CRYBA1

protein-coding

crystallin beta A1, 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. Beta-crystallins, the most heterogeneous, differ by the presence of the C-terminal extension (present in the basic group, none in the acidic group). Beta-crystallins form aggregates of different sizes and are able to self-associate to form dimers or to form heterodimers with other beta-crystallins. This gene, a beta acidic group member, encodes two proteins (crystallin, beta A3 and crystallin, beta A1) from a single mRNA, the latter protein is 17 aa shorter than crystallin, beta A3 and is generated by use of an alternate translation initiation site. Deletion of exons 3 and 4 causes the autosomal dominant disease 'zonular cataract with sutural opacities'. [provided by RefSeq, Jul 2008]

Previous symbols:

CRYB1

MANE transcript

NM_005208.5

Inheritance

ClinVar variants

P:19U:43B:9

Top phenotype

Cataract 10, multiple types

gnomAD constraint

pLI —, LoF o/e 0.57

Max pathogenic AF

—

Genomic locus

chr17:29,246,859-29,254,494

External References & Databases

Ensembl (ENSG00000108255)

Transcript & Mutation Effects

hg38 • Region Span ~7.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cataract 10 multiple typesDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0010948

Submitter: G2P

early-onset sutural cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020372

Submitter: Orphanet

early-onset nuclear cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020376

Submitter: Orphanet

early-onset posterior polar cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020378

Submitter: Orphanet

early-onset lamellar cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018611

Submitter: Orphanet

cataract 10 multiple typesDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0010948

Submitter: Ambry Genetics

cataract 10 multiple typesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0010948

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Cataract 10, multiple typesAD

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

Refs: 7573044; 9788845; 17653060; 20142846; 21686330; 21850182; 21866213; 22665976

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CRYBA1 variants in ClinVar

6 Conditions Cataloged

Cataract 10 multiple typesTotal: 46

not providedTotal: 25

Inborn genetic diseasesTotal: 25

CRYBA1-related disorderTotal: 14

not specifiedTotal: 6

Bilateral congenital or childhood onset cataractsTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005208.5. 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				3 clinvar	1 clinvar	4
missense	1 clinvar	1 clinvar	37 clinvar	5 clinvar		44
nonsense	1 clinvar		3 clinvar			4
start loss						0
frameshift	1 clinvar	5 clinvar	2 clinvar			8
splice donor/acceptor (+/-2bp)	1 clinvar	9 clinvar	1 clinvar			11
Total	4	15	43	8	1	71

Highest pathogenic variant AF is 0.000030097983

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005208.5	RefSeq	NP_005199.2	6	MANE Select
ENST00000225387.8	Ensembl	ENSP00000225387.3	6	MANE Select
ENST00000484605.1	Ensembl	ENSP00000464368.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of cytokine production
lens development in camera-type eye
visual perception
negative regulation of phosphatidylinositol 3-kinase signaling
negative regulation of TOR signaling

Molecular Function

molecular_function
structural constituent of eye lens
protein binding

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000225387
Coding exons: 6
Length: 7632
Individuals with no LoFs: 125716
Homozygous LoFs: 0
Heterozygous LoFs: 32
Defined: 125748
p: 0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.626	109	129	0.845	0.00000756	1436
Missense (PolyPhen)		34	43.922	0.7741		509
Synonymous	-0.563	48	43.3	1.11	0.00000248	356
Loss of Function	1.56	9	15.7	0.574	8.71e-7	157

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00054	0.00054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00020	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Crystallins are the dominant structural components of the vertebrate eye lens.;
Disease: DISEASE: Cataract 10, multiple types (CTRCT10) [MIM:600881]: 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. CTRCT10 includes congenital zonular with sutural opacities, among others. This is a form of zonular cataract with an erect Y-shaped anterior and an inverted Y-shaped posterior sutural opacities. 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:15016766, ECO:0000269|PubMed:9788845}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.177

Intolerance Scores

LoFtool: 0.768
RVIS EVS: 0.44
RVIS percentile EVS: 77.7

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.210

Gene Damage Prediction

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