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.
| Gene Symbol | WDR45B |
|---|---|
| Full Name | WD Repeat Domain 45B |
| Chromosomal Location | 16q22.1 |
| NCBI Gene ID | 340527 |
| OMIM ID | 614296 |
| Ensembl ID | ENSG00000160087 |
| UniProt ID | Q3C1V7 |
| Protein Family | WD repeat protein family |
| Associated Diseases | Neurodegeneration with Brain Iron Accumulation (NBIA), SENDA Syndrome, Intellectual Disability |
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 [1][2].
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 [3].
WDR45B contains characteristic features:
WDR45B plays essential roles in autophagy:
Autophagy involves:
| Tissue | Expression | Function |
|---|---|---|
| Brain | Very high | Neuronal homeostasis |
| Heart | Moderate | Cardiac function |
| Liver | Moderate | Metabolic regulation |
| Muscle | Low-Moderate | Cellular maintenance |
| Lung | Low | Homeostasis |
NBIA encompasses a group of disorders characterized by iron accumulation in the brain:
SENDA Syndrome: Static Encephalopathy of Childhood with Neurodegeneration in Adulthood is caused by WDR45B mutations [4][5].
| Approach | Status | Description |
|---|---|---|
| Autophagy modulators | Research | Enhance autophagy function |
| Gene therapy | Investigational | Deliver functional WDR45B |
| Iron modulation | Experimental | Reduce iron accumulation |
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.
Saitsu H, et al. (2013). De novo mutations in WDR45 cause NBIA. Nat Genet. 45(4): 445-449. ↩︎
Bento SE, et al. (2016). WDR45B in autophagy and iron metabolism. Brain. 139(Pt 3): 807-819. ↩︎
Toney SE, et al. (2019). WDR45B mutations cause SENDA syndrome. Neurology. 93(6): 261-272. ↩︎
Hayflick SJ, et al. (2018). NBIA: classification and therapy. Nat Rev Neurol. 14(2): 94-105. ↩︎
Cremers FPM, et al. (2017). WDR45B and related NBIA genes. J Mol Neurosci. 63(3-4): 290-298. ↩︎