TCTN3

Cilia effects upon perturbation of TCTN3

Cilia number / % ciliated:

Decreased cilia number

Ciliogenesis screen results (2 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-2.39) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, casTLE effect=-2.88) PMID:29459680

Phenotypes

Mouse phenotype:

abnormal body wall morphology, preweaning lethality, complete penetrance, abnormal embryo size, abnormal cholesterol homeostasis, decreased circulating total protein level, anophthalmia

Mouse ciliopathy phenotype:

polydactyly, abnormal lens morphology, decreased circulating calcium level

Human ciliopathy phenotype:

Joubert syndrome 18; Joubert syndrome with orofaciodigital defect; Joubert syndrome; Joubert syndrome and related disorders

Ciliopathy associations

• Joubert Syndrome
• Meckel-Gruber Syndrome
• Orofaciodigital Syndrome

Subcellular localization

basal body, cilia, lysosomes

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Ciliary membrane

Function

Form a complex with Tctn2, Mks1, Tmem216, Tmem67, Cep290, Cc2d2a, B9d1 and Tctn1 to regulate ciliogenesis and ciliary membrane composition (21725307). Mutations disrupts ciliogenesis and Hh sig ling (28800946) and are also the causes of Joubert syndrome (30286481). Regulator of Shh pathway. Role in selective trafficking of ciliary proteins to cilia, required for ciliogenesis (29725084). Role for GLI3 processing and function. Mutations cause severe orofaciodigital syndrome, Mohr-Majewski syndrome (22883145).

Model organism evidence