BBS4

Cilia effects upon perturbation of BBS4

Cilia number / % ciliated:

Decreased cilia number

Loss-of-function effect:

Shorter cilia

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-3.44) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, casTLE effect=-3.87) PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Phenotypes

Mouse phenotype:

preweaning lethality, incomplete penetrance, increased startle reflex, decreased exploration in new environment, decreased thigmotaxis, hyperactivity

Human ciliopathy phenotype:

Bardet-Biedl syndrome 4; Bardet-Biedl syndrome; Bardet-Biedl syndrome 1

Ciliopathy associations

• Bardet-Biedl Syndrome

References: PMID:12016587, PMID:15654695, PMID:23142271, PMID:11381270, PMID:12016587

Subcellular localization

basal body, centrosome, cilia

References: PMID:20603001, PMID:17574030, PMID:22072986, PMID:18299575

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Actin & cytoskeleton regulation
• Reproduction & sperm
• Cell migration & adhesion
• Signaling (Hedgehog, GPCRs, ion channels)
• Ciliary membrane
• Transition zone
• ECM & connective tissue
• Transcription regulation

Function

Mutated in Bardet-Biedl syndrome (type 4) (OMIM :600374,PMID:11381270). Forms part of BBSome, important for RAB8-mediated membrane protein trafficking (20603001,PMID:17574030,PMID:22072986). Fewer mutant cells were ciliated [48% ± 6 for wild-type (WT) cells versus 23% ± 7 for Bbs4 null cells, P < 0.0001] and their cilia were shorter (2.55 μm ± 0.41 for WT cells versus 2.16 μm ± 0.23 for Bbs4 null cells, P < 0.0001)(PMID: 23716571).