ACTA1

actin alpha 1, skeletal muscle

2 disorders 1 causative 1 untyped 1q42.13 gene with protein product

HGNC:129 Monarch NCBI Gene 58 ENSG00000143632 UniProt P68133 OMIM 102610

Previous symbols: ACTA. Aliases: NEM3.

Normal function · from ai-gene-review (P68133, commit 79fe13b38970) · AI-generated, not KB evidence

ACTA1 encodes skeletal muscle alpha-actin, the predominant sarcomeric actin isoform in mature skeletal muscle. Globular actin binds adenine nucleotides and polymerizes into polarized thin filaments whose interaction with myosin transmits contractile force. Actin also binds muscle alpha-actinin, helping organize the thin filament at the Z-disc. ATP hydrolysis and subsequent phosphate release accompany filament assembly and influence filament dynamics. ACTA1 expression changes during muscle development alongside cardiac alpha-actin. Pathogenic variants can disturb folding, polymerization and interactions within the contractile apparatus, causing congenital myopathies including nemaline myopathy; both dominant and recessive inheritance occur.

ACTA1 polymerizes into the actin backbone of skeletal-muscle thin filaments, contributing their structural integrity and directly participating in thin-filament assembly.

molecular function: structural constituent of cytoskeleton · directly involved in: skeletal muscle thin filament assembly · locations: striated muscle thin filament; sarcomere; actin filament; actin cytoskeleton; cytosol

ACTA1 binds ATP and hydrolyzes it during filament assembly. Hydrolysis and subsequent phosphate release influence actin filament dynamics; oriented subunit assembly gives the filament structural polarity.

molecular function: ATP hydrolysis activity · locations: actin filament

ACTA1 provides the myosin-binding surface and force-transmitting thin filament used in skeletal-muscle contraction. Myosin heads, rather than actin subunits, couple the power stroke to the myosin ATPase cycle.

molecular function: myosin binding · directly involved in: skeletal muscle contraction · locations: striated muscle thin filament

Binding to muscle alpha-actinin connects the ACTA1 thin filament to the Z-disc organization machinery. Human patient-muscle actin exhibits altered alpha-actinin affinity, supporting this specific interaction.

molecular function: muscle alpha-actinin binding · locations: striated muscle thin filament

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
ACTA1-Related Nemaline Myopathy	causative de novogermline dominant negativeloss of function	mechanism: ACTA1 Variant in Skeletal Muscle Alpha-Actin; Absence of Functional Skeletal Muscle Alpha-Actin; Incorporation of Mutant Alpha-Actin into the Thin Filament
Nemaline Myopathy	untyped Causative	mechanism: Nuclear Envelope Disruption (ACTA1); Thin Filament Dysfunction subtype: NEM3 diagnosis: Molecular genetic testing for causative NM variants

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
alpha-actinopathy MONDO:0100084	AD	Definitive 2024-02-26	no dismech entry
alpha-actinopathy MONDO:0100084	AR	Definitive 2024-02-26	no dismech entry

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.