Gene Symbol: WDFY3
Description: WD repeat and FYVE domain containing 3
Alias: ALFY, BCHS, MCPH18, ZFYVE25, WD repeat and FYVE domain-containing protein 3, autophagy-linked FYVE protein
Species: human
Products:     WDFY3

Top Publications

  1. Hocking L, Mellis D, McCabe P, Helfrich M, Rogers M. Functional interaction between sequestosome-1/p62 and autophagy-linked FYVE-containing protein WDFY3 in human osteoclasts. Biochem Biophys Res Commun. 2010;402:543-8 pubmed publisher
    ..in human osteoclast-like cells between SQSTM1 and Autophagy-Linked FYVE domain-containing protein (ALFY/WDFY3). Endogenous ALFY and SQSTM1 both localised within the nuclei of osteoclasts and their mononuclear precursors...
  2. Liu H, Zhang Q, Lou Q, Zhang X, Cui Y, Wang P, et al. Differential Analysis of lncRNA, miRNA and mRNA Expression Profiles and the Prognostic Value of lncRNA in Esophageal Cancer. Pathol Oncol Res. 2019;: pubmed publisher
    ..Notably, we found 8 lncRNAs (WDFY3-AS2, CASC8, UGDH-AS1, RAP2C-AS1, AC007128.1, AC016205.1, AC092803.2 and AC079949...
  3. Durocher M, Ander B, Jickling G, Hamade F, Hull H, Knepp B, et al. Inflammatory, regulatory, and autophagy co-expression modules and hub genes underlie the peripheral immune response to human intracerebral hemorrhage. J Neuroinflammation. 2019;16:56 pubmed publisher
    ..LCK, FYN, SKAP1, ITK, AMBRA1, NLRC4, IL6R, IL17RA, GAB2, MXD1, PIK3CD, NUMB, MAPK14, DDX24, EVL, TDP1, ATG3, WDFY3, GSK3B, STAT3, STX3, CSF3R, PIP4K2A, ANXA3, DGAT2, LRP10, FLOT2, ANK1, CR1, SLC4A1, and DYSF, have been implicated ..
  4. Eenjes E, Dragich J, Kampinga H, Yamamoto A. Distinguishing aggregate formation and aggregate clearance using cell-based assays. J Cell Sci. 2016;129:1260-70 pubmed publisher
    ..implicated in the autophagic clearance of expanded polyglutamine inclusions, HspB7 and Alfy (also known as WDFY3), actually affect very distinct cellular processes to affect aggregate burden...
  5. Napoli E, Song G, Panoutsopoulos A, Riyadh M, Kaushik G, Halmai J, et al. Beyond autophagy: a novel role for autism-linked Wdfy3 in brain mitophagy. Sci Rep. 2018;8:11348 pubmed publisher
    WD repeat and FYVE domain-containing 3 (WDFY3; also known as Autophagy-Linked FYVE or Alfy) is an identified intellectual disability, developmental delay and autism risk gene...
  6. Han H, Wei W, Duan W, Guo Y, Li Y, Wang J, et al. Autophagy-linked FYVE protein (Alfy) promotes autophagic removal of misfolded proteins involved in amyotrophic lateral sclerosis (ALS). In Vitro Cell Dev Biol Anim. 2015;51:249-63 pubmed publisher
    Autophagy-linked FYVE (Alfy) is a protein implicated in the selective degradation of aggregated proteins...
  7. Wu D, Adamopoulos I. Loss of WDFY3 ameliorates severity of serum transfer-induced arthritis independently of autophagy. Cell Immunol. 2017;316:61-69 pubmed publisher
    b>WDFY3 is a master regulator of selective autophagy that we recently showed to interact with TRAF6 and augment RANKL-induced osteoclastogenesis in vitro and in vivo via the NF-κB pathway...
  8. Zhang Z, Wang S, Liu W. EMT-related long non-coding RNA in hepatocellular carcinoma: A study with TCGA database. Biochem Biophys Res Commun. 2018;503:1530-1536 pubmed publisher
    ..Especially, lncRNA WDFY3-AS2-, LINC00472-, MIAT-, and MEG3-associated genes were significantly enriched in EMT-linked pathways...
  9. Orosco L, Ross A, Cates S, Scott S, Wu D, Sohn J, et al. Loss of Wdfy3 in mice alters cerebral cortical neurogenesis reflecting aspects of the autism pathology. Nat Commun. 2014;5:4692 pubmed publisher
    ..Here we describe the neurodevelopmental defects in mice that carry deleterious alleles of the Wdfy3 gene, recently recognized as causative in ASDs...

More Information


  1. Wu D, Gu R, Sarin R, Zavodovskaya R, Chen C, Christiansen B, et al. Autophagy-linked FYVE containing protein WDFY3 interacts with TRAF6 and modulates RANKL-induced osteoclastogenesis. J Autoimmun. 2016;73:73-84 pubmed publisher
    ..However, the role of autophagy-linked FYVE containing protein, WDFY3, in osteoclast biology remains elusive...
  2. Dragich J, Kuwajima T, Hirose Ikeda M, Yoon M, Eenjes E, Bosco J, et al. Autophagy linked FYVE (Alfy/WDFY3) is required for establishing neuronal connectivity in the mammalian brain. elife. 2016;5: pubmed publisher
    ..The Autophagy linked FYVE protein (Alfy), previously identified as a molecular scaffold between the ubiquitinated cargo and the ..
  3. Wang T, Guo H, Xiong B, Stessman H, Wu H, Coe B, et al. De novo genic mutations among a Chinese autism spectrum disorder cohort. Nat Commun. 2016;7:13316 pubmed publisher
    ..1% of patients) followed by CHD8, DSCAM, MECP2, POGZ, WDFY3 and ASH1L...
  4. Tsai T, Wang H, Hung C, Lin P, Lee Y, Chen H, et al. Wheat germ agglutinin-induced paraptosis-like cell death and protective autophagy is mediated by autophagy-linked FYVE inhibition. Oncotarget. 2017;8:91209-91222 pubmed publisher
    ..WGA-induced autophagy antagonized paraptosis in HeLa and CaSKi cells, which expressed autophagy-linked FYVE (Alfy) protein, but not in SiHa cells that did not express Alfy...
  5. Simonsen A, Birkeland H, Gillooly D, Mizushima N, Kuma A, Yoshimori T, et al. Alfy, a novel FYVE-domain-containing protein associated with protein granules and autophagic membranes. J Cell Sci. 2004;117:4239-51 pubmed
    ..Here, we describe a novel giant FYVE-domain-containing protein, named autophagy-linked FYVE protein (Alfy)...
  6. Isakson P, Lystad A, Breen K, Koster G, Stenmark H, Simonsen A. TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody ring degradation by selective autophagy. Autophagy. 2013;9:1955-64 pubmed
    ..this study we showed that the ubiquitin-binding autophagy receptor SQSTM1/p62 and the interacting adaptor protein WDFY3/ALFY form a complex with the ubiquitin E3 ligase TRAF6 and that these proteins, as well as NBR1, are important for ..
  7. Iossifov I, O Roak B, Sanders S, Ronemus M, Krumm N, Levy D, et al. The contribution of de novo coding mutations to autism spectrum disorder. Nature. 2014;515:216-21 pubmed publisher
    ..Most of the significance for the latter comes from affected females. ..
  8. Puorro G, Marsili A, Sapone F, Pane C, De Rosa A, Peluso S, et al. Peripheral markers of autophagy in polyglutamine diseases. Neurol Sci. 2018;39:149-152 pubmed publisher
    ..HD patients showed increased expression of MAP1LC3B (+ 43%; p = 0.048), SQSTM1 (+ 49%; p = 0.002), and WDFY3 (+ 89%; p < 0.001). SCA2 patients had increased expression of WDFY3 (+ 69%; p < 0.001)...
  9. Komatsu M, Waguri S, Koike M, Sou Y, Ueno T, Hara T, et al. Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell. 2007;131:1149-63 pubmed
  10. Wang C, Saar V, Leung K, Chen L, Wong G. Human amyloid ? peptide and tau co-expression impairs behavior and causes specific gene expression changes in Caenorhabditis elegans. Neurobiol Dis. 2018;109:88-101 pubmed publisher
    ..ptc-3), the Rab GTPase activating protein, TBC1D16 (tbc-16), the WD repeat and FYVE domain-containing protein 3, WDFY3 (wdfy-3), ADP-ribosylation factor guanine nucleotide exchange factor 2, ARFGEF2 (agef-1), Early B-cell Factor, ..
  11. Wang N, Zimmerman K, Raab R, McKown R, Hutnik C, Talla V, et al. Lacritin rescues stressed epithelia via rapid forkhead box O3 (FOXO3)-associated autophagy that restores metabolism. J Biol Chem. 2013;288:18146-61 pubmed publisher
    ..Lacritin targets the cell surface proteoglycan syndecan-1 via its C-terminal amino acids Leu(108)-Leu(109)-Phe(112) and is also available in saliva, plasma, and lung lavage. Thus, lacritin may promote epithelial homeostasis widely. ..
  12. Yamamoto A, Simonsen A. Alfy-dependent elimination of aggregated proteins by macroautophagy: can there be too much of a good thing?. Autophagy. 2011;7:346-50 pubmed
  13. Schläfli A, Isakson P, Garattini E, Simonsen A, Tschan M. The autophagy scaffold protein ALFY is critical for the granulocytic differentiation of AML cells. Sci Rep. 2017;7:12980 pubmed publisher
    ..In this study, we aimed at identifying if the autophagy-linked FYVE-domain containing protein (ALFY/WDFY3) is involved in autophagic degradation of protein aggregates contributes to ATRA therapy-induced autophagy...
  14. Clausen T, Lamark T, Isakson P, Finley K, Larsen K, Brech A, et al. p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy. Autophagy. 2010;6:330-44 pubmed
    ..We show here that p62 is required to recruit the large phosphoinositide-binding protein ALFY to cytoplasmic p62 bodies generated upon amino acid starvation or puromycin-treatment...
  15. Filimonenko M, Isakson P, Finley K, Anderson M, Jeong H, Melia T, et al. The selective macroautophagic degradation of aggregated proteins requires the PI3P-binding protein Alfy. Mol Cell. 2010;38:265-79 pubmed publisher
    ..Here, we report that Alfy, a phosphatidylinositol 3-phosphate-binding protein, is central to the selective elimination of aggregated proteins...
  16. Kadir R, Harel T, Markus B, Perez Y, Bakhrat A, Cohen I, et al. ALFY-Controlled DVL3 Autophagy Regulates Wnt Signaling, Determining Human Brain Size. PLoS Genet. 2016;12:e1005919 pubmed publisher
    ..We now show through linkage analysis and whole exome sequencing, that a dominant mutation in ALFY, encoding an autophagy scaffold protein, causes human primary microcephaly...
  17. Suzuki E, Maverakis E, Sarin R, Bouchareychas L, Kuchroo V, Nestle F, et al. T Cell-Independent Mechanisms Associated with Neutrophil Extracellular Trap Formation and Selective Autophagy in IL-17A-Mediated Epidermal Hyperplasia. J Immunol. 2016;197:4403-4412 pubmed
    ..trap formation and/or neutrophils with conditional deletion of the master regulator of selective autophagy, Wdfy3. Our data demonstrate a novel T cell-independent mechanism that is associated with neutrophil extracellular trap ..
  18. Deretic V. A master conductor for aggregate clearance by autophagy. Dev Cell. 2010;18:694-6 pubmed publisher
    ..provide evidence that the phosphatidylinositol 3-phosphate (PI3P) binding protein, Alfy, interacts with p62, Atg5, and PI3P to coordinate target recognition with site-specific activation of autophagic ..
  19. Lystad A, Ichimura Y, Takagi K, Yang Y, Pankiv S, Kanegae Y, et al. Structural determinants in GABARAP required for the selective binding and recruitment of ALFY to LC3B-positive structures. EMBO Rep. 2014;15:557-65 pubmed publisher
    ..Here, we show that ALFY binds selectively to LC3C and the GABARAPs through a LIR in its WD40 domain...
  20. Iossifov I, Ronemus M, Levy D, Wang Z, Hakker I, Rosenbaum J, et al. De novo gene disruptions in children on the autistic spectrum. Neuron. 2012;74:285-99 pubmed publisher
    ..We find FMRP-associated genes are under greater purifying selection than the remainder of genes and suggest they are especially dosage-sensitive targets of cognitive disorders. ..
  21. Leparc G, Mitra R. Non-EST-based prediction of novel alternatively spliced cassette exons with cell signaling function in Caenorhabditis elegans and human. Nucleic Acids Res. 2007;35:3192-202 pubmed
    ..Overall, PASE was able to uncover 59 novel alternative cassette exons in C. elegans and humans through a genome-wide ab initio prediction method that enriches for exons involved in signaling. ..