CRYAA

Chr 21

crystallin alpha A

Also known as: CRYA1, CTRCT9, HSPB4

NCBI Gene: 1409 ENSG00000160202 UniProt: P02489

Alpha-A crystallin is a small heat shock protein that acts as a molecular chaperone and contributes to lens transparency and refractive index, and is required for correct formation of lens intermediate filaments. Mutations cause cataract 9, multiple types, with both autosomal dominant and autosomal recessive inheritance patterns reported. The cataracts are typically congenital, affecting the lens from birth.

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. Post-translational modifications decrease the ability to chaperone. 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. Defects in this gene cause autosomal dominant congenital cataract (ADCC). [provided by RefSeq, Jan 2014]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCataract 9, multiple types

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.99

LOEUF

LOF*

Mechanism· G2P

Some data sources returned errors (1)

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