DKK3

dickkopf WNT signaling pathway inhibitor 3

Ensembl:
ENSG00000050165
UniProt:
Q9UBP4
OMIM:
605416
Synonyms:
CRRL, REIC, RIG

Cilia effects upon perturbation of DKK3

Ciliogenesis screen results (4 screens)

  • Wheway et al. 2015 (siRNA) [siRNA]: No effect PMID:26167766
  • Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
  • Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381
  • Elliott et al. 2025 (CRISPRa) [CRISPRa]: Disassembly Trigger (casTLE Effect=-2.57) PMID:41160700

Phenotypes

Mouse phenotype:
increased defecation amount; decreased mean corpuscular hemoglobin concentration; increased mean corpuscular volume; increased cellular hemoglobin content

Subcellular localization

cilia associated gene, cytosol, nuclear bodies, vesicles

Functional category

  • Signaling (Hedgehog, GPCRs, ion channels)

Function

DKK3, a secreted canonical Wnt regulator and WNT4, a noncanonical Wnt ligand act together to facilitate a canonical to noncanonical Wnt signaling switch during multiciliated cell formation. In primary human airway epithelial cells, DKK3 and WNT4 CRISPR knockout blocks, whereas ectopic expression promotes, multiciliated cell formation by inhibiting canonical Wnt signaling. Wnt4 and Dkk3 single-knockout mice also display defective ciliated cells. DKK3 and WNT4 are co-secreted from basal stem cells and act directly on multiciliated cells via KREMEN1 and FZD6, respectively(PMID: 37505110).

Model organism evidence

Mus musculus (1 reference)

A WNT4- and DKK3-driven canonical to noncanonical Wnt signaling switch controls multiciliogenesis.

PMIDs: 37505110