CRYGC
protein-codingcrystallin gamma C, the group of Beta-gamma crystallins
Gene summary
This gene encodes a member of the beta/gamma-crystallin family of proteins. Crystallins constitute the major proteins of vertebrate eye lens and maintain the transparency and refractive index of the lens. This gene and several family members are present in a gene cluster on chromosome 2. Mutations in this gene have been shown to cause multiple types of cataract, including Coppock-like cataract and zonular pulverulent cataract, among others. [provided by RefSeq, Jan 2015]
- CRYG3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0020376
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0011430
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0100436
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0100436
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0100436
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0015300
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0018611
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 CRYGC variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020989.4. 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 | 9 | 2 | 11 | |||
| missense | 3 | 3 | 48 | 7 | 2 | 63 |
| nonsense | 5 | 8 | 13 | |||
| start loss | 0 | |||||
| frameshift | 7 | 8 | 1 | 1 | 17 | |
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 15 | 19 | 52 | 17 | 4 | 107 |
Highest pathogenic variant AF is 0.00002044559
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_066269.1 | 3 | MANE Select | |
| Ensembl | ENSP00000282141.3 | 3 | MANE Select |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- visual perception
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
- ENST00000282141
- Coding exons
- 3
- Length
- 1694
- Individuals with no LoFs
- 125624
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 124
- Defined
- 125748
- p
- 0.000493
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.604 | 127 | 109 | 1.16 | 0.00000779 | 1139 |
| Missense (PolyPhen) | 24 | 30.291 | 0.79232 | 351 | ||
| Synonymous | -0.628 | 48 | 42.8 | 1.12 | 0.00000269 | 326 |
| Loss of Function | 0.929 | 6 | 9.01 | 0.666 | 4.77e-7 | 87 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000064 | 0.000062 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.0045 | 0.0045 | notable |
| European (Non-Finnish) | 0.00018 | 0.00018 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Crystallins are the dominant structural components of the vertebrate eye lens.;
- Disease
- DISEASE: Cataract 2, multiple types (CTRCT2) [MIM:604307]: 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. CTRCT2 includes Coppock-like cataract, among others. Coppock-like cataract is a congenital pulverulent disk-like opacity involving the embryonic nucleus with many tiny white dots in the lamellar portion of the lens. It is usually bilateral and dominantly inherited. In some cases, CTRCT2 is associated with microcornea without any other systemic anomaly or dysmorphism. Microcornea is defined by a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye. {ECO:0000269|PubMed:10521291, ECO:0000269|PubMed:10914683, ECO:0000269|PubMed:12011157, ECO:0000269|PubMed:12601044, ECO:0000269|PubMed:18587492, ECO:0000269|PubMed:22052681, ECO:0000269|PubMed:22876111}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.396
Intolerance Scores
- LoFtool
- 0.465
- RVIS EVS
- 0.33
- RVIS percentile EVS
- 73.27
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.578
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |