Actin alpha skeletal muscle (ACTA1) (ACTA1)

Actin alpha skeletal muscle (ACTA1) is a highly conserved protein that serves as the primary constituent of the thin filaments in skeletal muscle sarcomeres [UniProt P68133]. It is essential for muscle contraction, providing the structural scaffold that interacts with myosin to generate mechanical force [NCBI Gene 58]. Mutations in the ACTA1 gene are a leading cause of congenital myopathies, including Nemaline Myopathy, Actin Myopathy, and Core-rod Myopathy [OMIM 102610]. These conditions typically present as severe muscle weakness, respiratory distress, and the presence of abnormal protein aggregates called nemaline rods [PubMed 21280071]. In the context of genetic correction, ACTA1 is the target of advanced therapies designed to restore functional protein levels or repair underlying genetic defects [PubMed 30103144]. These therapeutic payloads often utilize adeno-associated virus (AAV) vectors for gene replacement or CRISPR-based systems for precise genomic editing [PubMed 28106369]. Managing ACTA1-related disorders is challenging due to the dominant-negative nature of many mutations, requiring strategies that either silence the mutant allele or provide sufficient wild-type protein to overcome the pathology [PubMed 25605830]. Current research is heavily focused on optimizing delivery to skeletal muscle and minimizing off-target effects or immune responses to the therapeutic payload [PubMed 33053377].

Other names

Alpha-actin-1Skeletal muscle alpha-actinACTAASMACFTDNEM1NEM2NEM3

Gene replacement or gene editing to restore functional alpha-skeletal muscle actin levels or correct pathogenic mutations.