CRYAA

crystallin alpha A, the group of Small heat shock proteins

Basic information

Region (hg38): 21:43169008-43172810

Previous symbols: [ "CRYA1" ]

Links

ENSG00000160202 ∙ NCBI:1409 ∙ OMIM:123580 ∙ HGNC:2388 ∙ Uniprot:P02489 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cataract 9 multiple types (Definitive), mode of inheritance: AR
• cataract 9 multiple types (Definitive), mode of inheritance: AD
• 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

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the CRYAA gene.

• Cataract 9 multiple types (7 variants)
• not provided (3 variants)
• Cataract 9, multiple types, with microcornea (1 variants)
• Developmental cataract (1 variants)
• Inborn genetic diseases (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	12	6	19
missense	8	2	25			35
nonsense		1				1
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding			9	10	8	27
Total	8	3	36	22	14

Highest pathogenic variant AF is 0.0000260

Variants in CRYAA

This is a list of pathogenic ClinVar variants found in the CRYAA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
21-43169038-G-A			Likely benign (Oct 01, 2018)
21-43169070-C-G		Cataract 9 multiple types	Uncertain significance (Jan 12, 2018)
21-43169105-C-T		not specified • Cataract 9 multiple types	Benign (Jan 31, 2024)
21-43169126-G-A		Cataract 9, autosomal recessive	Likely pathogenic (Oct 18, 2019)
21-43169133-C-T		Cataract 9, multiple types, with microcornea • Cataract 9 multiple types • Developmental cataract • Abnormality of the eye	Pathogenic/Likely pathogenic (Sep 29, 2021)
21-43169134-G-A		Cataract 9 multiple types	Uncertain significance (Jun 27, 2022)
21-43169149-T-C		Cataract 9 multiple types • not specified	Uncertain significance (Oct 14, 2023)
21-43169153-C-T		Cataract 9 multiple types	Benign (Jan 31, 2024)
21-43169160-C-T		Cataract 9, multiple types, with microcornea • Developmental cataract • Cataract 9 multiple types • CRYAA-related disorder	Pathogenic/Likely pathogenic (Mar 23, 2023)
21-43169161-G-A		Cataract 9 multiple types	Pathogenic (Dec 10, 2023)
21-43169169-G-A		not specified	Uncertain significance (Nov 22, 2023)
21-43169174-G-C		Cataract 9 multiple types	Uncertain significance (Jul 17, 2023)
21-43169180-C-T			Likely benign (Jun 10, 2018)
21-43169210-G-A		Cataract 9 multiple types	Likely benign (Feb 17, 2020)
21-43169232-A-G		not specified	Uncertain significance (Feb 17, 2022)
21-43169241-T-G		Developmental cataract	Likely pathogenic (Jan 09, 2015)
21-43169244-C-T		Cataract 9 multiple types	Pathogenic (Jun 23, 2023)
21-43169245-G-A			Uncertain significance (Nov 01, 2016)
21-43169253-C-T		Cataract 9 multiple types • CRYAA-related disorder	Conflicting classifications of pathogenicity (Dec 02, 2023)
21-43169258-C-T		Cataract 9 multiple types	Likely benign (Oct 21, 2022)
21-43169259-C-T		Cataract 9 multiple types • Developmental cataract	Pathogenic (May 02, 2022)
21-43169260-G-C		Cataract 9 multiple types	Pathogenic (Jul 28, 2023)
21-43169265-G-A		Cataract 9 multiple types • not specified	Uncertain significance (Dec 19, 2024)
21-43169302-C-T		Cataract 9 multiple types	Likely benign (Dec 11, 2023)
21-43169303-G-A		Cataract 9 multiple types	Likely benign (Nov 25, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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