CRYBB3

protein-coding

crystallin beta B3, 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 basic group member, is part of a gene cluster with beta-A4, beta-B1, and beta-B2. Mutations in this gene result in cataract congenital nuclear autosomal recessive type 2. [provided by RefSeq, Feb 2013]

Previous symbols:

CRYB3

MANE transcript

NM_004076.5

Inheritance

AD, AR, SD

ClinVar variants

P:8U:82B:21

Top phenotype

Cataract 22, multiple types

gnomAD constraint

pLI —, LoF o/e 1.14

Max pathogenic AF

—

Genomic locus

chr22:25,199,858-25,207,359

External References & Databases

Ensembl (ENSG00000100053)

Transcript & Mutation Effects

hg38 • Region Span ~7.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

early-onset non-syndromic cataractLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0011060

Submitter: Ambry Genetics

cataract 22 multiple typesMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0012336

Submitter: Ambry Genetics

cataract 22 multiple typesDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012336

Submitter: G2P

early-onset anterior polar cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020373

Submitter: Orphanet

cataract 22 multiple typesMODERATE

Inheritance Pattern: SD

Disease ID:MONDO:0012336

Submitter: Ambry Genetics

early-onset nuclear cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020376

Submitter: Orphanet

cataract 22 multiple typesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012336

Submitter: Labcorp Genetics (formerly Invitae)

cataract 22 multiple typesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0012336

Submitter: Labcorp Genetics (formerly Invitae)

cataract 22 multiple typesMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0012336

Submitter: G2P

Clinical Genomic Database (CGD)

Cataract 22, multiple typesAD/AR

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: 15914629; 27326458; 28418495; 23508780

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CRYBB3 variants in ClinVar

8 Conditions Cataloged

Cataract 22 multiple typesTotal: 58

Inborn genetic diseasesTotal: 54

not providedTotal: 31

CRYBB3-related disorderTotal: 9

not specifiedTotal: 5

Developmental cataractTotal: 2

CataractTotal: 1

MicrophthalmiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004076.5. 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			4 clinvar	11 clinvar		15
missense	3 clinvar	3 clinvar	76 clinvar	8 clinvar		90
nonsense			1 clinvar	1 clinvar		2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)		2 clinvar	1 clinvar	1 clinvar		4
Total	3	5	82	21	0	111

Highest pathogenic variant AF is 0.000017969318

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004076.5	RefSeq	NP_004067.1	5	MANE Select
ENST00000215855.7	Ensembl	ENSP00000215855.2	5	MANE Select
ENST00000404334.1	Ensembl	ENSP00000386123.1	4	Standard
ENST00000404334.2	Ensembl	ENSP00000386123.1	4	Standard

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

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000215855
Coding exons: 5
Length: 7514
Individuals with no LoFs: 125354
Homozygous LoFs: 2
Heterozygous LoFs: 392
Defined: 125748
p: 0.00157

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.126	151	147	1.03	0.0000111	1392
Missense (PolyPhen)		46	52.782	0.87151		521
Synonymous	-0.461	58	53.7	1.08	0.00000386	392
Loss of Function	-0.462	15	13.2	1.14	7.74e-7	115

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0055	0.0054	notable
Latino/Admixed American	0.00038	0.00038	rare
Ashkenazi Jewish	0.019	0.019	notable
East Asian	0.0017	0.0017	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00043	0.00043	rare
South Asian	0.00029	0.00029	rare
Other	0.0021	0.0021	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Crystallins are the dominant structural components of the vertebrate eye lens.;
Disease: DISEASE: Cataract 22, multiple types (CTRCT22) [MIM:609741]: 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. CTRCT22 includes nuclear cataract among others. Nuclear cataracts affect the central nucleus of the eye, and are often not highly visually significant. The density of the opacities varies greatly from fine dots to a dense, white and chalk-like, central cataract. The condition is usually bilateral. Nuclear cataracts are often combined with opacified cortical fibers encircling the nuclear opacity, which are referred to as cortical riders. {ECO:0000269|PubMed:15914629, ECO:0000269|PubMed:23508780}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.125

Intolerance Scores

LoFtool: 0.808
RVIS EVS: 0.82
RVIS percentile EVS: 87.99

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.376

Gene Damage Prediction

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