ACTN3: Alpha-Actinin-3 and Its Role in Muscle Performance
Comprehensive genomic and proteomic overview of the ACTN3 gene, including its association with athletic performance, muscle function, and disease.
Gene Information Card
| Symbol | ACTN3 |
|---|---|
| Full Name | Actinin Alpha 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 11q13.2 |
| NCBI Gene ID | 89 ncbi.nlm.nih.gov/gene/89 |
| Ensembl ID | ENSG00000048740 |
| UniProt ID | Q08043 |
| OMIM ID | 102574 |
| HGNC ID | 165 |
| Aliases | alpha-actinin-3, actinin-3, F-actin cross-linking protein |
Description
ACTN3 encodes alpha-actinin-3, a member of the spectrin family of actin-binding proteins. It is specifically expressed in fast-twitch (type II) skeletal muscle fibers, where it cross-links actin filaments at the Z-disc of the sarcomere. A common nonsense polymorphism (R577X) results in complete loss of alpha-actinin-3 protein in approximately 18% of the global population, yet is not associated with overt muscle disease. The variant has been linked to differences in muscle performance, with the R allele associated with sprint/power performance and the X allele with endurance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Muscular dystrophy (rare association) | Loss of alpha-actinin-3 may contribute to Z-disc instability in specific myopathies | Case reports; limited evidence |
| Athletic performance (non-disease) | R577X polymorphism influences muscle fiber composition and contractile properties | Multiple GWAS and cohort studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 24.5 | High |
| Heart | 0.8 | Low |
| Brain | 0.1 | Not detected |
| Liver | 0.0 | Not detected |
| Kidney | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Skeletal muscle myotubes | 28.3 | High expression |
| RD (rhabdomyosarcoma) | 15.2 | Moderate expression |
| HeLa | 0.0 | No expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R577X (rs1815739) | Nonsense | ~18% homozygous X/X in Europeans | Loss of alpha-actinin-3 protein; associated with endurance performance |
| Q523R (rs540874) | Missense | ~5% in East Asians | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
R577X nonsense mutation leads to complete loss of alpha-actinin-3 protein; common in human populations without overt disease.
Gain of Function (GOF)
No known gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations described.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003779 – actin binding | • GO:0005865 – striated muscle thin filament |
| • GO:0030018 – Z disc | • GO:0051015 – actin filament binding |
| • GO:0006936 – muscle contraction |
Pathways
• Actin cytoskeleton regulation (Reactome: R-HSA-5663222)
• Striated muscle contraction (Reactome: R-HSA-390522)
Protein Summary
Alpha-actinin-3 is a 100 kDa protein that forms antiparallel homodimers, cross-linking actin filaments in the Z-disc of fast-twitch skeletal muscle fibers. It is essential for maintaining sarcomeric integrity and force transmission during rapid contractions. The R577X polymorphism leads to protein truncation and absence of alpha-actinin-3, which is compensated by alpha-actinin-2 in slow-twitch fibers, explaining the lack of disease phenotype. This gene is a classic example of a 'gene for performance' rather than a disease gene.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ACTN3 Knockout HEK293 Cell Line | EDJ-KQ4004 | Human | 89 | Details Get a Quote |
| ACTN3 Knockout HeLa Cell Line | EDJ-KQ52543 | Human | 89 | Details Get a Quote |
| ACTN3 Knockout A-549 Cell Line | EDJ-KQ61027 | Human | 89 | Details Get a Quote |
| ACTN3 Knockout HCT 116 Cell Line | EDJ-KQ69502 | Human | 89 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
