IFT74

intraflagellar transport 74

Ensembl:
ENSG00000096872
UniProt:
Q96LB3
OMIM:
608040
Synonyms:
CCDC2, CMG-1, CMG1, FLJ22621

Cilia effects upon perturbation of IFT74

Cilia number / % ciliated:
Decreased cilia number
Loss-of-function effect:
Shorter cilia
Overexpression effect:
No effect

Ciliogenesis screen results (3 screens)

  • Wheway et al. 2015 (siRNA) [siRNA]: No effect PMID:26167766
  • Breslow et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, casTLE effect=-2.5) PMID:29459680
  • Pusapati et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, neg_rank=828, lfc=-2.08) PMID:30270045

Phenotypes

Mouse phenotype:
increased startle reflex, limb grasping
Mouse ciliopathy phenotype:
male infertility
Human ciliopathy phenotype:
Joubert syndrome 40; Bardet-Biedl syndrome 22

Ciliopathy associations

  • Bardet-Biedl Syndrome
  • Joubert Syndrome
  • Male Infertility
  • Mucociliary Clearance Disorder
  • Skeletal Ciliopathy

Subcellular localization

basal body, centrosome, cilia, nucleus

Functional category

  • Ciliary assembly/disassembly
  • Actin & cytoskeleton regulation
  • Reproduction & sperm
  • Cell migration & adhesion

Function

Component of IFT complex B. Interacts with IFT81 to stabilise IFT-B complex. This interaction is required for binding and transport of tubulin to regulate cilium length, required for ciliogenesis (23990561). Essential for normal mouse spermatogenesis and sperm flagella formation by transporting cargo proteins and modulating axoneme and microtubule assembly (31004481).

Model organism evidence

Mus musculus (2 references)

This activation controls CDKL5 localization in steady-state cilia, down-regulates its IFT-mediated transport as flagella reach steady-state, controls ciliary abundance of IFT proteins, and controls phosphorylation of the tubulin-binding domain of IFT74, thereby influencing flagellar length.

IFT74 variants cause skeletal ciliopathy and motile cilia defects in mice and humans.

PMIDs: 41385589, 37315079