TTC21B

tetratricopeptide repeat domain 21B

Ensembl:
ENSG00000123607
UniProt:
Q7Z4L5
OMIM:
612014
Synonyms:
CFAP60, FAP60, FLA17, FLJ11457, IFT139

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

Subcellular localization

cilia, nucleus

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).

Model organism evidence

Mus musculus (3 references)

Here, we examine the role of Ttc21b, a component of the intraflagellar transport-A complex, during mouse forebrain development by using a Ttc21balien null allele.

Here, using mouse fibroblast cells, we investigated the function of IFT139 (Thm1, TTC21B) in Hedgehog signaling, cilia structure, and ciliary protein localization, as well as the effect of the P209L ciliopathy mutation on cell proliferation and Hedgehog signaling.

PMIDs: 41384431, 41099179, 39868177