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Symbol WNT5A contributors: shn/ - updated : 27-01-2016
HGNC name wingless-type MMTV integration site family, member 5A
HGNC id 12784
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Nervousbrain   lowly
Reproductivefemale systemovary  moderately Homo sapiens
Skeletonappendicular skeleton     Homo sapiens
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectivedenseligamentperidontal ligamenthighly Homo sapiens
SystemCellPubmedSpeciesStageRna symbol
Reproductiveepithelial cell Homo sapiens
Skeletonosteoblast Homo sapiens
cell lineage
cell lines
physiological period fetal, neonatal, pregnancy
  • developing face, ventral area of midbrain and limbs
  • neonatal heart and lung
  • a hydrophobic signal sequence
  • 21 conserved cysteine residues
  • conjugated GlycoP
    interspecies homolog to Drosophila wingless (wg) segment polarity gene
    ortholog to Wnt5a, Mus musculus
    ortholog to Wnt5a, Rattus norvegicus
    ortholog to wnt5a, Danio rerio
  • WNT gene family
  • CATEGORY protooncogene , signaling
    basic FUNCTION
  • modulating cell fate and cell behavior during vertebrate development
  • regulates hematopoiesis by the antagonism of the canonical Wnt pathway, resulting in a pool of quiescent hematopoietic stem cells, and regulates hematopoietic stem cell function in a paracrine fashion through several distinct mechanisms including modulating canonical Wnt signaling
  • involved in control cell orientation, polarity, and directional movement in response to positional cues from chemokine gradients
  • have crucial roles in adipogenesis as positive regulator
  • acts in vivo to promote beta-catenin degradation in regulating mammalian limb development and possibly in suppressing tumor formation
  • acts through noncanonical Wnt signaling to promote angiogenesis
  • activating TMOD1, while gelsolin, known as an actin-severing protein, is down-regulated by WNT5A
  • promotes axon differentiation
  • critically involved in inflammatory macrophage signaling in sepsis and is a target for antiinflammatory mediators
  • Wnt5a-mediated non-canonical Wnt signalling regulated endothelial cell proliferation
  • role in regulation of ventral midbrain morphogenesis, dopaminergic progenitor cell division, and differentiation of NR4A2+ dopaminergic precursors
  • activates calpain-1, leading to the cleavage of filamin A, resulting in a remodeling of the cytoskeleton and an increase in melanoma cell motility
  • negatively regulates both proliferation and migration of dental papilla cells, suggesting its important role in odontogenesis via controlling the dental papilla cells
  • critical mediator of CXCL12-CXCR4 signaling and migration in human and murine T cells
  • enhances cardiac gene expressions of endothelial progenitor cells via an activation of PKC delta
  • a regulator of fibroblast proliferation and resistance to apoptosis
  • regulates skin epidermal differentiation
  • regulates signaling pathways by binding to FZD2
  • regulates the assembly and function of the excitatory postsynaptic region in the mature central nervous system
  • stimulates focal adhesion dynamics through DVL1 and APC
  • in addition to the planar cell polarity pathway, WNT5a has been shown to activate at least two other branches of the non-canonical Wnt pathway
  • antagonizes canonical WNT/CTNNB1 signaling and induces cellular senescence by activating the histone repressor A/promyelocytic leukemia senescence pathway
  • WNT5a/FZD2 signaling pathway contributed to increasing intracellular Ca˛&
  • 8314; in nerve cells under physiological and pathological conditions
  • WNT5A and WNT11 are essential regulators of the response of second heart field progenitors to WNT/CTNNB1 signaling and they act by restraining WNT/CTNNB1 signaling during cardiac development
  • WNT5A and ROR2 signaling are of substantial importance for BMP2-mediated osteoblastic differentiation
  • mediates CTNNB1–independent signaling and promotes Rho/Rac GTPase activity in specific cell types
  • stimulated bacterial internalization and restricted killing
  • may exert its stimulatory effects on macrophages through autocrine and/or paracrine modes upon binding to the FZD5 receptor
  • WNT5A and WNT11 regulate epithelial-mesenchymal transition (EMT) by inducing p38 (MAPK14) phosphorylation
  • CELLULAR PROCESS cell communication
    signaling signal transduction
  • WNT5A–FZD5 signaling in macrophages promotes phagocytosis through lipid raft clustering concomitant with RAC1–PI3 kinase–IKB kinase activation
  • WNT5A/ROR2 signaling appears to be involved in BMP2-mediated osteoblast differentiation in a Smad independent pathway
  • potentially part of the PRICKLE1/WNT5A/PCP signaling, regulating cell polarity and affecting expression of multiple factors to stunt limb growth through altered patterns of gene expression, including the PCP genes WNT5a and VANGL2
  • a component
    small molecule
  • frizzled homolog 1, FZD1 (Gazit et al, 1999)
  • receptor tyrosine kinase-like orphan receptor 2, ROR2
  • FZD2
  • ability of WNT5A–FZD5 signaling to stimulate phagocytosis of E. coli but not its killing makes it a likely mediator of uncontrolled inflammation or sepsis during infection
  • ROR2 binds to WNT5A directly through its Fz-like CRD and may serve as a co-receptor in WNT5A-induced signaling
  • WNT5A-ROR2 signaling might be required for expression of MMP13 gene during the development of the cartilaginous tissue
  • WNT5A potentiates PGC chemotaxis toward secreted KITLG by redistribution of ROR2 within the cell
  • WNT5A activates noncanonical WNT signaling through ROR2
  • WNT5A signaling is a substantial constituent for BMP2-mediated osteoblastic differentiation
  • CAMK2A is crucial for the regulation between NOTCH1 and WNT5A signaling
  • WNT5A inhibited the physical association between RBPJ and NCOR2 suggesting that WNT5A induced CAMK2A activation plays a critical role in the endogenous RBPJ-NCOR2 binding
  • FHL2 controls the osteogenic differentiation of mesenchymal stromal cells (MSC), bone formation and bone mass through modulation of WNT molecules, WNT10B, WNT3A, WNT5A
  • MCAM acting potentially as a functional WNT5A receptor in regulating cell migration and convergent extension, turning off the canonical Wnt signalling branch
  • monocyte-secreted WNT5A interacts with FZD5 in microvascular endothelial cells and induces angiogenesis through tissue factor signaling
  • WNT5A expressed in periodontal ligament (PDL) tissue plays specific roles in inducing collagen production by PDL cells through TGFB1-mediated upregulation of periostin expression
  • RNA helicase MOV10 plays a role in WNT5A synthesis and secretion
  • cell & other
    Other regulated by PAX2 and may be involved in blastemal predominant Wilms tumorigenesis (importance of PAX2 in the regulation of WNT5A)
    stimulated by CaSR in myofibroblasts
    corresponding disease(s) RBNS2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    aberrantly methylated from the early stages of colorectal cancers
    tumoral       loss of function
    inactivated by aberrant methylation in acute lymphoblastic leukaemia
    tumoral     --over  
    by hypomethylation in prostate cancer
    tumoral     --low  
    in epithelial ovarian cancer
    tumoral     --over  
    in melanoma and is thought to be a critical regulator of cell movement during metastasis
    Variant & Polymorphism
    Candidate gene
    Therapy target
    WNT5A-ROR2 signaling can be a target of cancer therapies to prevent cancer cells from undergoing invasion and metastasis
    by reconstituting WNT5A signaling may offer an effective new strategy for EOC therapy
  • Wnt5a-/- mice exhibit dwarfism, facial abnormalities, short limbs and tails, dysplasia of lungs and genitals, and ventricular septal defects
  • Wnt5a-/- mice display a defect in (mid)brain morphogenesis, including an impairment in midbrain elongation and a rounded ventricular cavity