CRYGS: Crystallin Gamma S – A Key Lens Protein in Cataract Formation
Comprehensive genomic and proteomic analysis of CRYGS, its role in lens transparency, and associated genetic variants in congenital and age-related cataracts.
Gene Information Card
| Symbol | CRYGS |
|---|---|
| Full Name | crystallin gamma S |
| Gene Type | protein-coding |
| Chromosomal Location | 3q27.3 |
| NCBI Gene ID | 1427 ncbi.nlm.nih.gov/gene/1427 |
| Ensembl ID | ENSG00000163687 |
| UniProt ID | P22914 |
| OMIM ID | 123730 |
| HGNC ID | 2417 |
| Aliases | CRYG8, gamma-crystallin S, gammaS-crystallin |
Description
CRYGS encodes gamma-crystallin S, a member of the beta/gamma-crystallin family that constitutes the major structural proteins of the vertebrate eye lens. Gamma-crystallins are characterized by their high refractive index and stability, contributing to lens transparency and optical clarity. CRYGS is specifically expressed in the lens and is essential for maintaining lens fiber cell structure. Mutations in CRYGS are associated with autosomal dominant congenital cataracts, particularly Coppock-like cataract and other forms of progressive lens opacification.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cataract 2 (CTRCT2) – Coppock-like cataract | Missense mutations (e.g., p.Gly18Val, p.Arg14Cys) disrupt protein folding and solubility, leading to aggregation and lens opacity. | ClinVar, OMIM |
| Autosomal dominant congenital cataract | Dominant-negative or gain-of-toxic-function mechanisms due to misfolded gamma-crystallin S accumulating in lens fibers. | NCBI Gene, PubMed |
| Age-related cataract | Reduced expression or oxidative damage to CRYGS protein may contribute to lens clouding with aging. | UniProt, literature review |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lens | High (nTPM not available in GTEx) | Tissue-specific, high expression |
| Retina | Low | Minimal expression |
| Other tissues | Not detected | Lens-specific expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Lens epithelial cells (HLE-B3) | High | Major structural protein |
| Lens fiber cells | Very high | Differentiation-dependent upregulation |
| ARPE-19 (retinal pigment epithelium) | Low | Non-lens cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.52G>T (p.Gly18Val) | Missense | Rare | Dominant congenital cataract; disrupts Greek-key motif |
| c.40C>T (p.Arg14Cys) | Missense | Rare | Cataract; alters protein stability |
| c.109G>A (p.Gly37Ser) | Missense | Rare | Coppock-like cataract; reduced solubility |
Mutation functional classification
Loss of Function (LOF)
Not typical; homozygous loss may be lethal or cause severe lens defects.
Gain of Function (GOF)
Misfolded protein aggregates exert toxic gain-of-function in lens fibers.
Dominant Negative (DN)
Mutant gamma-crystallin S interferes with wild-type protein, promoting aggregation.
View complete mutation data：
Gene Ontology (GO)
| • structural constituent of eye lens | • protein homodimerization activity |
| • identical protein binding | • lens development in camera-type eye |
| • visual perception | • response to oxidative stress |
Pathways
• Lens fiber cell differentiation
• Crystallin aggregation in cataract
Protein Summary
Gamma-crystallin S (CRYGS) is a 178-amino acid protein with four Greek-key motifs arranged in two domains. It is a major component of the lens cytoplasm, providing high refractive index and transparency. The protein is highly soluble and stable, but mutations can cause misfolding, aggregation, and cataract formation. Post-translational modifications such as deamidation and oxidation are associated with age-related lens opacification.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CRYGS Knockout HEK293 Cell Line | EDJ-KQ4358 | Human | 1427 | Details Get a Quote |
| CRYGS Knockout A-549 Cell Line | EDJ-KQ26859 | Human | 1427 | Details Get a Quote |
| CRYGS Knockout HCT 116 Cell Line | EDJ-KQ26860 | Human | 1427 | Details Get a Quote |
| CRYGS Knockout HeLa Cell Line | EDJ-KQ26861 | Human | 1427 | Details Get a Quote |
