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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CRYBB2
crystallin beta B2
Chromosome 22 · 22q11.23
NCBI Gene: 1415Ensembl: ENSG00000244752.4HGNC: HGNC:2398UniProt: P43320
70PubMed Papers
21Diseases
0Drugs
15Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingidentical protein bindingvisual perceptionstructural constituent of eye lensCataract-microcornea syndromeTotal congenital cataractCataract with Y-shaped suture opacitiespulverulent cataract
✦AI Summary

CRYBB2 encodes βB2-crystallin, a dominant structural protein of the vertebrate eye lens critical for lens transparency and visual perception 1. As a lens-specific structural component, CRYBB2 maintains protein-protein interactions essential for lens fiber cell organization and solubility 2. Mutations in CRYBB2 cause autosomal dominant congenital cataracts through various mechanisms: missense mutations can increase protein hydrophobicity, impair solubility, or alter disulfide bonding patterns, leading to protein aggregation and lens opacity 23. De novo gene conversion events between CRYBB2 and its pseudogene CRYBB2P1 represent an important mutational mechanism in cataract families 14. Beyond ocular function, CRYBB2 is expressed in brain regions including the hippocampus and cerebral cortex, where it influences sensorimotor gating and memory function 5. In diabetic retinopathy, CRYBB2 expression increases in males but not females, suggesting sex-dependent roles in retinal stress responses 6. CRYBB2 variants have also been associated with schizophrenia-related endophenotypes affecting cognitive performance 57. Exon 6 represents a particularly mutation-susceptible region for cataract-causing variants 2.

Sources cited
1
CRYBB2 mutations cause congenital cataracts; de novo gene conversion between CRYBB2 and pseudogene CRYBB2P1 as disease mechanism
PMID: 25489230
2
CRYBB2 W151C mutation causes central nuclear cataract; exon 6 is a critical mutation-susceptible region; mutations increase protein hydrophobicity and impair solubility
PMID: 15452067
3
CRYBB2 c.563G>A mutation causes autosomal dominant early-onset cataract with variable severity and associated elongation of axial length
PMID: 32498547
4
Gene conversion in CRYBB2 exon 6 from pseudogene CRYBB2P1 causes autosomal dominant cataract; independent gene conversions occur in different families
PMID: 17234267
5
CRYBB2 is expressed in brain regions including hippocampus and cerebral cortex; CRYBB2 polymorphisms associate with antisaccade performance, memory function, and sensorimotor gating
PMID: 32317624
6
CRYBB2 expression increases in male diabetic retina but not female, indicating sex-dependent role in retinal stress responses to diabetes
PMID: 39354039
7
CRYBB2 mutations are involved in neurological disorders including schizophrenia, extending beyond its structural role in the lens
PMID: 26593886
Disease Associationsⓘ21
Cataract-microcornea syndromeOpen Targets
0.78Strong
Total congenital cataractOpen Targets
0.63Moderate
Cataract with Y-shaped suture opacitiesOpen Targets
0.63Moderate
pulverulent cataractOpen Targets
0.57Moderate
early-onset non-syndromic cataractOpen Targets
0.47Moderate
Nuclear pulverulent cataractOpen Targets
0.46Moderate
Developmental cataractOpen Targets
0.45Moderate
cataractOpen Targets
0.42Moderate
early-onset nuclear cataractOpen Targets
0.40Weak
cataract - microcornea syndromeOpen Targets
0.39Weak
cerulean cataractOpen Targets
0.37Weak
early-onset sutural cataractOpen Targets
0.37Weak
total early-onset cataractOpen Targets
0.37Weak
genetic disorderOpen Targets
0.34Weak
COVID-19Open Targets
0.30Weak
neurodegenerative diseaseOpen Targets
0.29Weak
spinal muscular atrophyOpen Targets
0.14Weak
Atrophy/Degeneration affecting the central nervous systemOpen Targets
0.13Weak
Alzheimer diseaseOpen Targets
0.12Weak
Partial congenital cataractOpen Targets
0.11Weak
Cataract 3, multiple typesUniProt
Pathogenic Variants15
NM_000496.3(CRYBB2):c.355G>A (p.Gly119Arg)Pathogenic
Cataract 3 multiple types|not provided
★★☆☆2025→ Residue 119
NM_000496.3(CRYBB2):c.562C>T (p.Arg188Cys)Pathogenic
Cataract 3 multiple types|not provided
★★☆☆2025→ Residue 188
NM_000496.3(CRYBB2):c.563G>A (p.Arg188His)Pathogenic
not provided|Cataract 3 multiple types
★★☆☆2025→ Residue 188
NM_000496.3(CRYBB2):c.463C>T (p.Gln155Ter)Pathogenic
Cataract 3 multiple types|Developmental cataract|not provided|CRYBB2-related disorder
★★☆☆2024→ Residue 155
NM_000496.3(CRYBB2):c.54+1G>APathogenic
Cataract 3 multiple types
★☆☆☆2025
NM_000496.3(CRYBB2):c.230G>T (p.Gly77Val)Likely pathogenic
Cataract 3 multiple types
★☆☆☆2025→ Residue 77
NM_000496.3(CRYBB2):c.470C>T (p.Pro157Leu)Pathogenic
Cataract 3 multiple types
★☆☆☆2022→ Residue 157
NM_000496.3(CRYBB2):c.173C>T (p.Pro58Leu)Likely pathogenic
Cataract 3 multiple types
★☆☆☆2021→ Residue 58
NM_000496.3(CRYBB2):c.427T>C (p.Ser143Pro)Likely pathogenic
Cataract 3 multiple types
★☆☆☆2020→ Residue 143
NM_000496.3(CRYBB2):c.446G>T (p.Gly149Val)Likely pathogenic
Cataract 3 multiple types
★☆☆☆2020→ Residue 149
NM_000496.3(CRYBB2):c.161T>G (p.Val54Gly)Likely pathogenic
Cataract 3 multiple types
★☆☆☆2017→ Residue 54
NM_000496.3(CRYBB2):c.551T>G (p.Val184Gly)Likely pathogenic
Cataract 3 multiple types
★☆☆☆2017→ Residue 184
NM_000496.3(CRYBB2):c.563G>T (p.Arg188Leu)Pathogenic
Developmental cataract
☆☆☆☆2016→ Residue 188
NM_000496.3(CRYBB2):c.556T>C (p.Ser186Pro)Likely pathogenic
Developmental cataract
☆☆☆☆2015→ Residue 186
NM_000496.3(CRYBB2):c.471C>T (p.Pro157=)Pathogenic
Cataract 3 multiple types
☆☆☆☆2007→ Residue 157
View on ClinVar ↗
Related Genes
CRYBA4Shared pathway100%TMEM114Protein interaction94%MIPProtein interaction89%GJA8Protein interaction86%PITX3Protein interaction85%TRNT1Protein interaction80%
Tissue Expression6 tissues
Liver
100%
Lung
62%
Ovary
46%
Brain
23%
Bone Marrow
15%
Heart
0%
Gene Interaction Network
Click a node to explore
CRYBB2CRYBA4TMEM114MIPGJA8PITX3TRNT1
PROTEIN STRUCTURE
Preparing viewer…
PDB1YTQ · 1.70 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.77LoF Tolerant
pLIⓘ
0.09Tolerant
Observed/Expected LoF0.46 [0.29–0.77]
RankingsWhere CRYBB2 stands among ~20K protein-coding genes
  • #6,705of 20,598
    Most Researched70
  • #2,456of 5,498
    Most Pathogenic Variants15
  • #6,168of 17,882
    Most Constrained (LOEUF)0.77
Genes detectedCRYBB2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Congenital cataracts: de novo gene conversion event in CRYBB2.
PMID: 25489230
Mol Vis · 2014
1.00
2
Sex differences in the development of experimental diabetic retinopathy.
PMID: 39354039
Sci Rep · 2024
0.90
3
Mutation analysis of congenital cataracts in Indian families: identification of SNPS and a new causative allele in CRYBB2 gene.
PMID: 15452067
Invest Ophthalmol Vis Sci · 2004
0.80
4
From eyeless to neurological diseases.
PMID: 26593886
Exp Eye Res · 2017
0.70
5
Polymorphisms in CRYBB2 encoding βB2-crystallin are associated with antisaccade performance and memory function.
PMID: 32317624
Transl Psychiatry · 2020
0.60