BBS2 (Q9BXC9) curation notes

(See BBS2-ai-review.yaml for the structured review.)

Identity and structure

Core complex membership (BBSome)

Function — ciliary membrane protein trafficking

Function — receptor signaling / obesity (cargo trafficking)

Disease

Specific annotations evaluated

protein binding (GO:0005515) IPI annotations

Mouse/ISS-transferred BP terms (GO_REF:0000024, from mouse Q9CWF6)

Key references verified

2026-09-30 BBS2 source-complete review

The normal local GOA projection recovers 89 distinct source assertions from 92 raw rows, including 22 partner-specific assertions absent from the inherited 67-row review. Three full source keys occur twice in the raw file; these exact duplicates do not represent additional distinct assertions. Qualifiers, evidence, source references and WITH/FROM identities are retained, including BBS7 isoform 2 and the separately tested NRF1/FNDC3B isoforms. No new annotation is proposed by this consultation.

This assessment supersedes the earlier cilia-only reasons for removing microvillus and stereocilium locations. PMID:25605782 directly localizes mouse Bbs2 at both actin-rich sites despite the paper's Bbs8/Ift20 title. PMID:18032602 explicitly includes Bbs2-null brain morphology despite its Bbs1-focused title. These are contextual transferred assertions, not new human assays. The earlier RNF2/BBS7-only concern is also superseded: PMID:22302990 includes tagged BBS2–RNF2 co-IP. RNF2 is an E3 ligase, supporting ubiquitin protein ligase binding; endogenous co-IP and yeast screening in that paper were BBS7 experiments.

The inherited interaction-partner labels require correction: Q9NRI5 is DISC1, P68104 is EEF1A1, and Q15154 is PCM1. The source identifiers themselves remain unchanged. Canonical BBS7 interactions can be refined to heterodimerization and canonical BBS9 interactions to the integral BBSome scaffold role, with independent primary structural/assembly grounding identified separately from each original interaction assay. The BBS7 isoform-2 assertion remains non-core because the structural construct's precise isoform has not been established here. Supported remaining interactions are kept as non-core under the user-supplied ActionEnum; lack of a specific mechanism is not evidence that an observed interaction is false.

One scaffold core is sufficient. The structural paper PMID:31530639 uses low-resolution negative-stain EM, cross-linking/MS and integrative modeling, not high-resolution cryo-EM. No ARL6 GTPase, BBS1/7 cargo-recognition or CCT folding activity is assigned to BBS2. Some cilia initially form in Bbs2-null mice, so broad cilium-assembly annotations do not imply a universal initiation requirement. Adipogenesis remains undecided because the traced PMID:17379567 evidence available here is an expression study, not a demonstrated BBS2-performed differentiation step.

No provider report was present. The first normal provider attempt stopped at a UV tool-directory configuration error; a corrected attempt using the established writable directories failed at offline dependency resolution before generating a provider report. No manual text has been labeled as a provider report. The normal existing-PMID command found all 24 requested records cached. The consultation's source-read-limits.json distinguishes complete abstracts, selected primary Results/Methods and uninspected images/supplements; several caches marked full-text available contain only partial article bodies. Additional normal-source acquisition is owned separately and must be recorded before final integration.

The five additional normal sources were recovered through Source87 and imported without source editing. The integrated review has 16 ACCEPT, 56 KEEP_AS_NON_CORE, 15 MODIFY and two UNDECIDED decisions, with one scaffold core and no NEW annotation. The earlier notes remain as historical context; the corrections above govern this revision.

Validation of this revision — 2026-09-30

Focused validation passed with 26 advisories, all concerning supported generic protein-binding rows retained as non-core under the supplied review criteria. These advisories remain disclosed; they do not provide evidence that the interactions are false. The generated Codex EDIT history and rendering passed. The exact source census contains 89 distinct assertions from 92 raw rows, with no new assertion. This is focused validation, not a new claim that repository-wide reference checks passed.

2026-09-30 response to PR3590 scientific review

The GO hierarchy was checked again against the official stereocilium page: it explicitly lists neuron projection as an is_a parent (accessed 2026-09-30). The reviewer's proposed sibling-only relationship was not supported by this ontology release. The PAINT localization and its original supporting entities are retained.

The RNF2 decision now rests on the BBS2/RNF2 interaction curated with IPI and on the partner's ubiquitin-ligase identity; it no longer requires a figure-level assertion unavailable in the cached abstract. Short verbatim anchors were added for mouse Bbs2 localization in microvilli/stereocilia and for the Bbs2-null brain findings (PMID:25605782; PMID:18032602). The scaffold core now includes the ciliary protein-localization process and membrane/basal-body locations, with evidence from BBS2 depletion and curated direct localization (PMID:22072986; PMID:19081074; PMID:18299575). Individual refined interaction reasons identify their own partner and source paper.

The action totals and all 89 source keys remain unchanged. Generic interaction observations remain non-core under the user's explicit ActionEnum criteria; the reviewer request to remove otherwise supported interactions solely because the term is broad conflicts with those criteria. No new annotations or source records are introduced in this response.

2026-10-09 — project instruction and bounded review follow-up

The authority for supported generic-binding retention is the standing explicit
user instruction in the
ClinGen project.
It directs KEEP_AS_NON_CORE for a supported, biologically correct GO:0005515
annotation when no evidence-backed finer term is established, MODIFY when such
a refinement is supported, and UNDECIDED when the relevant evidence cannot be
adjudicated. This instruction takes precedence over the generic-binding skill
default and validator advisory. Earlier ActionEnum-only explanations were
incomplete; no repository-wide policy change or additional maintainer sign-off
is claimed. The repeated generic-interaction reasons now identify this authority
and the lack of an established finer function for the particular pair.

The stereocilium relationship was independently rechecked using the
QuickGO is_a-only ancestor API
on 2026-10-09. Its GO:0032420 result explicitly includes GO:0043005 among the
ancestors. The annotation reason now links to that checkable response rather
than relying on interpretation of the AmiGO neighborhood display. This
corroborates the ontology statement; the PAINT assertion and its source
entities remain intact.

The BBS7 isoform-2 suggestion was assessed separately from the policy issue.
UniProt Q8IWZ6 identifies
Q8IWZ6-2 as lacking canonical residues 673–715. The current source assertion
records interaction with that isoform, and it remains supported non-core
binding. The precise structural construct and transfer of the dimerization
mechanism to the shortened isoform were not established in this follow-up.
This makes no claim that isoform 2 lacks the interface or cannot heterodimerize.
A narrower annotation can follow a verified construct/interface comparison;
uniformity with the canonical partner alone is insufficient.

The previously accepted RNF2 refinement, five supporting quotations, and
ciliary process/location synthesis remain unchanged. All 89 source assertions,
annotation actions, core functions and reference records are preserved:
16 ACCEPT, 56 KEEP_AS_NON_CORE, 15 MODIFY and two UNDECIDED. The 26 generic
binding advisories remain an acknowledged consequence of the explicit project
instruction. This entry supersedes the earlier policy-authority explanation;
prior journal entries remain historical.