BBS4

Bardet-Biedl syndrome 4

Ensembl:
ENSG00000140463
UniProt:
Q96RK4
OMIM:
600374

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

  • Acrocallosal Syndrome
  • Bardet-Biedl Syndrome

Subcellular localization

basal body, centrosome, cilia

Functional category

  • Ciliary assembly/disassembly
  • Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
  • Actin & cytoskeleton regulation
  • T cell biology
  • 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).

Model organism evidence

Mus musculus (4 references)

Here, we identify robust cilia-tanycyte contacts; we term HUGS ( H ypothalamic, U nifying G lia-cilia S tructures) and discover that these connections are disrupted in a mouse ciliopathy model ( Bbs4 ) exhibiting hypothalamic dysfunction.

Primary cilia and BBS4 are required for postnatal pituitary development.

PMIDs: 41613416, 41512914, 40801568, 40791458

Danio rerio (1 reference)

Based on our previous in vitro results supporting the role of a novel Bbs4-cilia-Fstl1 axis in adipocyte differentiation, we evaluated the in vivo relevance of the zebrafish orthologous genes fstl1a and fstl1b in primary cilia and adipose tissue development.

PMIDs: 39644214