- Tools
- Downloads
- Links
- Community
- About
- Help
FB2026_01
,
released March 12, 2026
Multiple diseases are associated with the human gene crystallin alpha B (CRYAB), including several forms of myofibrillar myopathy (MFM), cardiomyopathy (with or without MFM), and cataracts (with or without MFM). This model uses a specific variant associated with myopathy, myofibrillar, 2A, adult-onset (MFM2A); MFM2A exhibits autosomal dominant inheritance. There are multiple alpha crystallins and related small heat shock proteins in both human and Drosophila. Most closely related to CRYAB is the fly gene l(2)efl, for which multiple genetic reagents have been generated, including RNAi constructs, over-expression constructs, and a targeted CRISPR activation construct.
The human Hsap\CRYAB gene has been introduced into flies, including a tagged wild-type construct and a variant implicated in disease. Expression of the mutant R120G allele, but not the wild-type gene, in the fly heart causes phenotypes associated with cardiomyopathy.
Variants implicated in MFM2A have been assessed using transgenic constructs of the human gene and analogous mutations in fly gene; see the 'Disease-Implicated Variants' table below.
Genetic characterization of l(2)efl includes assessment of RNAi-effected loss-of-function phenotypes: using muscle-specific drivers, muscle structure defects and locomotor defects are observed in larvae; using a cardiac-specific driver, heart defects are observed in adults.
[updated Aug. 2025 by FlyBase; FBrf0222196]
Myofibrillar myopathy is characterized by slowly progressive weakness that can involve both proximal and distal muscles. Distal muscle weakness is present in about 80% of individuals and is more pronounced than proximal weakness in about 25%. A minority of individuals experience sensory symptoms, muscle stiffness, aching, or cramps. Peripheral neuropathy is present in about 20% of affected individuals. Overt cardiomyopathy is present in 15%-30%. [from Gene Reviews, Myofibrillar Myopathy; 2017.08.14]
Myofibrillar myopathy (MFM) is a noncommittal term that refers to a group of morphologically homogeneous, but genetically heterogeneous chronic neuromuscular disorders. [from MIM:601419; 2017.08.14]
[MYOPATHY, MYOFIBRILLAR, 2A, ADULT-ONSET; MFM2A](https://omim.org/entry/608810)
[CRYSTALLIN, ALPHA-B; CRYAB](https://omim.org/entry/123590)
Myofibrillar myopathy primarily affects skeletal muscles; in some cases, the muscles of the heart are also affected. [from Genetics Home Reference, myofibrillar myopathy; 2017.08.14]
Alpha-B crystallin-related myofibrillar myopathy is an autosomal dominant muscular disorder characterized by adult onset of progressive muscle weakness affecting both the proximal and distal muscles and associated with respiratory insufficiency, cardiomyopathy, and cataracts. There is phenotypic variability both within and between families (Fardeau et al., 1978, pubmed: 570292; Selcen and Engel, 2003, pubmed:14681890). Mutations of CRYAB are also associated with cardiomyopathy or cataracts without causing myofibrillar myopathy. [from MIM:608810; 2017.08.14]
Myofibrillar myopathy-2 (MFM2) is caused by heterozygous mutation in the alpha-B-crystallin gene (CRYAB). [from MIM:608810; 2017.08.14]
Microscopy of muscle biopsies from affected individuals shows 'rubbed out' areas of the intermyofibrillar network in type I fibers on oxidative staining. Electron microscopy shows subsarcolemmal and intermyofibrillar accumulation of dense granulo-filamentous material with various degenerative changes. Vicart et al., 1998; pubmed:9731540). [from MIM:608810; 2017.08.14]
Alpha crystallins are composed of two gene products: alpha-A and alpha-B, for acidic and basic, respectively. Alpha crystallins can be induced by heat shock and are members of the small heat shock protein (HSP20) family. They have chaperone-like activity, preventing aggregation of various proteins under a wide range of stress conditions. Two additional functions of alpha crystallins are an autokinase activity and participation in the intracellular architecture. Alpha-A and alpha-B gene products are differentially expressed: alpha-A is preferentially restricted to the lens and alpha-B is expressed widely in many tissues and organs. [from Gene Cards, CRYAB; 2017.08.14]
Crystallins are the dominant structural components of the vertebrate eye lens.
The eye lens of vertebrates is a classic example of the re-engineering of existing protein components to perform a new function (Slingsby, et al., 2013; pubmed:23389822). The bulk of the lens is formed from proteins belonging to two superfamilies, the alpha crystallins and the beta-gamma crystallins. The crystallins impart transparency to the lens and are organized to create a refractive index gradient.
One to one (reciprocal best hit): 1 human to 1 Drosophila; multiple lower-scoring orthologs in both species.
Moderate-scoring ortholog of human gene CRYAB (reciprocal best hit, 1 Drosophila to 1 human); multiple lower-scoring orthologs in both species. Dmel\l(2)efl shares 44% identity and 60% similarity with CRYAB.