BBS10

BBS10 is a vertebrate-specific chaperonin-like protein that functions in a common genetic pathway with other Bardet-Biedl syndrome genes to support basal body and primary cilium function (PMID:16582908). At the basal body, BBS10 acts within a chaperone complex required for assembly of the BBSome multiprotein complex (PMID:26273430). Its C-terminal domain mediates protein stability and direct physical interactions with the chaperonin-like protein BBS12 and the core BBSome subunit BBS7; C-terminal truncating mutations accelerate degradation through the ubiquitin-proteasome pathway, impair these interactions, and alter ciliary length, although mutant protein still localizes normally to primary cilia (PMID:40914337). Complete loss of BBS10 in mice produces obesity, retinal degeneration, and renal dysfunction, with renal-epithelium-specific knockout causing no renal impairment, establishing that renal phenotypes arise from systemic rather than renal-cell-intrinsic loss (PMID:26273430). Interactome analysis in renal cells implicates BBS10 in extraciliary processes including cellular metabolism and proliferation, with knockout cells showing increased proliferation, elevated ATP production, and upregulated aerobic glycolysis (PMID:36012682).

1. 2006 Medium

   Established BBS10 as a Bardet-Biedl disease gene and placed it genetically within the shared BBS ciliary pathway rather than as an isolated factor.

   Evidence Positional cloning, sequence analysis identifying a chaperonin-like domain, and zebrafish morpholino epistasis with other bbs morphants

   PMID:16582908

   Open questions at the time

   • Chaperonin-like activity inferred from sequence, not biochemically demonstrated
   • Direct molecular partners not yet identified
   • Mechanism by which it supports basal body function unresolved
2. 2015 High

   Determined that BBS10 localizes to a basal body chaperone complex and that its systemic, not renal-intrinsic, loss drives renal dysfunction, resolving the tissue origin of the phenotype.

   Evidence Complete and renal-epithelium-specific Cre-lox mouse knockouts with histology, physiological readouts, and ciliary immunofluorescence

   PMID:26273430

   Open questions at the time

   • Systemic factor mediating renal dysfunction not identified
   • Molecular composition of the chaperone complex not defined here
   • Link between basal body localization and the multi-organ phenotypes not mechanistically traced
3. 2015 Low

   Framed BBS10 together with BBS6 and BBS12 as a chaperonin-like module for BBSome assembly using a patient-derived cellular model.

   Evidence iPSC line generated from a BBS patient homozygous for c.271insT (p.Cys91fsX95)

   PMID:30312873

   Open questions at the time

   • BBSome assembly role cited from prior literature, not directly demonstrated in this study
   • No functional assay of the chaperonin module performed
   • Patient mutation phenotype not characterized at the protein level
4. 2022 Medium

   Extended BBS10 function beyond cilia by linking it to metabolism and proliferation through interactome and cellular phenotyping.

   Evidence MS-based interactome of stably knocked-out Bbs10 IMCD3 cells with proliferation assays, ATP measurement, and metabolomics

   PMID:36012682

   Open questions at the time

   • Interactors are putative and not individually validated
   • Causal link between specific interactors and the metabolic/proliferative phenotypes not established
   • Direct versus indirect nature of the metabolic role unclear
5. 2025 Medium

   Defined the mechanistic basis of C-terminal truncating mutations: loss of protein stability and disrupted partner binding rather than mislocalization.

   Evidence Transfection of mutant constructs in HEK293T and hTERT-RPE1 cells with Western blot stability assays, reciprocal co-IP for BBS12 and BBS7, proteasome inhibition, and ciliary immunofluorescence

   PMID:40914337

   Open questions at the time

   • No structural model of the C-terminal interaction interface
   • Stoichiometry and order of BBS10-BBS12-BBS7 assembly not determined
   • Whether reduced ciliary length is a direct consequence of impaired BBSome assembly not established

• How the BBS10/BBS6/BBS12 chaperonin-like module mechanically drives BBSome assembly, and what systemic signal links its loss to obesity and organ-specific degeneration, remains unresolved.
• No reconstituted biochemical demonstration of chaperonin-like assembly activity
• Systemic mediator of renal and metabolic phenotypes unidentified
• No structural characterization of BBS10 or its complexes