Back to discover

Protein / target

Protein Wnt-5a

Encoded byWNT5AP41221Homo sapiensSwiss-Prot
UniProt: P41221Ensembl: ENSG00000114251HGNC: HGNC:12784NCBI Gene: 7474
Antibody-tractable
Druggability
UniProt loc high conf
1
Research papers

Protein at a glance

Biological role

Receptor tyrosine kinase-like orphan receptor binding

Strongest disease association

Nephrolithiasis

Via encoding gene WNT5A · Genetic evidence · score 0.62

Research activity

Emerging research

1 papers · latest 2023

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Ligand for members of the frizzled family of seven transmembrane receptors.

View complete UniProt function annotation

Ligand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-catenin signaling. In the presence of ROR2, inhibits the canonical Wnt pathway by promoting beta-catenin degradation through a GSK3-independent pathway which involves down-regulation of beta-catenin-induced reporter gene expression (By similarity). Suppression of the canonical pathway allows chondrogenesis to occur and inhibits tumor formation. Stimulates cell migration. Decreases proliferation, migration, invasiveness and clonogenicity of carcinoma cells and may act as a tumor suppressor (PubMed:15735754). Mediates motility of melanoma cells (PubMed:17426020). Required during embryogenesis for extension of the primary anterior-posterior axis and for outgrowth of limbs and the genital tubercle. Inhibits type II collagen expression in chondrocytes (By similarity)

Subcellular location

Secreted, extracellular space, extracellular matrixSecreted
Domains and Gene Ontology detail (110)

Gene Ontology

  • Ccell surface
  • Cclathrin-coated endocytic vesicle membrane
  • Cendocytic vesicle membrane
  • Cendoplasmic reticulum lumen
  • Cextracellular exosome
  • Cextracellular matrix
  • Cextracellular region
  • Cextracellular space
  • Cglutamatergic synapse
  • CGolgi lumen
  • Cplasma membrane
  • Cpostsynapse

380 aa · 42 kDa · 2 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell migrationUniProt · GOExcitatory neurotransmissionGOInhibitory neurotransmissionGOCell proliferation & survivalGOTranscriptional regulationUniProt · GOImmune signallingGO
View supporting evidence

Cell migration

  • ·Ligand for members of the frizzled family of seven transmembrane receptors. Can activate…
  • ·positive regulation of endothelial cell migration
  • ·positive regulation of T cell chemotaxis

Excitatory neurotransmission

  • ·glutamatergic synapse
  • ·excitatory synapse assembly

Inhibitory neurotransmission

  • ·inhibitory synapse assembly

Cell proliferation & survival

  • ·negative regulation of cell proliferation in midbrain

Transcriptional regulation

  • ·Ligand for members of the frizzled family of seven transmembrane receptors. Can activate…
  • ·negative regulation of DNA-templated transcription
  • ·positive regulation of DNA-templated transcription
  • ·positive regulation of gene expression

Immune signalling

  • ·cytokine activity
  • ·inflammatory response
  • ·negative regulation of fat cell differentiation
  • ·positive regulation of cytokine production involved in immune response

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene WNT5A

Gene-level evidence surfaced through the gene WNT5Athat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Nephrolithiasis
0.62Moderately supported

Genetic evidence dominant · Open Targets 0.37

Gram-Negative Bacterial Infections
0.53Moderately supported

Genetic evidence dominant · Open Targets 0.32

Liver Diseases
0.52Moderately supported

Genetic evidence dominant · Open Targets 0.32

Brain Neoplasms
0.45Limited support

Genetic evidence dominant · Open Targets 0.27

Ureterolithiasis
0.43Limited support

Genetic evidence dominant · Open Targets 0.26

View evidence synthesis (5)
NephrolithiasisModerately supported
0.62
agreement 0.50–0.74
Genetic100%

Open Targets aggregate 0.37 · 1 independent evidence family

Gram-Negative Bacterial InfectionsModerately supported
0.53
agreement 0.41–0.65
Genetic100%

Open Targets aggregate 0.32 · 1 independent evidence family

Liver DiseasesModerately supported
0.52
agreement 0.38–0.66
Genetic100%Literature0%

Open Targets aggregate 0.32 · 2 independent evidence families

Brain NeoplasmsLimited support
0.45
agreement 0.31–0.58
Genetic99%Literature1%

Open Targets aggregate 0.27 · 2 independent evidence families

UreterolithiasisLimited support
0.43
agreement 0.31–0.55
Genetic100%

Open Targets aggregate 0.26 · 1 independent evidence family

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Nephrolithiasis0.37
Gram-Negative Bacterial Infections0.32
Liver Diseases0.32
Brain Neoplasms0.27
Ureterolithiasis0.26

Tractability

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (4)
AB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database Ubiquitination

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 2023

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

ROR2 homodimerization is sufficient to activate a neuronal Wnt/calcium signaling pathway.8 cites

Riquelme R · The Journal of biological chemistry · 2023

Recent

ROR2 homodimerization is sufficient to activate a neuronal Wnt/calcium signaling pathway.

Riquelme R · The Journal of biological chemistry · 2023

Europe PMC papers linked directly to this protein.