ACTN3
protein-codingactinin alpha 3, the group of Actinins
Gene summary
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, Apr 2024]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal
Intervention: General
Rationale: The clinical relevance is unclear
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ACTN3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001104.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 19 | 20 | |||
| missense | 195 | 7 | 6 | 208 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 197 | 26 | 6 | 229 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001095.2 | 21 | MANE Select | |
| Ensembl | ENSP00000426797.1 | 21 | MANE Select | |
| RefSeq | NP_001245300.2 | 21 | Standard | |
| Ensembl | ENSP00000422007.1 | 21 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| actn3a | Danio rerio | Structure: atrium Quality: dilated abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human)
- Arrhythmogenic Right Ventricular Cardiomyopathy
- Striated Muscle Contraction
- erk and pi-3 kinase are necessary for collagen binding in corneal epithelia
- ucalpain and friends in cell spread
Biological Process
- regulation of the force of skeletal muscle contraction
- skeletal muscle atrophy
- transition between fast and slow fiber
- response to denervation involved in regulation of muscle adaptation
- muscle filament sliding
Molecular Function
- actin binding
- integrin binding
- calcium ion binding
- protein binding
- structural constituent of muscle
Cellular Component
- cytosol
- actin filament
- focal adhesion
- pseudopodium
- extracellular exosome
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein.;
Essentials
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.539