Affinage

BBS7

BBSome complex member BBS7 · UniProt Q8IWZ6

Length
715 aa
Mass
80.4 kDa
Annotated
2026-04-28
20 papers in source corpus 6 papers cited in narrative 6 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BBS7 is a core subunit of the BBSome complex that is essential for its assembly and stability, functioning in intraflagellar transport (IFT)-dependent trafficking of specific membrane proteins at cilia (PMID:23572516, PMID:15231740). BBS7 localizes to the base of cilia and moves bidirectionally along the ciliary axoneme; loss of BBS7 disrupts IFT particle composition and motility, causing structural and functional cilia defects (PMID:15231740). BBS7 and BBS2 are mutually required for protein stability, and BBS7 loss selectively alters ciliary membrane protein trafficking—for example, causing accumulation of dopamine D1 receptor at the ciliary membrane without affecting polycystin or bitter taste receptor localization (PMID:23572516). Mutations in BBS7 cause Bardet-Biedl syndrome, a multisystem ciliopathy (PMID:12567324).

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2003 Medium

    Identification of BBS7 as a disease gene established that a third member of a structurally related protein family (with BBS1 and BBS2) underlies Bardet-Biedl syndrome, raising the question of whether these proteins share a common molecular function.

    Evidence Positional cloning and mutation screening in BBS patient cohorts

    PMID:12567324

    Open questions at the time
    • No biochemical function or subcellular localization was determined
    • Structural similarity to BBS1/BBS2 was inferred computationally but not tested functionally
  2. 2004 High

    Demonstration that BBS-7 localizes to the ciliary base, undergoes IFT-like bidirectional transport, and selectively regulates IFT particle composition established BBS-7 as an IFT-associated protein rather than a structural ciliary component.

    Evidence Live fluorescence imaging and loss-of-function mutant analysis in C. elegans

    PMID:15231740

    Open questions at the time
    • Mechanism by which BBS-7 selectively affects certain IFT components (OSM-5, CHE-11) but not others (CHE-2) was not resolved
    • Whether BBS-7 functions within a multi-protein complex was unknown
  3. 2013 High

    Knockout studies revealed that BBS7 is required for BBSome assembly and mutual BBS2-BBS7 protein stabilization, and that BBS7 selectively controls trafficking of specific ciliary membrane receptors (D1R accumulates, but polycystins and taste receptors are unaffected), resolving the question of whether BBSome function is globally or selectively required for ciliary protein transport.

    Evidence Bbs7 knockout mouse, co-immunoprecipitation, immunofluorescence of ciliary membrane proteins, western blot for protein stability

    PMID:23572516

    Open questions at the time
    • Molecular basis for cargo selectivity (why D1R but not polycystins) is unknown
    • Whether BBS7 directly contacts specific cargo or acts indirectly through BBSome conformation is unresolved
    • Interaction with the BBS chaperonin complex was shown but the mechanistic role of this interaction in BBSome assembly was not dissected
  4. 2014 Medium

    Genetic epistasis in zebrafish and a forward genetic screen in C. elegans independently confirmed BBS7's role in IFT-dependent retrograde transport balance and ciliary receptor (PKD-2) localization, and established that BBS7 functions independently of the planar cell polarity pathway.

    Evidence Zebrafish morpholino knockdown with melanosome transport and Kupffer's vesicle assays; C. elegans forward genetic screen with PKD-2 localization imaging

    PMID:24938409 PMID:25486278

    Open questions at the time
    • Morpholino-based knockdown in zebrafish lacks genetic confirmation with stable mutants
    • How pk2 or ift22 knockdown suppresses the bbs7 retrograde transport phenotype mechanistically is unclear
    • Whether the glial cell defects observed in C. elegans bbs-7 mutants are cell-autonomous is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular determinants of BBSome cargo selectivity mediated by BBS7, the structural basis for BBS7–BBS2 co-stabilization, and the precise role of BBS7 within the BBS chaperonin assembly pathway remain unresolved.
  • No structural model of BBS7 within the BBSome at atomic resolution reported in the timeline
  • Direct binding interface between BBS7 and specific cargo receptors has not been mapped
  • Whether BBS7 has enzymatic or regulatory activity beyond its scaffolding role is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005929 cilium 3
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-9609507 Protein localization 2
Partners
BBS1BBS2BBS4BBS5BBS8BBS9
Complex memberships
BBSome

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 C. elegans BBS-7 localizes predominantly at the base of cilia and moves bidirectionally along the ciliary axoneme like IFT proteins; loss of BBS-7 causes structural and functional cilia defects and disrupts normal localization/motility of IFT proteins OSM-5/Polaris and CHE-11 (and to a lesser extent CHE-2), demonstrating that BBS-7 plays a selective role in the assembly and/or function of IFT particle components. Live imaging of fluorescently tagged proteins in C. elegans, loss-of-function mutant analysis, behavioral assays for cilia function Genes & development High 15231740
2003 BBS7 was identified as a novel BBS protein that shares structural features (overlapping motifs) with BBS1 and BBS2, defining a potential functional domain present in three known BBS proteins; BBS2L1 (BBS7) mutations cause Bardet-Biedl syndrome, establishing BBS7 as a disease gene. Phylogenetic and genomic sequence analysis, positional cloning, mutation screening in BBS patients American journal of human genetics Medium 12567324
2013 BBS7 is required for BBSome formation: Bbs7 knockout mice lack a properly assembled BBSome complex, and BBS7 and BBS2 depend on each other for protein stability. BBS7 also physically interacts with the BBS chaperonin complex. Loss of BBS7 causes selective accumulation of dopamine D1 receptor at the ciliary membrane but does not affect localization of polycystin-1, polycystin-2, or bitter taste receptors, revealing a selective role in ciliary membrane protein trafficking. Bbs7 knockout mouse generation, co-immunoprecipitation, immunofluorescence/localization of BBSome subunits and ciliary membrane proteins, western blot for protein stability Journal of cell science High 23572516
2014 In zebrafish, bbs7 knockdown disrupts formation of the Kupffer's vesicle (a ciliated organ) and causes a retrograde intraflagellar transport delay in melanosomes. Planar cell polarity (PCP) and BBS function independently in cilia: bbs7 activity is not required for Prickle2 (Pk2) asymmetric localization, and BBSome complex formation is preserved in Pk2-deficient mice. Knockdown of pk2 or ift22 suppresses the bbs7-related retrograde transport delay, placing BBS7 in the anterograde/retrograde IFT balance pathway. Zebrafish gene knockdown (morpholino), Kupffer's vesicle analysis, melanosome transport assay, neural tube cell polarity measurement, BBSome Co-IP in Pk2-/- mouse tissue Developmental biology Medium 24938409
2014 A missense mutation (my13) in C. elegans bbs-7 disrupts PKD-2 receptor localization to cilia, impairs cilia-mediated sensory behaviors, compromises cilia structural integrity, and also affects the glial cells that support cilia, confirming bbs-7 as the causative locus via forward genetic screening. Forward genetic screen, Sanger sequencing to identify lesion, behavioral assays, fluorescence imaging of receptor localization, structural analysis of cilia PloS one Medium 25486278
2021 BBS7 knockdown in periodontal ligament cells suppresses Sonic hedgehog (SHH) signaling activity, impairs cell migration, and reduces angiogenesis in vitro, indicating BBS7 regulates primary cilia-dependent SHH signaling for tissue homeostasis. siRNA knockdown, RT-qPCR, Western blot, wound healing assay, tubule formation assay Frontiers in cell and developmental biology Low 34957122

Source papers

Stage 0 corpus · 20 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport. Genes & development 284 15231740
2003 Identification of a novel Bardet-Biedl syndrome protein, BBS7, that shares structural features with BBS1 and BBS2. American journal of human genetics 172 12567324
2013 BBS7 is required for BBSome formation and its absence in mice results in Bardet-Biedl syndrome phenotypes and selective abnormalities in membrane protein trafficking. Journal of cell science 105 23572516
2015 Targeted multi-gene panel testing for the diagnosis of Bardet Biedl syndrome: Identification of nine novel mutations across BBS1, BBS2, BBS4, BBS7, BBS9, BBS10 genes. European journal of medical genetics 39 26518167
2009 BBS7 and TTC8 (BBS8) mutations play a minor role in the mutational load of Bardet-Biedl syndrome in a multiethnic population. Human mutation 34 19402160
2021 Bardet-Biedl syndrome-7 (BBS7) shows treatment potential and a cone-rod dystrophy phenotype that recapitulates the non-human primate model. Ophthalmic genetics 16 33729075
2008 A novel mutation in BBS7 gene causes Bardet-Biedl syndrome in a Chinese family. Molecular vision 16 19093007
2015 Exome Sequencing of a Family with Bardet-Biedl Syndrome Identifies the Common Russian Mutation c.1967_1968delTAinsC in BBS7. Molecular syndromology 9 26557828
2021 BBS7-SHH Signaling Activity Regulates Primary Cilia for Periodontal Homeostasis. Frontiers in cell and developmental biology 8 34957122
2019 Identification of a homozygous BBS7 frameshift mutation in two (related) Chinese Miao families with Bardet-Biedl Syndrome. Journal of the Chinese Medical Association : JCMA 8 30839500
2014 Functional characterization of Prickle2 and BBS7 identify overlapping phenotypes yet distinct mechanisms. Developmental biology 7 24938409
2022 Novel Mutations in the MKKS, BBS7, and ALMS1 Genes in Iranian Children with Clinically Suspected Bardet-Biedl Syndrome. Case reports in ophthalmological medicine 6 35912300
2022 Dental Anomalies in Ciliopathies: Lessons from Patients with BBS2, BBS7, and EVC2 Mutations. Genes 5 36672825
2020 A novel missense variant in the BBS7 gene underlying Bardet-Biedl syndrome in a consanguineous Pakistani family. Clinical dysmorphology 5 31469663
2022 A 5' UTR Mutation Contributes to Down-Regulation of Bbs7 in the Berlin Fat Mouse. International journal of molecular sciences 4 36361806
2021 A deletion containing a CTCF-element in intron 8 of the Bbs7 gene is partially responsible for juvenile obesity in the Berlin Fat Mouse. Mammalian genome : official journal of the International Mammalian Genome Society 4 34910225
2019 RIN2 and BBS7 variants as cause of a coincidental syndrome. European journal of medical genetics 3 31521835
2014 Identification and characterization of a novel allele of Caenorhabditis elegans bbs-7. PloS one 3 25486278
2025 A Rare Case of Bardet-Biedl Syndrome Caused by a Heterozygous Point Variant in BBS7 and a CNV Involved BBS7. Molecular syndromology 0 41064051
2024 Spectrum of pathogenic variants and high prevalence of pathogenic BBS7 variants in Russian patients with Bardet-Biedl syndrome. Frontiers in genetics 0 39092430