CRYAB

Chr 11ADAR

crystallin alpha B

Also known as: CMD1II, CRYA2, CTPP2, CTRCT16, HEL-S-101, HSPB5, MFM2, MFM2A

NCBI Gene: 1410 ENSG00000109846 UniProt: P02511 OMIM: 123590

Alpha-B crystallin functions as a molecular chaperone that prevents protein aggregation under stress conditions and contributes to lens transparency. Mutations cause autosomal dominant or recessive disorders including dilated cardiomyopathy, cataracts, and myofibrillar myopathies with either adult or infantile onset depending on the specific variant. The gene is not highly constrained against loss-of-function variation, reflecting its tolerance to certain types of genetic variants.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Mammalian lens crystallins are divided into alpha, beta, and gamma families. 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 act as molecular chaperones although they do not renature proteins and release them in the fashion of a true chaperone; instead they hold them in large soluble aggregates. These heterogeneous aggregates consist of 30-40 subunits; the alpha-A and alpha-B subunits have a 3:1 ratio, respectively. Two additional functions of alpha crystallins are an autokinase activity and participation in the intracellular architecture. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. 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. Elevated expression of alpha-B crystallin occurs in many neurological diseases; a missense mutation cosegregated in a family with a desmin-related myopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2019]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cardiomyopathy, dilated, 1IIMIM #615184

Cataract 16, multiple typesMIM #613763

ADAR

Myopathy, myofibrillar, 2A, adult-onsetMIM #608810

Myopathy, myofibrillar, 2B, infantile-onsetMIM #613869

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.43

LOEUF

Multiple*

Mechanism· G2P

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GeneReview available — CRYAB