TTC21B

Cilia effects upon perturbation of TTC21B

Loss-of-function effect:

Shorter cilia

Ciliogenesis screen results (2 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-8.81) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, casTLE effect=-3.68) PMID:29459680

Phenotypes

Human ciliopathy phenotype:

nephronophthisis; Nephronophthisis; Infantile nephronophthisis

Ciliopathy associations

• Bardet-Biedl Syndrome
• Bilateral Polycystic Kidney Disease
• Cranioectodermal Dysplasia (Sensenbrenner)
• Joubert Syndrome
• Nephronophthisis
• Short-Rib Thoracic Dysplasia
• Skeletal Ciliopathy

References: PMID:21258341, PMID:25492405, PMID:35112343, PMID:32238723, PMID:33599192, PMID:38671463, PMID:36273201, PMID:33517396, PMID:27515926, PMID:33875766, PMID:22791528, PMID:33547761

Subcellular localization

cilia, nucleus, ciliary tip, basal body

References: PMID:41410385, PMID:41005307, PMID:24876116, PMID:21258341, PMID:29615573

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Actin & cytoskeleton regulation
• Signaling (Hedgehog, GPCRs, ion channels)

Function

Encodes a retrograde intraflagellar transport-A complex, associates with the motor protein dynein2 to regulate retrograde trafficking in the primary cilium. Knockdown induces microtubule anchoring defects (24876116). Mutated in nephronophthisis, syndromic Jeune Asphyxiating Thoracic Dystrophy (21258341), Focal Segmental glomerulosclerosis (24876116) and Joubert Syndrome (29615573).