Gene: BBS1 / "BBSome complex member BBS1" / Bardet-Biedl syndrome 1 protein. Human, HGNC:966. 593 aa, chromosome 11.
BBS1 is a core subunit of the BBSome (GO:0034464), an octameric, coat-like protein complex
(BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9, BBIP1/BBIP10). The BBSome is structurally related
to COPI/COPII/clathrin coats and functions as a cargo adaptor that traffics specific transmembrane
proteins (notably ciliary GPCRs and Hedgehog-pathway components) into and out of the primary cilium
by coupling them to intraflagellar transport (IFT).
Human BBS1 is Q8NFJ9, HGNC:966, NCBI Gene582. The 60 original source
assertions and all three alternative-product objects must be preserved.
Q8NFJ9-2 is named product3 (DPP3-BBS1) in the source; this is not a basis for
assigning every canonical BBS1 assay to that fusion product.
PMID:25402481(https://pubmed.ncbi.nlm.nih.gov/25402481/) directly measures
binding between recombinant human BBS1 N-terminal domain and human ARL6,
with an affinity of approximately0.54 micromolar in the reported assay.
The crystal complex is algal, whereas the human biochemical experiments
are separate. The human BBS1 domain was produced in High Five cells and
ARL6 in E. coli. A one-residue construct-boundary difference between the
Results and Methods is not evidence for natural isoform specificity.
Selected affinity Results and the purification, ITC, pulldown and
cell-assay Methods were read. The first core therefore uses small GTPase
binding; it does not give BBS1 ARL6's catalytic activity.
PMID:20603001(https://pubmed.ncbi.nlm.nih.gov/20603001/) establishes the
BBSome as an ARL6-GTP effector. Bovine retinal BBSome purification, human
RPE-cell localization and individual BBS1-domain experiments are distinct
parts of the evidence. Selected Results and main Methods through the
purification/liposome assays were inspected; some pulldown procedures
refer to supplementary methods that were not fully read. Complex-level
cargo recognition is not automatically assigned to isolated BBS1.
The old review dismissed four Smoothened/Patched binding annotations as
genetic or localization evidence only. The actual full-text Results,
Figures2–3 captions and Methods in
PMID:22228099(https://pubmed.ncbi.nlm.nih.gov/22228099/) include human
tagged BBS constructs in293T cells, reciprocal immunoprecipitation and
receptor-tail mapping. The BBS1-associated segments include Smoothened's
cytoplasmic tail and Patched1's C-terminal region. The binding observations
are supported even though the abstract foregrounds mouse genetics and
Hedgehog signaling. They do not establish purified binary affinities. One receptor
binding core can represent this shared cargo-recognition role.
PMID:22302990(https://pubmed.ncbi.nlm.nih.gov/22302990/) has an
abstract-only local cache. Separately indexed original Results and
Figure3C explicitly include tagged BBS1 among proteins co-precipitating
RNF2. The BBS7 bait and endogenous-IP experiments are not relabeled as
BBS1 experiments. RNF2 is a ubiquitin ligase; binding that partner is
better represented by ubiquitin protein ligase binding than by binding
a sequence-specific RNA-polymerase-II transcription factor. Changes in
RNF2 abundance after BBS1 depletion do not make BBS1 a protease.
The mouse Bbs1 donor annotation supports the contextual motile-cilium and
ciliary-beat roles in
PMID:18299575(https://pubmed.ncbi.nlm.nih.gov/18299575/). The available
cache contains an abstract and Discussion but omits the Results and
supplementary Methods despite its full-text flag. The independent
consultation inspected indexed Results/Figure6A and the official MGI
donor mapping. Direct human localization in that paper concerns BBS2
and BBS4 and must not be transferred to BBS1. A primary-cilium-only
rationale cannot dismiss the mouse Bbs1 airway findings.
PMID:21471969(https://pubmed.ncbi.nlm.nih.gov/21471969/) provides
context for the phosphoprotein-binding transfer. Indexed original
Results, Figure1 and Methods summary distinguish mouse DISC1 S710
phosphodead/phosphomimetic constructs and phosphorylation-dependent
BBS1 association in HT22 cells. Human DISC1 S713 biochemical experiments
are a separate assay. This supports a contextual interaction and
centrosomal recruitment in mouse cortical development; BBS1 is not
the kinase. The full supplementary files were not read. Its normal
cache fetch failed once with DNS errors; the recovered normal record
is now bound to this proposal.
PMID:17980398 describes retinal imaging in human BBS1/BBS10 patients,
not a mouse experiment. An experimental annotation must not be
rejected from that abstract alone. PMID:24939912 distinguishes ciliary
PC1 targeting from plasma-membrane targeting and cilium length.
PMID:32814053 is the Haenig neurodegenerative interactome; findings
from a separate BBS1 assembly paper must not be attributed to it.
Supported generic interactions are retained as non-core unless a
specific molecular activity is established. PAINT assertions are
not judged by donor count or by the source paper's title. No new
biological-process annotation is proposed from an isolated knockout
phenotype. Cilium assembly and physiological outcomes are retained
as context where justified; they do not require additional duplicate
core functions.
The standard Falcon invocation with perplexity-lite fallback stopped
before either provider started because the pinned client dependency
was unavailable offline. The standard publication command found all
23 original PMIDs already cached. No provider report or downloaded
source content was authored manually. Final decisions, source binding,
history and validation will be recorded after integration.
This reassessment supersedes earlier journal statements dismissing SMO/PTCH and RNF2 interactions or presuming absence of a motile-cilium role. All 60 original assertions remain:31 ACCEPT,23 KEEP_AS_NON_CORE and six MODIFY; no NEW assertion is added. Three products and two molecular cores are retained. The LEPR generic-binding row is refined to signaling receptor binding with the annotation consultant’s specific concurrence.
The exact independently reviewed proposal was applied on 2026-09-30. Focused validation passed with 14 advisories, all for supported generic protein-binding annotations retained as non-core under the supplied ActionEnum. These recommendations do not establish that the interactions are incorrect. Rendering passed; all 60 source objects and three products remain unchanged. No repository-wide validation pass is claimed. The new Codex EDIT history records this reassessment.
The earlier 60-row audit covered the legacy review groups, not every distinct WITH/FROM tuple. A normal offline seed-goa projection with title fetching disabled recovered 23 additional partner-specific rows and backfilled 43 supporting-entity lists. The immutable GOA contains 86 raw lines representing 83 distinct source tuples; three repeated projected tuples are retained once. The review now contains all 83 distinct tuples: 31 ACCEPT, 46 KEEP_AS_NON_CORE and six MODIFY. All prior 60 judgments, three alternative products, two molecular cores and 35 references are preserved.
The added rows retain source-attributed interactions separately for BBSome subunits, RAB3IP isoforms, EEF1A1, PCM1 and PARK7. They do not inherit receptor-, RNF2- or ARL6-specific refinements. The RAB3IP isoforms identify partners, not BBS1 isoforms. Abstract-only sources and uninspected supplementary pair matrices remain explicitly limited; co-complex affinity purification is not treated as purified binary binding. The BioPlex 33961781 cache contains Introduction and Discussion despite its full-text flag. Generic binding remains non-core under the supplied ActionEnum. No new quotation or autonomous molecular activity is asserted.
This correction supersedes the earlier completeness claim while preserving that history and the unexecuted 60-row native packet. No branch, commit or PR was created from the superseded packet. Independent biological review accepted the 23 supplemental judgments and exact source projection before this application.
Focused validation after the source-completeness repair passed with 37 generic-binding non-core advisories, retained under the supplied ActionEnum (58b8c6). Rendering passed (f6d9e0), and the separate Codex EDIT history passed schema validation (a71a1e). Raw/source bytes remain unchanged; no repository-wide validation claim is made. The first history scaffold command used an ambiguous actor option and stopped before creation; the corrected actor-name command generated the new record normally.
The 83 source annotations, their actions, partner identities, three alternative products and two core activities are unchanged. The description now names the eight BBSome subunits and makes the coat and receptor-recognition roles explicit. This does not add an autonomous GTPase, universal ciliogenesis or direct receptor-activation claim.
Short primary-source anchors now accompany the experimental PTCH1 and SMO rows, the LEPR refinement, contextual mouse motile-cilium and beat phenotypes, and phosphorylation-sensitive DISC1 association. The two receptor quotations were moved from the core to their experimental rows; the receptor core retains the source citation without repeating those quotations. The ARL6 core retains its human binding anchor. The current BBSome roster includes BBIP1, identified after the foundational seven-subunit study; that older complex-identification quotation is used only with its own source annotation.
The PMID:23943788 annotation remains accepted with explicit curator deference. Its complete available cache contains the abstract, Introduction and Discussion, but omits Results and Methods. That text foregrounds BBS4/CEP290 and does not expose the BBS1-specific assay. The new row anchor is clearly labeled corroboration from the independent PC1-trafficking study PMID:24939912. The separate source experiments are not conflated. Mouse DISC1 S710 and human S713, mouse airway phenotypes and human localization, and cell-lysate association versus purified binary binding remain distinct.
Repeated policy and audit boilerplate has been replaced by partner- and study-specific biological reasons. Detailed source access and supplementary-pair limits are retained in the corresponding reference reviews. All 37 generic binding rows remain KEEP_AS_NON_CORE under the supplied ActionEnum: the recorded associations are retained, but no additional informative molecular activity is established. No interaction is declared false merely because its label is broad. The exact Q8TAM2 partner in the PMID:24939912 generic interaction row is TTC8/BBS8. Its previous PC1-focused summary conflated the paper’s cargo experiments with the distinct GOA partner; the summary is corrected without changing the source object or action. PMID/DOI and figure-label spacing in authored prose is repaired.
The evidence check counts all quoted text across the proposed YAML and this new notes appendix, including repeated occurrences; each source remains within 25 words. Existing journal entries are preserved as historical text. No source cache, raw GOA, UniProt record or generated research file was changed. This temporary proposal has not been canonically applied or fully validated.
The ClinGen project's curation instructions record the user's explicit instruction to retain a supported, biologically correct generic protein-binding annotation as KEEP_AS_NON_CORE when no evidence-backed, more specific replacement is established. They require MODIFY for a supported refinement and UNDECIDED when the relevant evidence cannot be accessed or adjudicated. The instruction is specific to this campaign and takes precedence over the annotation-reviewer skill's general informational-exclusion recommendation.
This explicit project instruction is the authority for the retained generic interactions. It supersedes the earlier journal explanations based on the ActionEnum alone. The 2026-09-30 re-review on head 969a250d4 accepted the biological judgments and restored evidence anchors; its remaining request to remove all 37 non-core generic-binding rows applied the general policy. The project instruction resolves that policy question. The source-access limitations in the reference reviews remain in force: retention does not claim that an uninspected supplementary pair matrix was independently verified or turn a co-complex association into purified binary binding.
This clarification preserves all 83 annotation decisions (31 ACCEPT, 46 KEEP_AS_NON_CORE and six MODIFY), including the four evidence-backed refinements of generic-binding rows. The 37 generic-binding advisories are expected under the campaign instruction; their presence does not invalidate the supported retention decisions.