ACTN3

Chr 11

actinin alpha 3

Also known as: ACTN3D

NCBI Gene: 89 ENSG00000248746 UniProt: Q08043

Alpha-actinin-3 is an F-actin cross-linking protein that functions as a structural component of the sarcomeric Z line in skeletal muscle, anchoring actin filaments to intracellular structures. Autosomal recessive mutations cause alpha-actinin-3 deficiency, though this primarily affects athletic performance rather than causing pathological muscle disease. The non-functional allele is notably associated with elite endurance athlete status, while the functional allele is linked to sprinting performance.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (2)

gnomad: Error: gnomAD API error: 400

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in ACTN3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 27

1,426 rare PASS variants

Rare truncating (LoF)

1 in 250

203 rare PASS variants

Rare synonymous (reference)

1 in 58

531 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ACTN3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 42	1 in 440
South Asian	~43k	1 in 27	1 in 180
Remaining (unassigned)	~30k	1 in 26	1 in 290
European (Finnish)	~27k	1 in 120	1 in 870
Admixed American	~22k	1 in 33	1 in 310
African / African American	~21k	1 in 29	1 in 180
East Asian	~20k	1 in 38	1 in 650
Ashkenazi Jewish	~13k	1 in 81	1 in 2,000
Middle Eastern	~2,884	1 in 26	1 in 270

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 21 coding exons well covered in gnomAD exomes and genomes.? see exons ↓