ACTN2

Chr 1AD

actinin alpha 2

Also known as: CMD1AA, CMH23, CMYO8, CMYP8, MPD6, MYOCOZ

NCBI Gene: 88ENSG00000077522UniProt: P35609OMIM: 102573

Alpha actinins belong to the spectrin gene superfamily which represents a diverse group of cytoskeletal proteins, including the alpha and beta spectrins and dystrophins. Alpha actinin is an actin-binding protein with multiple roles in different cell types. In nonmuscle cells, the cytoskeletal isoform is found along microfilament bundles and adherens-type junctions, where it is involved in binding actin to the membrane. In contrast, skeletal, cardiac, and smooth muscle isoforms are localized to the Z-disc and analogous dense bodies, where they help anchor the myofibrillar actin filaments. This gene encodes a muscle-specific, alpha actinin isoform that is expressed in both skeletal and cardiac muscles. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2013]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cardiomyopathy, dilated, 1AA, with or without LVNCMIM #612158
AD
Cardiomyopathy, hypertrophic, 23, with or without LVNCMIM #612158
AD
Congenital myopathy 8MIM #618654
AD
Myopathy, distal, 6, adult onsetMIM #618655
AD
UniProtCardiomyopathy, familial hypertrophic, 23, with or without left ventricular non-compaction

Clinical highlights

Gene-disease validity (ClinGen)
ACTN2-related cardiac and skeletal myopathy · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
—
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.24
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
📖
GeneReview available — ACTN2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.24LOEUF
pLI 1.000
Z-score 5.73
OE 0.12 (0.07–0.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
1.29Z-score
OE missense 0.84 (0.78–0.91)
446 obs / 529.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.12 (0.07–0.24)
0≤0.351.4
Missense OE?0.84 (0.78–0.91)
0≤0.61.4
Synonymous OE?0.97
0≤1.21.6
LoF obs/exp: 6 / 49.6Missense obs/exp: 446 / 529.7Syn Z: 0.33

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ACTN2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients