GeneBe

CRYBB2

protein-coding

crystallin beta B2, 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-B3. A chain-terminating mutation was found to cause type 2 cerulean cataracts. [provided by RefSeq, Jul 2008]

Previous symbols:
  • CCA2
  • CRYB2A
  • CRYB2

MANE transcript

NM_000496.3

Inheritance

AD

ClinVar variants

P:20U:74B:15

Top phenotype

Cataract 3, multiple types

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr22:25,212,564-25,231,870

External References & Databases

Ensembl (ENSG00000244752)NCBI Gene (1415)OMIM (123620)HGNC:2398GenCCUniProt (P43320)AlphaFoldClinVar (CRYBB2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~19.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cataract 3 multiple typesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011104

Submitter: Ambry Genetics

early-onset posterior subcapsular cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018610

Submitter: Orphanet

total early-onset cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0021548

Submitter: Orphanet

early-onset nuclear cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020376

Submitter: Orphanet

cataract 3 multiple typesDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011104

Submitter: G2P

cataract 3 multiple typesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011104

Submitter: Labcorp Genetics (formerly Invitae)

cerulean cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020374

Submitter: Orphanet

early-onset sutural cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020372

Submitter: Orphanet

cataract - microcornea syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015300

Submitter: Orphanet

pulverulent cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011430

Submitter: Orphanet

cataract 3 multiple typesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011104

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

Clinical Genomic Database (CGD)

Cataract 3, 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: 2240043; 8812489; 9158139; 10634616; 11424921; 17234267; 18617901; 19649175; 21031021; 21245961; 22312185; 22846113Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CRYBB2 variants in ClinVar

7 Conditions Cataloged
Cataract 3 multiple typesTotal: 62
not providedTotal: 33
Inborn genetic diseasesTotal: 27
CRYBB2-related disorderTotal: 26
not specifiedTotal: 8
Developmental cataractTotal: 4
Bilateral congenital or childhood onset cataractsTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000496.3. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
8
clinvar
2
clinvar
 11
missense
3
clinvar
12
clinvar
66
clinvar
4
clinvar
1
clinvar
 86
nonsense
1
clinvar
2
clinvar
3
clinvar
 6
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
1
clinvar
4
clinvar
 5
Total61474123109

Highest pathogenic variant AF is 0.000034073197

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000496.3RefSeqNP_000487.15MANE Select
ENST00000398215.3EnsemblENSP00000381273.25MANE Select
ENST00000651629.1EnsemblENSP00000498905.15Standard
ENST00000855619.1EnsemblENSP00000525678.15Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • visual perception
  • camera-type eye development
  • response to stimulus

Molecular Function

  • structural molecule activity
  • structural constituent of eye lens
  • identical protein binding
  • protein homodimerization activity

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000398215
Coding exons
5
Length
12348
Individuals with no LoFs
125733
Homozygous LoFs
0
Heterozygous LoFs
14
Defined
125747
p
0.0000557
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.07911250.7300.000007791354
Missense (PolyPhen)3347.4390.69563490
Synonymous-0.1775149.41.030.00000323366
Loss of Function2.66313.60.2218.76e-7125

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000970.000097rare
South Asian0.0000330.000033rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Crystallins are the dominant structural components of the vertebrate eye lens.;
Disease
DISEASE: Cataract 3, multiple types (CTRCT3) [MIM:601547]: 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. CTRCT3 includes congenital cerulean and sutural cataract with punctate and cerulean opacities, among others. Cerulean cataract is characterized by peripheral bluish and white opacifications organized in concentric layers with occasional central lesions arranged radially. The opacities are observed in the superficial layers of the fetal nucleus as well as the adult nucleus of the lens. Involvement is usually bilateral. Visual acuity is only mildly reduced in childhood. In adulthood, the opacifications may progress, making lens extraction necessary. Histologically the lesions are described as fusiform cavities between lens fibers which contain a deeply staining granular material. Although the lesions may take on various colors, a dull blue is the most common appearance and is responsible for the designation cerulean cataract. Sutural cataract with punctate and cerulean opacities is characterized by white opacification around the anterior and posterior Y sutures, and grayish and bluish, spindle shaped, oval punctate and cerulean opacities of various sizes arranged in lamellar form. The spots are more concentrated towards the peripheral layers and do not delineate the embryonal or fetal nucleus. Phenotypic variation with respect to the size and density of the sutural opacities as well as the number and position of punctate and cerulean spots is observed among affected subjects. {ECO:0000269|PubMed:10634616, ECO:0000269|PubMed:9158139}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.133

Intolerance Scores

LoFtool
0.445
RVIS EVS
0.3
RVIS percentile EVS
72.01

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.801

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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