CRYGD: Crystallin Gamma D – A Key Lens Protein in Cataract Formation
Comprehensive biomedical overview of the CRYGD gene, its protein product, associated diseases, expression patterns, and mutational landscape.
Gene Information Card
| Symbol | CRYGD |
|---|---|
| Full Name | crystallin gamma D |
| Gene Type | protein-coding |
| Chromosomal Location | 2q33.3 |
| NCBI Gene ID | 1421 ncbi.nlm.nih.gov/gene/1421 |
| Ensembl ID | ENSG00000160207 |
| UniProt ID | P07320 |
| OMIM ID | 123690 |
| HGNC ID | 2411 |
| Aliases | CRYG4, gamma-D-crystallin, CCL |
Description
CRYGD (crystallin gamma D) is a protein-coding gene located on chromosome 2q33.3. It encodes gamma-crystallin D, a major structural protein of the vertebrate eye lens. Gamma-crystallins are characterized by their high refractive index and stability, contributing to lens transparency. Mutations in CRYGD are a well-established cause of autosomal dominant congenital cataracts, often presenting as pulverulent, lamellar, or cerulean types. The protein is composed of four Greek key motifs forming two domains, and its solubility is critical for lens clarity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital cataract (various types, e.g., pulverulent, lamellar, cerulean) | Missense mutations disrupt protein folding, reduce solubility, and promote aggregation, leading to lens opacification. | ClinVar, OMIM (123690) |
| Cataract 4 (CTRCT4) | Dominant-negative or gain-of-function mutations cause abnormal crystallin aggregation. | OMIM (115700) |
| Age-related cataract | Polymorphisms and oxidative modifications may contribute to late-onset lens opacity. | NCBI Gene, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lens | High | Tissue-specific, major structural protein |
| Retina | Low | Minor expression detected |
| Brain | Not detected | - |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| ARPE-19 (retinal pigment epithelium) | Not expressed | - |
| HLE-B3 (human lens epithelial) | High | Endogenous expression |
| HeLa | Not detected | - |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.109G>A (p.Gly37Arg) | Missense | Rare | Dominant congenital cataract; reduces protein solubility |
| c.176G>A (p.Arg59His) | Missense | Rare | Cerulean cataract; alters surface charge and aggregation propensity |
| c.394C>T (p.Pro132Thr) | Missense | Rare | Lamellar cataract; disrupts Greek key motif |
| c.418C>T (p.Arg140Cys) | Missense | Rare | Pulverulent cataract; promotes disulfide cross-linking and aggregation |
Mutation functional classification
Loss of Function (LOF)
Not typically observed; most mutations are dominant-negative or gain-of-function.
Gain of Function (GOF)
Mutations increase aggregation propensity, leading to toxic protein aggregates in lens fibers.
Dominant Negative (DN)
Mutant gamma-D crystallin interferes with wild-type protein folding and solubility, causing co-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 | • protein stabilization |
Pathways
• Lens fiber cell differentiation
• Crystallin aggregation in cataract
Protein Summary
Gamma-crystallin D is a 173-amino-acid protein (molecular weight ~20.6 kDa) composed of two domains, each containing two Greek key motifs. It is synthesized in lens fiber cells and contributes to the high refractive index of the lens. The protein is highly soluble under normal conditions but prone to aggregation when mutated. Post-translational modifications such as deamidation and oxidation are associated with age-related cataract. UniProt ID: P07320.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CRYGD Knockout HEK293 Cell Line | EDJ-KQ3635 | Human | 1421 | Details Get a Quote |
| CRYGD Knockout HeLa Cell Line | EDJ-KQ52997 | Human | 1421 | Details Get a Quote |
| CRYGD Knockout A-549 Cell Line | EDJ-KQ61464 | Human | 1421 | Details Get a Quote |
| CRYGD Knockout HCT 116 Cell Line | EDJ-KQ69961 | Human | 1421 | Details Get a Quote |
