CRYBA4

crystallin beta A4, the group of Beta-gamma crystallins

Basic information

Region (hg38): 22:26621963-26630669

Links

ENSG00000196431 ∙ NCBI:1413 ∙ OMIM:123631 ∙ HGNC:2396 ∙ Uniprot:P53673 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cataract 23 (Moderate), mode of inheritance: AD
• cataract 23 (Limited), mode of inheritance: AD
• cataract - microcornea syndrome (Supportive), mode of inheritance: AD
• early-onset lamellar cataract (Supportive), mode of inheritance: AD
• cataract 23 (Strong), mode of inheritance: AD
• cataract 23 (Limited), mode of inheritance: AR
• cataract 23 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cataract 23	AD	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	16960806; 20577656

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CRYBA4 gene.

• Cataract_23 (53 variants)
• not_provided (20 variants)
• Inborn_genetic_diseases (15 variants)
• CRYBA4-related_disorder (6 variants)
• not_specified (1 variants)
• Developmental_cataract (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CRYBA4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001886.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				17	1	18
missense	3	1	33	6		43
nonsense			1			1
start loss						0
frameshift			1			1
splice donor/acceptor (+/-2bp)			2	2		4
Total	3	1	37	25	1

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CRYBA4	protein_coding	protein_coding	ENST00000354760	5	8709

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.50e-9	0.183	124688	5	1055	125748	0.00422

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.694	105	127	0.827	0.00000854	1271
Missense in Polyphen		31	51.076	0.60694		528
Synonymous	-0.287	56	53.3	1.05	0.00000398	368
Loss of Function	0.411	14	15.8	0.888	0.00000114	122

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00334	0.00333
Ashkenazi Jewish	0.00109	0.00109
East Asian	0.000707	0.000707
Finnish	0.00759	0.00747
European (Non-Finnish)	0.00600	0.00597
Middle Eastern	0.000707	0.000707
South Asian	0.00255	0.00255
Other	0.00408	0.00408

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Crystallins are the dominant structural components of the vertebrate eye lens.
• Disease: DISEASE: Cataract 23, multiple types (CTRCT23) [MIM:610425]: 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. CTRCT23 is a zonular cataract. Zonular or lamellar cataracts are opacities, broad or narrow, usually consisting of powdery white dots affecting only certain layers or zones between the cortex and nucleus of an otherwise clear lens. The opacity may be so dense as to render the entire central region of the lens completely opaque, or so translucent that vision is hardly if at all impeded. Zonular cataracts generally do not involve the embryonic nucleus, though sometimes they involve the fetal nucleus. Usually sharply separated from a clear cortex outside them, they may have projections from their outer edges known as riders or spokes. {ECO:0000269|PubMed:16960806, ECO:0000269|PubMed:20577656}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cellular response to heat stress;HSF1 activation;Attenuation phase;HSF1-dependent transactivation;Regulation of HSF1-mediated heat shock response;Cellular responses to stress;Cellular responses to external stimuli;Cellular response to heat stress (Consensus)

Recessive Scores

• pRec: 0.133

Intolerance Scores

• loftool: 0.740
• rvis_EVS: 0.22
• rvis_percentile_EVS: 68.13

Haploinsufficiency Scores

• pHI: 0.209
• hipred: N
• hipred_score: 0.300
• ghis: 0.424

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.299

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cryba4

Gene ontology

• Biological process: visual perception;camera-type eye development
• Cellular component: cellular_component
• Molecular function: molecular_function;structural constituent of eye lens;protein binding