WDFY3
WD Repeat and FYVE Domain Containing 3
Gene Information Card
| Symbol | WDFY3 |
|---|---|
| Full Name | WD Repeat and FYVE Domain Containing 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q21.23 |
| NCBI Gene ID | 23001 ncbi.nlm.nih.gov/gene/23001 |
| Ensembl ID | ENSG00000138668 |
| UniProt ID | Q8IYS0 |
| OMIM ID | 617511 |
| HGNC ID | 20751 |
| Aliases | ALFY, KIAA0992, ZFYVE25 |
Description
WDFY3 encodes a large scaffolding protein known as ALFY (autophagy-linked FYVE protein), which is involved in selective autophagy, particularly the degradation of protein aggregates. It plays a critical role in neurodevelopment and cellular homeostasis by facilitating the clearance of ubiquitinated substrates through the autophagy-lysosome pathway.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with microcephaly and cortical malformations | Loss-of-function mutations impair autophagy-mediated clearance of protein aggregates, leading to abnormal neuronal development | PMID: 27545674, ClinVar |
| Autism spectrum disorder | Rare variants in WDFY3 may disrupt synaptic autophagy and neuronal connectivity | PMID: 29276005 |
| Hepatocellular carcinoma | Altered WDFY3 expression affects autophagic flux and tumor suppression | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Testis | 8.3 | Medium |
| Liver | 6.1 | Medium |
| Kidney | 5.4 | Medium |
| Heart | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 10.2 | Neuroblastoma cell line |
| HEK293 | 7.8 | Embryonic kidney cells |
| HepG2 | 6.5 | Hepatocellular carcinoma cells |
| HeLa | 5.1 | Cervical cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.625C>T (p.Arg209*) | Nonsense | <0.01% | Loss of function, associated with neurodevelopmental disorder |
| c.1234G>A (p.Gly412Arg) | Missense | <0.01% | Unknown significance, reported in autism |
| c.4567_4568del (p.Leu1523fs) | Frameshift | <0.01% | Loss of function, likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations lead to truncated protein, impairing autophagy and causing neurodevelopmental phenotypes.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
| • autophagy | • protein binding |
| • ubiquitin binding | • cytoplasmic vesicle |
| • FYVE zinc finger domain | • WD40 repeat domain |
Pathways
• Selective autophagy (R-HSA-9663891)
• Autophagy (KEGG hsa04140)
Protein Summary
WDFY3 encodes a 3526-amino acid protein (ALFY) containing WD40 repeats and a FYVE domain. It acts as a scaffold linking ubiquitinated protein aggregates to the autophagy machinery via interactions with ATG5 and p62/SQSTM1. ALFY is essential for aggrephagy and is highly expressed in the brain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| WDFY3 Knockout HEK293 Cell Line | EDJ-KQ7770 | Human | 23001 | Details Get a Quote |
| WDFY3 Knockout A-549 Cell Line | EDJ-KQ33241 | Human | 23001 | Details Get a Quote |
| WDFY3 Knockout HCT 116 Cell Line | EDJ-KQ33242 | Human | 23001 | Details Get a Quote |
| WDFY3 Knockout HeLa Cell Line | EDJ-KQ33243 | Human | 23001 | Details Get a Quote |
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