WDR45B — WD Repeat Domain 45B

WDR45B — WD Repeat Domain 45B

Introduction

WDR45B is a WD repeat protein that plays a critical role in autophagy, specifically in the formation and function of autophagosomes. It is associated with Neurodegeneration with Brain Iron Accumulation (NBIA), particularly the SENDA (Static Encephalopathy of Childhood with Neurodegeneration in Adulthood) subtype. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene">
<table>
<tr><th>Gene Symbol</th><td>WDR45B</td></tr>
<tr><th>Full Name</th><td>WD Repeat Domain 45B</td></tr>
<tr><th>Chromosomal Location</th><td>16q22.1</td></tr>
<tr><th>NCBI Gene ID</th><td>[340527](https://www.ncbi.nlm.nih.gov/gene/340527)</td></tr>
<tr><th>OMIM ID</th><td>[614296](https://www.omim.org/entry/614296)</td></tr>
<tr><th>Ensembl ID</th><td>[ENSG00000160087](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000160087)</td></tr>
<tr><th>UniProt ID</th><td>[Q3C1V7](https://www.uniprot.org/uniprot/Q3C1V7)</td></tr>
<tr><th>Protein Family</th><td>WD repeat protein family</td></tr>
<tr><th>Associated Diseases</th><td>Neurodegeneration with Brain Iron Accumulation (NBIA), SENDA Syndrome, Intellectual Disability</td></tr>
</table>
</div>

Overview

WDR45B is a member of the WD repeat protein family, characterized by WD repeat motifs that form a beta-propeller structure. These proteins often serve as scaffolds for protein-protein interactions and are involved in various cellular processes [@saitsu2013][@bento2016].

WDR45B — WD Repeat Domain 45B

Introduction

WDR45B is a WD repeat protein that plays a critical role in autophagy, specifically in the formation and function of autophagosomes. It is associated with Neurodegeneration with Brain Iron Accumulation (NBIA), particularly the SENDA (Static Encephalopathy of Childhood with Neurodegeneration in Adulthood) subtype. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene">
<table>
<tr><th>Gene Symbol</th><td>WDR45B</td></tr>
<tr><th>Full Name</th><td>WD Repeat Domain 45B</td></tr>
<tr><th>Chromosomal Location</th><td>16q22.1</td></tr>
<tr><th>NCBI Gene ID</th><td>[340527](https://www.ncbi.nlm.nih.gov/gene/340527)</td></tr>
<tr><th>OMIM ID</th><td>[614296](https://www.omim.org/entry/614296)</td></tr>
<tr><th>Ensembl ID</th><td>[ENSG00000160087](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000160087)</td></tr>
<tr><th>UniProt ID</th><td>[Q3C1V7](https://www.uniprot.org/uniprot/Q3C1V7)</td></tr>
<tr><th>Protein Family</th><td>WD repeat protein family</td></tr>
<tr><th>Associated Diseases</th><td>Neurodegeneration with Brain Iron Accumulation (NBIA), SENDA Syndrome, Intellectual Disability</td></tr>
</table>
</div>

Overview

WDR45B is a member of the WD repeat protein family, characterized by WD repeat motifs that form a beta-propeller structure. These proteins often serve as scaffolds for protein-protein interactions and are involved in various cellular processes [@saitsu2013][@bento2016].

WDR45B is closely related to WDR45 (also known as WIPI4), and both proteins are involved in autophagy. WDR45B is particularly important for autophagosome formation and is expressed primarily in the brain [@toney2019].

Structure

WDR45B contains characteristic features:

• WD repeats: 5-6 WD repeat motifs forming a beta-propeller
• N-terminal region: Involved in protein interactions
• Phosphatidylinositol 3-phosphate binding: Required for autophagy function

Key Structural Features

Normal Function

Autophagy Regulation

WDR45B plays essential roles in autophagy:

• Autophagosome formation: Required for initiation of autophagy
• Selective autophagy: Involved in specific cargo recognition
• Lipid metabolism: Affects membrane dynamics
• Protein quality control: Clears damaged organelles and aggregates

Autophagy Process

[Autophagy](/entities/autophagy) involves:

Tissue Distribution

| Tissue | Expression | Function |
|--------|-----------|----------|
| Brain | Very high | Neuronal homeostasis |
| Heart | Moderate | Cardiac function |
| Liver | Moderate | Metabolic regulation |
| Muscle | Low-Moderate | Cellular maintenance |
| Lung | Low | Homeostasis |

Disease Associations

Neurodegeneration with Brain Iron Accumulation (NBIA)

NBIA encompasses a group of disorders characterized by iron accumulation in the brain:

• Iron deposition: Primarily in globus pallidus and substantia nigra
• Progressive movement disorders: Dystonia, parkinsonism, choreoathetosis
• Cognitive decline: Progressive intellectual disability
• Neuroimaging: T2 hypointensity in iron-affected regions

WDR45B-Associated Neurodegeneration

• Childhood onset: Developmental delay and static encephalopathy
• Adult neurodegeneration: Progressive deterioration in adulthood
• Movement disorders: Dystonia, spasticity, parkinsonism
• Iron accumulation: Characteristic MRI findings

Other Neurological Conditions

• Intellectual disability: Often with developmental delay
• Seizures: Variable seizure disorders
• Speech deficits: Often progressive

Therapeutic Implications

Current Management

• Iron chelation: Deferoxamine may be considered
• Movement disorder treatment: Botulinum toxin, medications
• Seizure control: Antiepileptic drugs
• Supportive care: Physical, occupational, speech therapy

Emerging Therapies

| Approach | Status | Description |
|----------|--------|-------------|
| Autophagy modulators | Research | Enhance autophagy function |
| Gene therapy | Investigational | Deliver functional WDR45B |
| Iron modulation | Experimental | Reduce iron accumulation |

Research Directions

Key Publications

See Also

• [Genes](/genes/)
• [Proteins](/proteins/)
• [Neurodegenerative Diseases](/diseases/)
• [Neurodegeneration with Brain Iron Accumulation](/diseases/nbia)
• [Autophagy](/mechanisms/autophagy)
• [Iron Metabolism](/mechanisms/iron-metabolism)
• [SENDA Syndrome](/diseases/senda-syndrome)

External Links

• [NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/340527)
• [UniProt](https://www.uniprot.org/uniprot/Q3C1V7)
• [Ensembl](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000160087)
• [OMIM](https://www.omim.org/entry/614296)
• [NBIA Alliance](https://www.nbiaalliance.org)

Background

The study of Wdr45B — Wd Repeat Domain 45B has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References