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Aliases for ACTN4 Gene

Aliases for ACTN4 Gene

  • Actinin Alpha 4 2 3 5
  • Focal Segmental Glomerulosclerosis 1 2 3
  • Non-Muscle Alpha-Actinin 4 3 4
  • Alpha-Actinin-4 3
  • ACTININ-4 3
  • FSGS1 3
  • FSGS 3

External Ids for ACTN4 Gene

Previous HGNC Symbols for ACTN4 Gene

  • FSGS1

Previous GeneCards Identifiers for ACTN4 Gene

  • GC19P039725
  • GC19P039529
  • GC19P043814
  • GC19P043830
  • GC19P039138
  • GC19P035584

Summaries for ACTN4 Gene

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 Glomerulosclerosis, Focal Segmental, 1 and Familial Idiopathic Steroid-Resistant Nephrotic Syndrome With Focal Segmental Hyalinosis. Among its related pathways are Primary Focal Segmental Glomerulosclerosis FSGS and Tight junction. GO annotations related to this gene include poly(A) RNA binding and protein homodimerization activity. An important paralog of this gene is ACTN1.

UniProtKB/Swiss-Prot for ACTN4 Gene

  • F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (Probable). 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 (PubMed:15772161). 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 (By similarity). May also function as a transcriptional coactivator, stimulating transcription mediated by the nuclear hormone receptors PPARG and RARA (PubMed:22351778).

Gene Wiki entry for ACTN4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ACTN4 Gene

Genomics for ACTN4 Gene

Regulatory Elements for ACTN4 Gene


Enhancers around ACTN4 on UCSC Golden Path with GeneCards custom track

Promoters for ACTN4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000346304 1384 3601 HDGF PKNOX1 CREB3L1 WRNIP1 ZFP64 ARID4B SIN3A DMAP1 ZNF2 YY1

Genomic Location for ACTN4 Gene

Chromosome:
19
Start:
38,647,616 bp from pter
End:
38,731,583 bp from pter
Size:
83,968 bases
Orientation:
Plus strand

Genomic View for ACTN4 Gene

Genes around ACTN4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ACTN4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ACTN4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ACTN4 Gene

Proteins for ACTN4 Gene

  • Protein details for ACTN4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O43707-ACTN4_HUMAN
    Recommended name:
    Alpha-actinin-4
    Protein Accession:
    O43707
    Secondary Accessions:
    • A4K467
    • D6PXK4
    • O76048

    Protein attributes for ACTN4 Gene

    Size:
    911 amino acids
    Molecular mass:
    104854 Da
    Quaternary structure:
    • 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. Interacts with PPARG and RARA.
    SequenceCaution:
    • Sequence=AAC17470.1; Type=Frameshift; Positions=19, 26, 124, 130, 589, 594, 787, 806; Evidence={ECO:0000305}; Sequence=BAA24447.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for ACTN4 Gene

    Alternative splice isoforms for ACTN4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ACTN4 Gene

Post-translational modifications for ACTN4 Gene

  • Ubiquitination at Lys 181, Lys 233, Lys 378, Lys 625, Lys 632, and Lys 859
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for ACTN4 (ACTN4)
  • Cloud-Clone Corp. Antibodies for ACTN4

No data available for DME Specific Peptides for ACTN4 Gene

Domains & Families for ACTN4 Gene

Gene Families for ACTN4 Gene

Suggested Antigen Peptide Sequences for ACTN4 Gene

Graphical View of Domain Structure for InterPro Entry

O43707

UniProtKB/Swiss-Prot:

ACTN4_HUMAN :
  • Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif that mediates interaction with nuclear receptors.
  • Belongs to the alpha-actinin family.
  • Contains 4 spectrin repeats.
Domain:
  • Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif that mediates interaction with nuclear receptors.
  • Contains 1 actin-binding domain.
  • Contains 2 CH (calponin-homology) domains.
  • Contains 2 EF-hand domains.
Family:
  • Belongs to the alpha-actinin family.
Similarity:
  • Contains 4 spectrin repeats.
genes like me logo Genes that share domains with ACTN4: view

Function for ACTN4 Gene

Molecular function for ACTN4 Gene

UniProtKB/Swiss-Prot Function:
F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (Probable). 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 (PubMed:15772161). 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 (By similarity). May also function as a transcriptional coactivator, stimulating transcription mediated by the nuclear hormone receptors PPARG and RARA (PubMed:22351778).

Gene Ontology (GO) - Molecular Function for ACTN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IDA 25411248
GO:0001882 nucleoside binding IDA 12411747
GO:0003779 actin binding IEA,TAS 8104223
GO:0005178 integrin binding TAS 8104223
GO:0005509 calcium ion binding IEA --
genes like me logo Genes that share ontologies with ACTN4: view
genes like me logo Genes that share phenotypes with ACTN4: view

Human Phenotype Ontology for ACTN4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for ACTN4 Gene

MGI Knock Outs for ACTN4:

Animal Model Products

miRNA for ACTN4 Gene

miRTarBase miRNAs that target ACTN4

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for ACTN4 Gene

Localization for ACTN4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ACTN4 Gene

Nucleus. Cytoplasm. Cell junction. 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). {ECO:0000269 PubMed:17289661, ECO:0000269 PubMed:9508771}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ACTN4 gene
Compartment Confidence
extracellular 5
nucleus 5
cytosol 5
cytoskeleton 4
plasma membrane 1
endosome 1

Gene Ontology (GO) - Cellular Components for ACTN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001725 stress fiber IEA --
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IDA 16502470
GO:0005622 intracellular IDA 21784188
GO:0005634 nucleus IDA 9508771
genes like me logo Genes that share ontologies with ACTN4: view

Pathways & Interactions for ACTN4 Gene

genes like me logo Genes that share pathways with ACTN4: view

SIGNOR curated interactions for ACTN4 Gene

Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for ACTN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001666 response to hypoxia IEA --
GO:0002576 platelet degranulation TAS --
GO:0006810 transport IEA --
GO:0015031 protein transport IEA --
GO:0030050 vesicle transport along actin filament IMP 25918384
genes like me logo Genes that share ontologies with ACTN4: view

Drugs & Compounds for ACTN4 Gene

(4) Drugs for ACTN4 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with ACTN4: view

Transcripts for ACTN4 Gene

Unigene Clusters for ACTN4 Gene

Actinin, alpha 4:
Representative Sequences:

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for ACTN4 Gene

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: -
SP6:
SP7: - - - - - - - - - - - - - - - - - - - - - - -
SP8:
SP9:

ExUns: 20a · 20b ^ 21a · 21b ^ 22a · 22b ^ 23a · 23b · 23c · 23d ^ 24
SP1: - - -
SP2:
SP3: - - -
SP4:
SP5:
SP6: - - -
SP7: - - - - - - - - - -
SP8: - -
SP9:

Relevant External Links for ACTN4 Gene

GeneLoc Exon Structure for
ACTN4
ECgene alternative splicing isoforms for
ACTN4

Expression for ACTN4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ACTN4 Gene

mRNA differential expression in normal tissues according to GTEx for ACTN4 Gene

This gene is overexpressed in Artery - Tibial (x4.6).

Protein differential expression in normal tissues from HIPED for ACTN4 Gene

This gene is overexpressed in Bone marrow stromal cell (9.3) and Amniocyte (7.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for ACTN4 Gene



Protein tissue co-expression partners for ACTN4 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of ACTN4 Gene:

ACTN4

SOURCE GeneReport for Unigene cluster for ACTN4 Gene:

Hs.270291

mRNA Expression by UniProt/SwissProt for ACTN4 Gene:

O43707-ACTN4_HUMAN
Tissue specificity: Widely expressed.
genes like me logo Genes that share expression patterns with ACTN4: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery for ACTN4 Gene

Orthologs for ACTN4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for ACTN4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ACTN4 34 35
  • 99.41 (n)
oppossum
(Monodelphis domestica)
Mammalia ACTN4 35
  • 96 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 35
  • 96 (a)
OneToMany
-- 35
  • 88 (a)
OneToMany
cow
(Bos Taurus)
Mammalia ACTN4 34 35
  • 94.51 (n)
dog
(Canis familiaris)
Mammalia ACTN4 34 35
  • 93.08 (n)
rat
(Rattus norvegicus)
Mammalia Actn4 34
  • 90.78 (n)
mouse
(Mus musculus)
Mammalia Actn4 34 16 35
  • 90.34 (n)
chicken
(Gallus gallus)
Aves ACTN1 35
  • 93 (a)
OneToMany
ACTN4 34 35
  • 86.95 (n)
lizard
(Anolis carolinensis)
Reptilia ACTN4 35
  • 91 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia actn4 34
  • 78.36 (n)
zebrafish
(Danio rerio)
Actinopterygii ACTN4 (3 of 3) 35
  • 97 (a)
OneToMany
ACTN4 (1 of 3) 35
  • 84 (a)
OneToMany
ACTN4 (2 of 3) 35
  • 83 (a)
OneToMany
actn4 34
  • 79.32 (n)
wufb53f05 34
fruit fly
(Drosophila melanogaster)
Insecta Actn 36
  • 67 (a)
worm
(Caenorhabditis elegans)
Secernentea sma-1 35
  • 8 (a)
ManyToMany
bread mold
(Neurospora crassa)
Ascomycetes NCU06429 34
  • 50.58 (n)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes ain1 34
  • 44.86 (n)
Species where no ortholog for ACTN4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for ACTN4 Gene

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

Paralogs for ACTN4 Gene

Pseudogenes.org Pseudogenes for ACTN4 Gene

genes like me logo Genes that share paralogs with ACTN4: view

Variants for ACTN4 Gene

Sequence variations from dbSNP and Humsavar for ACTN4 Gene

SNP ID Clin Chr 19 pos Sequence Context AA Info Type
rs201128110 Focal segmental glomerulosclerosis 1 (FSGS1) [MIM:603278] 38,718,062(+) ACGAG(A/G)CCTGG intron-variant, reference, missense
rs28939374 Focal segmental glomerulosclerosis 1 (FSGS1) [MIM:603278]
rs28939375 Focal segmental glomerulosclerosis 1 (FSGS1) [MIM:603278]
rs28939376 Focal segmental glomerulosclerosis 1 (FSGS1) [MIM:603278]
VAR_072115 Focal segmental glomerulosclerosis 1 (FSGS1) [MIM:603278]

Structural Variations from Database of Genomic Variants (DGV) for ACTN4 Gene

Variant ID Type Subtype PubMed ID
dgv641e199 CNV deletion 23128226
esv22820 CNV loss 19812545
esv2718535 CNV deletion 23290073
esv3329584 CNV duplication 20981092
nsv1057901 CNV gain 25217958
nsv817834 CNV gain 17921354
nsv833826 CNV loss 17160897
nsv833827 CNV gain 17160897
nsv833828 CNV loss 17160897
nsv953298 CNV deletion 24416366
nsv953299 CNV deletion 24416366

Variation tolerance for ACTN4 Gene

Residual Variation Intolerance Score: 3.37% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.37; 42.10% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for ACTN4 Gene

Human Gene Mutation Database (HGMD)
ACTN4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ACTN4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ACTN4 Gene

Disorders for ACTN4 Gene

MalaCards: The human disease database

(12) MalaCards diseases for ACTN4 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
glomerulosclerosis, focal segmental, 1
  • segmental glomerulosclerosis
familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis
  • familial idiopathic steroid-resistant nephrotic syndrome with focal segmental glomerulosclerosis
glomerulosclerosis
focal segmental glomerulosclerosis
  • opitz-kaveggia syndrome
nephrotic syndrome, type 1
  • nephrotic syndrome
- elite association - COSMIC cancer census association via MalaCards
Search ACTN4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

ACTN4_HUMAN
  • 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. {ECO:0000269 PubMed:10700177, ECO:0000269 PubMed:18436095, ECO:0000269 PubMed:23890478}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for ACTN4

Genetic Association Database (GAD)
ACTN4
Human Genome Epidemiology (HuGE) Navigator
ACTN4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
ACTN4
genes like me logo Genes that share disorders with ACTN4: view

No data available for Genatlas for ACTN4 Gene

Publications for ACTN4 Gene

  1. Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. (PMID: 10700177) Kaplan J.M. … Pollak M.R. (Nat. Genet. 2000) 2 3 4 22 64
  2. ACTN4 gene mutations and single nucleotide polymorphisms in idiopathic focal segmental glomerulosclerosis. (PMID: 19142020) Dai S. … Chen N. (Nephron Clin Pract 2009) 3 22 46 64
  3. Familial focal segmental glomerulosclerosis associated with an ACTN4 mutation and paternal germline mosaicism. (PMID: 18436095) Choi H.J. … Cheong H.I. (Am. J. Kidney Dis. 2008) 3 4 22 64
  4. Association analysis of podocyte slit diaphragm genes as candidates for diabetic nephropathy. (PMID: 17968527) Ihalmo P. … Groop P.H. (Diabetologia 2008) 3 22 46 64
  5. The human non-muscle alpha-actinin protein encoded by the ACTN4 gene suppresses tumorigenicity of human neuroblastoma cells. (PMID: 10656685) Nikolopoulos S.N. … Ross R.A. (Oncogene 2000) 3 4 22 64

Products for ACTN4 Gene

Sources for ACTN4 Gene