ACTN3

Chr 11AR

actinin alpha 3

Also known as: ACTN3D

NCBI Gene: 89ENSG00000248746UniProt: Q08043

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]

Primary Disease Associations & Inheritance

[Alpha-actinin-3 deficiency]MIM #617749
AR
[Sprinting performance]MIM #617749
AR
246
ClinVar variants
10
Pathogenic / LP
—
pLI score
1
Active trials
Clinical Summary— ACTN3
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 199 VUS of 246 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

ClinVar Variant Classifications

246 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic2
VUS199
Likely Benign19
Benign17
8
Pathogenic
2
Likely Pathogenic
199
VUS
19
Likely Benign
17
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
2
0
2
VUS
0
191
7
1
199
Likely Benign
0
7
2
10
19
Benign
0
10
2
5
17
Total02082116245

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ACTN3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
ACTININ, ALPHA-3; ACTN3
MIM #102574 · *

[Alpha-actinin-3 deficiency]

MIM #617749

Molecular basis of disorder known

Autosomal recessive

[Sprinting performance]

MIM #617749

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention.
Wang Z et al.·Nat Genet
2022Meta-analysis
ACTN3 genotype is associated with human elite athletic performance.
Yang N et al.·Am J Hum Genet
2003
The association of the ACTN3 R577X and ACE I/D polymorphisms with athlete status in football: a systematic review and meta-analysis.
McAuley ABT et al.·J Sports Sci
2021Meta-analysis
ACTN3 R577X variant: could it be a determinant of sports performance in elite athletes in a Turkish population?
Canikli A et al.·J Genet
2022
alpha-actinin-3 and performance.
Yang N et al.·Med Sport Sci
2009
The Effect of Heterozygosity for the ACTN3 Null Allele on Human Muscle Performance.
Garton FC et al.·Med Sci Sports Exerc
2016Review
Muscular Strength and Quality of Life in Older Adults: The Role of ACTN3 R577X Polymorphism.
Fernández-Araque A et al.·Int J Environ Res Public Health
2021
Genes for elite power and sprint performance: ACTN3 leads the way.
Eynon N et al.·Sports Med
2013Review
Is evolutionary loss our gain? The role of ACTN3 p.Arg577Ter (R577X) genotype in athletic performance, ageing, and disease.
Houweling PJ et al.·Hum Mutat
2018Review
ACTN3: A genetic influence on muscle function and athletic performance.
MacArthur DG et al.·Exerc Sport Sci Rev
2007Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Association of the ACTN3 Genotype with Muscle Function: A Systematic Review and Meta-analysis.
Kamiya-Saito M et al.·Int J Sports Med
2026Review
The Role of COL1A1, COL5A1, ACTN3, MMP3, and GDF5 Gene Variants in Common Sports Injuries: Systematic Review of ACL Rupture, Achilles Tendinopathy, and Stress Fractures.
Abboud S et al.·Genes (Basel)
2026Review
Higher Incidence and Longer Recovery Time from Non-Contact Muscle Injuries in ACTN3 XX Genotype Players from a Soccer Academy: A Three-Season Longitudinal Study.
Barthelemy B et al.·Sports Med Open
2026🔓 Open AccessNatural history
Managing Refractory Hypertension: A Case Study Exploring the Influence of ACE and ACTN3 Gene Polymorphisms.
Gasser B et al.·Pharmgenomics Pers Med
2025🔓 Open Access
ACTN3 c.1729C>T Polymorphism Might Not Be a Standalone Factor in Non-contact Musculoskeletal Injury: A Systematic Review and Meta-analysis.
Varillas-Delgado D et al.·Sports Med
2025Review
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Cancer

Onco Move - Improvement of Psychophysical Fitness in Adult Cancer Survivors

NOT YET RECRUITING
NCT07087652Phase NAGdansk University of Physical Education and SportStarted 2025-09-01
Onco Move multicomponent face-to-face training program

External Resources

Links to major genomics databases and tools