BBS1 (Bardet-Biedl syndrome 1 protein) is a core subunit of the BBSome, an octameric, coat-like protein complex (BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP1/BBIP10) that is structurally related to COPI, COPII and clathrin coats. The BBSome acts as a cargo adaptor that sorts specific transmembrane proteins, notably ciliary G-protein-coupled receptors and Hedgehog-pathway components such as Smoothened, into and out of the primary cilium by coupling them to intraflagellar transport. BBS1 contributes a seven-bladed beta-propeller that provides a principal cargo-recognition surface and binds the GTP-loaded Arf-like GTPase ARL6/BBS3, which recruits the BBSome to the ciliary membrane. The BBSome cooperates with the Rab8 guanine-nucleotide exchange factor RAB3IP/Rabin8 to promote ciliary membrane biogenesis. BBS1 is predominantly found at the ciliary membrane and in the cytoplasm, with pools at the centrosome/basal body and centriolar satellites. Loss of BBS1 function causes Bardet-Biedl syndrome, an autosomal recessive ciliopathy featuring retinal degeneration, obesity, polydactyly, renal malformation, hypogenitalism and intellectual disability; BBS1 is the most commonly mutated BBS gene, with M390R the most frequent allele.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0034464 BBSome | IBA GO_REF:0000033 | ACCEPT | Summary: BBSome membership is the central, defining feature of BBS1, supported by multiple direct experimental annotations (IDA) and phylogeny (IBA). This is a core annotation. |
| GO:0005813 centrosome | IBA GO_REF:0000033 | ACCEPT | Summary: BBS1 and BBSome subunits localize at/near the centrosome and basal body, consistent with UniProt subcellular location and IDA (PMID:18762586). Accept as a supported localization, though the centrosome/satellite pool is staging rather than the primary site of cargo-coat action. |
| GO:0061512 protein localization to cilium | IBA GO_REF:0000033 | ACCEPT | Summary: The core function of the BBSome is to sort membrane proteins to/from the cilium. This is well supported (IMP PMID:23943788; IBA) and represents a core BBS1 process. |
| GO:1905515 non-motile cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: BBS1/BBSome act on non-motile (primary/sensory) cilia and are required for ciliogenesis (IMP PMID:17574030, PMID:17980398). Non-motile cilium assembly is the appropriate, specific term. |
| GO:0005113 patched binding | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: This MF is propagated by phylogeny from the experimental IPI annotation (PMID:22228099), which is a genetic-interaction / ciliary-accumulation study showing the BBSome regulates SMO and PTCH1 ciliary levels, not a direct BBS1-PTCH1 binding assay. The binding claim is over-interpreted; the underlying biology (regulation of Hedgehog cargo trafficking) is better captured by ciliary trafficking / Hedgehog regulation terms. Reason: Direct patched binding by BBS1 is not demonstrated; the source evidence shows regulation of PTCH1 ciliary localization via the BBSome, not a molecular binding function. |
| GO:0005119 smoothened binding | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: As with patched binding, this is propagated from PMID:22228099, where loss of BBS genes causes SMO accumulation in cilia and reduced Shh response. The BBSome regulates SMO ciliary trafficking; direct BBS1-SMO binding is not established. Over-annotation of a trafficking role as a binding function. Reason: Evidence supports BBSome-dependent regulation of Smoothened ciliary localization, not a direct molecular binding activity of BBS1. |
| GO:0005930 axoneme | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The BBSome acts mainly at the ciliary membrane and ciliary base/transition zone and moves along the axoneme with IFT; an axonemal pool exists but is not the primary functional site for BBS1. Retain as a non-core localization. Reason: BBSome cargo-coat function is centered on the ciliary membrane; axonemal presence reflects IFT-coupled movement rather than a distinct core site of action. |
| GO:0001895 retina homeostasis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: BBS1 mutations cause retinal degeneration and photoreceptor loss, so this is biologically plausible as a downstream physiological consequence of ciliary dysfunction. It is not a core molecular/cellular function of BBS1. Reason: Retina homeostasis is a tissue-level consequence of BBS1 loss (photoreceptor cilium defects), not a direct core function. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Consistent with UniProt subcellular location (Cytoplasm). A cytoplasmic pool of BBS1/BBSome exists prior to ciliary recruitment. Accept, though more specific terms (cytosol, ciliary membrane) are also annotated. |
| GO:0008104 intracellular protein localization | IEA GO_REF:0000117 | MODIFY | Summary: This is an over-general ARBA prediction. BBS1's role in protein localization is specifically trafficking of membrane cargo to/from the cilium, already captured more precisely by GO:0061512 (protein localization to cilium). Reason: A more specific term exists that captures the actual function; the generic term adds no value. Proposed replacements: protein localization to cilium |
| GO:0034451 centriolar satellite | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: BBS proteins associate with centriolar satellites (UniProt subcellular location; PMID:24550735, PMID:18762586). However, the BBSome is dispensable for centriolar satellite function, so this is a staging/regulatory pool rather than a core site of action. Reason: Centriolar satellite localization is supported but represents a non-core pool; the BBSome's coat/cargo function operates at the ciliary membrane. |
| GO:0034464 BBSome | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate of the core BBSome membership annotation, here by IEA. Correct and core. |
| GO:0060170 ciliary membrane | IEA GO_REF:0000044 | ACCEPT | Summary: The BBSome associates with the ciliary membrane where it acts as a cargo coat; directly supported (IDA PMID:19081074) and by UniProt (Cell projection, cilium membrane). Core localization. |
| GO:1905515 non-motile cilium assembly | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate (IEA) of the experimentally and phylogenetically supported non-motile cilium assembly annotation. Correct. |
| GO:0005515 protein binding | IPI PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | MARK AS OVER ANNOTATED | Summary: Generic protein binding IPI annotations to BBSome subunits and partners (here BBS2, BBS4, BBS7, BBS9, RAB3IP). Per curation guidelines this uninformative term should not be promoted; the meaningful content (BBSome assembly; small GTPase / GEF interaction) is captured by the BBSome part_of annotation and the proposed small GTPase binding term. Flag as over-annotated. Reason: protein binding is uninformative; the underlying interactions establish complex membership, already captured by GO:0034464. |
| GO:0005515 protein binding | IPI PMID:18000879 Novel interaction partners of Bardet-Biedl syndrome proteins... | MARK AS OVER ANNOTATED | Summary: Interactions reported in an early BBS interaction screen (ALDOB, EEF1A1, PCM1, PARK7). Uninformative protein binding term; several partners are likely non-specific or staging interactions. Reason: Uninformative MF term; no specific core function is established by these interactions. |
| GO:0005515 protein binding | IPI PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | MARK AS OVER ANNOTATED | Summary: BBS1-BBS4 interaction supporting BBSome membership; uninformative generic term. Reason: Establishes complex membership only; covered by GO:0034464. |
| GO:0005515 protein binding | IPI PMID:19150989 Requirement of Bardet-Biedl syndrome proteins for leptin rec... | MARK AS OVER ANNOTATED | Summary: BBS1 interaction with the leptin receptor (LEPR). Biologically meaningful (cargo/signaling), but recorded as uninformative protein binding. The functional process is captured by the LEPR surface-trafficking IMP annotation (GO:0043001). Reason: Uninformative MF term; the relevant signaling-cargo role is recorded elsewhere. |
| GO:0005515 protein binding | IPI PMID:20080638 BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family c... | MARK AS OVER ANNOTATED | Summary: BBS1 interactions with BBS7/BBS9 in the chaperonin-assisted assembly study. Uninformative generic term; supports BBSome assembly. Reason: Establishes complex assembly only; covered by GO:0034464. |
| GO:0005515 protein binding | IPI PMID:20603001 The conserved Bardet-Biedl syndrome proteins assemble a coat... | MODIFY | Summary: Interaction with ARL6/BBS3 (Q9H0F7) in the BBSome-coat study. This is the functionally important small GTPase interaction, but annotated only as generic protein binding. A more informative MF term (small GTPase binding) is proposed. Reason: ARL6/BBS3 is a small monomeric GTPase; the specific MF small GTPase binding is informative and replaces the uninformative generic term. Proposed replacements: small GTPase binding |
| GO:0005515 protein binding | IPI PMID:22139371 Bardet-Biedl syndrome 3 (Bbs3) knockout mouse model reveals ... | MODIFY | Summary: Interaction with ARL6/BBS3 from the Bbs3 knockout study. Same as above; the informative MF is small GTPase binding. Reason: ARL6 is a small monomeric GTPase; replace uninformative term with small GTPase binding. Proposed replacements: small GTPase binding |
| GO:0005515 protein binding | IPI PMID:22500027 Intrinsic protein-protein interaction-mediated and chaperoni... | MARK AS OVER ANNOTATED | Summary: Interactions with BBS subunits (BBS9, BBS7, BBS4, BBS2) in the sequential BBSome-assembly study. Uninformative generic term; supports complex assembly. Reason: Establishes BBSome assembly; covered by GO:0034464. |
| GO:0005515 protein binding | IPI PMID:25402481 Structural basis for membrane targeting of the BBSome by ARL... | MODIFY | Summary: Structural study of BBS1 beta-propeller binding ARL6/BBS3-GTP. This is a direct, well-defined small GTPase interaction, annotated here only as generic protein binding. Replace with the specific informative MF. Reason: Direct structural evidence for BBS1 binding the small GTPase ARL6; small GTPase binding is the informative MF. Proposed replacements: small GTPase binding |
| GO:0005515 protein binding | IPI PMID:25552655 Nephrocystin proteins NPHP5 and Cep290 regulate BBSome integ... | MARK AS OVER ANNOTATED | Summary: Interaction with NPHP5/IQCB1 (Q15051), a regulator of BBSome integrity and ciliary trafficking. Uninformative generic term. Reason: Uninformative MF; the regulatory relationship is contextual, not a core BBS1 function. |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | MARK AS OVER ANNOTATED | Summary: BBSome-subunit interactions detected in an organelle proteome landscape. Uninformative generic term supporting complex membership. Reason: High-throughput interactome data establishing complex membership; covered by GO:0034464. |
| GO:0005515 protein binding | IPI PMID:29039417 Protein interaction perturbation profiling at amino-acid res... | MARK AS OVER ANNOTATED | Summary: BBS9 interaction from amino-acid-resolution interaction perturbation profiling. Uninformative generic term. Reason: Establishes complex interaction; covered by GO:0034464. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Interactome-mapping hits (DCTN1, PARK7) from a neurodegenerative-disease network study. Uninformative generic term; likely network-screen interactions of uncertain specificity. Reason: High-throughput interactome data; no specific core function established. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: BBSome-subunit interactions from a proteome-scale interactome. Uninformative generic term supporting complex membership. Reason: High-throughput data establishing complex membership; covered by GO:0034464. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: BBSome-subunit interactions from a multimodal cell-map foundation study. Uninformative generic term supporting complex membership. Reason: High-throughput data establishing complex membership; covered by GO:0034464. |
| GO:0005102 signaling receptor binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: The BBSome recognizes ciliary GPCR cargo (e.g. SSTR3 ciliary targeting signal, LEPR, PC1), so signaling receptor binding is defensible but generic. Retain as non-core; the specific cargo-recognition role is captured by protein localization to cilium. Reason: Plausible but generic; the informative function is cargo sorting to the cilium. |
| GO:0005813 centrosome | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate (IEA) of the centrosome localization supported by IDA (PMID:18762586) and UniProt. |
| GO:0005929 cilium | IEA GO_REF:0000107 | ACCEPT | Summary: BBS1 localizes to the cilium; supported broadly. More specific ciliary membrane is also annotated. Accept as a correct localization. |
| GO:0031514 motile cilium | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: BBS1/BBSome function is established in non-motile (primary/sensory) cilia. The motile cilium localization is an Ensembl IEA transfer that does not reflect the primary biology of BBS1 in humans. Reason: BBS1 acts on non-motile primary cilia; motile-cilium localization is an over-propagated electronic inference not supported by the core literature. |
| GO:0045444 fat cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BBS proteins influence adipogenesis and BBS causes obesity, so a role in fat cell differentiation is plausible as a downstream physiological consequence. Not a core molecular function of BBS1. Reason: Downstream/physiological role linked to obesity phenotype, not a direct core function. |
| GO:0051219 phosphoprotein binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: An Ensembl IEA transfer with no strong supporting evidence in the BBS1 literature for a defined phosphoprotein-binding activity. Uninformative and weakly supported. Reason: No experimental support for a specific phosphoprotein-binding molecular function in BBS1; electronic transfer of uncertain validity. |
| GO:0060271 cilium assembly | IEA GO_REF:0000107 | ACCEPT | Summary: BBS1 is required for ciliogenesis (IMP PMID:17574030; NAS PMID:19081074). The more specific non-motile cilium assembly is also annotated; cilium assembly is a correct (parent) process term. |
| GO:0060296 regulation of cilium beat frequency involved in ciliary motility | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: This is a motile-cilia process. BBS1/BBSome act on non-motile primary cilia; this Ensembl IEA term is mis-propagated and contradicts the established primary-cilium biology of BBS1. Reason: Ciliary beat-frequency regulation applies to motile cilia; BBS1's role is in non-motile primary cilia, so this electronic annotation is inappropriate. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5617815 | ACCEPT | Summary: Reactome places the BBSome (BBSome binds RAB3IP step) in the cytosol prior to ciliary recruitment. Consistent with a cytoplasmic/cytosolic pool of the assembled complex. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624125 | ACCEPT | Summary: Reactome cytosolic localization for BBSome formation. Consistent with cytoplasmic assembly of the complex. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624126 | ACCEPT | Summary: Reactome cytosolic localization (ARL6:GTP and BBSome bind ciliary cargo). Accept as a supported localization step. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624127 | ACCEPT | Summary: Reactome cytosolic localization (cargo targeting to cilium). Accept as a supported step. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624129 | ACCEPT | Summary: Reactome cytosolic localization (LZTFL1 binds BBSome, preventing premature ciliary traffic). Consistent with cytosolic regulation of BBSome ciliary entry. |
| GO:0034464 BBSome | IPI PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: Direct evidence (ComplexPortal IPI) for BBS1 as a BBSome subunit. Core annotation. |
| GO:0060170 ciliary membrane | IDA PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: Direct experimental localization (IDA) of the BBSome to the ciliary membrane. Core localization where the BBSome coat acts. |
| GO:0060271 cilium assembly | NAS PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: Cilium assembly role; this paper links a BBSome subunit (BBIP10) to ciliogenesis, microtubule stability and acetylation. Correct process for BBS1/BBSome. The more specific non-motile cilium assembly is also annotated. |
| GO:0005515 protein binding | IPI PMID:18762586 Recruitment of PCM1 to the centrosome by the cooperative act... | MARK AS OVER ANNOTATED | Summary: BBS1 interaction with PCM1 (Q9NRI5), a centriolar satellite protein. Uninformative generic term; relates to centrosome/satellite association. Reason: Uninformative MF; supports the non-core centriolar-satellite/centrosome association. |
| GO:0005813 centrosome | IDA PMID:18762586 Recruitment of PCM1 to the centrosome by the cooperative act... | ACCEPT | Summary: Direct experimental evidence (IDA) for BBS1/BBS4 at the centrosome (DISC1/BBS4/PCM1 study). Supports centrosome localization. |
| GO:0061512 protein localization to cilium | IMP PMID:23943788 BBS mutations modify phenotypic expression of CEP290-related... | ACCEPT | Summary: IMP evidence that BBSome components modulate ciliary localization of cargo (CEP290 module); a core BBS1 process. Experimental annotation by an expert curator who read the full text. Supporting Evidence: PMID:23943788 components of the BBSome, a protein complex composed of seven Bardet-Biedl syndrome (BBS) proteins, physically and genetically interact with CEP290 and modulate the expression of disease phenotypes caused by CEP290 mutations. |
| GO:0005515 protein binding | IPI PMID:24939912 Bardet-Biedl syndrome proteins 1 and 3 regulate the ciliary ... | MARK AS OVER ANNOTATED | Summary: BBS1 interaction with polycystin-1/PKD1 (Q8TAM2). Biologically meaningful cargo interaction (BBS1 is the subunit whose loss impairs PC1 ciliary trafficking), but recorded as uninformative generic term; the functional consequence is captured by protein localization to cilium. Reason: Uninformative MF term; the PC1 cargo-trafficking role is captured by ciliary-localization process annotations. |
| GO:0034464 BBSome | IDA PMID:24550735 The centriolar satellite protein AZI1 interacts with BBS4 an... | ACCEPT | Summary: Direct experimental BBSome membership (AZI1/BBS4 ciliary-trafficking study). Core annotation. |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:22302990 Direct role of Bardet-Biedl syndrome proteins in transcripti... | MARK AS OVER ANNOTATED | Summary: This paper primarily demonstrates a nuclear/transcriptional role and RNF2 (PcG) interaction for BBS7, then proposes a similar role for other BBS proteins. The BBS1-RNF2 IPI extrapolates a transcription-factor-binding MF to BBS1 that is not the established core function of this cytoplasmic ciliary trafficking subunit. Over-annotation. Reason: The transcriptional/RNF2 role is established chiefly for BBS7; attributing an RNA Pol II TF binding molecular function to BBS1 is a weakly supported extrapolation, not a core BBS1 function. |
| GO:0005113 patched binding | IPI PMID:22228099 BBS proteins interact genetically with the IFT pathway to in... | MARK AS OVER ANNOTATED | Summary: PMID:22228099 is a genetic-interaction / ciliary-accumulation study (loss of BBS genes leads to PTCH1 and SMO accumulation in cilia and a reduced Shh response). It does not demonstrate direct BBS1-PTCH1 molecular binding. The patched binding MF over-interprets a trafficking/regulatory readout. Rather than REMOVE this experimental IPI, it is flagged as an over-annotation because the binding interpretation is not supported by the assay performed. Reason: The cited experiment shows BBSome-dependent regulation of PTCH1 ciliary levels, not a direct binding activity of BBS1. |
| GO:0005119 smoothened binding | IPI PMID:22228099 BBS proteins interact genetically with the IFT pathway to in... | MARK AS OVER ANNOTATED | Summary: Same source as above; SMO accumulates in cilia upon BBS loss with decreased Shh response. This supports BBSome regulation of SMO ciliary trafficking, not a direct BBS1-SMO binding function. Reason: Evidence is for regulation of Smoothened ciliary localization via the BBSome, not direct molecular binding by BBS1. |
| GO:0005515 protein binding | IPI PMID:16327777 Dissection of epistasis in oligogenic Bardet-Biedl syndrome. | MARK AS OVER ANNOTATED | Summary: BBS1 interaction with CCDC28B (Q9BUN5), an oligogenic modifier of BBS. Uninformative generic term; relevant to disease modification rather than a defined core molecular function. Reason: Uninformative MF; CCDC28B is a modifier/interactor, not a core functional partner defining a molecular activity. |
| GO:0034464 BBSome | IDA PMID:20080638 BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family c... | ACCEPT | Summary: Direct experimental BBSome membership from the chaperonin-assisted assembly study. Core annotation. |
| GO:0043001 Golgi to plasma membrane protein transport | IMP PMID:19150989 Requirement of Bardet-Biedl syndrome proteins for leptin rec... | KEEP AS NON CORE | Summary: IMP evidence that BBS proteins are required for leptin receptor signaling, reflecting defective LEPR surface trafficking when BBS function is lost. A real but non-core, cargo-specific role; experimental annotation by a curator who read the full text. Reason: Reflects a specific cargo (LEPR) trafficking consequence relevant to obesity, not the core ciliary-coat function; retain as a supported non-core process. |
| GO:0034464 BBSome | IDA PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | ACCEPT | Summary: Original biochemical identification of the BBSome (IDA). Core annotation. Supporting Evidence: PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis. |
| GO:0060271 cilium assembly | IMP PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | ACCEPT | Summary: IMP evidence that BBS1/BBSome is required for ciliogenesis. Core process; the more specific non-motile cilium assembly is also annotated. |
| GO:0045494 photoreceptor cell maintenance | IMP PMID:17980398 Retinal morphology in patients with BBS1 and BBS10 related B... | KEEP AS NON CORE | Summary: BBS1 patients show progressive retinal/photoreceptor degeneration (OCT study). This is a tissue-level physiological consequence of ciliary dysfunction in photoreceptors, not a core molecular function. Retain as supported non-core. Reason: Photoreceptor maintenance is a downstream consequence of BBS1 ciliary function in the connecting cilium, not a direct core activity. |
| GO:1905515 non-motile cilium assembly | IMP PMID:17980398 Retinal morphology in patients with BBS1 and BBS10 related B... | ACCEPT | Summary: Non-motile (primary/photoreceptor) cilium assembly role inferred from BBS1 patient retinal phenotypes. Consistent with the core ciliogenic function of BBS1. |
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Download this section (compressed HTML)Q: Does the BBS1 beta-propeller directly contribute cargo-recognition specificity for particular ciliary GPCRs, distinct from its ARL6/BBS3 membrane-targeting role?
Suggested experts: Nachury MV, Lorentzen E
Q: Should the Hedgehog-related annotations (patched binding, smoothened binding) be reframed as BBSome-mediated regulation of Smoothened/Patched1 ciliary trafficking rather than direct binding molecular functions?
Suggested experts: Sheffield VC, Nachury MV
Experiment: Use cryo-EM of the reconstituted human BBSome with defined GPCR ciliary-targeting-signal peptides, combined with structure-guided BBS1 beta-propeller mutants tested in ciliary cargo import/export assays in BBS1-null cells.
Hypothesis: BBS1 provides a direct cargo-recognition surface for ciliary GPCRs that is separable from ARL6-mediated membrane targeting.
Type: structural and functional cargo-binding assay
Experiment: Quantify ARL6-GTP binding affinity and ciliary BBSome recruitment for wild-type versus M390R and other propeller variants using purified proteins and live-cell ciliary localization assays.
Hypothesis: Disease alleles of BBS1 (e.g. M390R) impair ARL6/BBS3-GTP binding and thereby reduce BBSome recruitment to the ciliary membrane.
Type: variant biochemistry and ciliary localization assay
Experiment: Assess motile-cilia structure and beat frequency in BBS1-deficient airway/ependymal cells to confirm absence of a primary motile-cilia defect attributable to BBS1.
Hypothesis: The motile cilium and ciliary beat frequency electronic annotations do not reflect a genuine BBS1 role and should be retracted in human.
Type: motile cilia functional assay
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