WDFY3

Chr 4q21.23

WD repeat and FYVE domain containing 3

Aliases:: KIAA0993, ALFY, ZFYVE25
MANE:: ENST00000295888.9

OMIM: 617485 ↗NCBI: 23001 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

WDFY3 · Q8IZQ1

Mean pLDDT

Not published

AlphaFold has not published a prediction for this sequence. This is common for very long proteins.

Confidence breakdown

Check AlphaFold DB

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe microcephaly
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Disease associations (Open Targets)

Autosomal dominant microcephaly
0.69
hereditary disease
0.54
neurodevelopmental disorder
0.50
Neurodevelopmental delay
0.49
complex neurodevelopmental disorder
0.46
syndromic intellectual disability
0.44
neurodegenerative disease
0.36
liver disorder
0.33
autism spectrum disorder
0.32
benign digestive system neoplasm
0.30

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

WD repeat and FYVE domain-containing protein 3

Required for selective macroautophagy (aggrephagy). Acts as an adapter protein by linking specific proteins destined for degradation to the core autophagic machinery members, such as the ATG5-ATG12-ATG16L E3-like ligase, SQSTM1 and LC3 (PubMed:20417604). Along with p62/SQSTM1, involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures). Along with SQSTM1, required to recruit ubiquitinated proteins to PML bodies in the nucleus (PubMed:20168092). Important for normal brain development. Essential for the formation of axonal tracts throughout the brain and spinal cord, including the formation of the major forebrain commissures. Involved in the ability of neural cells to respond to guidance cues. Required for cortical neurons to respond to the trophic effects of netrin-1/NTN1 (By similarity). Regulates Wnt signaling through the removal of DVL3 aggregates, likely in an autophagy-dependent manner. This process may be important for the determination of brain size during embryonic development (PubMed:27008544). May regulate osteoclastogenesis by acting on the TNFSF11/RANKL - TRAF6 pathway (By similarity). After cytokinetic abscission, involved in midbody remnant degradation (PubMed:24128730). In vitro strongly binds to phosphatidylinositol 3-phosphate (PtdIns3P) (PubMed:15292400)