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Review
. 2022 Mar;190(1):9-19.
doi: 10.1002/ajmg.c.31970. Epub 2022 Apr 4.

Bardet-Biedl syndrome: The pleiotropic role of the chaperonin-like BBS6, 10, and 12 proteins

Neha Gupta  1   2 , Mariavittoria D'Acierno  1   2 , Enrica Zona  1 , Giovambattista Capasso  2 , Miriam Zacchia  1
Affiliations
Review

Bardet-Biedl syndrome: The pleiotropic role of the chaperonin-like BBS6, 10, and 12 proteins

Neha Gupta et al. Am J Med Genet C Semin Med Genet. 2022 Mar.

Abstract

Bardet-Biedl syndrome (BBS) is a rare pleiotropic disorder known as a ciliopathy. Despite significant genetic heterogeneity, BBS1 and BBS10 are responsible for major diagnosis in western countries. It is well established that eight BBS proteins, namely BBS1, 2, 4, 5, 7, 8, 9, and 18, form the BBSome, a multiprotein complex serving as a regulator of ciliary membrane protein composition. Less information is available for BBS6, BBS10, and BBS12, three proteins showing sequence homology with the CCT/TRiC family of group II chaperonins. Even though their chaperonin function is debated, scientific evidence demonstrated that they are required for initial BBSome assembly in vitro. Recent studies suggest that genotype may partially predict clinical outcomes. Indeed, patients carrying truncating mutations in any gene show the most severe phenotype; moreover, mutations in chaperonin-like BBS proteins correlated with severe kidney impairment. This study is a critical review of the literature on genetics, expression level, cellular localization and function of BBS proteins, focusing primarily on the chaperonin-like BBS proteins, and aiming to provide some clues to understand the pathomechanisms of disease in this setting.

Keywords: BBS10; BBS12 and ciliopathies; BBS6/MKKS; Bardet-Biedl syndrome; chaperonin-like proteins; chaperonopathies.

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Conflict of interest statement

Authors have no competing interests.

Figures

FIGURE 1
FIGURE 1
(a) Table with interaction network of BBS6, BBS10 and BBS12 proteins according to CORUM‐Helmholtz Zentrum München, UniProt, Gene Ontology Resource, STRING Search tool in Homo sapiens (Humans); in the panel, (b) Graphical interaction between BBS‐Chaperonin complex (image source: CORUM. Circles (nodes) represent proteins, whereas the lines (edges) connecting two circles signify an interaction between two proteins
FIGURE 2
FIGURE 2
The structure of the primary cilium indicates the formation of the BBSome complex and highlights the biological role of chaperone‐like‐BBS proteins
See this image and copyright information in PMC

References

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Supplementary concepts