Alternative titles; symbols
HGNC Approved Gene Symbol: CRYBB3
Cytogenetic location: 22q11.23 Genomic coordinates (GRCh38): 22:25,199,858-25,207,359 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 22q11.23 | Cataract 22 | 609741 | Autosomal dominant; Autosomal recessive | 3 |
Beta-crystallins consist of similar N-terminal and C-terminal domains separated by a short connecting peptide. Each domain folds into 2 similar 'Greek key' motifs, with distinctive beta-sheet folding. Different beta-crystallin proteins can interact with each other to form oligomers of different sizes ranging from dimers to octamers and can also interact with other lens proteins. The protein-protein interactions are predicted to be key in maintaining the transparency of the lens (summary by Qi et al., 2004).
Aarts et al. (1987) isolated and characterized human and rat genomic clones containing sequences for beta-B2 crystallin (CRYBB2; 123620) and/or beta-B3 crystallin.
Lampi et al. (1997) cloned the 5-prime portion of the CRYBB3 gene, which they designated beta-B3, by 5-prime RACE-PCR of lens RNA with primers based on the known sequence of CRYBB3. The beta-B3 gene encodes a predicted 211-amino acid protein. The calculated 24,224-dalton molecular weight of the protein matched the value determined experimentally by mass spectrometry and by analysis of tryptic peptides. Lampi et al. (1997) found that beta-B3 is 1 of 11 major soluble proteins in the young human lens.
Aarts et al. (1987) determined that in both the human and the rat genome, the single-copy CRYB3 gene is linked to the CRYB2 gene, separated by 20 kb in the human and 11 kb in the rat, and oriented head-to-tail with respect to transcription.
Hulsebos et al. (1991) mapped the CRYBB2 and CRYBB3 genes to chromosome 22q11.2-q12. Hulsebos et al. (1995) demonstrated by interspecific backcross analysis that the homologs of the CRYBB2, CRYBB3, and CRYBA4 (123631) genes are located in the central region of mouse chromosome 5.
Riazuddin et al. (2005) found homozygosity for a missense mutation in the CRYBB3 gene (G165R; 123630.0001) in 2 Pakistani families with autosomal recessive congenital nuclear cataract (CTRCT22; 609741). They noted that all theretofore described mutations in beta-crystallins had been associated with autosomal dominant cataracts, suggesting that beta-B3 crystallin may have a function in addition to that of a structural protein.
In 5 affected members of a 4-generation Caucasian Italian family segregating multiple types of autosomal dominant congenital cataract with incomplete penetrance, Reis et al. (2013) identified heterozygosity for a missense mutation in the CRYBB3 gene (V194E; 123630.0002).
In 2 Pakistani families with autosomal recessive congenital nuclear cataract mapping to chromosome 22q11.2 (CTRCT22; 609741), Riazuddin et al. (2005) identified homozygous a G-to-C transition at nucleotide 493 in exon 6 of the CRYBB3 gene that cosegregated with the disease. This mutation resulted in the change of a highly conserved glycine to arginine at codon 165 (G165R) that was predicted to result in incorrect folding of the crystallin.
In 5 affected members of a 4-generation Caucasian Italian family segregating multiple types of autosomal dominant congenital cataract (CTRCT22; 609741) with incomplete penetrance, Reis et al. (2013) identified heterozygosity for a c.581T-A transversion in the CRYBB3 gene, resulting in a val194-to-glu (V194E) substitution at a highly conserved residue within the Greek key motif IV. The mutation was also detected in 1 unaffected family member but was not found in 12,999 control chromosomes from the Exome Variant Server database. The substitution of hydrophobic valine with hydrophilic glutamic acid was predicted to cause destabilization of the domain structure of the Greek key motif IV and to affect CRYBB3 protein folding.
Aarts, H. J. M., Den Dunnen, J. T., Lubsen, N. H., Schoenmakers, J. G. G. Linkage between the beta-B2 and beta-B3 crystallin genes in man and rat: a remnant of an ancient beta-crystallin gene cluster. Gene 59: 127-135, 1987. [PubMed: 3436525] [Full Text: https://doi.org/10.1016/0378-1119(87)90273-3]
Hulsebos, T. J. M., Bijlsma, E. K., Geurts van Kessel, A. H. M., Brakenhoff, R. H., Westerveld, A. Direct assignment of the human beta-B2 and beta-B3 and crystallin genes to 22q11.2-q12: markers for neurofibromatosis 2. Cytogenet. Cell Genet. 56: 171-175, 1991. [PubMed: 2055112] [Full Text: https://doi.org/10.1159/000133080]
Hulsebos, T. J. M., Jenkins, N. A., Gilbert, D. J., Copeland, N. G. The beta crystallin genes on human chromosome 22 define a new region of homology with mouse chromosome 5. Genomics 25: 574-576, 1995. [PubMed: 7789995] [Full Text: https://doi.org/10.1016/0888-7543(95)80062-q]
Lampi, K. J., Ma, Z., Shih, M., Shearer, T. R., Smith, J. B., Smith, D. L., David, L. L. Sequence analysis of beta-A3, beta-B3, and beta-A4 crystallins completes the identification of the major proteins in young human lens. J. Biol. Chem. 272: 2268-2275, 1997. [PubMed: 8999933] [Full Text: https://doi.org/10.1074/jbc.272.4.2268]
Qi, Y., Jia, H., Huang, S., Lin, H., Gu, J., Su, H., Zhang, T., Gao, Y., Qu, L., Li, D., Li, Y. A deletion mutation in the beta-A1/A3 crystallin gene (CRYBA1/A3) is associated with autosomal dominant congenital nuclear cataract in a Chinese family. Hum. Genet. 114: 192-197, 2004. [PubMed: 14598164] [Full Text: https://doi.org/10.1007/s00439-003-1049-7]
Reis, L. M., Tyler, R. C., Muheisen, S., Raggio, V., Salviati, L., Han, D. P., Costakos, D., Yonath, H., Hall, S., Power, P., Semina, E. V. Whole exome sequencing in dominant cataract identifies a new causative factor, CRYBA2, and a variety of novel alleles in known genes. Hum. Genet. 132: 761-770, 2013. [PubMed: 23508780] [Full Text: https://doi.org/10.1007/s00439-013-1289-0]
Riazuddin, S. A., Yasmeen, A., Yao, W., Sergeev, Y. V., Zhang, Q., Zulfiqar, F., Riaz, A., Riazuddin, S., Hejtmancik, J. F. Mutations in beta-B3-crystallin associated with autosomal recessive cataract in two Pakistani families. Invest. Ophthal. Vis. Sci. 46: 2100-2106, 2005. [PubMed: 15914629] [Full Text: https://doi.org/10.1167/iovs.04-1481]