This is a mechanism module, not a specific disease. Disorder entries reference individual nodes via conforms_to (e.g., "bbsome_trafficking#BBSome-Dependent Ciliary Cargo Trafficking Failure"). Scope discipline: this module covers the BBSome machine plus its dedicated operators (ARL6, LZTFL1, and the BBSome-recycling GTPase IFT27). General IFT-B particle subunits (IFT74, IFT172), transition-zone proteins (CEP290, MKS1, SDCCAG8, NPHP1) and basal-body/other ciliary proteins are shared infrastructure and are modeled in the ciliopathy_dysfunction module, even though variants in those genes also cause the Bardet-Biedl syndrome phenotype. A disease may conform to both modules: its BBSome-core nodes conform here while its transition-zone node conforms to ciliopathy_dysfunction.
BBSome Subunit Deficiency
trigger
The initiating lesion in this arm is a biallelic loss-of-function variant in a core BBSome subunit gene (BBS1, BBS2, BBS4, BBS5, BBS7, TTC8/BBS8, BBS9, or BBIP1/BBS18). Because the assembled complex is obligate and highly interconnected, loss of any one subunit destabilizes the whole BBSome. Conforming entries substitute the disorder-specific subunit gene.
Downstream
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Defective BBSome Assembly
Loss of an obligate subunit prevents formation of a stable, functional BBSome.
BBS Chaperonin Assembly Defect
trigger
The initiating lesion in this arm is a biallelic variant in one of the chaperonin-like BBS genes (MKKS/BBS6, BBS10, BBS12). These three proteins form a CCT/TRiC-associated BBS-chaperonin complex required to fold and assemble the BBSome from its subunits; their loss prevents the complex from being built even when subunit genes are intact. Conforming entries substitute the disorder-specific chaperonin gene.
Downstream
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Defective BBSome Assembly
Without the BBS-chaperonin complex, subunits cannot be folded and assembled into the BBSome.
Defective BBSome Assembly
Convergence node: loss of an obligate subunit (subunit arm) or of the chaperonin assembly machinery (chaperonin arm) prevents formation of a stable, functional BBSome. The native complex is highly interconnected and obligate, so partial complexes are non-functional.
Downstream
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BBSome-Dependent Ciliary Cargo Trafficking Failure
An unassembled or unstable BBSome cannot traffic ciliary cargo.
BBSome Membrane Recruitment and Retrograde IFT Coupling
trigger
Independent trigger arm acting on an intact BBSome. The ARF-like GTPase ARL6/BBS3 recruits the autoinhibited BBSome to the ciliary membrane, where the regulator LZTFL1/BBS17 tunes its trafficking and the BBSome couples to retrograde intraflagellar transport (IFT) trains for ciliary exit of cargo. The general IFT-B machinery is shared infrastructure (modeled in ciliopathy_dysfunction); here it is the train the BBSome boards. Loss of ARL6, LZTFL1, or the BBSome-recycling GTPase IFT27 blocks BBSome-dependent cargo movement even when the BBSome is fully assembled.
Downstream
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BBSome-Dependent Ciliary Cargo Trafficking Failure
Defective membrane recruitment and IFT coupling stall BBSome-dependent cargo transport.
BBSome-Dependent Ciliary Cargo Trafficking Failure
convergent phenotype
Shared output node and the conformance anchor for the BBSome-opathies. Whether the BBSome fails to assemble or fails to be recruited and coupled to IFT, the common consequence is loss of BBSome-dependent trafficking of signaling receptors (e.g. GPCRs) and other cargo into and out of the ciliary compartment. Downstream, the disorder-specific organ branches are determined by which cilia-dependent cell types depend most on this cargo flux.