TUBB4B

Cilia effects upon perturbation of TUBB4B

Cilia number / % ciliated:

Decrease

Loss-of-function effect:

Decrease

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-4.56) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Pusapati et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, neg_rank=567, lfc=-2.08) PMID:30270045

Phenotypes

Mouse phenotype:

abnormal coat/ hair morphology, abnormal coat appearance, preweaning lethality, incomplete penetrance

Human ciliopathy phenotype:

Primary ciliary dyskinesia (12 patients), Leber congenital amaurosis; dominant-negative tubulinopathy affecting axonemal microtubules

Ciliopathy associations

• Leber Congenital Amaurosis
• Primary Ciliary Dyskinesia

Subcellular localization

basal body, cilia, cytosol, nucleus

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Actin & cytoskeleton regulation
• T cell biology
• Reproduction & sperm
• Viral interactions
• Protein processing & maturation
• Cell migration & adhesion
• Signaling (Hedgehog, GPCRs, ion channels)

Function

Beta tubulin isoform. Component of the cytoskeleton, centrosomes and protofilaments, structures that associate laterally to form a microtubule. Mutations in TUBB4B Cause a Distinctive Sensorineural Disease of LCA with hearing loss TUBB4B variants cause PCD (12 patients) and LCA in dominant-negative manner. Distinct variants differentially affect microtubule dynamics and cilia formation, stratifying patients into 3 classes of ciliopathic disease. TUBB4B is a distinct tubulin isotype with organelle-specific function in axonemal microtubules (PMID:38662826).

Model organism evidence