CRYGD
protein-codingcrystallin gamma D, the group of Beta-gamma crystallins
Gene summary
Crystallins are separated into two classes: taxon-specific, or enzyme, and ubiquitous. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. Since lens central fiber cells lose their nuclei during development, these crystallins are made and then retained throughout life, making them extremely stable proteins. Mammalian lens crystallins are divided into alpha, beta, and gamma families; beta and gamma crystallins are also considered as a superfamily. Alpha and beta families are further divided into acidic and basic groups. Seven protein regions exist in crystallins: four homologous motifs, a connecting peptide, and N- and C-terminal extensions. Gamma-crystallins are a homogeneous group of highly symmetrical, monomeric proteins typically lacking connecting peptides and terminal extensions. They are differentially regulated after early development. Four gamma-crystallin genes (gamma-A through gamma-D) and three pseudogenes (gamma-E, gamma-F, gamma-G) are tandemly organized in a genomic segment as a gene cluster. Whether due to aging or mutations in specific genes, gamma-crystallins have been involved in cataract formation. [provided by RefSeq, Jul 2008]
- CRYG4
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0007281
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0007281
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0015300
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0018611
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0007281
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0020375
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0020376
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0011430
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0020374
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CRYGD variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006891.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 6 | 2 | 10 | ||
| missense | 4 | 4 | 35 | 7 | 3 | 53 |
| nonsense | 2 | 5 | 1 | 8 | ||
| start loss | 0 | |||||
| frameshift | 1 | 3 | 5 | 9 | ||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 7 | 12 | 43 | 13 | 6 | 81 |
Highest pathogenic variant AF is 0.000027293187
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_008822.2 | 3 | MANE Select | |
| Ensembl | ENSP00000264376.4 | 3 | MANE Select | |
| Ensembl | ENSP00000803603.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- lens development in camera-type eye
- visual perception
- cellular response to reactive oxygen species
- lens fiber cell differentiation
Molecular Function
- structural constituent of eye lens
- protein binding
Cellular Component
- nucleus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000264376
- Coding exons
- 3
- Length
- 2895
- Individuals with no LoFs
- 124179
- Homozygous LoFs
- 19
- Heterozygous LoFs
- 1550
- Defined
- 125748
- p
- 0.00626
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0808 | 106 | 108 | 0.978 | 0.00000714 | 1138 |
| Missense (PolyPhen) | 31 | 27.035 | 1.1467 | 336 | ||
| Synonymous | -0.520 | 48 | 43.6 | 1.10 | 0.00000287 | 325 |
| Loss of Function | 0.584 | 6 | 7.75 | 0.774 | 4.10e-7 | 79 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0013 | 0.0012 | notable |
| Latino/Admixed American | 0.031 | 0.031 | notable |
| Ashkenazi Jewish | 0.0044 | 0.0043 | notable |
| East Asian | 0.0028 | 0.0028 | notable |
| Finnish | 0.00033 | 0.00032 | rare |
| European (Non-Finnish) | 0.0028 | 0.0027 | notable |
| South Asian | 0.0016 | 0.0015 | notable |
| Other | 0.0046 | 0.0046 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Crystallins are the dominant structural components of the vertebrate eye lens.;
- Disease
- DISEASE: Cataract 4, multiple types (CTRCT4) [MIM:115700]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT4 includes crystalline aculeiform, congenital cerulean and non-nuclear polymorphic cataracts, among others. Crystalline aculeiform cataract is characterized by fiberglass-like or needle-like crystals projecting in different directions, through or close to the axial region of the lens. Non- nuclear polymorphic cataract is a partial opacity with variable location between the fetal nucleus of the lens and the equator. The fetal nucleus is normal. The opacities are irregular and look similar to a bunch of grapes and may be present simultaneously in different lens layers. Congenital cerulean cataract is characterized by peripheral bluish and white opacifications organized in concentric layers with occasional central lesions arranged radially. The opacities are observed in the superficial layers of the fetal nucleus as well as the adult nucleus of the lens. Involvement is usually bilateral. Visual acuity is only mildly reduced in childhood. In adulthood, the opacifications may progress, making lens extraction necessary. Histologically the lesions are described as fusiform cavities between lens fibers which contain a deeply staining granular material. Although the lesions may take on various colors, a dull blue is the most common appearance and is responsible for the designation cerulean cataract. {ECO:0000269|PubMed:10521291, ECO:0000269|PubMed:10688888, ECO:0000269|PubMed:10915766, ECO:0000269|PubMed:11371638, ECO:0000269|PubMed:12011157, ECO:0000269|PubMed:12676897, ECO:0000269|PubMed:15709761, ECO:0000269|PubMed:16943771, ECO:0000269|PubMed:17564961, ECO:0000269|PubMed:21031598, ECO:0000269|PubMed:9927684}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.147
Intolerance Scores
- LoFtool
- 0.585
- RVIS EVS
- 0.06
- RVIS percentile EVS
- 58.26
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.204
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |