CRYAA
crystallin alpha A, the group of Small heat shock proteins
Basic information
Region (hg38): 21:43169008-43172810
Previous symbols: [ "CRYA1" ]
Links
Phenotypes
GenCC
Source:
- cataract 9 multiple types (Definitive), mode of inheritance: AR
- cataract - microcornea syndrome (Supportive), mode of inheritance: AD
- early-onset anterior polar cataract (Supportive), mode of inheritance: AD
- early-onset nuclear cataract (Supportive), mode of inheritance: AD
- total early-onset cataract (Supportive), mode of inheritance: AD
- early-onset lamellar cataract (Supportive), mode of inheritance: AD
- cataract 9 multiple types (Strong), mode of inheritance: AD
- cataract 9 multiple types (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cataract 9, multiple types | AD/AR | General | 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 | Ophthalmologic | 9467006; 11006246; 14512969; 16564818; 17296897; 18302245; 20465443; 20606865; 21866213; 22065922; 22216983; 23255486 |
ClinVar
This is a list of variants' phenotypes submitted to
- Cataract_9_multiple_types (56 variants)
- not_provided (32 variants)
- not_specified (24 variants)
- CRYAA-related_disorder (7 variants)
- Developmental_cataract (6 variants)
- Cataract_9,_multiple_types,_with_microcornea (3 variants)
- Cataract_9,_autosomal_recessive (1 variants)
- Inborn_genetic_diseases (1 variants)
- Abnormality_of_the_eye (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CRYAA gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000394.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 17 | 23 | ||||
| missense | 35 | 48 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 7 | 7 | 36 | 18 | 5 |
Highest pathogenic variant AF is 0.0000052104174
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CRYAA | protein_coding | protein_coding | ENST00000291554 | 3 | 3798 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.174 | 0.774 | 125470 | 0 | 2 | 125472 | 0.00000797 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.348 | 107 | 118 | 0.910 | 0.00000956 | 1118 |
| Missense in Polyphen | 31 | 38.871 | 0.79752 | 348 | ||
| Synonymous | -0.649 | 60 | 53.9 | 1.11 | 0.00000465 | 358 |
| Loss of Function | 1.61 | 2 | 6.38 | 0.314 | 3.44e-7 | 64 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000617 | 0.0000617 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Contributes to the transparency and refractive index of the lens. Has chaperone-like activity, preventing aggregation of various proteins under a wide range of stress conditions. {ECO:0000269|PubMed:22120592}.;
- Disease
- DISEASE: Note=Alpha-crystallin A 1-172 is found at nearly twofold higher levels in diabetic lenses than in age-matched control lenses. {ECO:0000269|PubMed:12356833}.; DISEASE: Cataract 9, multiple types (CTRCT9) [MIM:604219]: 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. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT9 includes nuclear, zonular central nuclear, anterior polar, cortical, embryonal, anterior subcapsular, fan-shaped, and total cataracts, among others. In some cases cataract 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:11123904, ECO:0000269|PubMed:14512969, ECO:0000269|PubMed:16453125, ECO:0000269|PubMed:18302245, ECO:0000269|PubMed:18407550, ECO:0000269|PubMed:23508780, ECO:0000269|PubMed:9467006}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
(Consensus)
Recessive Scores
- pRec
- 0.260
Intolerance Scores
- loftool
- 0.255
- rvis_EVS
- -0.38
- rvis_percentile_EVS
- 27.69
Haploinsufficiency Scores
- pHI
- 0.170
- hipred
- Y
- hipred_score
- 0.503
- ghis
- 0.441
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.641
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cryaa
- Phenotype
- cellular phenotype; vision/eye phenotype;
Zebrafish Information Network
- Gene name
- cryaa
- Affected structure
- eye
- Phenotype tag
- abnormal
- Phenotype quality
- opaque
Gene ontology
- Biological process
- visual perception;negative regulation of intracellular transport;protein refolding;negative regulation of apoptotic process;protein stabilization;response to stimulus;protein homooligomerization
- Cellular component
- nucleus;nucleoplasm;cytoplasm;cytosol
- Molecular function
- structural constituent of eye lens;protein binding;identical protein binding;metal ion binding;unfolded protein binding