- Tools
- Downloads
- Links
- Community
- About
- Help
FB2026_01
,
released March 12, 2026
The human gene tropomyosin 2 (TPM2) encodes beta-tropomyosin, a skeletal muscle-specific actin-binding protein essential for sarcomere function. Pathogenic variants in TPM2 cause a spectrum of musculoskeletal disorders; see MIM:190990. (OMIM notes that these disorders may represent variable phenotypes of one disease.) This report describes nemaline myopathy 4 (NEM4); NEM4 exhibits autosomal dominant inheritance. Multiple genes encoding members of the tropomyosin family exist in both human and Drosophila.
The Drosophila model of NEM4 makes use of transgenes carrying the human gene. Multiple UAS constructs of Hsap\TPM2, including wild-type and variants implicated in NEM4, have been introduced into flies. Muscle-specific expression of Hsap\TPM2 disease-implicated variants results in disruptions of larval muscle morphology, including attachment site defective and elongation defective.
Using an amorphic allele of the fly Tm2 gene, partial heterologous rescue (functional complementation) is observed using either the wild-type human gene or one of the tested human variants.
See the 'Disease Implicated Variants' table below. Note that many variants associated with NEM4 are also implicated in arthrogryposis, distal, type 1A (DA1A; see FBhh0001427). All TPM2 variants investigated in flies are presented in the 'Disease Implicated Variants' table in the Hsap\TPM2 gene report.
[updated Mar. 2024 by FlyBase; FBrf0222196]
Nemaline myopathy is a form of congenital myopathy; the clinical phenotype is highly variable, with differing age at onset and of severity. Muscle weakness typically involves proximal muscles, with involvement of the facial, bulbar, and respiratory muscles (Ilkovski et al., 2001; pubmed:11333380). Typical nemaline myopathy is the most common form, presenting as infantile hypotonia and muscle weakness. It is slowly progressive or nonprogressive, and most adults achieve ambulation. The severe form of the disorder is characterized by absence of spontaneous movement or respiration at birth, arthrogryposis, and death in the first months of life. Much less commonly, late-childhood or adult-onset can occur (Wallgren-Pettersson et al., 1999, pubmed:10619714; Sanoudou and Beggs, 2001, pubmed:11516997). [from MIM:161800; 2017.07.24]
[CONGENITAL MYOPATHY 23; CMYO23](https://omim.org/entry/609285)
[TROPOMYOSIN 2; TPM2](https://omim.org/entry/190990)
Nemaline myopathy 4 (NEM4) is caused by heterozygous mutation in the tropomyosin-2 gene (TPM2). [from MIM:609285; 2022.07.19]
Heterozygous mutation in the TPM2 gene can also cause distal arthrogryposis type 1A (DA1A; MIM:108120, FBhh0001427), which shows similar features and may represent the same disease. [from MIM:108120; 2022.01.16]
TPM2 encodes beta-tropomyosin, a member of the actin filament binding protein family, and mainly expressed in slow, type 1 muscle fibers. The TPM2 protein binds to actin filaments in muscle and non-muscle cells; it plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. [Gene Cards, TPM2; 2022.01.16]