CRYAA: Crystallin Alpha A – Key Lens Protein in Cataract and Cancer
Comprehensive genomic, functional, and clinical overview of CRYAA (HGNC:2389) from NCBI, Ensembl, UniProt, OMIM, HGNC, COSMIC, and ClinVar.
Gene Information Card
| Symbol | CRYAA |
|---|---|
| Full Name | crystallin alpha A |
| Gene Type | protein-coding |
| Chromosomal Location | 21q22.3 |
| NCBI Gene ID | 1409 ncbi.nlm.nih.gov/gene/1409 |
| Ensembl ID | ENSG00000160211 |
| UniProt ID | P02489 |
| OMIM ID | 123580 |
| HGNC ID | 2389 |
| Aliases | CRYA1, HSPB4, CTRCT9 |
Description
CRYAA encodes alpha-crystallin A, a member of the small heat shock protein family (HSPB4). It functions as a molecular chaperone, preventing protein aggregation in the lens and maintaining transparency. Mutations in CRYAA are associated with autosomal dominant congenital cataract (ADCC) and may contribute to cancer progression via altered chaperone activity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal dominant congenital cataract (ADCC) | Missense mutations (e.g., R116C, R49C) disrupt chaperone function, leading to protein aggregation and lens opacity. | ClinVar, OMIM #123580 |
| Cataract 9 multiple types (CTRCT9) | Dominant-negative or loss-of-function mutations cause early-onset cataract. | OMIM #604219 |
| Breast cancer | CRYAA overexpression correlates with poor prognosis; chaperone activity may protect tumor cells from stress-induced apoptosis. | COSMIC, PubMed studies |
| Lung cancer | CRYAA upregulation in non-small cell lung cancer linked to chemoresistance. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lens | — | High |
| Retina | — | Moderate |
| Heart | — | Low |
| Skeletal muscle | — | Low |
| Kidney | — | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| ARPE-19 (retinal pigment epithelium) | — | Endogenous expression |
| HLE-B3 (human lens epithelial) | — | High expression |
| MCF-7 (breast cancer) | — | Overexpressed |
| A549 (lung cancer) | — | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R116C | Missense | Rare | Dominant-negative; disrupts chaperone activity; causes congenital cataract |
| R49C | Missense | Rare | Loss of chaperone function; cataract |
| W9X | Nonsense | Rare | Truncation; loss of function; cataract |
| G98R | Missense | Rare | Impaired oligomerization; cataract |
| D2N | Missense | Rare | Reduced stability; cataract |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., W9X) produce truncated proteins lacking chaperone activity.
Gain of Function (GOF)
Not well-documented; some missense mutations may cause toxic aggregation.
Dominant Negative (DN)
Missense mutations (e.g., R116C, R49C) interfere with wild-type CRYAA function, leading to cataract.
View complete mutation data：
Gene Ontology (GO)
| • structural constituent of eye lens (GO:0005212) | • response to heat (GO:0009408) |
| • heat shock protein binding (GO:0031072) | • protein refolding (GO:0042026) |
| • unfolded protein binding (GO:0051082) | • cytoplasm (GO:0005737) |
| • nucleus (GO:0005634) |
Pathways
• Unfolded protein response (UPR)
• Small heat shock protein (sHSP) pathway
• Protein processing in endoplasmic reticulum (KEGG: hsa04141)
Protein Summary
Alpha-crystallin A (UniProt P02489) is a 173-amino-acid protein with a conserved alpha-crystallin domain. It forms large oligomeric complexes that bind partially unfolded proteins, preventing aggregation. Post-translational modifications (phosphorylation, deamidation) modulate chaperone activity. In the lens, it is essential for transparency; in other tissues, it protects against stress-induced apoptosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CRYAA Knockout HEK293 Cell Line | EDJ-KQ50208 | Human | 1409 | Details Get a Quote |
| CRYAA Knockout HeLa Cell Line | EDJ-KQ52986 | Human | 1409 | Details Get a Quote |
| CRYAA Knockout A-549 Cell Line | EDJ-KQ61453 | Human | 1409 | Details Get a Quote |
| CRYAA Knockout HCT 116 Cell Line | EDJ-KQ69950 | Human | 1409 | Details Get a Quote |
