WDR45B
WD Repeat Domain 45B: A Key Regulator of Autophagy and Neurodevelopment
Gene Information Card
| Symbol | WDR45B |
|---|---|
| Full Name | WD Repeat Domain 45B |
| Gene Type | Protein coding |
| Chromosomal Location | 17q25.3 |
| NCBI Gene ID | 56270 ncbi.nlm.nih.gov/gene/56270 |
| Ensembl ID | ENSG00000108379 |
| UniProt ID | Q5MNZ6 |
| OMIM ID | 609226 |
| HGNC ID | 28912 |
| Aliases | WIPI3, WDR45B, WIPI-3 |
Description
WDR45B (WD Repeat Domain 45B) encodes a member of the WD40 repeat protein family, specifically a homolog of yeast Atg18. The protein, also known as WIPI3, is a component of the autophagy machinery, functioning in autophagosome formation by binding phosphatidylinositol 3-phosphate (PI3P) and regulating membrane dynamics. WDR45B is essential for normal autophagic flux and is highly expressed in the brain. Mutations in WDR45B cause a neurodevelopmental disorder characterized by global developmental delay, intellectual disability, epilepsy, and autistic features, often with a phenotype overlapping beta-propeller protein-associated neurodegeneration (BPAN).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with global developmental delay, intellectual disability, epilepsy, and autistic features | Loss-of-function mutations impair autophagy, leading to accumulation of autophagic substrates and neuronal dysfunction | ClinVar, OMIM |
| Beta-propeller protein-associated neurodegeneration (BPAN) (phenotypic overlap) | Impaired autophagy due to WDR45B deficiency disrupts neuronal homeostasis and iron metabolism | OMIM, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | High |
| Testis | 8.1 | Medium |
| Thyroid | 6.5 | Medium |
| Adrenal gland | 5.9 | Medium |
| Liver | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 12.4 | High expression; relevant for neuronal autophagy studies |
| HEK293 (embryonic kidney) | 9.7 | Moderate expression; common model for autophagy assays |
| HeLa (cervical carcinoma) | 7.3 | Moderate expression; used in autophagy flux experiments |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.97C>T (p.Arg33*) | Nonsense | Rare | Loss of function; truncation leads to nonsense-mediated decay |
| c.346G>A (p.Gly116Arg) | Missense | Rare | Likely loss of function; disrupts WD40 domain structure |
| c.568_569del (p.Leu190Valfs*12) | Frameshift | Rare | Loss of function; premature truncation |
| c.754C>T (p.Arg252Trp) | Missense | Rare | Uncertain significance; may impair PI3P binding |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations are loss-of-function (nonsense, frameshift, missense) that reduce or abolish WDR45B protein function, impairing autophagy.
Gain of Function (GOF)
No evidence for gain-of-function mutations in WDR45B.
Dominant Negative (DN)
No evidence for dominant-negative effects; disease inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • autophagy (GO:0006914) | • pre-autophagosomal structure membrane (GO:0034045) |
| • phosphatidylinositol-3-phosphate binding (GO:0036092) | • protein binding (GO:0005515) |
| • macroautophagy (GO:0016236) | • intracellular membrane-bounded organelle (GO:0043231) |
Pathways
• Autophagy - animal (KEGG: hsa04140)
• mTOR signaling pathway (KEGG: hsa04150)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
Protein Summary
WDR45B (WIPI3) is a 397-amino acid protein containing seven WD40 repeats that form a beta-propeller structure. It localizes to the pre-autophagosomal membrane and binds phosphatidylinositol 3-phosphate (PI3P) via its conserved FRRG motif, which is essential for autophagosome nucleation. The protein interacts with other autophagy regulators such as ATG2 and ATG9. Loss of WDR45B function leads to impaired autophagic flux, accumulation of p62 and ubiquitinated proteins, and neuronal vulnerability. WDR45B is ubiquitously expressed but shows highest levels in brain, consistent with its role in neurodevelopment.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| WDR45B Knockout HEK293 Cell Line | EDJ-KQ17387 | Human | 56270 | Details Get a Quote |
| WDR45B Knockout HeLa Cell Line | EDJ-KQ48333 | Human | 56270 | Details Get a Quote |
| WDR45B Knockout A-549 Cell Line | EDJ-KQ49508 | Human | 56270 | Details Get a Quote |
| WDR45B Knockout HCT 116 Cell Line | EDJ-KQ49509 | Human | 56270 | Details Get a Quote |
