This gene encodes a member of the alpha-actin binding protein gene family. The encoded protein is primarily expressed in skeletal muscle and functions as a structural component of sarcomeric Z line. This protein is involved in crosslinking actin containing thin filaments. An allelic polymorphism in this gene results in both coding and non-coding variants; the reference genome r... See more...

Aliases for ACTN3 Gene

Aliases for ACTN3 Gene

  • Actinin Alpha 3 (Gene/Pseudogene) 2 3 5
  • F-Actin Cross-Linking Protein 3 4
  • Actinin, Alpha 3 2 3
  • Alpha-Actinin-3 3 4
  • Alpha-Actinin Skeletal Muscle Isoform 3 4
  • Alpha-Actinin Skeletal Muscle 3
  • ACTN3D 3

External Ids for ACTN3 Gene

Previous GeneCards Identifiers for ACTN3 Gene

  • GC11P068848
  • GC11P067996
  • GC11P066564
  • GC11P066089
  • GC11P066070
  • GC11P066314
  • GC11P062643

Summaries for ACTN3 Gene

Entrez Gene Summary for ACTN3 Gene

  • This gene encodes a member of the alpha-actin binding protein gene family. The encoded protein is primarily expressed in skeletal muscle and functions as a structural component of sarcomeric Z line. This protein is involved in crosslinking actin containing thin filaments. An allelic polymorphism in this gene results in both coding and non-coding variants; the reference genome represents the coding allele. The non-functional allele of this gene is associated with elite athlete status. [provided by RefSeq, Feb 2014]

GeneCards Summary for ACTN3 Gene

ACTN3 (Actinin Alpha 3 (Gene/Pseudogene)) is a Protein Coding gene. Diseases associated with ACTN3 include Actn3 Deficiency and Glycogen Storage Disease V. Among its related pathways are Cell adhesion_Endothelial cell contacts by junctional mechanisms and Sertoli-Sertoli Cell Junction Dynamics. Gene Ontology (GO) annotations related to this gene include calcium ion binding and actin binding. An important paralog of this gene is ACTN2.

UniProtKB/Swiss-Prot Summary for ACTN3 Gene

  • F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein.

Gene Wiki entry for ACTN3 Gene

Additional gene information for ACTN3 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ACTN3 Gene

Genomics for ACTN3 Gene

GeneHancer (GH) Regulatory Elements for ACTN3 Gene

Promoters and enhancers for ACTN3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH11J066542 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 519.4 -0.4 -403 6.2 HNRNPK EP300 SIN3A NRF1 POLR2G SP1 PHF8 ZFX CTCF ZIC2 ACTN3 lnc-BBS1-1 ZDHHC24 CTSF DPP3 RIN1 piR-45993
GH11J066567 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 57.5 +23.2 23205 3.6 EP300 TCF12 NRF1 POLR2A AFF1 ZNF510 HES1 TOE1 MYC MXI1 CTSF ACTN3 DPP3 piR-43106-036
GH11J066636 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 47.4 +93.7 93712 7.4 ZBTB40 ZNF217 EP300 CTCF SIN3A NRF1 MYC TCF12 POLR2G SP1 RBM4 NONHSAG008756.2 ACTN3 MRPL11 EIF1AD ENSG00000254855 RELA CD248 CLCF1 RBM4B
GH11J066464 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 44.1 -79.6 -79621 3.7 CTCF NRF1 POLR2G USF1 SP1 PHF8 ZFX ZIC2 POLR2A ZBTB11 MRPL11 PELI3 ACTN3 DPP3 ENSG00000255517 piR-57418
GH11J066478 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 43.6 -66.1 -66052 3.3 ZBTB40 ZNF217 EP300 CTCF SIN3A NRF1 TCF12 USF1 POLR2G SP1 MRPL11 DPP3 ENSG00000255517 LOC101928069 lnc-MRPL11-2 ACTN3 EIF1AD PCNX3 ENSG00000254855 KDM2A
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ACTN3 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ACTN3

Top Transcription factor binding sites by QIAGEN in the ACTN3 gene promoter:
  • HSF1 (long)
  • HSF1short
  • p53
  • Pax-5
  • POU2F1
  • POU2F1a
  • STAT1
  • STAT1alpha
  • STAT5A

Genomic Locations for ACTN3 Gene

Genomic Locations for ACTN3 Gene
chr11:66,546,395-66,563,334
(GRCh38/hg38)
Size:
16,940 bases
Orientation:
Plus strand
chr11:66,313,866-66,330,800
(GRCh37/hg19)
Size:
16,935 bases
Orientation:
Plus strand

Genomic View for ACTN3 Gene

Genes around ACTN3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ACTN3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ACTN3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ACTN3 Gene

Proteins for ACTN3 Gene

  • Protein details for ACTN3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q08043-ACTN3_HUMAN
    Recommended name:
    Alpha-actinin-3
    Protein Accession:
    Q08043
    Secondary Accessions:
    • A6NP77
    • Q4KKV2

    Protein attributes for ACTN3 Gene

    Size:
    901 amino acids
    Molecular mass:
    103241 Da
    Quaternary structure:
    • Homodimer; antiparallel. Also forms heterodimers with ACTN2. Interacts with MYOZ1.
    SequenceCaution:
    • Sequence=AP002748; Type=Miscellaneous discrepancy; Note=According to the human genome assembly there is a stop codon in position 577 which is only found in 18% of the world population.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for ACTN3 Gene

neXtProt entry for ACTN3 Gene

Post-translational modifications for ACTN3 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for ACTN3 Gene

No data available for DME Specific Peptides for ACTN3 Gene

Domains & Families for ACTN3 Gene

Gene Families for ACTN3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for ACTN3 Gene

Blocks:
  • Actin-binding, actinin-type
  • Calponin-like actin-binding
  • Spectrin repeat
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for ACTN3 Gene

GenScript: Design optimal peptide antigens:
  • F-actin cross-linking protein (ACTN3_HUMAN)
  • ACTN3 protein (Q4JCP9_HUMAN)
  • ACTN3 protein (Q4VAM3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q08043

UniProtKB/Swiss-Prot:

ACTN3_HUMAN :
  • Belongs to the alpha-actinin family.
Family:
  • Belongs to the alpha-actinin family.
genes like me logo Genes that share domains with ACTN3: view

Function for ACTN3 Gene

Molecular function for ACTN3 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.
GENATLAS Biochemistry:
actinin,alpha 3,actin filament cross-linking,calcium insensitive,expressed in skeletal muscle,type 2 (fast) fibres

Phenotypes From GWAS Catalog for ACTN3 Gene

Gene Ontology (GO) - Molecular Function for ACTN3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003779 actin binding IEA --
GO:0005178 integrin binding TAS 8104223
GO:0005509 calcium ion binding IEA --
GO:0005515 protein binding IPI,IEA 11171996
GO:0008307 structural constituent of muscle TAS 1339456
genes like me logo Genes that share ontologies with ACTN3: view
genes like me logo Genes that share phenotypes with ACTN3: view

Animal Model Products

CRISPR Products

Clone Products

  • Addgene plasmids for ACTN3

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for ACTN3 Gene

Localization for ACTN3 Gene

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 ACTN3 gene
Compartment Confidence
cytoskeleton 4
cytosol 4
plasma membrane 2
extracellular 2
mitochondrion 2
nucleus 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Actin filaments (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ACTN3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
GO:0005884 actin filament TAS 1339456
GO:0005903 brush border IEA --
GO:0005925 focal adhesion IMP 16807302
GO:0030017 sarcomere IEA --
genes like me logo Genes that share ontologies with ACTN3: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for ACTN3 Gene

Pathways & Interactions for ACTN3 Gene

PathCards logo

SuperPathways for ACTN3 Gene

SuperPathway Contained pathways
1 Sertoli-Sertoli Cell Junction Dynamics
.38
.38
.36
2 Arrhythmogenic right ventricular cardiomyopathy (ARVC)
3 Striated Muscle Contraction
4 Cytoskeleton remodeling Regulation of actin cytoskeleton by Rho GTPases
.49
.37
5 B Cell Receptor Signaling Pathway (sino)
genes like me logo Genes that share pathways with ACTN3: view

Pathways by source for ACTN3 Gene

6 GeneGo (Thomson Reuters) pathways for ACTN3 Gene
  • Cell adhesion Integrin-mediated cell adhesion and migration
  • Cell adhesion_Endothelial cell contacts by junctional mechanisms
  • Cell adhesion_Endothelial cell contacts by non-junctional mechanisms
  • Cytoskeleton remodeling Fibronectin-binding integrins in cell motility
  • Cytoskeleton remodeling Integrin outside-in signaling
6 Qiagen pathways for ACTN3 Gene
  • Epithelial Adherens Junctions
  • Epithelial Tight Junctions
  • Germ Cell-Sertoli Cell Junction Dynamics
  • ILK Signaling
  • Remodeling of Adherens Junctions

Gene Ontology (GO) - Biological Process for ACTN3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006936 muscle contraction IEA --
GO:0014728 regulation of the force of skeletal muscle contraction ISS --
GO:0014732 skeletal muscle atrophy ISS --
GO:0014883 transition between fast and slow fiber ISS --
GO:0014894 response to denervation involved in regulation of muscle adaptation ISS --
genes like me logo Genes that share ontologies with ACTN3: view

No data available for SIGNOR curated interactions for ACTN3 Gene

Drugs & Compounds for ACTN3 Gene

(1) Drugs for ACTN3 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with ACTN3: view

Transcripts for ACTN3 Gene

mRNA/cDNA for ACTN3 Gene

2 REFSEQ mRNAs :
15 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

  • Addgene plasmids for ACTN3

Alternative Splicing Database (ASD) splice patterns (SP) for ACTN3 Gene

No ASD Table

Relevant External Links for ACTN3 Gene

GeneLoc Exon Structure for
ACTN3

Expression for ACTN3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ACTN3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ACTN3 Gene

This gene is overexpressed in Muscle - Skeletal (x50.6).

Protein differential expression in normal tissues from HIPED for ACTN3 Gene

This gene is overexpressed in Ovary (46.3), Heart (6.6), and Fetal heart (6.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ACTN3 Gene



Protein tissue co-expression partners for ACTN3 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ACTN3

SOURCE GeneReport for Unigene cluster for ACTN3 Gene:

Hs.654432

mRNA Expression by UniProt/SwissProt for ACTN3 Gene:

Q08043-ACTN3_HUMAN
Tissue specificity: Expressed only in a subset of type 2 skeletal muscle fibers.
genes like me logo Genes that share expression patterns with ACTN3: view

No data available for Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for ACTN3 Gene

Orthologs for ACTN3 Gene

This gene was present in the common ancestor of animals.

Orthologs for ACTN3 Gene

Organism Taxonomy Gene Similarity Type Details
zebrafish
(Danio rerio)
Actinopterygii Dr.5066 30
fruit fly
(Drosophila melanogaster)
Insecta Actn 32
  • 66 (a)
Species where no ortholog for ACTN3 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)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • chimpanzee (Pan troglodytes)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • cow (Bos Taurus)
  • dog (Canis familiaris)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • mouse (Mus musculus)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rat (Rattus norvegicus)
  • 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)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for ACTN3 Gene

ENSEMBL:
Gene Tree for ACTN3 (if available)
TreeFam:
Gene Tree for ACTN3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ACTN3: view image

Paralogs for ACTN3 Gene

(16) SIMAP similar genes for ACTN3 Gene using alignment to 4 proteins:

  • ACTN3_HUMAN
  • D6RH00_HUMAN
  • Q4JCP9_HUMAN
  • Q4VAM3_HUMAN
genes like me logo Genes that share paralogs with ACTN3: view

Variants for ACTN3 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for ACTN3 Gene

ACTN3_HUMAN-Q08043
About 18% of the world population lack a functional ACTN3 due to a stop codon polymorphism at position 577. The absence of a functional ACTN3 expression is not correlated with a disease state [MIM:617749].

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ACTN3 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
rs1815739 Conflicting Interpretations, Affects: ACTININ, ALPHA-3 POLYMORPHISM; Sprinting performance; ACTN3 deficiency 66,560,624(+) C/T NONSENSE
rs1671064 - p.Arg523Gln
rs2229456 - p.Glu635Ala
rs540874 - p.Gln776Arg
rs618838 - p.Cys628Arg

Additional dbSNP identifiers (rs#s) for ACTN3 Gene

Structural Variations from Database of Genomic Variants (DGV) for ACTN3 Gene

Variant ID Type Subtype PubMed ID
esv2744639 CNV deletion 23290073
esv3626696 CNV loss 21293372
nsv1143689 CNV deletion 24896259
nsv522277 CNV loss 19592680

Additional Variant Information for ACTN3 Gene

Human Gene Mutation Database (HGMD)
ACTN3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ACTN3

SNP Genotyping and Copy Number Assay Products

No data available for Variation tolerance for ACTN3 Gene

Disorders for ACTN3 Gene

MalaCards: The human disease database

(6) MalaCards diseases for ACTN3 Gene - From: OMIM, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
actn3 deficiency
  • alpha-actinin-3 deficiency
glycogen storage disease v
  • gsd5
myasthenic syndrome, congenital, 4c, associated with acetylcholine receptor deficiency
  • cms4c
muscular dystrophy
  • muscular dystrophies
arrhythmogenic right ventricular cardiomyopathy
  • arrhythmogenic right ventricular dysplasia
- elite association - COSMIC cancer census association via MalaCards
Search ACTN3 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for ACTN3

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with ACTN3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ACTN3 Gene

Publications for ACTN3 Gene

  1. Cloning and characterization of two human skeletal muscle alpha-actinin genes located on chromosomes 1 and 11. (PMID: 1339456) Beggs AH … Kunkel LM (The Journal of biological chemistry 1992) 2 3 4 23 54
  2. ACTN3 and ACE genotypes in elite Jamaican and US sprinters. (PMID: 20010124) Scott RA … Pitsiladis YP (Medicine and science in sports and exercise 2010) 3 23 41 54
  3. Endurance performance: genes or gene combinations? (PMID: 18651373) Gómez-Gallego F … Lucia A (International journal of sports medicine 2009) 3 23 41 54
  4. Human angiotensin-converting enzyme I/D and alpha-actinin 3 R577X genotypes and muscle functional and contractile properties. (PMID: 18676575) McCauley T … Folland JP (Experimental physiology 2009) 3 23 41 54
  5. Is there an ACE ID - ACTN3 R577X polymorphisms interaction that influences sprint performance? (PMID: 20013558) Eynon N … Meckel Y (International journal of sports medicine 2009) 3 23 41 54

Products for ACTN3 Gene

Sources for ACTN3 Gene