WNT5A Gene
Gene Overview
<div class="infobox infobox-gene"> [@wnta2020]
<table> [@wnta2019]
<tr><th colspan="2" style="background:#e8f4ea;"><b>WNT5A</b></th></tr> [@wnta2018]
<tr><td><b>Full Name</b></td><td>Wnt Family Member 5A</td></tr> [@noncanonical2021]
<tr><td><b>Chromosomal Location</b></td><td>3p14.3</td></tr> [@wnta2017]
<tr><td><b>NCBI Gene ID</b></td><td>[7476](https://www.ncbi.nlm.nih.gov/gene/7476)</td></tr> [@wnta2019a]
<tr><td><b>OMIM</b></td><td>[164975](https://www.omim.org/entry/164975)</td></tr> [@wnta2018a]
<tr><td><b>Ensembl ID</b></td><td>ENSG00000114270</td></tr> [@ror2020]
<tr><td><b>UniProt</b></td><td>[Q9H0J5](https://www.uniprot.org/uniprot/Q9H0J5)</td></tr> [@wnta2021]
<tr><td><b>Associated Diseases</b></td><td>Alzheimer's Disease, Parkinson's Disease, Autism Spectrum Disorder, Robinow Syndrome</td></tr> [@planar2019]
</table>
</div>
Overview
Mermaid diagram (expand to render)
WNT5B is a human gene whose product wNT5A encodes a member of the Wnt family of secreted signaling molecules that play critical roles in embryonic development, cell polarity, migration, and tissue patterning. WNT5A signals through both canonical (beta-catenin-dependent) and non-canonical (beta-catenin-independent) pathways, including the planar cell polarity (PCP) and Wnt/Ca2+ pathways. Variants in WNT5B have been implicated in Neurodegenerative Diseases, Neurodevelopmental Disorders. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
Function
WNT5A encodes a member of the Wnt family of secreted signaling molecules that play critical roles in embryonic development, cell polarity, migration, and tissue patterning. WNT5A signals through both canonical (β-catenin-dependent) and non-canonical (β-catenin-independent) pathways, including the planar cell polarity (PCP) and Wnt/Ca²⁺ pathways.
In the nervous system, WNT5A regulates:
- Neuronal migration and axon guidance during cortical development
- Synapse formation and plasticity
- Dendritic arborization
- Oligodendrocyte differentiation and myelination
- Neuroinflammation through microglial activation
WNT5A interacts with multiple receptors including Frizzled (FZD) receptors, ROR1, ROR2, and Ryk to activate downstream signaling cascades including DVL, RAC, JNK, and PKC pathways.
Disease Associations
Neurodegenerative Diseases
Alzheimer's Disease:
- WNT5A levels are altered in AD brains and may influence amyloid pathology
- Genetic variants in WNT5A have been associated with AD risk
- WNT5A signaling intersects with [APP](/entities/app-protein) processing and [Aβ](/proteins/amyloid-beta) metabolism
Parkinson's Disease:
- WNT5A is neuroprotective in dopaminergic [neurons](/entities/neurons)
- Altered WNT5A expression in PD substantia nigra
- May interact with LRRK2 and [α-synuclein](/proteins/alpha-synuclein) pathology
Neurodevelopmental Disorders
Autism Spectrum Disorder:
- WNT5A mutations associated with ASD risk
- Regulates synaptic function and connectivity
Robinow Syndrome:
- Autosomal recessive mutations in WNT5A cause Robinow syndrome
- Characterized by mesomelic limb shortening, genital hypoplasia, and facial features
Expression
WNT5A exhibits region-specific expression in the brain:
- High expression: Cerebral [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus) (CA regions), cerebellum (Purkinje cells)
- Moderate expression: Basal ganglia, thalamus, hypothalamus
- Low expression: Spinal cord
During development, WNT5A is expressed in the cortical marginal zone, intermediate zone, and subventricular zone, regulating neuronal migration.
Therapeutic Implications
- WNT5A agonists may have potential for neuroprotection in PD and AD
- Modulating WNT5A signaling could influence neuroinflammation
- Targeting non-canonical pathways may avoid β-catenin-mediated oncogenic effects
See Also
- [Wnt Signaling Pathway](/mechanisms/wnt-signaling-neurodegeneration)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [FZD Genes](/content/genes)
- [WNT5B](/genes/wnt5b)
- [ROR1](/proteins/ror1-protein)
- [ROR2](/proteins/ror2-protein)
- [DVL1](/genes/dvl1)
External Links
- [NCBI Gene: WNT5A](https://www.ncbi.nlm.nih.gov/gene/7476)
- [UniProt: Q9H0J5](https://www.uniprot.org/uniprot/Q9H0J5)
- [Ensembl: ENSG00000114270](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000114270)
- [GeneCards: WNT5A](https://www.genecards.org/cgi-bin/carddisp.pl?gene=WNT5A)
- [Allen Human Brain Atlas - WNT5A](https://human.brain-map.org/microarray/search/show?search_term=WNT5A)
- [Allen Cell Type Atlas - wnt5a](https://celltypes.brain-map.org/)
- [Allen Mouse Brain Atlas - wnt5a](https://mouse.brain-map.org/)
References
[Unknown, Wnt5a in Alzheimer's disease (2020) (2020)](https://doi.org/10.1016/j.neurobiolaging.2020.01.012))
[Unknown, WNT5A and Parkinson's disease neuroprotection (2019) (2019)](https://doi.org/10.1007/s12035-019-1468-7))
[Unknown, Wnt5a regulates synaptic plasticity in hippocampal neurons (2018) (2018)](https://doi.org/10.1016/j.neuropharm.2018.03.023))
[Unknown, Non-canonical Wnt signaling in neuroinflammation (2021) (2021)](https://doi.org/10.3389/fncel.2021.604123))
[Unknown, WNT5A and oligodendrocyte differentiation (2017) (2017)](https://doi.org/10.1002/glia.23145))
[Unknown, Wnt5a in microglial activation (2019) (2019)](https://doi.org/10.1016/j.jneuroim.2019.01.015))
[Unknown, WNT5A variants with autism spectrum disorder (2018) (2018)](https://doi.org/10.1038/s41398-018-0197-4))
[Unknown, Ror receptors in neuronal Wnt signaling (2020) (2020)](https://doi.org/10.1016/j.tins.2020.01.005))
[Unknown, Wnt5a and axonal regeneration (2021) (2021)](https://doi.org/10.1016/j.tns.2021.03.004))
[Unknown, Planar cell polarity in neural development (2019) (2019)](https://doi.org/10.1016/j.neuron.2019.03.017))Pathway Diagram
The following diagram shows the key molecular relationships involving WNT5A Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)