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FB2026_01
,
released March 12, 2026
This report describes general characteristics of myopathies associated with the human ACTA1 gene, which encodes the alpha actin found in human skeletal muscle. There are multiple actins in both human and fly; all share a high level of conservation. Several other actin genes in human are implicated in myopathy and other diseases, including ACTB, ACTG2, ACTG1, and ACTC1. The fly models of myopathy described in this report use the fly Act88F gene, for which many amorphic alleles, loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. See also the human disease model reports for 'nemaline myopathy 3' (FBhh0000582) and 'myopathy, congenital fiber-type disproportion' (FBhh0000583).
The human ACTA1 gene has not been introduced into flies.
Animals homozygous for loss-of-function mutations of Dmel\Act88F exhibit locomotor defects, most conspicuously, they are flightless; abnormalities observed in the indirect flight muscle have been extensively described; females exhibit reduced fertility. Heterozygotes show mild defects in the indirect flight muscles. Many variants associated with myopathy (primarily with NEM3) have been investigated in flies, as analogous mutations in the fly Act88F gene. Genetic and physical interactions of Dmel\Act88F have been described; see below and in the Act88F gene report.
Variant(s) implicated in human disease tested (as analogous mutation in fly gene): G16R in the fly Act88F gene [corresponds to G17R (G15R) in the human ACTA1 gene, implicated in NEM3]; V164M in the fly Act88F gene [corresponds to V165M (V163M) in the human ACTA1 gene, implicated in NEM3]; V164L in the fly Act88F gene [corresponds to V165L (V163L) in the human ACTA1 gene, implicated in NEM3]; I137M in the fly Act88F gene [corresponds to I138M (I136M) in the human ACTA1 gene, implicated in NEM3]; D155N in the fly Act88F gene [corresponds to D156N (D154N) in the human ACTA1 gene, implicated in NEM3]; G269D in the fly Act88F gene [corresponds to G270D (G268D) in the human ACTA1 gene, implicated in NEM3]; R257C in the fly Act88F gene [corresponds to R258C (R256C) in the human ACTA1 gene, implicated in NEM3]; R373H in the fly Act88F gene [corresponds to R374H (R372H) in the human ACTA1 gene, implicated in NEM3]; A139V in the fly Act88F gene [corresponds to A140V (A138V) in the human ACTA1 gene, implicated in NEM3, designated Act88FM320]; D293V in the fly Act88F gene [corresponds to D294V (D292V) in the human ACTA1 gene, implicated in CFTD].
[updated Jul. 2017 by FlyBase; FBrf0222196]
Myopathy caused by mutations in the ACTA1 gene can show a range of clinical and pathologic phenotypes. Some patients have classic rods, whereas others may also show intranuclear rods, clumped filaments, cores, or fiber-type disproportion, all of which are nonspecific pathologic findings and not characteristic of a specific congenital myopathy. The spectrum of clinical phenotypes caused by mutations in ACTA1 may result from different mutations, modifying factors affecting the severity of the disorder, variability in clinical care, or a combination of these factors (Nowak et al., 1999, pubmed:10508519; Kaindl et al., 2004, pubmed:15520409). [from MIM:161800; 2017.07.24]
The ACTA1 gene encodes skeletal muscle alpha-actin, which is the predominant actin isoform in the sarcomeric thin filaments of adult skeletal muscle, and essential, along with myosin, for muscle contraction (Laing, et al., 2009; pubmed:19562689).
Alpha, beta and gamma actin isoforms have been identified, with alpha actins being a major constituent of the contractile apparatus, while beta and gamma actins are involved in the regulation of cell motility. [from Gene Cards, ACTA1; 2017.07.24]
The ACTA1 gene encodes skeletal muscle alpha-actin, the principal actin isoform in adult skeletal muscle, which forms the core of the thin filament of the sarcomere where it interacts with a variety of proteins to produce the force for muscle contraction (Laing et al., 2009; pubmed:19562689). [from MIM:102610; 2017.07.24]
Many to many: there are multiple actins in both species.
There are multiple actins in both species (many to many). The actins are very highly conserved; Dmel\Act88F shares 93% identity and 96% similarity with the human ACTA1 gene; it shares a similar level of orthology with human ACTA2 and a slightly higher level with ACTB (96% identity and 99% similarity).