- 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 arthrogryposis, distal, type 1A (DA1A); DA1A exhibits autosomal dominant inheritance. Multiple genes encoding members of the tropomyosin family exist in both human and Drosophila.
The Drosophila model of DA1A makes use of transgenes carrying the human gene. Multiple UAS constructs of Hsap\TPM2, including wild-type and variants implicated in DA1A, have been introduced into flies. Muscle-specific expression of Hsap\TPM2 disease-implicated variants results in disruptions of larval muscle morphology, including attachment site defects and elongation defects.
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 multiple variants associated with DA1A are also implicated in nemaline myopathy 4 (NEM4; see FBhh0001466). 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]
The distal arthrogryposes are a group of disorders characterized by contractures mainly involving the distal parts of the limbs. The hands have a characteristic position with medially overlapping fingers, clenched fists, ulnar deviation of fingers, and camptodactyly, and the feet have deformities. Contractures at other joints are variable; there are no associated visceral anomalies, and intelligence is normal. The various phenotypic forms of distal arthrogryposis are classified hierarchically according to the proportion of features they share with one another and are designated DA1 through DA10 (summary by Bamshad et al. 2009; pubmed:19571066). [from MIM:108120; 2020.10.17]
[ARTHROGRYPOSIS, DISTAL, TYPE 1A; DA1A](https://omim.org/entry/108120)
[TROPOMYOSIN 2; TPM2](https://omim.org/entry/190990)
The prototypic distal arthrogryposis is type 1 (DA1) is characterized largely by camptodactyly and clubfoot. [from MIM:108120; 2022.01.16]
Distal arthrogryposis type 1A (DA1A) and type 2B4 (DA2B4) are caused by heterozygous mutation in the TPM2 gene. from MIM:108120; 2022.01.16]
Heterozygous mutation in the TPM2 gene can also cause nemaline myopathy-4 (NEM4; MIM:609285), which shows similar features and may be identical to DA1A. [from MIM:108120; 2022.01.16]
The tropomyosin family comprises highly conserved, widely distributed actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells. [Gene Cards, TPM1; 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]
Many to many: multiple genes in both species.