Affinage

BBS7

BBSome complex member BBS7 · UniProt Q8IWZ6

Length
715 aa
Mass
80.4 kDa
Annotated
2026-06-09
20 papers in source corpus 8 papers cited in narrative 8 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/5 claims corpus-supported (80%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BBS7 is a core component of the ciliary trafficking machinery that operates at the base of cilia and moves bidirectionally along the ciliary axoneme together with intraflagellar transport (IFT) proteins, where it selectively regulates IFT particle assembly and motility (PMID:15231740). It is required for assembly of the BBSome complex: in its absence the BBSome fails to form, and BBS7 and BBS2 mutually depend on one another for protein stability (PMID:23572516). Through this activity BBS7 controls the ciliary targeting of specific membrane receptors—loss of BBS7 causes abnormal accumulation of the dopamine D1 receptor at the ciliary membrane while sparing polycystin-1, polycystin-2, and bitter taste receptors, and disrupts ciliary localization of the PKD-2 receptor and cilia structural integrity—indicating a selective rather than global role in ciliary cargo trafficking (PMID:23572516, PMID:25486278). Epistasis in zebrafish places BBS7 in the retrograde arm of IFT (PMID:24938409), and it supports primary cilium-dependent Sonic hedgehog signaling (PMID:34957122). Mutations in BBS7 cause Bardet-Biedl syndrome (PMID:12567324), and reduced Bbs7 expression contributes to obesity in mouse models (PMID:34910225, PMID:36361806).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2003 Medium

    Established BBS7 as a Bardet-Biedl syndrome disease gene and placed it in a structurally related group with other BBS proteins, framing the question of what shared molecular function these proteins carry out.

    Evidence Positional cloning and mutation screening in BBS patients with computational sequence comparison to BBS2

    PMID:12567324

    Open questions at the time
    • Structural similarity to BBS2 inferred computationally, not experimentally
    • No molecular function assigned at this stage
  2. 2004 High

    Defined the cellular activity of BBS7 by showing it localizes to the ciliary base, moves bidirectionally along the axoneme, and is needed for normal IFT protein localization and motility, establishing it as a selective regulator of IFT.

    Evidence C. elegans loss-of-function genetics with live imaging of GFP-tagged IFT proteins and IFT motility

    PMID:15231740

    Open questions at the time
    • Did not resolve whether BBS7 acts within a discrete complex
    • Mechanism of selective IFT regulation unknown
  3. 2013 High

    Showed BBS7 is required for BBSome assembly and mutually stabilizes BBS2, and that it selectively controls ciliary trafficking of specific membrane receptors, distinguishing cargo-selective from general ciliary roles.

    Evidence Bbs7 knockout mouse with BBSome complex analysis, protein stability Western blots, and ciliary receptor immunofluorescence

    PMID:23572516

    Open questions at the time
    • Mechanism of cargo selectivity (why D1R but not polycystins) unresolved
    • Direct binding interface with BBS2 not mapped
  4. 2014 Medium

    Refined the directionality of BBS7's transport role by showing it acts in retrograde IFT, and confirmed its conserved requirement for ciliary receptor localization and cilia structure via a defined missense allele.

    Evidence Zebrafish morpholino epistasis (melanosome transport, ift22/pk2 double knockdown) and a C. elegans bbs-7 missense allele phenotyped for PKD-2 localization and cilia integrity

    PMID:24938409 PMID:25486278

    Open questions at the time
    • Morpholino knockdown carries off-target risk
    • Did not separate retrograde IFT role from BBSome-assembly role mechanistically
  5. 2021 Medium

    Linked BBS7 to primary cilium-dependent Sonic hedgehog signaling and to a regulatory, expression-level contribution to obesity, broadening its physiological reach beyond structural ciliary roles.

    Evidence siRNA knockdown in PDL cells with SHH readouts and migration/angiogenesis assays; CRISPR deletion of a Bbs7 intronic CTCF element complementing a mouse obesity phenotype

    PMID:34910225 PMID:34957122

    Open questions at the time
    • SHH placement is knockdown-level without rescue or epistasis
    • Obesity complementation only partial; regulatory rather than protein-level mechanism
  6. 2022 Medium

    Identified a specific cis-regulatory variant reducing BBS7 expression, mechanistically connecting genotype to lowered Bbs7 levels in an obesity model.

    Evidence Cell-based dual-luciferase reporter assay comparing 5' UTR haplotypes

    PMID:36361806

    Open questions at the time
    • In vitro reporter does not establish in vivo expression effect
    • Single regulatory variant; combined effect with other loci unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How BBS7 achieves cargo selectivity and how its BBSome-assembly role is mechanistically separable from its retrograde IFT function remain unresolved.
  • No structural model of the BBS7-BBS2 interface or BBSome incorporation
  • Determinants of selective ciliary cargo recognition unknown
  • Direct biochemical link between BBSome assembly and IFT directionality not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 1
Localization
GO:0005929 cilium 2 GO:0005856 cytoskeleton 1
Pathway
R-HSA-9609507 Protein localization 2 R-HSA-1266738 Developmental Biology 1 R-HSA-162582 Signal Transduction 1
Partners
BBS2
Complex memberships
BBSome

Evidence

Reading pass · 8 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, similar to IFT proteins. Loss of BBS-7 causes structural and functional defects in cilia and is required for normal localization/motility of IFT proteins OSM-5/Polaris and CHE-11 (and to a lesser extent CHE-2), establishing BBS-7 as a selective regulator of IFT particle assembly/function. C. elegans loss-of-function genetics, fluorescence microscopy of GFP-tagged proteins, live imaging of IFT particle motility Genes & development High 15231740
2003 BBS7 (initially named BBS2L1) shares structural/sequence similarity with two discrete overlapping regions of BBS2, defining a potential functional domain present in at least three BBS proteins. Mutations in BBS7 cause Bardet-Biedl syndrome, establishing it 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: in Bbs7 knockout mice, the BBSome complex fails to assemble. BBS7 and BBS2 depend on each other for protein stability. BBS7 absence leads to abnormal accumulation of the dopamine D1 receptor at the ciliary membrane, but does not affect localization of polycystin-1, polycystin-2, or bitter taste receptors, indicating selective roles in ciliary membrane protein trafficking. Bbs7 knockout mouse generation, co-immunoprecipitation/BBSome complex analysis, immunofluorescence of 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), but bbs7 activity is not required for Prickle2 (Pk2) asymmetric localization in the neural tube, indicating BBS7 does not regulate PCP protein asymmetry. BBS7 knockdown causes a retrograde intracellular melanosome transport delay; this delay is suppressed by pk2 knockdown and by knockdown of the anterograde IFT component ift22, suggesting BBS7 functions in retrograde intraflagellar transport. Zebrafish morpholino knockdown, Kupffer's vesicle imaging, melanosome transport assays, genetic epistasis (double knockdown) Developmental biology Medium 24938409
2014 A missense mutation (my13) in C. elegans bbs-7 disrupts ciliary localization of the PKD-2 receptor, impairs cilia-mediated sensory behaviors, compromises cilia structural integrity, and affects the glial cells that support cilia, further confirming the conserved role of BBS-7 in ciliary receptor localization and cilia structure. Forward genetic screen, phenotypic characterization (behavioral assays, fluorescence microscopy of cilia structure and receptor localization), Sanger sequencing to identify causative mutation PloS one Medium 25486278
2021 BBS7 knockdown in periodontal ligament (PDL) cells suppresses Sonic hedgehog (SHH/Shh) signaling activity, reduces primary cilia formation, and impairs cell migration and angiogenesis in vitro, indicating BBS7 is required for primary cilia-mediated Shh signaling in PDL homeostasis. siRNA knockdown in PDL cells, RT-qPCR, Western blot, wound healing assay, tubule formation assay Frontiers in cell and developmental biology Low 34957122
2021 A deletion in intron 8 of Bbs7 containing a CTCF-element, introduced into B6N mice via CRISPR/Cas9, partially complements the juvenile obesity phenotype of the Berlin Fat Mouse (BFMI), providing in vivo evidence that reduced Bbs7 expression contributes to obesity. CRISPR/Cas9 deletion in mice, complementation cross, quantitative MRI body composition measurement Mammalian genome Medium 34910225
2022 A single nucleotide polymorphism (rs29947545) in the 5' UTR of Bbs7 significantly reduces reporter gene expression in a cell-based dual-luciferase assay, identifying a regulatory variant that contributes to reduced Bbs7 expression in the Berlin Fat Mouse. Cell-based dual-luciferase reporter assay comparing BFMI and B6N promoter/5' UTR haplotypes International journal of molecular sciences Medium 36361806

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 285 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

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