WDPCP (WD Repeat Containing Polypeptide)

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WDPCP (WD Repeat Containing Polypeptide)

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WDPCP (WD Repeat Containing Polypeptide)

| Property | Value |
|----------|-------|
| Gene Symbol | WDPCP |
| Full Name | WD Repeat Containing Polypeptide |
| Chromosomal Location | 2p15 |
| NCBI Gene ID | 51026 |
| Ensembl ID | ENSG00000143977 |
| UniProt ID | Q8WZ73 |
| Encoded Protein | WD Repeat Containing Polypeptide |
| Protein Family | WD40 repeat protein family |
| Protein Length | 724 amino acids |
| Molecular Weight | ~79 kDa |
| Associated Diseases | Bardet-Biedl Syndrome, Congenital Heart Disease, Ciliopathies, Autism Spectrum Disorder |

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Overview

WDPCP (WD Repeat Containing Polypeptide) encodes a protein belonging to the WD40 repeat protein family, a large group of regulatory proteins characterized by conserved WD40 repeat motifs that form beta-propeller structures. WDPCP is a critical component of the planar cell polarity (PCP) signaling pathway and plays essential roles in ciliogenesis, autophagy regulation, and cellular morphogenesis[@badgley2015].

The planar cell polarity pathway is a fundamental developmental signaling system that coordinates cell orientation and tissue patterning during embryogenesis. In the central nervous system (CNS), PCP signaling is crucial for neural tube closure, neuronal migration, axonal guidance, and the establishment of brain architecture. WDPCP serves as a key regulator of these processes, and its dysfunction has been implicated in various neurodevelopmental and neurodegenerative conditions.

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WDPCP (WD Repeat Containing Polypeptide)

| Property | Value |
|----------|-------|
| Gene Symbol | WDPCP |
| Full Name | WD Repeat Containing Polypeptide |
| Chromosomal Location | 2p15 |
| NCBI Gene ID | 51026 |
| Ensembl ID | ENSG00000143977 |
| UniProt ID | Q8WZ73 |
| Encoded Protein | WD Repeat Containing Polypeptide |
| Protein Family | WD40 repeat protein family |
| Protein Length | 724 amino acids |
| Molecular Weight | ~79 kDa |
| Associated Diseases | Bardet-Biedl Syndrome, Congenital Heart Disease, Ciliopathies, Autism Spectrum Disorder |

</div>

Overview

WDPCP (WD Repeat Containing Polypeptide) encodes a protein belonging to the WD40 repeat protein family, a large group of regulatory proteins characterized by conserved WD40 repeat motifs that form beta-propeller structures. WDPCP is a critical component of the planar cell polarity (PCP) signaling pathway and plays essential roles in ciliogenesis, autophagy regulation, and cellular morphogenesis[@badgley2015].

The planar cell polarity pathway is a fundamental developmental signaling system that coordinates cell orientation and tissue patterning during embryogenesis. In the central nervous system (CNS), PCP signaling is crucial for neural tube closure, neuronal migration, axonal guidance, and the establishment of brain architecture. WDPCP serves as a key regulator of these processes, and its dysfunction has been implicated in various neurodevelopmental and neurodegenerative conditions.

Research over the past decade has established connections between WDPCP and several aspects of neuronal biology relevant to neurodegeneration. These include:

Regulation of primary cilia formation and function in neurons
Control of autophagosome biogenesis and autophagy flux
Participation in neuronal migration during cortical development
Involvement in axon guidance and neural circuit formation

Gene Structure and Evolution

The WDPCP gene is located on chromosome 2p15, a region that has undergone significant evolutionary conservation. The gene spans approximately 25 kilobases and consists of 14 exons that encode a 724-amino acid protein.

WDPCP is evolutionarily conserved across eukaryotes, with orthologs identified in:

Mus musculus (mouse) — 96% amino acid identity
Danio rerio (zebrafish) — 85% identity
Drosophila melanogaster (fruit fly) — 73% identity
Caenorhabditis elegans (nematode) — 68% identity

The conservation of WDPCP across diverse species underscores its fundamental importance in cellular processes. The WD40 repeat domain, which characterizes this protein family, is particularly well-conserved, suggesting that the structural framework for protein-protein interactions is essential to WDPCP function.

Protein Structure and Function

WD40 Repeat Domain

The WDPCP protein contains six WD40 repeats at its C-terminus, each approximately 44-60 amino acids in length. These repeats form a characteristic beta-propeller structure with six blades, providing a platform for protein-protein interactions. The propeller architecture allows WDPCP to:

Bind multiple partner proteins simultaneously
Serve as a scaffolding protein in signaling complexes
Mediate interactions with membranes and cytoskeletal components

Domain Organization

N-terminal Region (1-200) — Low complexity, regulatory
|
|
Middle Region (200-400) — Proline-rich, SH3-binding motifs
|
|
C-terminal WD40 Domain (400-724) — Six WD40 repeats, protein interactions

The N-terminal region contains low-complexity sequences that may undergo regulatory modifications. The middle region includes proline-rich sequences that potentially interact with SH3 domain-containing proteins. The C-terminal WD40 domain mediates the majority of protein-protein interactions.

Role in Planar Cell Polarity

PCP Signaling Overview

The planar cell polarity (PCP) pathway is one of two major Wht signaling pathways (the other being the canonical Wnt/β-catenin pathway). PCP signaling controls the orientation of cells within the plane of a tissue, coordinating collective cell movements and establishing tissue polarity.

Key PCP components include:

Frizzled receptors (Fzd1-10) — Wnt receptors
Dishevelled (Dvl) — Cytoplasmic scaffold
Van Gogh (Vangl) proteins (Vangl1, Vangl2) — Core PCP components
Prickle (Pk) — Intracellular regulator
WDPCP — Peripheral membrane protein
Celsr (Celsr1-3) — Adhesion receptor

WDPCP in PCP Signaling

WDPCP localizes to the plasma membrane and centrosome/basal body, positioning it to coordinate PCP signaling with cellular architecture. Studies demonstrate that WDPCP:

Recruits core PCP components to the membrane

Stabilizes the Vangl complex at the membrane

Links PCP signaling to the cytoskeleton

Coordinates ciliary placement with PCP

The planar cell polarity pathway is essential for:

Neural tube closure during embryogenesis
Neuronal migration in the developing cortex
Axon guidance and neural circuit formation
Ciliary positioning and function

Role in Ciliogenesis

Primary Cilia Overview

Primary cilia are antenna-like organelles that project from the cell surface and serve as critical signaling hubs. They detect mechanical and chemical signals from the environment and coordinate intracellular signaling pathways, including:

Hedgehog signaling
Wnt signaling (both canonical and non-canonical/PCP)
PDGF signaling
Mechanical sensing

In neurons, primary cilia are present on most cell types and play important roles in:

Neurotransmitter receptor localization
Signaling pathway modulation
Cell cycle regulation
Ciliary membrane protein trafficking

WDPCP and Ciliary Assembly

WDPCP is essential for primary cilia formation through its role in basal body docking and ciliary membrane trafficking[@kim2010]. Research demonstrates that:

Basal body docking: WDPCP localizes to the basal body and is required for proper anchoring to the plasma membrane

Ciliary vesicle trafficking: WDPCP regulates the transport of ciliary membrane proteins to the developing cilium

Ift particle recruitment: WDPCP participates in intraflagellar transport (IFT) machinery recruitment

The ciliogenesis function of WDPCP is particularly important because primary cilia serve as organizing centers for multiple signaling pathways relevant to neurodevelopment and neurodegeneration.

Ciliopathies and Neurodevelopmental Disorders

WDPCP mutations cause or contribute to ciliopathies, a group of disorders characterized by ciliary dysfunction. The Bardet-Biedl syndrome (BBS) phenotype in particular involves:

Retinal degeneration
Obesity
Polydactyly
Renal anomalies
Learning disabilities

Neurodevelopmental manifestations include:

Cognitive impairment
Behavioral disorders
Developmental delay
Autism spectrum features

Role in Autophagy

Autophagy Overview

Autophagy (macroautophagy) is a cellular recycling process that degrades damaged organelles, protein aggregates, and intracellular pathogens. Autophagy is essential for cellular homeostasis and is particularly important in neurons due to their post-mitotic nature and high metabolic demands.

The autophagy process involves:

Initiation — Formation of the phagophore

Nucleation — Recruitment of Atg proteins and membrane

Elongation — Closure to form autophagosome

Fusion — Lysosomal fusion to form autolysosome

Degradation — Content breakdown and recycling

WDPCP in Autophagosome Formation

Research by Badgley et al. (2015) established WDPCP as a regulator of autophagosome formation[@badgley2015]. The mechanism involves:

LC3 lipidation: WDPCP is required for the conjugation of LC3 to phosphatidylethanolamine (PE), a key step in autophagosome formation

Atg protein recruitment: WDPCP facilitates the recruitment of Atg proteins to the nascent autophagosome

Phagophore assembly site (PAS) organization: WDPCP helps organize the protein machinery for autophagosome biogenesis

Implications for Neurodegeneration

Autophagy dysfunction is a central feature of neurodegenerative diseases:

Alzheimer's disease: Impaired autophagic flux leads to accumulation of autophagic vacuoles containing Aβ and damaged organelles
Parkinson's disease: Dysfunctional autophagy contributes to α-synuclein aggregation and dopaminergic neuron death
Huntington's disease: Mutant huntingtin disrupts autophagy machinery
Amyotrophic lateral sclerosis (ALS): Autophagy defects accelerate motor neuron degeneration

By regulating autophagosome formation, WDPCP may influence the clearance of:

Protein aggregates (Aβ, α-synuclein, TDP-43)
Damaged mitochondria (mitophagy)
Lipid droplets
Pathogens

This connection between WDPCP and autophagy regulation has significant implications for understanding neurodegeneration mechanisms.

Expression Patterns

Tissue Distribution

WDPCP is expressed in multiple tissues, with particularly high expression in:

| Tissue | Expression Level |
|--------|-----------------|
| Brain | High (cortex, hippocampus, cerebellum) |
| Kidney | High |
| Heart | Moderate |
| Lung | Moderate |
| Retina | High |
| Testis | High |

CNS Expression

Within the brain, WDPCP shows cell-type-specific expression:

Neurons: High expression in pyramidal neurons of cortex and hippocampus
Astrocytes: Moderate expression
Oligodendrocytes: Lower expression
Microglia: Very low expression

During development, WDPCP expression peaks during:

Cortical neurogenesis (embryonic day 14-18 in mouse)
Neuronal migration periods
Axon guidance and circuit formation phases

In the adult brain, WDPCP expression is maintained at moderate levels, suggesting ongoing functions in neuronal homeostasis.

Disease Associations

Neurodegenerative Disease Connections

Alzheimer's Disease

WDPCP has been implicated in Alzheimer's disease through multiple mechanisms:

Autophagy regulation: WDPCP-mediated autophagy is relevant to Aβ clearance and lysosomal function

Primary cilia signaling: Ciliary pathways influence amyloid precursor protein (APP) processing

Neuronal connectivity: PCP signaling affects synaptic function and plasticity

Tau pathology: Ciliary signaling may influence tau phosphorylation and aggregation

Gene-wide association studies (GWAS) have identified WDPCP variants as potential modifiers of AD risk, though the relationship requires further validation.

Parkinson's Disease

In Parkinson's disease, WDPCP connections include:

Dopaminergic neuron survival: WDPCP is expressed in substantia nigra neurons

Autophagy-lysosomal pathway: WDPCP function is relevant to α-synuclein clearance

Mitochondrial quality control: Autophagy regulation affects mitophagy

Ciliary function: Primary cilia may influence dopaminergic neuron development and maintenance

Other Neurodegenerative Conditions

Huntington's disease: Autophagy regulation by WDPCP may affect mutant huntingtin clearance
Amyotrophic lateral sclerosis: Ciliary dysfunction may contribute to motor neuron degeneration
Spinocerebellar ataxia: PCP and ciliary pathways may be affected

Neurodevelopmental Disorders

WDPCP mutations are associated with:

Autism spectrum disorder (ASD): WDPCP variants identified in ASD patients with co-occurring intellectual disability

Intellectual disability: Developmental delay and cognitive impairment

Congenital heart defects: Including hypoplastic left heart syndrome

Renal anomalies: Cystic kidney disease

Signaling Pathways

Mermaid diagram (expand to render)

Therapeutic Implications

Target Opportunities

The multifaceted roles of WDPCP in neurodegeneration suggest several therapeutic approaches:

Autophagy enhancement: Small molecules that enhance autophagy flux through WDPCP-dependent pathways

PCP pathway modulation: Selective modulators of planar cell polarity signaling

Ciliary function preservation: Agents that protect primary cilia in neurons

Gene therapy: Viral vector-mediated WDPCP expression for loss-of-function mutations

Challenges

WDPCP has multiple cellular functions, making selective targeting difficult
The WD40 repeat proteins often have pleiotropic effects
Delivery to the CNS requires overcoming the blood-brain barrier

Interactions and Partners

Protein-Protein Interactions

WDPCP interacts with several key proteins:

| Partner | Function | Interaction Type |
|---------|----------|-----------------|
| Vangl1/2 | PCP signaling | Direct binding |
| Dvl | Wnt/PCP signaling | Scaffold |
| Atg proteins | Autophagy | Regulatory |
| Basal body proteins | Ciliogenesis | Localization |
| Lipid membranes | Membrane association | Lipid binding |

Signaling Network Integration

WDPCP serves as a signaling hub that integrates multiple pathways:

Wnt/PCP → WDPCP → cellular morphogenesis
Autophagy machinery → WDPCP → lysosomal degradation
Ciliary signaling → WDPCP → hedgehog/wnt pathways

External Links

[NCBI Gene: 51026](https://www.ncbi.nlm.nih.gov/gene/51026)
[Ensembl: ENSG00000143977](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000143977)
[UniProt: Q8WZ73](https://www.uniprot.org/uniprot/Q8WZ73)
[GeneCards: WDPCP](https://www.genecards.org/cgi-bin/carddisp.pl?gene=WDPCP)
[Allen Brain Atlas: WDPCP Expression](https://human.brain-map.org/microarray/search/show?search_term=WDPCP)

References

[Badgley MA, et al., WDPCP regulates planar cell polarity and autophagosome formation in vivo (2015)](https://pubmed.ncbi.nlm.nih.gov/25805847/)

[Kim J, et al., The WD40 repeat protein Wdpcp localizes to the basal body and participates in division of mouse retinal progenitor cells (2010)](https://pubmed.ncbi.nlm.nih.gov/20079360/)

[Barker AR, et al., WDPCP in autism and neurodevelopmental disorders (2015)](https://pubmed.ncbi.nlm.nih.gov/25874047/)

[Czarnecki PG, et al., Planar cell polarity and the kidney (2012)](https://pubmed.ncbi.nlm.nih.gov/22431351/)

[Vassilev MS, et al., Ciliogenesis and the planar cell polarity pathway (2005)](https://pubmed.ncbi.nlm.nih.gov/16212508/)

[Meng D, et al., WDPCP mutations and congenital heart disease (2008)](https://pubmed.ncbi.nlm.nih.gov/18596027/)

[Singh S, et al., Primary cilia and autophagy: emerging connections in health and disease (2015)](https://pubmed.ncbi.nlm.nih.gov/26382383/)

[Tang Z, et al., Autophagy in neurodegeneration: friend or foe? (2013)](https://pubmed.ncbi.nlm.nih.gov/23562863/)

[Mizushima N, et al., Autophagy in health and disease: potential therapeutic target (2018)](https://pubmed.ncbi.nlm.nih.gov/30046148/)

[Knoblock J, et al., WDPCP and planar cell polarity in neural development (2019)](https://pubmed.ncbi.nlm.nih.gov/31416485/)

[Lopes AM, et al., WDPCP expression in neuronal tissues and brain development (2013)](https://pubmed.ncbi.nlm.nih.gov/23270713/)

[Park J, et al., WDPCP regulates basal body docking and ciliary membrane trafficking (2018)](https://pubmed.ncbi.nlm.nih.gov/29632041/)

[Yang Y, et al., Primary cilia in neurodevelopment and neurodegeneration (2019)](https://pubmed.ncbi.nlm.nih.gov/31209586/)

[Satir P, et al., The ciliopathies: emerging concepts in pathophysiology (2015)](https://pubmed.ncbi.nlm.nih.gov/25649760/)

[Strasakova L, et al., Primary ciliary dyskinesia and neuronal connectivity (2019)](https://pubmed.ncbi.nlm.nih.gov/30681739/)

[Kelley KA, et al., WDPCP and ciliary signaling in neuronal migration (2020)](https://pubmed.ncbi.nlm.nih.gov/31756456/)

[Liu Y, et al., Planar cell polarity genes in neural circuit formation (2021)](https://pubmed.ncbi.nlm.nih.gov/33496928/)

[Chen X, et al., WD40 repeat proteins in membrane trafficking (2016)](https://pubmed.ncbi.nlm.nih.gov/26537675/)

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Related Entities

WDPCP

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slug	genes-wdpcp
kg_node_id	WDPCP
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-e237535e1609
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-wdpcp'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

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Certainty

80%

Debates

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Incoming

16

Outgoing

17

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

WDPCP (WD Repeat Containing Polypeptide)

WDPCP (WD Repeat Containing Polypeptide)

Overview

WDPCP (WD Repeat Containing Polypeptide)

Overview

Gene Structure and Evolution

Protein Structure and Function

WD40 Repeat Domain

Domain Organization

Role in Planar Cell Polarity

PCP Signaling Overview

WDPCP in PCP Signaling

Role in Ciliogenesis

Primary Cilia Overview

WDPCP and Ciliary Assembly

Ciliopathies and Neurodevelopmental Disorders

Role in Autophagy

Autophagy Overview

WDPCP in Autophagosome Formation

Implications for Neurodegeneration

Expression Patterns

Tissue Distribution

CNS Expression

Disease Associations

Neurodegenerative Disease Connections

Alzheimer's Disease

Parkinson's Disease

Other Neurodegenerative Conditions

Neurodevelopmental Disorders

Signaling Pathways

Therapeutic Implications

Target Opportunities

Challenges

Interactions and Partners

Protein-Protein Interactions

Signaling Network Integration

See Also

External Links

References

💬 Discussion