The human BBSome

Reviewing GO annotations for the 14 genes of a ciliary coat complex

AI Gene Review · projects/HUMAN_BBSOME · 2026

Bottom line

  • The BBSome is an 8-subunit coat that sorts GPCRs and Hedgehog components into and out of the primary cilium; its loss causes Bardet–Biedl syndrome.
  • We reviewed every GO annotation on 14 genes (8 subunits, ARL6 recruiter, 2 regulators, 3 assembly chaperonins) and built a reusable BBSome module.
  • Main corrections: protein binding → BBSome membership or specific MF; chaperonins are assembly factors, not subunits; two over-propagated BBS2 IEA localizations removed.

Who does what inside the complex

Why this complex

  • Well bounded: one complex, cryo-EM structures (2020), a clear disease.
  • A test of whether per-gene review recovers the division of labour:
    • cargo recognition and ARL6 binding: BBS1
    • membrane recruitment: ARL6-GTP
    • assembly: MKKS / BBS10 / BBS12 + CCT/TRiC
  • The failure mode to avoid: copying one generic "cilium" story onto every subunit.

What a review looks like

BBS1 review page: each GOA row gets an action and a reason. BBSome membership is accepted; a propagated "patched binding" row is marked over-annotated.

Results across 14 genes

Gene Ann. ACCEPT Non-core Over-ann. MODIFY REMOVE
BBS1 60 26 7 23 4 0
BBS2 67 16 24 25 0 2
BBS4 110 42 37 31 0 0
MKKS 60 5 21 32 2 0
TTC8 45 23 10 12 0 0
BBIP1 22 11 8 3 0 0

Six of 14 shown; full table in projects/HUMAN_BBSOME.md.

Cross-cutting findings

  1. protein binding (GO:0005515) IPI rows flagged throughout; biology captured by GO:0034464 BBSome or specific MF (BBS1 → small GTPase binding for ARL6).
  2. Chaperonins are not subunits: MKKS, BBS10, BBS12 get GO:0044183 protein folding chaperone, replacing obsolete GO:0051082.
  3. A GO:0061629 RNA Pol II TF binding row from a BBS7-centric study (PMID:22302990) was flagged as miscited across the scaffold subunits.
  4. BBS2 microvillus / stereocilium IEA rows removed as unsupported.

The BBSome module

modules/bbsome.yaml: composition, assembly, ARL6 recruitment and cargo trafficking, grounded in GO:0034464.

Status and next steps

  • ✅ 14/14 gene reviews validate; module validates.
  • ⬜ Pathway/summary integration (optional).
  • Out of scope, candidates for their own modules: IFT (IFT27/BBS19, IFT172/BBS20) and the transition zone (MKS1, CEP290).

Read more: projects/HUMAN_BBSOME.md · modules/bbsome.yaml · genes/human/<GENE>/