TMEM67

Cilia effects upon perturbation of TMEM67

Cilia number / % ciliated:

Incrased cilia number

Loss-of-function effect:

Longer cilia

Overexpression effect:

Unknown

Ciliogenesis screen results (2 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: No effect PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, casTLE effect=-1.01) PMID:29459680

Phenotypes

Mouse phenotype:

preweaning lethality, complete penetrance, increased exploration in new environment, increased grip strength

Human ciliopathy phenotype:

Joubert syndrome with hepatic defect; nephronophthisis 11; Meckel syndrome, type 3; Joubert syndrome 6; Meckel syndrome; Joubert syndrome; Bardet-Biedl syndrome 14; Nephronophthisis; nephronophthisis; Joubert syndrome and related disorders

Ciliopathy associations

• Autosomal Recessive Polycystic Kidney Disease
• Bardet-Biedl Syndrome
• COACH Syndrome
• Joubert Syndrome
• Meckel-Gruber Syndrome
• Nephronophthisis
• RHYNS Syndrome

References: PMID:16415887, PMID:19574260, PMID:17160906, PMID:17377820, PMID:9375913, PMID:18327255, PMID:2929661, PMID:19508969, PMID:19058225, PMID:28860541, PMID:23456819

Subcellular localization

basal body, centrosome, cilia, lysosomes

References: PMID:26035863, PMID:22247471, PMID:23393159, PMID:19515853, PMID:21422230

Functional category

• Ciliary assembly/disassembly
• Actin & cytoskeleton regulation
• Signaling (Hedgehog, GPCRs, ion channels)
• Ciliary membrane
• Transition zone
• Cilia length regulation

Function

Also known as Meckelin or MKS3. Component of the MKS-JBTS module at the transition zone. Essential for phosphorylation of the non- canonical Wnt receptor ROR2. Negative regulator of Shh signalling. Required for centriolar migration to the apical membrane during cell polarisation, regulation of actin cytoskeleton remodelling and RhoA activity (26035863). Required for the elongation and maintenance of the outer segments in retina. It may play a role in photoreceptor intraciliary transport (22247471). Mutations are a major cause of MKS, JBTS and NPHP (23393159). MKS function is required for ciliary structure and function, plays a role in regulating cilia length and number through modulating centrosome duplication (19515853). In complex with other TZ proteins, it contributes to an early ciliogenic event and establish basal body/TZ membrane attachments (21422230).