/HRS, MYO5B and TRIM3. Interacts with BAIAP1 and PDLIM2
Sequence caution: Sequence=AAC17470.1; Type=Frameshift; Positions=19, 26, 124, 130, 589, 594, 787, 806;
Sequence=BAA24447.1; Type=Erroneous initiation;
3 PDB 3D structures from and Proteopedia for ACTN4:
1WLX (3D)        1YDI (3D)        2R0O (3D)    
Secondary accessions: A4K467 D6PXK4 O76048
Alternative splicing: 3 isoforms:  O43707-1   O43707-2   O43707-3   (Does not colocalize with actin cytoskeleton structures)

Explore the universe of human proteins at neXtProt for ACTN4: NX_O43707

Explore proteomics data for ACTN4 at MOPED

Post-translational modifications: 

  • Ubiquitination2 at Lys54, Lys181, Lys233, Lys350, Lys378, Lys417, Lys625, Lys632, Lys859
  • Modification sites at PhosphoSitePlus

  • See ACTN4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_004915.2  
    ENSEMBL proteins: 
     ENSP00000252699   ENSP00000439497   ENSP00000467190   ENSP00000465176   ENSP00000398393  
     ENSP00000411187  
    Reactome Protein details: O43707

    ACTN4 Human Recombinant Protein Products:

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    OriGene Protein Over-expression Lysate for ACTN4
    OriGene MassSpec for ACTN4
    OriGene Custom Protein Services for ACTN4
    GenScript Custom Purified and Recombinant Proteins Services for ACTN4
    Novus Biologicals ACTN4 Proteins
    Novus Biologicals ACTN4 Lysates
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for ACTN4

    ACTN4 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of ACTN4
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    LSBio Antibodies in human, mouse, rat for ACTN4

    ACTN4 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for ACTN4
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for ACTN4
    Cloud-Clone Corp. CLIAs for ACTN4


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    EFHAND: EF-hand domain containing

    Selected InterPro protein domains (see all 8):
     IPR014837 EF-hand_Ca_insen
     IPR002017 Spectrin_repeat
     IPR011992 EF-hand-dom_pair
     IPR002048 EF_hand_dom
     IPR018159 Spectrin/alpha-actinin

    Graphical View of Domain Structure for InterPro Entry O43707

    ProtoNet protein and cluster: O43707

    3 Blocks protein domains:
    IPB001589 Actin-binding
    IPB001715 Calponin-like actin-binding
    IPB002017 Spectrin repeat


    UniProtKB/Swiss-Prot: ACTN4_HUMAN, O43707
    Similarity: Belongs to the alpha-actinin family
    Similarity: Contains 1 actin-binding domain
    Similarity: Contains 2 CH (calponin-homology) domains
    Similarity: Contains 2 EF-hand domains
    Similarity: Contains 4 spectrin repeats


    ACTN4 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: ACTN4_HUMAN, O43707
    Function: F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures.
    This is a bundling protein. Probably involved in vesicular trafficking via its association with the CART complex.
    The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation. Involved
    in tight junction assembly in epithelial cells probably through interaction with MICALL2. Links MICALL2 to the
    actin cytoskeleton and recruits it to the tight junctions

         Gene Ontology (GO): Selected molecular function terms (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001882nucleoside binding IDA12411747
    GO:0003779actin binding TAS8104223
    GO:0005178integrin binding TAS8104223
    GO:0005509calcium ion binding IEA--
    GO:0005515protein binding IPI15619032
         
    ACTN4 for ontologies           About GeneDecksing


    Phenotypes:
         8 MGI mutant phenotypes (inferred from 3 alleles(MGI details for Actn4):
     cardiovascular system  cellular  growth/size/body  hematopoietic system  homeostasis/metabolism 
     immune system  mortality/aging  renal/urinary system 

    ACTN4 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-out Actn4tm1Plk for ACTN4

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for ACTN4
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for ACTN4

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for ACTN4
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for ACTN4

    miRNA
    Products:
        
    miRTarBase miRNAs that target ACTN4:
    hsa-mir-378a-5p (MIRT043999), hsa-mir-652-3p (MIRT039568), hsa-mir-935 (MIRT036683), hsa-mir-23a-3p (MIRT050392), hsa-mir-339-5p (MIRT042783), hsa-mir-185-5p (MIRT045364), hsa-mir-769-5p (MIRT039177), hsa-mir-1 (MIRT023681), hsa-mir-296-3p (MIRT038369), hsa-mir-193b-3p (MIRT041470), hsa-mir-615-3p (MIRT040028), hsa-mir-26a-5p (MIRT050151), hsa-mir-320a (MIRT044609), hsa-mir-744-5p (MIRT037676), hsa-let-7b-5p (MIRT051940), hsa-mir-92b-3p (MIRT040634), hsa-mir-23b-3p (MIRT046259), hsa-mir-182-5p (MIRT047208), hsa-let-7c-5p (MIRT051747), hsa-mir-16-5p (MIRT051105), hsa-mir-96-5p (MIRT048735), hsa-mir-324-3p (MIRT043003), hsa-mir-324-5p (MIRT043214)

    Block miRNA regulation of human, mouse, rat ACTN4 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate ACTN4 (see all 44):
    hsa-miR-142-5p hsa-miR-548j hsa-miR-4307 hsa-miR-548k hsa-miR-605 hsa-miR-374a hsa-miR-3921 hsa-miR-548l
    SwitchGear 3'UTR luciferase reporter plasmidACTN4 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for ACTN4
    Predesigned siRNA for gene silencing in human, mouse, rat ACTN4

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for ACTN4

    Clone
    Products:
         
    OriGene clones in human, mouse for ACTN4 (see all 7)
    OriGene ORF clones in mouse, rat for ACTN4
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: ACTN4 (NM_004924)
    Sino Biological Human cDNA Clone for ACTN4
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for ACTN4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat ACTN4

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for ACTN4
    Browse ESI BIO Cell Lines and PureStem Progenitors for ACTN4 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ACTN4


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    ACTN4_HUMAN, O43707: Nucleus. Cytoplasm. Cell junction (By similarity). Note=Localized in cytoplasmic mRNP
    granules containing untranslated mRNAs. Colocalizes with actin stress fibers. Nuclear translocation can be
    induced by the PI3 kinase inhibitor wortmannin or by cytochalasin D. Exclusively localized in the nucleus in a
    limited number of cell lines (breast cancer cell line MCF-7, oral floor cancer IMC-2, and bladder cancer KU-7)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    extracellular5
    nucleus5
    cytoskeleton3
    cytosol3
    endosome1
    plasma membrane1

    Gene Ontology (GO): Selected cellular component terms (see all 15):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001725stress fiber IEA--
    GO:0005576extracellular region TAS--
    GO:0005634nucleus IDA9508771
    GO:0005737cytoplasm IDA9508771
    GO:0005911cell-cell junction IEA--

    ACTN4 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for ACTN4 About   (see all 22)  
    See pathways by source

    SuperPathContained pathways About
    1Hypertrophic cardiomyopathy (HCM)
    Arrhythmogenic right ventricular cardiomyopathy (ARVC)0.54
    Arrhythmogenic right ventricular cardiomyopathy0.54
    2Sertoli-Sertoli Cell Junction Dynamics
    Sertoli-Sertoli Cell Junction Dynamics0.38
    Epithelial Tight Junctions0.36
    Germ Cell-Sertoli Cell Junction Dynamics0.38
    3Cell adhesion Integrin mediated cell adhesion and migration
    Cell adhesion Integrin mediated cell adhesion and migration0.49
    Cytoskeleton remodeling Fibronectin binding integrins in cell motility0.32
    Cytoskeleton remodeling Integrin outside in signaling0.37
    4Response to elevated platelet cytosolic Ca2+
    Response to elevated platelet cytosolic Ca2+0.94
    Platelet degranulation0.94
    5Hemostasis
    Hemostasis0.43
    Platelet activation, signaling and aggregation0.43

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for ACTN4 (see all 6)
        Sertoli-Sertoli Cell Junction Dynamics
    ILK Signaling
    Remodeling of Adherens Junctions
    Epithelial Tight Junctions
    Germ Cell-Sertoli Cell Junction Dynamics

    Selected GeneGo (Thomson Reuters) Pathways for ACTN4 (see all 6)
        Cell adhesion Endothelial cell contacts by non-junctional mechanisms
    Cytoskeleton remodeling Integrin outside-in signaling
    Cell adhesion Integrin-mediated cell adhesion and migration
    Cell adhesion Endothelial cell contacts by junctional mechanisms
    Inhibitory action of Lipoxins on neutrophil migration

    2 BioSystems Pathways for ACTN4
        Striated Muscle Contraction
    Arrhythmogenic right ventricular cardiomyopathy


    2 Reactome Pathways for ACTN4
        Nephrin interactions
    Platelet degranulation


    Selected Kegg Pathways  (Kegg details for ACTN4) (see all 9):
        Focal adhesion
    Adherens junction
    Tight junction
    Leukocyte transendothelial migration
    Regulation of actin cytoskeleton


    ACTN4 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including ACTN4: 
              Adherens Junctions in human mouse rat
              Tight Junctions in human mouse rat
              Focal Adhesions in human mouse rat
              Cell Motility in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for ACTN4

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for ACTN4 (O437071, 2, 3 ENSP000002526994) via UniProtKB, MINT, STRING, and/or I2D (see all 263)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    TJP1Q071571, 2, 3, ENSP000002815374EBI-351526,EBI-79553 MINT-3088497 MINT-3088449 MINT-3088309 MINT-2984673 I2D: score=7 STRING: ENSP00000281537
    MYOZ1Q9NP982, 3, ENSP000003522724MINT-68245 I2D: score=5 STRING: ENSP00000352272
    SACSQ9NZJ42, 3, ENSP000003717294MINT-2856495 I2D: score=3 STRING: ENSP00000371729
    CTNNB1P352221, 3, ENSP000003444564EBI-351526,EBI-491549 I2D: score=1 STRING: ENSP00000344456
    MAP3K3Q997592, 3MINT-48410 I2D: score=2 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 13):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001666response to hypoxia IEA--
    GO:0002576platelet degranulation TAS--
    GO:0007596blood coagulation TAS--
    GO:0008104protein localization ----
    GO:0015031protein transport IEA--

    ACTN4 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for ACTN4

    4 Novoseek inferred chemical compound relationships for ACTN4 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tyrosine 5.23 8 19833736 (1), 19920151 (1)
    calcium 0 3 15843471 (1), 19206166 (1)
    threonine 0 1 12239280 (1)
    serine 0 1 12239280 (1)



    ACTN4 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for ACTN4 gene: 
    NM_004924.4  

    Unigene Cluster for ACTN4:

    Actinin, alpha 4
    Hs.270291  [show with all ESTs]
    Unigene Representative Sequence: NM_004924
    11 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000588618 ENST00000252699(uc010egc.2 uc002oja.2 uc021uug.1)
    ENST00000390009 ENST00000589528 ENST00000495553 ENST00000586538 ENST00000489451
    ENST00000440400 ENST00000497637 ENST00000477174 ENST00000424234
    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate ACTN4 (see all 44):
    hsa-miR-142-5p hsa-miR-548j hsa-miR-4307 hsa-miR-548k hsa-miR-605 hsa-miR-374a hsa-miR-3921 hsa-miR-548l
    SwitchGear 3'UTR luciferase reporter plasmidACTN4 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat ACTN4
    Clone
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    OriGene clones in human, mouse for ACTN4 (see all 7)
    OriGene ORF clones in mouse, rat for ACTN4
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: ACTN4 (NM_004924)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for ACTN4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat ACTN4
    Primer
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    OriGene qPCR primer pairs and template standards for ACTN4
    OriGene qSTAR qPCR primer pairs in human, mouse for ACTN4
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat ACTN4
      QuantiTect SYBR Green Assays in human, mouse, rat ACTN4
      QuantiFast Probe-based Assays in human, mouse, rat ACTN4

    Additional mRNA sequence: 

    AK299955.1 AK304554.1 AK309361.1 AK309363.1 AK309364.1 BC005033.1 BC015620.2 BC107062.1 
    BX647098.1 D89980.1 DQ431186.1 GU987085.1 Z36797.1 

    Selected DOTS entries (see all 50):

    DT.454297  DT.92038152  DT.100857867  DT.95220089  DT.87077774  DT.100857868  DT.100857861  DT.100857862 
    DT.95249964  DT.95211807  DT.91923640  DT.95220202  DT.92330587  DT.102839407  DT.100857884  DT.121498871 
    DT.121498968  DT.100034739  DT.100857877  DT.92459345  DT.92459353  DT.95339553  DT.100045174  DT.92459310 

    Selected AceView cDNA sequences (see all 987):

    F28413 AI983663 AA291649 BP431592 BM663421 BQ427452 BG108139 R27806 
    AI358422 BU540859 CN482283 BM052851 BF436966 D82247 CA393248 BQ941049 
    AW177739 BG288238 AI911171 BG419792 BQ895962 CA416360 BQ051502 BU179945 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for ACTN4 (see all 9)    About this scheme

    ExUns: 1a · 1b ^ 2 ^ 3a · 3b ^ 4a · 4b ^ 5 ^ 6 ^ 7a · 7b ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b ^ 13a · 13b ^ 14 ^ 15 ^ 16 ^ 17 ^ 18a · 18b ^ 19 ^
    SP1:                                                                          -                                                                                 
    SP2:                                                                    -                                                                                       
    SP3:                                                                                                                                                            
    SP4:                          -     -     -     -     -     -     -     -     -     -     -                                                                     
    SP5:                                                                    -                                                                                       

    ExUns: 20a · 20b ^ 21a · 21b ^ 22a · 22b ^ 23a · 23b · 23c · 23d ^ 24
    SP1:  -           -     -                                             
    SP2:                                                                  
    SP3:  -     -     -                                                   
    SP4:                                                                  
    SP5:                                                                  


    ECgene alternative splicing isoforms for ACTN4

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    ACTN4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: CGAGGGGCCA
    ACTN4 Expression
    About this image


    ACTN4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 21) fully expand
     
     Testis (Reproductive System)
             Leydig Cells Testis Interstitium
     
     Kidney (Urinary System)
             Podocytes Podocyte Layer
     
     Ovary (Reproductive System)
             Oviduct
     
     Epithelial Cells
             Podocytes Podocyte Layer
     
     Trophoblast (Extraembryonic Tissues)
             Trophoblast Cells Trophoblast
    ACTN4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    ACTN4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.270291

    UniProtKB/Swiss-Prot: ACTN4_HUMAN, O43707
    Tissue specificity: Widely expressed

        Pathway & Disease-focused RT2 Profiler PCR Arrays including ACTN4: 
              Adherens Junctions in human mouse rat
              Tight Junctions in human mouse rat
              Focal Adhesions in human mouse rat
              Cell Motility in human mouse rat

    Primer
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for ACTN4 gene from Selected species (see all 15)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Actn41 , 5 actinin alpha 41, 5 90.34(n)1
    97.8(a)1
      7 (16.94 cM)5
    605951  NM_021895.21  NP_068695.11 
     288932485 
    chicken
    (Gallus gallus)
    Aves ACTN41 actinin, alpha 4 86.95(n)
    92.92(a)
      396024  NM_205126.1  NP_990457.1 
    lizard
    (Anolis carolinensis)
    Reptilia ACTN46
    actinin, alpha 4
    91(a)
    1 ↔ 1
    GL343665.1(143759-312977)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia actn41 actinin, alpha 4 78.36(n)
    91.94(a)
      448522  NM_001006809.1  NP_001006810.1 
    zebrafish
    (Danio rerio)
    Actinopterygii wufb53f052 wufb53f05 79.58(n)   322221  BC054901.1 
    worm
    (Caenorhabditis elegans)
    Secernentea sma-16
    Protein SMA-1, isoform a
    8(a)
    many ↔ many
    V(11899564-11916623) WBGene00004855


    ENSEMBL Gene Tree for ACTN4 (if available)
    TreeFam Gene Tree for ACTN4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for ACTN4 gene
    SPTBN22  SPTA12  SYNE22  SPTBN42  SPTB2  SPTBN12  ACTN22  SPTBN52  
    SPTAN12  SYNE12  ACTN12  CLMN2  
    17 SIMAP similar genes for ACTN4 using alignment to 6 protein entries:     ACTN4_HUMAN (see all proteins):
    MLL-ACTN4    ACTN2    ACTN1    ACTN3    MACF1    HSpTB1
    SPTBN2    SPNB4    SPTBN4    SPTBN1    SPTB    CALM1
    CALM2    CALM3    SPTAN1    CETN3    CLMN

    ACTN4 for paralogs           About GeneDecksing


    2 Pseudogenes.org Pseudogenes for ACTN4
    PGOHUM00000244677 PGOHUM00000246045


    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for ACTN4 (see all 1937)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 19 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs289393761,2,4
    Focal segmental glomerulosclerosis 1 (FSGS1)4--see VAR_0103802 mis40--------
    rs289393751,2,4
    Focal segmental glomerulosclerosis 1 (FSGS1)4--see VAR_0103792 mis40--------
    rs289393741,2,4
    Focal segmental glomerulosclerosis 1 (FSGS1)4--see VAR_0103782 mis40--------
    rs1998032271,2
    C--35597129(+) ATGATC/TTTTTT 1 -- int10--------
    rs1490482981,2
    C--35616790(+) TGTGC-/GTGTGTGT
    /GTGTGTGTGT
    GTGTG
    1 -- int10--------
    rs114524021,2
    C--35631949(+) AGATAA/-TATCG 1 -- int11Minor allele frequency- -:0.00NA 2
    rs609375731,2
    C--39147787(+) TTTTTT/-GAGAT 1 -- int11Minor allele frequency- -:0.50NA 2
    rs584741891,2
    C--39151623(+) AGAGA-/GAACCAA 1 -- int10--------
    rs567443001,2
    C--39153017(+) GCACT-/GA    
       T
    /TGA
    GATGA
    2 -- cds10--------
    rs730326971,2
    C,F--39163197(+) ATTTGA/GTCTAT 1 -- int13Minor allele frequency- G:0.14NA WA 240

    HapMap Linkage Disequilibrium report for ACTN4 (39138267 - 39222223 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 10 variations for ACTN4:    About this table    
    Variant IDTypeSubtypePubMed ID
    dgv641e199CNV Deletion23128226
    esv2718535CNV Deletion23290073
    nsv911668CNV Loss21882294
    nsv833828CNV Loss17160897
    nsv911669CNV Loss21882294
    esv22820CNV Loss19812545
    nsv833826CNV Loss17160897
    nsv817834CNV Gain17921354
    nsv833827CNV Gain17160897
    nsv911667CNV Gain21882294

    Human Gene Mutation Database (HGMD): ACTN4
    Site Specific Mutation Identification with PCR Assays
    1 Copy Number PCR Panel containing ACTN4:
    Ovarian Cancer
    SeqTarget long-range PCR primers for resequencing ACTN4
    DNA2.0 Custom Variant and Variant Library Synthesis for ACTN4

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 604638   
    OMIM disorders: 603278  
    UniProtKB/Swiss-Prot: ACTN4_HUMAN, O43707
  • Focal segmental glomerulosclerosis 1 (FSGS1) [MIM:603278]: A renal pathology defined by the presence of
    segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive
    decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state
    requiring either dialysis therapy or kidney transplantation. Note=The disease is caused by mutations affecting
    the gene represented in this entry

  • Selected diseases for ACTN4 (see all 43):    
    About MalaCards
    focal segmental glomerulosclerosis    clear cell adenocarcinoma    ovarian clear cell adenocarcinoma    focal segmental glomerulosclerosis 2
    nephrosis    steroid-resistant nephrotic syndrome    thin basement membrane nephropathy    frasier syndrome
    crescentic glomerulonephritis    nephrotic syndrome    proteinuria    sickle cell anemia
    wilms tumor    protein s deficiency    endocarditis    glomerulonephritis
    diabetic nephropathy    esophageal cancer    pancreatic ductal adenocarcinoma    kidney disease

    3 diseases from the University of Copenhagen DISEASES database for ACTN4:
    Nephrotic syndrome     Glomerulonephritis     Proteinuria

    ACTN4 for disorders           About GeneDecksing

    Selected Novoseek inferred disease relationships for ACTN4 gene (see all 14)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    nphs1 90.9 7 15780077 (1), 18443213 (1), 16186681 (1), 16752799 (1) (see all 7)
    glomerulosclerosis, focal segmental 90.5 30 19666657 (2), 16251236 (2), 18436095 (2), 19142020 (2) (see all 17)
    nephrotic syndrome 78.9 13 15031339 (2), 15780077 (1), 11793093 (1), 19956976 (1) (see all 9)
    glomerulosclerosis 73.4 5 17082197 (1), 12782671 (1), 19956976 (1), 15627790 (1)
    proteinuria 71 9 11730159 (1), 11793093 (1), 17082197 (1), 12761234 (1) (see all 7)
    nephrosis 52.7 2 15031339 (1)
    renal disease 52.5 4 16841182 (1), 18164029 (1), 19652713 (1)
    renal failure chronic 41.1 3 12617336 (2)
    wilms tumor 31.7 2 14569107 (2)
    renal failure 31.4 2 17082197 (1), 19838113 (1)

    Genetic Association Database (GAD): ACTN4
    Human Genome Epidemiology (HuGE) Navigator: ACTN4 (8 documents)

    Export disorders for ACTN4 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for ACTN4 gene, integrated from 10 sources (see all 227):
    (articles sorted by number of sources associating them with ACTN4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. (PubMed id 10700177)1, 2, 3, 9 Kaplan J.M.... Pollak M.R. (Nat. Genet. 2000)
    2. ACTN4 gene mutations and single nucleotide polymorphisms in idiopathic focal segmental glomerulosclerosis. (PubMed id 19142020)1, 4, 9 Dai S....Chen N. (Nephron Clin Pract 2009)
    3. The human non-muscle alpha-actinin protein encoded by the ACTN4 gene suppresses tumorigenicity of human neuroblastoma cells. (PubMed id 10656685)1, 2, 9 Nikolopoulos S.N.... Ross R.A. (Oncogene 2000)
    4. Association analysis of podocyte slit diaphragm genes as candidates for diabetic nephropathy. (PubMed id 17968527)1, 4, 9 Ihalmo P....Groop P.H. (Diabetologia 2008)
    5. [Novel splicing isoform of actin-binding protein alpha-actinin 4 in epidermoid carcinoma cells A431]. (PubMed id 22567897)1, 2 Aksenova V.I.u....Tentler D.G. (Tsitologiia 2012)
    6. Human variation in alcohol response is influenced by variation in neuronal signaling genes. (PubMed id 20201926)1, 4 Joslyn G....White R.L. (Alcohol. Clin. Exp. Res. 2010)
    7. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PubMed id 20628086)1, 4 Bailey S.D....Anand S. (Diabetes Care 2010)
    8. The R229Q mutation in NPHS2 may predispose to proteinuria in thin-basement-membrane nephropathy. (PubMed id 18726620)1, 4 Tonna S....Savige J. (Pediatr. Nephrol. 2008)
    9. Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry. (PubMed id 17370265)1, 2 Denis N.J.... Figeys D. (Proteomics 2007)
    10. Molecular composition of IMP1 ribonucleoprotein granules. (PubMed id 17289661)1, 2 Joeson L.... Nielsen F.C. (Mol. Cell. Proteomics 2007)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 81 HGNC: 166 AceView: ACTN4 Ensembl:ENSG00000130402 euGenes: HUgn81
    ECgene: ACTN4 Kegg: 81 H-InvDB: ACTN4

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for ACTN4 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for ACTN4 Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=ACTN4[genesymbol]

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for ACTN4 gene:
    Search GeneIP for patents involving ACTN4

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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