id: Q96RK4
gene_symbol: BBS4
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: "BBS4 is a core subunit of the BBSome, an eight-subunit (BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9, BBIP1) coat-like complex that acts as a cargo adaptor for sorting membrane proteins into and out of the primary cilium in conjunction with the small GTPase ARL6/BBS3 and the Rab8 GEF Rabin8/RAB3IP. BBS4 is a tetratricopeptide-repeat (TPR) superhelical protein (about ten TPR repeats) that is added last during chaperonin (BBS6/BBS10/BBS12, CCT/TRiC) assisted assembly of the BBSome onto the BBS7-BBS2-BBS9 core. Beyond its role within the BBSome, BBS4 localizes to centriolar satellites, the pericentriolar material, the centrosome/basal body and the ciliary membrane, and acts as an adaptor for the p150-glued (DCTN1) subunit of the dynein/dynactin motor to recruit PCM1 and associated cargo (e.g. ninein) to the centrosome, cooperating with DISC1; loss of BBS4 mislocalizes PCM1 and de-anchors centrosomal microtubules. The BBSome regulates ciliary trafficking of signalling receptors (e.g. Smoothened, polycystin-1/PKD1) and is regulated by satellite proteins such as CEP131/AZI1 and the CEP290/NPHP5 module. Loss-of-function mutations cause Bardet-Biedl syndrome, a pleiotropic ciliopathy with retinal degeneration, obesity, polydactyly, renal malformation, hypogenitalism and cognitive impairment."
alternative_products:
- name: '1'
  id: Q96RK4-1
- name: '2'
  id: Q96RK4-2
  sequence_note: VSP_024410
- name: '3'
  id: Q96RK4-3
  sequence_note: VSP_047507
existing_annotations:
- term:
    id: GO:0060271
    label: cilium assembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: "Phylogenetically inferred ciliogenesis role, consistent with the well-established requirement of the BBSome for ciliary membrane biogenesis and ciliary trafficking. BBS4 contributes to ciliogenesis as a BBSome subunit rather than independently."
    action: ACCEPT
    reason: "Supported by experimental data on the BBSome and BBS4 loss-of-function phenotypes; appropriate IBA call."
- term:
    id: GO:0036064
    label: ciliary basal body
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: "BBS4 and the BBSome localize at/near the basal body. Experimentally corroborated by IDA annotations below."
    action: ACCEPT
    reason: "Consistent with experimental localization (PMID:15107855, PMID:18299575)."
- term:
    id: GO:0061512
    label: protein localization to cilium
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: "Core BBSome function: sorting/transport of membrane proteins to the cilium. Well supported and central to BBS4 biology."
    action: ACCEPT
    reason: "Core function; corroborated by experimental IMP annotations (PMID:23943788)."
- term:
    id: GO:0000226
    label: microtubule cytoskeleton organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: "BBS4 loss de-anchors centrosomal microtubules, so a microtubule-organization role is plausible, but this is a downstream consequence of PCM1/dynein-adaptor function rather than a distinct core process. The more specific term microtubule anchoring at centrosome (GO:0034454) captures the actual role better."
    action: KEEP_AS_NON_CORE
    reason: "General term; the specific microtubule-anchoring-at-centrosome annotation is the precise representation of this activity."
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  qualifier: located_in
  review:
    summary: "Nuclear localization is inferred electronically via inter-ontology links and rests on a weak generalization that BBS proteins have a nuclear/transcriptional role (PMID:22302990 is primarily a BBS7 study). BBS4 is overwhelmingly a cytoplasmic/centrosomal/ciliary protein; a stable nuclear pool is not well established."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Electronic inference; primary localization data place BBS4 at centrosome/satellites/cilium, not nucleus."
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: "BBS4 is a cytoplasmic protein (centriolar satellites/pericentriolar region). Correct but very general; more specific locations are annotated."
    action: KEEP_AS_NON_CORE
    reason: "Accurate but general parent term."
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: "BBS4 localizes to the centrosome; experimentally confirmed by IDA below."
    action: ACCEPT
    reason: "Corroborated by IDA (PMID:15107855, PMID:18762586, PMID:22500027, PMID:24550735)."
- term:
    id: GO:0005929
    label: cilium
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: "BBS4/BBSome localizes to the cilium; experimentally confirmed by IDA below."
    action: ACCEPT
    reason: "Corroborated by IDA (PMID:23943788, PMID:24550735)."
- term:
    id: GO:0007600
    label: sensory perception
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: "Generic sensory-perception term derived from BBS ciliopathy phenotypes (vision/olfaction). Too general and downstream of the molecular role."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Over-general phenotype-derived term; not a direct BBS4 function."
- term:
    id: GO:0031514
    label: motile cilium
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: "BBS4 localizes to motile cilia of airway epithelia (IDA, PMID:18299575). Most BBS4 biology concerns non-motile primary cilia, but the motile-cilium localization is experimentally supported."
    action: KEEP_AS_NON_CORE
    reason: "Supported by IDA (PMID:18299575); non-core relative to primary-cilium role."
- term:
    id: GO:0034451
    label: centriolar satellite
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: "BBS4 is a hallmark centriolar satellite protein; experimentally confirmed by IDA."
    action: ACCEPT
    reason: "Corroborated by IDA (PMID:15107855, PMID:23943788, PMID:24550735)."
- term:
    id: GO:0035869
    label: ciliary transition zone
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: "Transition-zone localization is supported by IDA (PMID:23943788)."
    action: ACCEPT
    reason: "Corroborated by experimental IDA."
- term:
    id: GO:0060170
    label: ciliary membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: "BBSome localizes to the ciliary membrane; confirmed by IDA below."
    action: ACCEPT
    reason: "Corroborated by IDA (PMID:17574030, PMID:19081074)."
- term:
    id: GO:0061512
    label: protein localization to cilium
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: "Duplicate (electronic) of the core protein-localization-to-cilium function."
    action: ACCEPT
    reason: "Core function; experimentally corroborated (PMID:23943788 IMP)."
- term:
    id: GO:0097730
    label: non-motile cilium
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: "Primary (non-motile) cilium localization; confirmed by IDA (PMID:17574030)."
    action: ACCEPT
    reason: "Corroborated by experimental IDA."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15107855
  qualifier: enables
  review:
    summary: "Generic protein-binding annotation from the PCM1/DCTN1 interaction study. Per curation guidelines, protein binding is uninformative; the specific adaptor activity and dynactin binding annotations from this paper capture the real function."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative MF; superseded by specific MF annotations from same reference."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16327777
  qualifier: enables
  review:
    summary: "Generic protein binding from the CCDC28B interaction (oligogenic BBS epistasis study). Real interaction but uninformative MF term."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding'; use specific interactors in notes."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17574030
  qualifier: enables
  review:
    summary: "Generic protein binding from BBSome identification; uninformative MF."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding'; BBSome part_of and tubulin binding capture the role."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18000879
  qualifier: enables
  review:
    summary: "Generic protein binding from the ALDOB interaction; uninformative MF."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding'."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18772192
  qualifier: enables
  review:
    summary: "Generic protein binding associated with the CEP290/PCM1 satellite study; uninformative MF."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding'."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19081074
  qualifier: enables
  review:
    summary: "Generic protein binding from the BBSome/BBIP10 study; uninformative MF."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding'; BBSome part_of captures the role."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20080638
  qualifier: enables
  review:
    summary: "Generic protein binding from the chaperonin/BBSome-assembly study; uninformative MF."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding'."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22500027
  qualifier: enables
  review:
    summary: "Generic protein binding from the BBSome sequential-assembly study; uninformative MF."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding'; BBSome part_of captures the role."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: "Generic protein binding from a high-throughput interactome (Rolland et al.); uninformative MF."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding' from HT interactome."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25552655
  qualifier: enables
  review:
    summary: "Generic protein binding from the NPHP5/CEP290 BBSome-integrity study; uninformative MF."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding'."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26871637
  qualifier: enables
  review:
    summary: "Generic protein binding from a splicing-isoform interactome screen; uninformative MF."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding' from HT interactome."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27173435
  qualifier: enables
  review:
    summary: "Generic protein binding from an organelle-proteome interactome study; uninformative MF."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding' from HT interactome."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29039417
  qualifier: enables
  review:
    summary: "Generic protein binding from an interaction-perturbation profiling study; uninformative MF."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding' from HT interactome."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: "Generic protein binding from the HuRI binary interactome; uninformative MF."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding' from HT interactome."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: "Generic protein binding from a neurodegeneration interactome map; uninformative MF."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding' from HT interactome."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: "Generic protein binding from the BioPlex dual-proteome interactome; uninformative MF."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding' from HT interactome."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: "Generic protein binding from a multimodal cell-map interactome study; uninformative MF."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding' from HT interactome."
- term:
    id: GO:0001750
    label: photoreceptor outer segment
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: "Inferred from mouse ortholog via Ensembl Compara. Plausible given the connecting-cilium localization in photoreceptors, but no direct human evidence; relevant to retinal ciliopathy phenotype."
    action: KEEP_AS_NON_CORE
    reason: "Electronic ortholog transfer; relevant to retinal degeneration phenotype, non-core."
- term:
    id: GO:0001917
    label: photoreceptor inner segment
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: "Inferred from mouse ortholog; plausible but no direct human evidence."
    action: KEEP_AS_NON_CORE
    reason: "Electronic ortholog transfer; non-core."
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: "Very general membrane term; BBS4 associates with the ciliary membrane via the BBSome but is not itself an integral membrane protein. Subsumed by the specific ciliary membrane annotation."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Over-general; ciliary membrane is the informative term."
- term:
    id: GO:0032391
    label: photoreceptor connecting cilium
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: "Inferred from mouse ortholog; UniProt notes connecting-cilium localization by similarity. Relevant to retinal phenotype."
    action: KEEP_AS_NON_CORE
    reason: "Electronic ortholog transfer; relevant but non-core for human."
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: part_of
  review:
    summary: "BBS4 is a core BBSome subunit; experimentally confirmed by multiple IDA/IPI annotations."
    action: ACCEPT
    reason: "Core; corroborated by IDA (PMID:17574030, PMID:20080638, PMID:24550735) and IPI."
- term:
    id: GO:0038108
    label: negative regulation of appetite by leptin-mediated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: "Derived from BBS mouse obesity phenotypes (leptin resistance). A downstream physiological consequence of ciliary dysfunction, not a direct molecular function of BBS4."
    action: KEEP_AS_NON_CORE
    reason: "Phenotype/physiology-derived; relevant to obesity, non-core."
- term:
    id: GO:0045444
    label: fat cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: "Adipogenesis link reflects BBS obesity biology (cilia regulate adipocyte differentiation). Downstream/physiological, not direct."
    action: KEEP_AS_NON_CORE
    reason: "Phenotype-derived; non-core."
- term:
    id: GO:0060271
    label: cilium assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: "Ciliogenesis role inferred from mouse ortholog; consistent with BBSome biology."
    action: ACCEPT
    reason: "Core; corroborated experimentally."
- term:
    id: GO:0060296
    label: regulation of cilium beat frequency involved in ciliary motility
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: "Derived from airway motile-cilia phenotypes (PMID:18299575). A motile-cilia function is plausible but peripheral to the core primary-cilium cargo-trafficking role."
    action: KEEP_AS_NON_CORE
    reason: "Motile-cilia phenotype; non-core relative to primary-cilium function."
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5617815
  qualifier: located_in
  review:
    summary: "Reactome cytosol annotation for the BBSome-binds-RAB3IP reaction. Cytosolic pool exists but the cilium/centrosome locations are the functionally informative ones."
    action: KEEP_AS_NON_CORE
    reason: "Pathway-database location; general but not incorrect."
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5624125
  qualifier: located_in
  review:
    summary: "Reactome cytosol annotation for BBSome formation reaction."
    action: KEEP_AS_NON_CORE
    reason: "Pathway-database location; general."
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5624126
  qualifier: located_in
  review:
    summary: "Reactome cytosol annotation for ARL6:GTP/BBSome cargo-binding reaction."
    action: KEEP_AS_NON_CORE
    reason: "Pathway-database location; general."
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5624127
  qualifier: located_in
  review:
    summary: "Reactome cytosol annotation for ARL6:GTP/BBSome cargo-targeting reaction."
    action: KEEP_AS_NON_CORE
    reason: "Pathway-database location; general."
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5624129
  qualifier: located_in
  review:
    summary: "Reactome cytosol annotation for the LZTFL1-binds-BBSome reaction."
    action: KEEP_AS_NON_CORE
    reason: "Pathway-database location; general."
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IPI
  original_reference_id: PMID:19081074
  qualifier: part_of
  review:
    summary: "BBS4 part of the BBSome (BBIP10 study). Core localization/complex assignment."
    action: ACCEPT
    reason: "Core complex membership; experimentally supported."
- term:
    id: GO:0060170
    label: ciliary membrane
  evidence_type: IDA
  original_reference_id: PMID:19081074
  qualifier: located_in
  review:
    summary: "BBSome localizes to the ciliary membrane (IDA). Core localization."
    action: ACCEPT
    reason: "Direct experimental localization."
- term:
    id: GO:0060271
    label: cilium assembly
  evidence_type: NAS
  original_reference_id: PMID:19081074
  qualifier: involved_in
  review:
    summary: "Asserted ciliogenesis role for BBSome subunits. Consistent with stronger experimental evidence for the BBSome's ciliogenic function."
    action: ACCEPT
    reason: "Core function, consistent with broader evidence."
- term:
    id: GO:0001947
    label: heart looping
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Transferred from mouse ortholog by sequence-similarity curator judgment; reflects left-right asymmetry defects (node cilia). Downstream developmental phenotype of ciliary dysfunction."
    action: KEEP_AS_NON_CORE
    reason: "Ortholog-transferred developmental phenotype; non-core."
- term:
    id: GO:0032402
    label: melanosome transport
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Classic BBS readout: bbs4 morphant zebrafish show retrograde melanosome transport delay (e.g. PMID:24550735, PMID:16399798). Reflects BBS4's role in dynein-based intracellular transport. Non-core relative to ciliary trafficking."
    action: KEEP_AS_NON_CORE
    reason: "Supported by zebrafish assays; intracellular-transport readout, non-core."
- term:
    id: GO:0060271
    label: cilium assembly
  evidence_type: ISS
  original_reference_id: PMID:16399798
  qualifier: involved_in
  review:
    summary: "Ciliogenesis/retrograde-trafficking role inferred from zebrafish BBS studies. Consistent with core BBSome function."
    action: ACCEPT
    reason: "Core function; supported across species."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33144677
  qualifier: enables
  review:
    summary: "Generic protein binding from the DLEC1 interaction (mouse spermatogenesis study). Uninformative MF term."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding'."
- term:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: IMP
  original_reference_id: PMID:15107855
  qualifier: enables
  review:
    summary: "Captures BBS4's central molecular function as a cargo adaptor: it bridges the dynein/dynactin p150-glued (DCTN1) subunit to PCM1 and associated cargo, and within the BBSome it functions as part of a cargo-sorting adaptor for ciliary membrane proteins. This is the best available informative MF for BBS4."
    action: ACCEPT
    reason: "Strong experimental support (PMID:15107855); represents the core molecular function of BBS4."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18762586
  qualifier: enables
  review:
    summary: "Generic protein binding from the DISC1/PCM1 centrosome-recruitment study. The functional content (PCM1 recruitment to centrosome) is captured by process annotations."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding'."
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IDA
  original_reference_id: PMID:18762586
  qualifier: located_in
  review:
    summary: "BBS4 localizes to the centrosome (DISC1/PCM1 study). Core localization."
    action: ACCEPT
    reason: "Direct experimental localization."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23943788
  qualifier: enables
  review:
    summary: "Generic protein binding from the CEP290 interaction study; uninformative MF."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding'."
- term:
    id: GO:0005929
    label: cilium
  evidence_type: IDA
  original_reference_id: PMID:23943788
  qualifier: located_in
  review:
    summary: "BBS4 localizes to the cilium (CEP290 study, full text available). Core localization."
    action: ACCEPT
    reason: "Direct experimental localization."
    supported_by:
    - reference_id: PMID:23943788
      supporting_text: "co-localizes with CEP290 to the transition zone (TZ) of primary cilia and centriolar satellites in ciliated cells"
- term:
    id: GO:0034451
    label: centriolar satellite
  evidence_type: IDA
  original_reference_id: PMID:23943788
  qualifier: located_in
  review:
    summary: "BBS4 localizes to centriolar satellites (CEP290 study). Core localization."
    action: ACCEPT
    reason: "Direct experimental localization."
    supported_by:
    - reference_id: PMID:23943788
      supporting_text: "co-localizes with CEP290 to the transition zone (TZ) of primary cilia and centriolar satellites in ciliated cells"
- term:
    id: GO:0035869
    label: ciliary transition zone
  evidence_type: IDA
  original_reference_id: PMID:23943788
  qualifier: located_in
  review:
    summary: "Transition-zone localization (CEP290 study). Supported."
    action: ACCEPT
    reason: "Direct experimental localization."
    supported_by:
    - reference_id: PMID:23943788
      supporting_text: "co-localizes with CEP290 to the transition zone (TZ) of primary cilia and centriolar satellites in ciliated cells"
- term:
    id: GO:0061512
    label: protein localization to cilium
  evidence_type: IMP
  original_reference_id: PMID:23943788
  qualifier: involved_in
  review:
    summary: "BBS4 required for protein localization to the cilium (mutant phenotype, CEP290-ciliopathy modifier study). Direct support for the core trafficking function."
    action: ACCEPT
    reason: "Core function with experimental (IMP) support."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24939912
  qualifier: enables
  review:
    summary: "Generic protein binding from the PKD1 ciliary-trafficking study; uninformative MF."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding'."
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IDA
  original_reference_id: PMID:24550735
  qualifier: part_of
  review:
    summary: "BBS4 part of the BBSome (AZI1/CEP131 study). Core complex membership."
    action: ACCEPT
    reason: "Direct experimental support."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24550735
  qualifier: enables
  review:
    summary: "Generic protein binding from the AZI1/CEP131 interaction; uninformative MF."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Uninformative 'protein binding'."
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IDA
  original_reference_id: PMID:24550735
  qualifier: located_in
  review:
    summary: "BBS4 localizes to the centrosome (AZI1 study). Core localization."
    action: ACCEPT
    reason: "Direct experimental localization."
- term:
    id: GO:0005929
    label: cilium
  evidence_type: IDA
  original_reference_id: PMID:24550735
  qualifier: located_in
  review:
    summary: "BBS4/BBSome localizes to the cilium (AZI1 study). Core localization."
    action: ACCEPT
    reason: "Direct experimental localization."
- term:
    id: GO:0034451
    label: centriolar satellite
  evidence_type: IDA
  original_reference_id: PMID:24550735
  qualifier: located_in
  review:
    summary: "BBS4 localizes to centriolar satellites (AZI1 study). Core localization."
    action: ACCEPT
    reason: "Direct experimental localization."
- term:
    id: GO:0000281
    label: mitotic cytokinesis
  evidence_type: IMP
  original_reference_id: PMID:15107855
  qualifier: involved_in
  review:
    summary: "BBS4 silencing causes arrest in cell division and apoptosis (PMID:15107855), but these are downstream secondary consequences of PCM1 mislocalization and microtubule de-anchoring, not a dedicated cytokinesis function of BBS4. BBS is not a cytokinesis disorder."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Secondary RNAi phenotype; not a core/direct BBS4 function."
- term:
    id: GO:0071539
    label: protein localization to centrosome
  evidence_type: IMP
  original_reference_id: PMID:15107855
  qualifier: involved_in
  review:
    summary: "BBS4 recruits PCM1 (and, with DISC1, ninein) to the centrosome via the dynein/dynactin motor (PMID:15107855, PMID:18762586). A genuine, well supported BBS4 process directly reflecting its adaptor activity."
    action: ACCEPT
    reason: "Strong experimental support; core process tied to adaptor function."
- term:
    id: GO:0061629
    label: RNA polymerase II-specific DNA-binding transcription factor binding
  evidence_type: IPI
  original_reference_id: PMID:22302990
  qualifier: enables
  review:
    summary: "Annotation rests on a study primarily of BBS7's nuclear/transcriptional role (interaction with the PcG protein RNF2), with only a generalized suggestion that other BBS proteins behave similarly. Evidence specifically for BBS4 binding an RNA Pol II transcription factor is weak, and BBS4 is not established as a nuclear protein."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Weak generalization from a BBS7-focused study; BBS4-specific transcription-factor-binding role not established."
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IDA
  original_reference_id: PMID:22500027
  qualifier: located_in
  review:
    summary: "BBS4 localizes to the centrosome (BBSome assembly study). Core localization."
    action: ACCEPT
    reason: "Direct experimental localization."
- term:
    id: GO:0038108
    label: negative regulation of appetite by leptin-mediated signaling pathway
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Ortholog-transferred from mouse obesity/leptin-resistance phenotypes. Downstream physiological consequence of ciliary dysfunction."
    action: KEEP_AS_NON_CORE
    reason: "Phenotype-derived; relevant to obesity, non-core."
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IDA
  original_reference_id: PMID:20080638
  qualifier: part_of
  review:
    summary: "BBS4 part of the BBSome (chaperonin assembly study). Core complex membership."
    action: ACCEPT
    reason: "Direct experimental support."
- term:
    id: GO:0000226
    label: microtubule cytoskeleton organization
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Ortholog-transferred microtubule-organization role. Reflects centrosomal microtubule de-anchoring on BBS4 loss; the specific microtubule anchoring at centrosome term is more precise."
    action: KEEP_AS_NON_CORE
    reason: "General; specific anchoring term preferred."
- term:
    id: GO:0001843
    label: neural tube closure
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Ortholog-transferred developmental phenotype (neural tube defects in BBS models). Downstream consequence of ciliary signalling dysfunction."
    action: KEEP_AS_NON_CORE
    reason: "Developmental phenotype; non-core."
- term:
    id: GO:0001895
    label: retina homeostasis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Ortholog-transferred; reflects retinal degeneration in BBS. Downstream physiological readout relevant to the disease."
    action: KEEP_AS_NON_CORE
    reason: "Phenotype-derived; relevant to retinal disease, non-core."
- term:
    id: GO:0007286
    label: spermatid development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Ortholog-transferred; reflects flagellum/sperm defects in BBS models (cf. DLEC1 interaction, PMID:33144677). Downstream developmental role."
    action: KEEP_AS_NON_CORE
    reason: "Developmental phenotype; non-core."
- term:
    id: GO:0007608
    label: sensory perception of smell
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Ortholog-transferred; olfactory ciliary dysfunction in BBS models. Downstream sensory phenotype."
    action: KEEP_AS_NON_CORE
    reason: "Phenotype-derived; non-core."
- term:
    id: GO:0016358
    label: dendrite development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Ortholog-transferred neuronal developmental term. Indirect, linked to centrosomal/PCM1 function in neurons (cf. PMID:18762586)."
    action: KEEP_AS_NON_CORE
    reason: "Developmental phenotype; non-core."
- term:
    id: GO:0019216
    label: regulation of lipid metabolic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Ortholog-transferred; reflects metabolic dysregulation in BBS obesity. Downstream physiological consequence."
    action: KEEP_AS_NON_CORE
    reason: "Phenotype-derived; non-core."
- term:
    id: GO:0021756
    label: striatum development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Ortholog-transferred brain-development term; indirect/downstream."
    action: KEEP_AS_NON_CORE
    reason: "Developmental phenotype; non-core."
- term:
    id: GO:0021766
    label: hippocampus development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Ortholog-transferred brain-development term; indirect/downstream."
    action: KEEP_AS_NON_CORE
    reason: "Developmental phenotype; non-core."
- term:
    id: GO:0021987
    label: cerebral cortex development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Ortholog-transferred; consistent with BBS4/DISC1/PCM1 role in cortical neuronal migration (PMID:18762586). Downstream developmental process."
    action: KEEP_AS_NON_CORE
    reason: "Developmental phenotype; non-core but biologically grounded."
- term:
    id: GO:0030534
    label: adult behavior
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Ortholog-transferred behavioral phenotype term; very indirect."
    action: KEEP_AS_NON_CORE
    reason: "Phenotype-derived; non-core."
- term:
    id: GO:0045444
    label: fat cell differentiation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Ortholog-transferred adipogenesis term; reflects BBS obesity biology."
    action: KEEP_AS_NON_CORE
    reason: "Phenotype-derived; non-core."
- term:
    id: GO:0045494
    label: photoreceptor cell maintenance
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Ortholog-transferred; reflects retinal degeneration in BBS. Downstream physiological role via connecting-cilium trafficking."
    action: KEEP_AS_NON_CORE
    reason: "Phenotype-derived; relevant to retinal disease, non-core."
- term:
    id: GO:0045724
    label: positive regulation of cilium assembly
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Ortholog-transferred; consistent with the BBSome's ciliogenesis-promoting role. A more regulatory framing of the cilium-assembly function."
    action: KEEP_AS_NON_CORE
    reason: "Consistent with core ciliogenesis function; retained as supporting."
- term:
    id: GO:0046548
    label: retinal rod cell development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Ortholog-transferred retinal-development term; downstream/indirect."
    action: KEEP_AS_NON_CORE
    reason: "Developmental phenotype; non-core."
- term:
    id: GO:0048854
    label: brain morphogenesis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Ortholog-transferred neurodevelopmental term; indirect."
    action: KEEP_AS_NON_CORE
    reason: "Developmental phenotype; non-core."
- term:
    id: GO:0060271
    label: cilium assembly
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Ortholog-transferred ciliogenesis role; consistent with core BBSome function."
    action: ACCEPT
    reason: "Core function; supported across species."
- term:
    id: GO:0060296
    label: regulation of cilium beat frequency involved in ciliary motility
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Ortholog-transferred motile-cilia function (cf. airway phenotype PMID:18299575). Peripheral to the primary-cilium cargo-trafficking role."
    action: KEEP_AS_NON_CORE
    reason: "Motile-cilia phenotype; non-core."
- term:
    id: GO:1905515
    label: non-motile cilium assembly
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: "Ortholog-transferred; specifically the primary (non-motile) cilium assembly role, which is BBS4's central biological context."
    action: ACCEPT
    reason: "Specific, core ciliogenesis term; well aligned with BBS4 biology."
- term:
    id: GO:0034451
    label: centriolar satellite
  evidence_type: IDA
  original_reference_id: PMID:15107855
  qualifier: located_in
  review:
    summary: "BBS4 localizes to centriolar satellites (original Kim et al. study). Core localization."
    action: ACCEPT
    reason: "Direct experimental localization (foundational paper)."
    supported_by:
    - reference_id: PMID:15107855
      supporting_text: "BBS4 localizes to the centriolar satellites of centrosomes and basal bodies of primary cilia"
- term:
    id: GO:0034452
    label: dynactin binding
  evidence_type: IDA
  original_reference_id: PMID:15107855
  qualifier: enables
  review:
    summary: "BBS4 binds the p150-glued (DCTN1) subunit of dynactin, the molecular basis of its adaptor function linking dynein-based transport to PCM1/cargo recruitment. Informative, experimentally supported MF."
    action: ACCEPT
    reason: "Direct experimental evidence; mechanistically central MF."
    supported_by:
    - reference_id: PMID:15107855
      supporting_text: "it functions as an adaptor of the p150(glued) subunit of the dynein transport machinery"
- term:
    id: GO:0034454
    label: microtubule anchoring at centrosome
  evidence_type: IMP
  original_reference_id: PMID:15107855
  qualifier: involved_in
  review:
    summary: "BBS4 silencing de-anchors centrosomal microtubules (PMID:15107855). A genuine, specific BBS4 process downstream of its PCM1-recruitment role."
    action: ACCEPT
    reason: "Specific, well-supported process directly tied to BBS4 function."
    supported_by:
    - reference_id: PMID:15107855
      supporting_text: "Silencing of BBS4 induces PCM1 mislocalization and concomitant deanchoring of centrosomal microtubules"
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IDA
  original_reference_id: PMID:17574030
  qualifier: part_of
  review:
    summary: "BBS4 part of the BBSome (founding BBSome paper). Core complex membership."
    action: ACCEPT
    reason: "Direct experimental support (BBSome discovery)."
    supported_by:
    - reference_id: PMID:17574030
      supporting_text: "we identify a complex composed of seven highly conserved BBS proteins"
- term:
    id: GO:0000242
    label: pericentriolar material
  evidence_type: IDA
  original_reference_id: PMID:15107855
  qualifier: located_in
  review:
    summary: "BBS4 localizes to the pericentriolar material (Kim et al.). Core localization."
    action: ACCEPT
    reason: "Direct experimental localization."
- term:
    id: GO:0005814
    label: centriole
  evidence_type: IDA
  original_reference_id: PMID:15107855
  qualifier: located_in
  review:
    summary: "BBS4 localizes near centrioles/basal bodies (Kim et al.). Supported."
    action: ACCEPT
    reason: "Direct experimental localization."
- term:
    id: GO:0031514
    label: motile cilium
  evidence_type: IDA
  original_reference_id: PMID:18299575
  qualifier: located_in
  review:
    summary: "BBS4 localizes to motile cilia of airway epithelia (PMID:18299575). Direct evidence; non-core relative to primary-cilium role."
    action: KEEP_AS_NON_CORE
    reason: "Supported by IDA; motile-cilium context is non-core."
- term:
    id: GO:0032465
    label: regulation of cytokinesis
  evidence_type: IMP
  original_reference_id: PMID:15107855
  qualifier: involved_in
  review:
    summary: "As with mitotic cytokinesis, the cell-division defect on BBS4 silencing is a secondary consequence of PCM1/microtubule disruption, not a dedicated cytokinesis-regulatory function."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Secondary RNAi phenotype; not a core/direct BBS4 function."
- term:
    id: GO:0036064
    label: ciliary basal body
  evidence_type: IDA
  original_reference_id: PMID:15107855
  qualifier: located_in
  review:
    summary: "BBS4 localizes to the ciliary basal body (Kim et al.). Core localization."
    action: ACCEPT
    reason: "Direct experimental localization."
- term:
    id: GO:0036064
    label: ciliary basal body
  evidence_type: IDA
  original_reference_id: PMID:18299575
  qualifier: located_in
  review:
    summary: "BBS4 at the basal body of airway cilia (PMID:18299575). Core localization."
    action: ACCEPT
    reason: "Direct experimental localization."
- term:
    id: GO:0043014
    label: alpha-tubulin binding
  evidence_type: IDA
  original_reference_id: PMID:17574030
  qualifier: enables
  review:
    summary: "Alpha-tubulin binding reported in the BBSome study. Plausible (BBS4/BBSome associates with microtubules), though this could partly reflect complex-level rather than BBS4-intrinsic binding. Retained as supporting molecular detail."
    action: KEEP_AS_NON_CORE
    reason: "Experimentally annotated MF; ancillary to the adaptor core function."
- term:
    id: GO:0048487
    label: beta-tubulin binding
  evidence_type: IDA
  original_reference_id: PMID:17574030
  qualifier: enables
  review:
    summary: "Beta-tubulin binding reported in the BBSome study; same caveats as alpha-tubulin binding. Retained as supporting molecular detail."
    action: KEEP_AS_NON_CORE
    reason: "Experimentally annotated MF; ancillary to the adaptor core function."
- term:
    id: GO:0051457
    label: maintenance of protein location in nucleus
  evidence_type: IGI
  original_reference_id: PMID:15107855
  qualifier: involved_in
  review:
    summary: "This term is poorly aligned with the Kim et al. study, which concerns cytoplasmic PCM1 recruitment to centrosomes, not nuclear protein retention. The annotation appears to be an over-interpretation; BBS4 is not established to maintain proteins in the nucleus."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Not supported by a credible nuclear-retention function; inconsistent with BBS4's cytoplasmic/centrosomal localization."
- term:
    id: GO:0060170
    label: ciliary membrane
  evidence_type: IDA
  original_reference_id: PMID:17574030
  qualifier: located_in
  review:
    summary: "BBSome at the ciliary membrane (founding paper). Core localization."
    action: ACCEPT
    reason: "Direct experimental localization."
    supported_by:
    - reference_id: PMID:17574030
      supporting_text: "but also to the membrane of the cilium"
- term:
    id: GO:0097730
    label: non-motile cilium
  evidence_type: IDA
  original_reference_id: PMID:17574030
  qualifier: located_in
  review:
    summary: "BBS4/BBSome in the primary (non-motile) cilium. Core localization."
    action: ACCEPT
    reason: "Direct experimental localization."
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IDA
  original_reference_id: PMID:14520415
  qualifier: located_in
  review:
    summary: "Centrosome localization reported in an early BBS basal-body review/study. Consistent with strong experimental evidence elsewhere."
    action: ACCEPT
    reason: "Corroborated by multiple independent IDA annotations."
- term:
    id: GO:0050893
    label: sensory processing
  evidence_type: TAS
  original_reference_id: PMID:14520415
  qualifier: involved_in
  review:
    summary: "TAS sensory-processing term from an early review framing BBS as a basal-body/cilia sensory disorder. Downstream/phenotypic, not a direct molecular function."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Phenotype-level TAS term; not a direct BBS4 function."
- term:
    id: GO:0007098
    label: centrosome cycle
  evidence_type: IMP
  original_reference_id: PMID:15107855
  qualifier: involved_in
  review:
    summary: "Annotation derives from cell-cycle/centrosome effects of BBS4 silencing (PMID:15107855). These are secondary consequences of PCM1/microtubule disruption rather than a dedicated centrosome-cycle function."
    action: MARK_AS_OVER_ANNOTATED
    reason: "Secondary RNAi phenotype; not a core/direct BBS4 function."
core_functions:
- description: "BBS4 is a cargo adaptor that links the dynein/dynactin motor (via the p150-glued/DCTN1 subunit) to pericentriolar material protein PCM1 and its associated cargo, recruiting them to centriolar satellites and the centrosome; this supports microtubule anchoring at the centrosome."
  molecular_function:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  directly_involved_in:
  - id: GO:0071539
    label: protein localization to centrosome
  - id: GO:0034454
    label: microtubule anchoring at centrosome
  locations:
  - id: GO:0034451
    label: centriolar satellite
  - id: GO:0000242
    label: pericentriolar material
  - id: GO:0005813
    label: centrosome
  supported_by:
  - reference_id: PMID:15107855
    supporting_text: "it functions as an adaptor of the p150(glued) subunit of the dynein transport machinery to recruit PCM1 (pericentriolar material 1 protein) and its associated cargo to the satellites"
    reference_section_type: ABSTRACT
  - reference_id: PMID:18762586
    supporting_text: "DISC1 and BBS4 are required for targeting PCM1 and other cargo proteins, such as ninein, to the centrosome in a synergistic manner"
    reference_section_type: ABSTRACT
- description: "As a core subunit of the BBSome, BBS4 contributes to a coat-like cargo adaptor that sorts and traffics membrane proteins to and within the primary cilium, supporting ciliogenesis and ciliary signalling."
  molecular_function:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  contributes_to_molecular_function:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  directly_involved_in:
  - id: GO:0061512
    label: protein localization to cilium
  - id: GO:0060271
    label: cilium assembly
  in_complex:
    id: GO:0034464
    label: BBSome
  locations:
  - id: GO:0060170
    label: ciliary membrane
  - id: GO:0036064
    label: ciliary basal body
  supported_by:
  - reference_id: PMID:17574030
    supporting_text: "we identify a complex composed of seven highly conserved BBS proteins. This complex, the BBSome, localizes to nonmembranous centriolar satellites in the cytoplasm but also to the membrane of the cilium"
    reference_section_type: ABSTRACT
  - reference_id: PMID:23943788
    supporting_text: "co-localizes with CEP290 to the transition zone (TZ) of primary cilia and centriolar satellites in ciliated cells"
    reference_section_type: ABSTRACT
proposed_new_terms: []
suggested_questions:
- question: "Is BBS4's alpha-/beta-tubulin binding an intrinsic property of BBS4 or a complex-level (BBSome) property, and what is its mechanistic role?"
- question: "Does BBS4 have any direct, stable nuclear/transcriptional function, or are the nucleus and transcription-factor-binding annotations generalizations from BBS7?"
- question: "To what extent are the cytokinesis/cell-cycle phenotypes of BBS4 loss direct versus secondary to PCM1 mislocalization and microtubule de-anchoring?"
suggested_experiments:
- description: "Use the cryo-EM BBSome structure (PDB 6XT9) and crosslinking-MS to map BBS4's direct binding partners within the BBSome and define its contribution to cargo (e.g. SMO, PKD1) recognition versus a purely structural role."
- description: "Acute degron-based depletion (vs. chronic RNAi) of BBS4 in ciliated cells with live imaging of PCM1, ninein, microtubule anchoring and cell-cycle progression to separate direct from secondary phenotypes."
- description: "Reconstitute the BBS4-DCTN1(p150-glued)-PCM1 module in vitro to test whether BBS4 is sufficient as an adaptor bridging dynactin to PCM1 cargo."
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on on inter-ontology
    links
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:14520415
  title: Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: "Early study/review establishing BBS as a basal-body/centrosome disorder; supports centrosome localization but the sensory-processing TAS term is phenotype-level."
- id: PMID:15107855
  title: The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region
    and is required for microtubule anchoring and cell cycle progression.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Foundational BBS4 paper; establishes adaptor activity (p150-glued/dynactin to PCM1), centriolar-satellite/PCM localization and microtubule anchoring. Cell-cycle/cytokinesis effects are secondary RNAi phenotypes."
- id: PMID:16327777
  title: Dissection of epistasis in oligogenic Bardet-Biedl syndrome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: "CCDC28B interaction; supports a protein-protein interaction only."
- id: PMID:16399798
  title: Bardet-Biedl syndrome genes are important in retrograde intracellular trafficking
    and Kupffer's vesicle cilia function.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: "Zebrafish study; supports BBS role in retrograde intracellular transport and cilia function (basis for melanosome-transport and cilium-assembly ISS)."
- id: PMID:17574030
  title: A core complex of BBS proteins cooperates with the GTPase Rab8 to promote
    ciliary membrane biogenesis.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "BBSome discovery paper; defines complex composition, ciliary-membrane and centriolar-satellite localization and ciliogenic function. Source of BBSome part_of and tubulin-binding IDAs."
- id: PMID:18000879
  title: Novel interaction partners of Bardet-Biedl syndrome proteins.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: "ALDOB interaction; supports a protein-protein interaction only."
- id: PMID:18299575
  title: Loss of Bardet-Biedl syndrome proteins alters the morphology and function
    of motile cilia in airway epithelia.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: "Supports BBS4 localization to motile cilia/basal bodies and a motile-cilia function (non-core relative to primary-cilium role)."
- id: PMID:18762586
  title: 'Recruitment of PCM1 to the centrosome by the cooperative action of DISC1
    and BBS4: a candidate for psychiatric illnesses.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Shows DISC1+BBS4 cooperatively recruit PCM1/ninein to the centrosome and link to cortical neuronal migration; supports adaptor/centrosome role and cerebral-cortex-development annotation."
- id: PMID:18772192
  title: CEP290 interacts with the centriolar satellite component PCM-1 and is required
    for Rab8 localization to the primary cilium.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: "CEP290/PCM1/Rab8 satellite study; contextual to BBS4 satellite biology."
- id: PMID:19081074
  title: A BBSome subunit links ciliogenesis, microtubule stability, and acetylation.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: "Identifies BBIP10 as a BBSome subunit; the microtubule-stability/acetylation function belongs to BBIP10, not BBS4. Supports BBSome membership and ciliary-membrane localization."
- id: PMID:20080638
  title: BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and
    mediate BBSome assembly.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: "Chaperonin-mediated BBSome assembly; supports BBS4 as a BBSome subunit requiring CCT/TRiC-assisted assembly."
- id: PMID:22072986
  title: A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: "LZTFL1 regulates BBSome ciliary trafficking and SMO; supports the BBSome's role in ciliary signalling-receptor trafficking."
- id: PMID:22302990
  title: Direct role of Bardet-Biedl syndrome proteins in transcriptional regulation.
  findings: []
  reference_review:
    relevance: LOW
    correctness: DISPUTED
    review_notes: "Primarily a BBS7 study (nuclear role, RNF2/PcG interaction); BBS4-specific transcription-factor-binding is a weak generalization and is treated as an over-annotation here."
- id: PMID:22500027
  title: Intrinsic protein-protein interaction-mediated and chaperonin-assisted sequential
    assembly of stable bardet-biedl syndrome protein complex, the BBSome.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Defines BBSome assembly order; BBS4 is added last to the BBS7-BBS2-BBS9 core. Supports BBSome membership and centrosome localization."
- id: PMID:23943788
  title: BBS mutations modify phenotypic expression of CEP290-related ciliopathies.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Full text available; supports CEP290 interaction, ciliary/satellite/transition-zone localization and BBS4's role in protein localization to cilium (IMP)."
- id: PMID:24550735
  title: The centriolar satellite protein AZI1 interacts with BBS4 and regulates ciliary
    trafficking of the BBSome.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "AZI1/CEP131 interacts with the BBSome through BBS4 and negatively regulates BBSome ciliary trafficking; zebrafish melanosome-transport delay. Supports BBSome membership, localizations and the melanosome-transport ISS."
- id: PMID:24939912
  title: Bardet-Biedl syndrome proteins 1 and 3 regulate the ciliary trafficking of
    polycystic kidney disease 1 protein.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: "BBSome (with BBS4 as subunit) regulates ciliary trafficking of PKD1; supports cargo-trafficking function."
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: "High-throughput interactome; generic protein-binding only."
- id: PMID:25552655
  title: Nephrocystin proteins NPHP5 and Cep290 regulate BBSome integrity, ciliary
    trafficking and cargo delivery.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: "NPHP5/CEP290 regulate BBSome integrity and cargo delivery; contextual to BBSome trafficking function."
- id: PMID:26871637
  title: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: "High-throughput interactome; generic protein-binding only."
- id: PMID:27173435
  title: An organelle-specific protein landscape identifies novel diseases and molecular
    mechanisms.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: "High-throughput interactome; generic protein-binding only."
- id: PMID:29039417
  title: Protein interaction perturbation profiling at amino-acid resolution.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: "High-throughput interactome; generic protein-binding only."
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: "HuRI high-throughput interactome; generic protein-binding only."
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: "High-throughput interactome; generic protein-binding only."
- id: PMID:33144677
  title: Dlec1 is required for spermatogenesis and male fertility in mice.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: "DLEC1 interaction in a mouse spermatogenesis study; supports a protein-protein interaction relevant to spermatid-development phenotype."
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: "BioPlex high-throughput interactome; generic protein-binding only."
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: "High-throughput cell-map interactome; generic protein-binding only."
- id: Reactome:R-HSA-5617815
  title: BBSome binds RAB3IP
  findings: []
- id: Reactome:R-HSA-5624125
  title: Formation of the BBSome
  findings: []
- id: Reactome:R-HSA-5624126
  title: ARL6:GTP and the BBSome bind ciliary cargo
  findings: []
- id: Reactome:R-HSA-5624127
  title: ARL6:GTP and the BBSome target cargo to the primary cilium
  findings: []
- id: Reactome:R-HSA-5624129
  title: LZTFL1 binds the BBSome and prevents its traffic to the cilium
  findings: []