Affinage

WDR45

WD repeat domain phosphoinositide-interacting protein 4 · UniProt Q9Y484

Length
360 aa
Mass
39.9 kDa
Annotated
2026-06-11
74 papers in source corpus 24 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

WDR45 (WIPI4) is a PI3P-binding WD40 β-propeller protein required for autophagy in human cells, where loss-of-function mutations impair autophagic flux and cause accumulation of aberrant early autophagic structures (PMID:23435086). Its central biochemical role is to form a rod-shaped complex with ATG2A in which WIPI4 binds one tip of the ATG2A rod, allowing the complex to tether PI3P-containing membranes to PI3P-free membranes and drive lipid transfer during phagophore expansion (PMID:30185561, PMID:30766969); cryo-EM of the ATG2A–WDR45 and ATG2A–WDR45–ATG9A assemblies resolved the architecture underlying this lipid extraction and re-equilibration (PMID:40116844). Beyond membrane tethering, WIPI4 scaffolds LKB1–AMPK–ULK1 signaling, being released from a WIPI4–ATG2/AMPK–ULK1 complex upon AMPK activation to translocate to nascent autophagosomes and control their size (PMID:28561066), and it acts together with WDR45B to target the tether EPG5 to late endosomes/lysosomes, promoting SNARE-dependent autophagosome–lysosome fusion in neural cells (PMID:33636118, PMID:34105435). WDR45 is required for basal neuronal autophagy and axonal homeostasis in vivo: CNS-specific knockout mice accumulate p62/ubiquitin-positive aggregates, develop axon spheroids, and show motor and cognitive deficits (PMID:26000824). WDR45 also governs iron handling through autophagy, being required for ferritinophagy via NCOA4 and for autophagic degradation of the transferrin receptor; its deficiency drives ferritin/iron imbalance, lipid peroxidation, and ferroptotic cell death (PMID:34837396, PMID:36751498, PMID:34012978). Independent of canonical autophagy, WIPI4 depletion redistributes ATG2A to ER–mitochondria contacts, increasing phosphatidylserine import and mitochondrial phosphatidylethanolamine synthesis to enable ferroptosis (PMID:38454050), and WDR45 loss elicits ER stress with UPR-driven neuronal apoptosis (PMID:31204559). The BPAN-causing mutations disrupt a conserved ATG2-binding site, with disease severity tracking the degree of lost ATG2 binding, establishing the WIPI4–ATG2 interaction as mechanistically central to disease (PMID:34368840).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2013 Medium

    Established that WDR45 is functionally required for autophagy in humans, converting a disease-gene association into a defined cellular defect.

    Evidence Autophagy flux assays and morphology in patient lymphoblastoid cells carrying loss-of-function mutations

    PMID:23435086

    Open questions at the time
    • Did not define the biochemical step WDR45 acts at
    • No molecular partner identified
  2. 2015 High

    Showed WDR45 is required for basal neuronal autophagy and axonal homeostasis in vivo, linking its loss to the neurodegenerative phenotype.

    Evidence CNS-specific conditional Wdr45 knockout mice with behavioral, histological, and flux readouts

    PMID:26000824

    Open questions at the time
    • Molecular mechanism connecting autophagy loss to axon spheroids unresolved
    • Cell-type specificity of vulnerability not addressed
  3. 2017 Medium

    Placed WIPI4 within upstream autophagy-initiation signaling, defining a regulatory rather than purely structural role.

    Evidence Co-IP, WIPI interactome, kinase screen, and translocation imaging implicating LKB1-AMPK-ULK1 and NUAK2/BRSK2

    PMID:28561066

    Open questions at the time
    • Single lab, not independently replicated
    • Mechanism of WIPI4 release from the complex unresolved
  4. 2018 High

    Defined WIPI4's core biochemical activity: tethering PI3P-containing to PI3P-free membranes via the ATG2A complex to support lipid transfer during phagophore expansion.

    Evidence Single-particle EM, cross-linking MS, and in vitro tethering assays of the ATG2A-WIPI4 complex

    PMID:30185561 PMID:30766969

    Open questions at the time
    • High-resolution structure not yet available
    • Directionality and rate of lipid transfer not quantified at this stage
  5. 2018 Medium

    Connected WDR45 loss to iron overload and oxidative stress in disease-relevant human neurons, framing the lysosomal-iron axis of pathology.

    Evidence Patient fibroblasts and iPSC-derived midbrain neurons with overexpression rescue, iron and mitochondrial/lysosomal assays

    PMID:30169597

    Open questions at the time
    • Molecular link between autophagy defect and iron accumulation not yet defined
    • Single lab
  6. 2021 Medium

    Identified the iron-handling mechanism: WDR45 enables ferritinophagy via NCOA4 and autophagic turnover of the transferrin receptor, whose failure drives ferroptosis.

    Evidence CRISPR knockout neuroblastoma cells and mutant-overexpression models with iron, lipid peroxidation, GPX4, and AAV rescue assays

    PMID:34012978 PMID:34837396 PMID:36751498

    Open questions at the time
    • NCOA4 reduction mechanism not defined
    • Relative contribution of TfRC vs ferritinophagy unresolved
  7. 2021 High

    Extended WDR45 function to autophagosome maturation, showing it and WDR45B recruit EPG5 to drive autophagosome-lysosome fusion in neural cells.

    Evidence DKO mouse neural cells, reciprocal Co-IP, BPAN-mutant rescue, and SNARE complex assays

    PMID:33636118 PMID:34105435

    Open questions at the time
    • Structural basis of WDR45-EPG5 interaction unknown
    • Redundancy between WDR45 and WDR45B not fully mapped
  8. 2021 Medium

    Linked WDR45 loss to ER stress and UPR-driven neuronal apoptosis, identifying a degradative-failure consequence amenable to pharmacological rescue.

    Evidence Constitutive Wdr45 KO mice with proteomics, IRE1/PERK immunoblotting, and TUDCA/rapamycin rescue

    PMID:31204559

    Open questions at the time
    • Causal order between ER stress and autophagy defect unclear
    • Single lab
  9. 2021 Medium

    Mapped the BPAN disease mechanism to disruption of the WIPI4-ATG2 binding site, with severity scaling to binding loss.

    Evidence Yeast two-hybrid, Co-IP, colocalization, and BPAN-mutant binding assays with Hsv2/Atg2 functional validation

    PMID:34368840

    Open questions at the time
    • Quantitative genotype-phenotype correlation in patients not established
    • Single lab
  10. 2021 Medium

    Documented mitochondrial respiratory and developmental/synaptic phenotypes of Wdr45 loss, broadening its physiological footprint beyond degradation.

    Evidence Whole-body KO mice (complex I assays) and in utero electroporation knockdown with synaptosome fractionation and RNAi rescue

    PMID:34043061 PMID:34799629

    Open questions at the time
    • Mechanism linking WDR45 to complex I activity unknown
    • Whether synaptic role is autophagy-dependent unresolved
  11. 2023 Medium

    Identified WDR45-controlled lipid pathways: ER-stress/p38-driven CMA degradation of ferritin and Lpcat1-dependent PC/LPC dysregulation in degenerating axons.

    Evidence Mutant-WDR45 HeLa cells with CMA assays and conditional DAergic-neuron KO mice with proteomics/lipidomics and Lpcat1 knockdown rescue

    PMID:36940732 PMID:39183331

    Open questions at the time
    • Integration of CMA, ferritinophagy, and lipid pathways into one model incomplete
    • Single lab per finding
  12. 2024 High

    Established an autophagy-independent ferroptosis mechanism, showing WIPI4 loss redistributes ATG2A to ER-mitochondria contacts to drive peroxidation-prone phosphatidylethanolamine synthesis.

    Evidence Knockdown in cells and zebrafish with lipidomics, fractionation, and live imaging of contact sites

    PMID:38454050

    Open questions at the time
    • Relative contribution of autophagy-dependent vs -independent ferroptosis in BPAN unresolved
  13. 2024 Medium

    Added a CMA-substrate axis whereby WDR45 loss elevates Fasn and causes lipid droplet accumulation, expanding its metabolic role.

    Evidence CRISPR Wdr45 KO SN4741 cells, Fasn-HSC70 Co-IP, and BODIPY lipid droplet staining

    PMID:38539242

    Open questions at the time
    • How WDR45 supports CMA mechanistically not defined
    • Single lab, two methods
  14. 2025 High

    Resolved the structural architecture of the ATG2A-WDR45 and ATG2A-WDR45-ATG9A complexes, defining the lipid-extraction mechanism at near-atomic detail.

    Evidence Cryo-EM structure determination with molecular dynamics simulations

    PMID:40116844

    Open questions at the time
    • Dynamics of the full transfer cycle in vivo not captured
    • Regulation of complex assembly not addressed
  15. 2025 Medium

    Uncovered a non-degradative function: WDR45 phase-separates with Caprin-1 via its WD5 domain to promote stress-granule disassembly, displacing G3BP1.

    Evidence Phase separation and competitive binding assays plus BPAN patient iPSC-derived neurons with SG recovery imaging

    PMID:40473629

    Open questions at the time
    • In vivo relevance of SG dysregulation to neurodegeneration not established
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How WDR45's multiple roles—membrane tethering, fusion, signaling scaffolding, iron/lipid metabolism, and stress-granule regulation—are integrated into a unified mechanism driving BPAN neurodegeneration remains unresolved.
  • No model reconciling autophagy-dependent and -independent pathologies
  • Hierarchy among iron, ER stress, and lipid phenotypes undefined
  • Therapeutic mechanism of candidate compounds not validated beyond preprint

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 3 GO:0060090 molecular adaptor activity 3 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005739 mitochondrion 1 GO:0005768 endosome 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-9612973 Autophagy 4 R-HSA-1430728 Metabolism 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-8953854 Metabolism of RNA 1
Partners
AMPKATG2AATG9ACAPRIN-1EPG5NCOA4ULK1WDR45B
Complex memberships
ATG2A-WDR45 (WIPI4) lipid-transfer complexATG2A-WDR45-ATG9A complexWIPI4-ATG2/AMPK-ULK1 signaling complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 ATG2A forms a rod-shaped complex with WIPI4 (WDR45). ATG2A can bridge neighboring vesicles through interactions at each tip; WIPI4 binds to one tip, enabling the ATG2A-WIPI4 complex to specifically tether PI3P-containing vesicles to PI3P-free vesicles, suggesting a role in ER-phagophore association and lipid membrane transfer during phagophore expansion. Single-particle electron microscopy, chemical cross-linking coupled with mass spectrometry, biochemical tethering assays Proceedings of the National Academy of Sciences of the United States of America High 30185561 30766969
2017 WIPI4 (WDR45) scaffolds LKB1-AMPK-ULK1 signaling for autophagy control: in response to LKB1-mediated AMPK stimulation, WIPI4 is released from a WIPI4-ATG2/AMPK-ULK1 complex and translocates to nascent autophagosomes where it controls their size. WIPI4 also interacts with the AMPK-related kinases NUAK2 and BRSK2 as upstream regulators. Co-immunoprecipitation, WIPI interactome analysis, functional kinase screen, translocation imaging Nature communications Medium 28561066
2021 WDR45 and WDR45B are specifically required for autophagosome maturation into autolysosomes in neural cells. They interact with the tether protein EPG5 and target it to late endosomes/lysosomes to promote autophagosome-lysosome fusion; loss of WDR45/45B dampens formation of the SNARE-EPG5 fusion machinery. BPAN-associated WDR45 mutations fail to rescue these defects due to impaired EPG5 binding. Double knockout (DKO) mouse neural cells, Co-IP, rescue experiments with BPAN mutants, fluorescence imaging of autophagosome maturation, SNARE complex assays Current biology : CB High 33636118 34105435
2021 WDR45 deficiency impairs ferritinophagy (autophagic degradation of ferritin) via reduced NCOA4 levels, leading to accumulation of ferric iron-containing ferritin and iron overload. AAV-mediated restoration of WDR45 rescued NCOA4 and ferritin levels in patient-derived cells. CRISPR-Cas9 WDR45 knockout neuroblastoma cells, immunoblotting, AAV rescue, iron measurement assays Journal of neurochemistry Medium 34837396 36751498
2024 WIPI4 (WDR45) depletion causes ferroptosis via an autophagy-independent mechanism: WIPI4 depletion increases ATG2A localization at ER-mitochondrial contact sites, enhancing phosphatidylserine import into mitochondria, which increases mitochondrial synthesis of phosphatidylethanolamine (a lipid prone to peroxidation), thereby enabling lipid peroxidation-driven ferroptosis. This was demonstrated in cell culture and in zebrafish. siRNA/shRNA knockdown in cell culture, zebrafish loss-of-function model, lipidomics, subcellular fractionation, live imaging of ER-mitochondria contact sites Nature cell biology High 38454050
2021 Loss of WDR45 leads to accumulation of ER proteins, elevated ER stress, and activation of the unfolded protein response (UPR) via ERN1/IRE1 and EIF2AK3/PERK pathways, ultimately causing neuronal apoptosis. Suppression of ER stress or mTOR inhibition (activating autophagy) alleviated cell death in wdr45 KO mouse neurons. Constitutive wdr45 KO mice, quantitative proteomics, ER stress pathway immunoblotting, pharmacological rescue (TUDCA, rapamycin), TUNEL apoptosis assay Autophagy Medium 31204559
2013 WDR45 (WIPI4) is required for normal autophagic flux: lymphoblastoid cells from patients with loss-of-function WDR45 mutations show severely impaired autophagic activity and accumulation of aberrant early autophagic structures, establishing WDR45 as functionally required for autophagy in human cells. Lymphoblastoid cell lines from patients, autophagy flux assays, protein expression analysis, aberrant autophagosome morphology by microscopy Nature genetics Medium 23435086
2015 CNS-specific Wdr45 knockout mice exhibit defective autophagic flux, SQSTM1/p62- and ubiquitin-positive protein aggregate accumulation in neurons and axons, poor motor coordination, impaired learning and memory, and extensive axon swelling with axon spheroids, establishing WDR45 as required for basal neuronal autophagy and axonal homeostasis in vivo. CNS-specific conditional Wdr45 knockout mouse (Nes-Wdr45fl/Y), behavioral testing, immunohistochemistry, autophagic flux assays Autophagy High 26000824
2018 Loss of WDR45 function in patient-derived fibroblasts and iPSC-derived midbrain neurons increases cellular iron levels and oxidative stress, accompanied by mitochondrial abnormalities and diminished lysosomal function. Restoring WDR45 levels partially rescued oxidative stress and susceptibility to iron treatment; autophagy activation reduced iron overload, indicating WDR45 is required for lysosomal degradation of iron-containing organelles. Patient-specific WDR45 mutant fibroblasts, iPSC-derived midbrain neurons, WDR45 overexpression rescue, iron assays, mitochondrial function assays, lysosomal activity assays Brain : a journal of neurology Medium 30169597
2021 WDR45 mutation impairs autophagic degradation of transferrin receptor (TfRC), causing TfRC accumulation and increased intracellular iron. Simultaneously, ferritin H (FTH) is decreased, leading to elevated ferrous iron (Fe2+), lipid peroxidation, ROS production, decreased GPX4, and ferroptotic cell death. WDR45 mutant overexpression in cell lines, chloroquine/ATG2A knockdown for autophagy inhibition, iron measurement, lipid peroxidation assay, ROS measurement, GPX4 western blot, cell viability assay Frontiers in molecular biosciences Medium 34012978
2021 A conserved ATG2 binding site in WIPI4 (WDR45) is disrupted by BPAN-causing mutations. Two WIPI4 residues involved in ATG2 binding are mutated in BPAN patients, and the severity of disease correlates with the degree of inhibition of ATG2 binding, establishing the WIPI4-ATG2 interaction as mechanistically critical for BPAN pathogenesis. Yeast two-hybrid, Co-IP, colocalization imaging in yeast, BPAN mutant binding assays, Hsv2/Atg2 functional analysis Human molecular genetics Medium 34368840
2023 WDR45 mutation activates chaperone-mediated autophagy (CMA) through ER stress/p38 signaling, promoting CMA-dependent degradation of ferritin heavy chain (FTH), thereby reducing FTH levels and increasing Fe2+ content. Inhibition of the ER stress/p38 pathway reduced CMA activity, elevated FTH, and decreased Fe2+ levels. HeLa cell overexpression of mutant WDR45, ER stress induction, p38 inhibitor, CMA activity assays, FTH immunoblotting, Fe2+ measurement Free radical biology & medicine Medium 36940732
2023 WDR45 deficiency causes axonal degeneration in midbrain dopaminergic neurons characterized by fragmented tubular ER accumulation. Proteomic and lipidomic analyses identified upregulation of Lpcat1 (lysophosphatidylcholine acyltransferase 1) and dysregulation of PC/LPC metabolism; knockdown of Lpcat1 in primary WDR45-deficient dopaminergic neurons ameliorated axonal degeneration. Conditional Wdr45 KO in midbrain DAergic neurons (WDR45cKO mice), transmission electron microscopy, proteomic analysis, lipidomic analysis, Lpcat1 knockdown in primary neurons Molecular neurodegeneration Medium 39183331
2021 Wdr45 knockout mice show decreased mitochondrial complex I (CI) activity in the brain, suggesting that mitochondrial dysfunction accompanies Wdr45 deficiency. Whole-body Wdr45 KO mouse (TALEN-generated), biochemical measurement of respiratory chain complex activity in brain tissue Mammalian genome : official journal of the International Mammalian Genome Society Medium 34043061
2021 Knockdown of Wdr45 during mouse brain development (via in utero electroporation) causes abnormal dendritic development and synaptogenesis during corticogenesis, and less-developed terminal arbors of callosal axons, phenotypes rescued by RNAi-resistant Wdr45. Wdr45 protein localizes to excitatory synapses as determined by biochemical fractionation. In utero electroporation knockdown in mice, dendritic morphology analysis, biochemical fractionation of synaptosomes, RNAi rescue experiment Scientific reports Medium 34799629
2025 Cryo-EM structures of the ATG2A-WDR45/WIPI4 and ATG2A-WDR45/WIPI4-ATG9A complexes were resolved, revealing the architecture for lipid transfer and re-equilibration during phagophore membrane expansion. Molecular dynamics simulations elucidated the mechanism by which ATG2A extracts lipids from donor membranes within this tripartite complex. Cryo-electron microscopy (cryo-EM) structure determination, molecular dynamics simulations Autophagy High 40116844
2024 WDR45 deficiency impairs chaperone-mediated autophagy (CMA), leading to accumulation of fatty acid synthase (Fasn) and subsequent lipid droplet (LD) accumulation in Wdr45 KO cells. Fasn is a CMA substrate (co-immunoprecipitated with HSC70), and defective CMA elevates Fasn levels, promoting LD formation. CRISPR-Cas9 Wdr45 KO SN4741 cells, Co-IP of Fasn with HSC70, lysosomal inhibitor/CMA activator treatments, BODIPY lipid droplet staining, western blotting Lipids in health and disease Medium 38539242
2025 WDR45 forms gel-like condensates via its WD5 domain and undergoes phase separation with Caprin-1 to regulate stress granule (SG) disassembly. WDR45 competitively displaces G3BP1 from Caprin-1 to promote SG disassembly. BPAN-associated WDR45 mutations impair condensate formation and Caprin-1 interaction, resulting in delayed SG disassembly. In iPSC-derived midbrain neurons from a BPAN patient, SG recovery was delayed, directly linking WDR45 dysfunction to SG dysregulation. Phase separation assays, Co-IP, competitive binding assays, iPSC-derived midbrain neurons from BPAN patient, stress granule imaging and recovery assays, domain mapping (WD5) Nature communications Medium 40473629
2021 In a Dictyostelium discoideum model, the WDR45 homolog Wdr45l is required for autophagy; its loss phenocopies Vmp1 (ER omegasome protein) deficiency with impaired autophagy, local PtdIns3P enrichment, and chronic ER stress activation. Additional mutation of Atg1 (upstream autophagy regulator) in Wdr45l mutants prevented aberrant PtdIns3P localization and rescued axenic growth, positioning Wdr45l downstream of Atg1 in the PtdIns3P pathway. CRISPR-generated Dictyostelium KO strains, PtdIns3P lipid reporter imaging, genetic epistasis (Atg1 double mutant), ER stress assays, growth assays Autophagy Medium 34328055
2024 WIPI4 (WDR45) depletion causes defective autophagy and aberrant autophagosome formation in iPSC-derived midbrain dopaminergic neurons from BPAN patients. A screen of FDA-approved drugs identified cardiac glycosides as correcting disease-related defective autophagosome formation and restoring BPAN-specific gene expression profiles, demonstrating the autophagy defect is pharmacologically tractable. iPSC-derived midbrain dopaminergic neuronal model (patient and isogenic lines), high-content imaging-based drug screen, gene expression profiling bioRxiv : the preprint server for biologypreprint Low 37745522
2025 In a Drosophila dwdr45 KO model, induction of autophagy improved shortened lifespan and seizure-like behavior but did not restore locomotor function, establishing by genetic epistasis that autophagy deficiency accounts for some but not all phenotypes caused by WDR45 loss. CRISPR/Cas9 dwdr45 KO Drosophila, pharmacological autophagy induction, behavioral phenotyping (locomotion, seizure, lifespan) bioRxivpreprint Low bio_10.1101_2025.02.06.636873

Source papers

Stage 0 corpus · 74 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 De novo mutations in the autophagy gene WDR45 cause static encephalopathy of childhood with neurodegeneration in adulthood. Nature genetics 377 23435086
2012 Exome sequencing reveals de novo WDR45 mutations causing a phenotypically distinct, X-linked dominant form of NBIA. American journal of human genetics 286 23176820
2018 Insights into autophagosome biogenesis from structural and biochemical analyses of the ATG2A-WIPI4 complex. Proceedings of the National Academy of Sciences of the United States of America 178 30185561
2017 WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy. Nature communications 173 28561066
2015 The autophagy gene Wdr45/Wipi4 regulates learning and memory function and axonal homeostasis. Autophagy 118 26000824
2019 WDR45 contributes to neurodegeneration through regulation of ER homeostasis and neuronal death. Autophagy 82 31204559
2018 Iron overload is accompanied by mitochondrial and lysosomal dysfunction in WDR45 mutant cells. Brain : a journal of neurology 60 30169597
2021 β-propeller proteins WDR45 and WDR45B regulate autophagosome maturation into autolysosomes in neural cells. Current biology : CB 53 33636118
2021 WDR45, one gene associated with multiple neurodevelopmental disorders. Autophagy 53 33843443
2017 Severe infantile onset developmental and epileptic encephalopathy caused by mutations in autophagy gene WDR45. Epilepsia 53 29171013
2021 WDR45 Mutation Impairs the Autophagic Degradation of Transferrin Receptor and Promotes Ferroptosis. Frontiers in molecular biosciences 46 34012978
2014 De novo WDR45 mutation in a patient showing clinically Rett syndrome with childhood iron deposition in brain. Journal of human genetics 44 24621584
2016 WDR45 mutations in three male patients with West syndrome. Journal of human genetics 42 27030146
2015 Early-onset epileptic encephalopathy as the initial clinical presentation of WDR45 deletion in a male patient. European journal of human genetics : EJHG 35 26173968
2024 Loss of WIPI4 in neurodegeneration causes autophagy-independent ferroptosis. Nature cell biology 34 38454050
2016 WDR45 mutations in Rett (-like) syndrome and developmental delay: Case report and an appraisal of the literature. Molecular and cellular probes 34 26790960
2021 A neurodegeneration gene, WDR45, links impaired ferritinophagy to iron accumulation. Journal of neurochemistry 30 34837396
2020 Phenotypic and Imaging Spectrum Associated With WDR45. Pediatric neurology 30 32387008
2015 Analysis of the C19orf12 and WDR45 genes in patients with neurodegeneration with brain iron accumulation. Journal of the neurological sciences 26 25592411
2015 Novel WDR45 Mutation and Pathognomonic BPAN Imaging in a Young Female With Mild Cognitive Delay. Pediatrics 23 26240209
2022 Mutant WDR45 Leads to Altered Ferritinophagy and Ferroptosis in β-Propeller Protein-Associated Neurodegeneration. International journal of molecular sciences 22 36076926
2024 Pathological characteristics of axons and alterations of proteomic and lipidomic profiles in midbrain dopaminergic neurodegeneration induced by WDR45-deficiency. Molecular neurodegeneration 19 39183331
2021 Physiological significance of WDR45, a responsible gene for β-propeller protein associated neurodegeneration (BPAN), in brain development. Scientific reports 19 34799629
2018 The rod-shaped ATG2A-WIPI4 complex tethers membranes in vitro. Contact (Thousand Oaks (Ventura County, Calif.)) 19 30766969
2015 Exome sequencing reveals a novel WDR45 frameshift mutation and inherited POLR3A heterozygous variants in a female with a complex phenotype and mixed brain MRI findings. European journal of medical genetics 19 26096995
2021 Quantitative retrospective natural history modeling of WDR45-related developmental and epileptic encephalopathy - a systematic cross-sectional analysis of 160 published cases. Autophagy 17 34818117
2014 A novel WDR45 mutation in a patient with static encephalopathy of childhood with neurodegeneration in adulthood (SENDA). American journal of medical genetics. Part A 17 25044655
2021 A conserved ATG2 binding site in WIPI4 and yeast Hsv2 is disrupted by mutations causing β-propeller protein-associated neurodegeneration. Human molecular genetics 15 34368840
2022 WDR45 variants cause ferrous iron loss due to impaired ferritinophagy associated with nuclear receptor coactivator 4 and WD repeat domain phosphoinositide interacting protein 4 reduction. Brain communications 14 36751498
2021 The BPAN and intellectual disability disease proteins WDR45 and WDR45B modulate autophagosome-lysosome fusion. Autophagy 14 34105435
2021 Iron Accumulation and Changes in Cellular Organelles in WDR45 Mutant Fibroblasts. International journal of molecular sciences 14 34769084
2021 A Dictyostelium model for BPAN disease reveals a functional relationship between the WDR45/WIPI4 homolog Wdr45l and Vmp1 in the regulation of autophagy-associated PtdIns3P and ER stress. Autophagy 13 34328055
2019 Functional evidence for a de novo mutation in WDR45 leading to BPAN in a Chinese girl. Molecular genetics & genomic medicine 13 31332960
2018 Early onset developmental delay and epilepsy in pediatric patients with WDR45 variants. European journal of medical genetics 13 29981852
2020 De novo variants in WDR45 underlie beta-propeller protein-associated neurodegeneration in five independent families. Molecular genetics & genomic medicine 12 33037762
2015 Epileptic spasms: a previously unreported manifestation of WDR45 gene mutation. Epileptic disorders : international epilepsy journal with videotape 12 26609730
2021 A comprehensive phenotypic characterization of a whole-body Wdr45 knock-out mouse. Mammalian genome : official journal of the International Mammalian Genome Society 11 34043061
2016 A novel WDR45 mutation in a patient with β-propeller protein-associated neurodegeneration. Neurology. Genetics 11 27957548
2019 Early-onset presentation of a new subtype of β-Propeller protein-associated neurodegeneration (BPAN) caused by a de novo WDR45 deletion in a 6 year-old female patient. European journal of medical genetics 10 31536831
2017 Clinical features of a female with WDR45 mutation complicated by infantile spasms: a case report and literature review. Brain & development 10 28551038
2023 WDR45 mutation dysregulates iron homeostasis by promoting the chaperone-mediated autophagic degradation of ferritin heavy chain in an ER stress/p38 dependent mechanism. Free radical biology & medicine 9 36940732
2019 A Novel and Mosaic WDR45 Nonsense Variant Causes Beta-Propeller Protein-Associated Neurodegeneration Identified Through Whole Exome Sequencing and X chromosome Heterozygosity Analysis. Neuromolecular medicine 9 30612247
2018 Functional mRNA analysis reveals aberrant splicing caused by novel intronic mutation in WDR45 in NBIA patient. American journal of medical genetics. Part A 7 29681108
2017 Japanese WDR45 de novo mutation diagnosed by exome analysis: A case report. Neurology and clinical neuroscience 7 28932395
2019 Is WDR45 the missing link for ER stress-induced autophagy in beta-propeller associated neurodegeneration? Autophagy 6 31525124
2016 [A woman with beta-propeller protein-associated neurodegeneration identified by the WDR45 mutation presenting as Rett-like syndrome in childhood]. No to hattatsu = Brain and development 6 27349085
2025 ATG2A-WDR45/WIPI4-ATG9A complex-mediated lipid transfer and equilibration during autophagosome formation. Autophagy 4 40116844
2024 Lipid droplet accumulation in Wdr45-deficient cells caused by impairment of chaperone-mediated autophagic degradation of Fasn. Lipids in health and disease 3 38539242
2024 A c.726C>G (p.Tyr242Ter) nonsense mutation-associated with splicing alteration (NASA) of WDR45 gene underlies β-propeller protein-associated neurodegeneration (BPAN). Heliyon 3 38765101
2024 Asymmetrical parkinsonism due to novel WDR45 variant with beta-propeller protein-associated neurodegeneration (BPAN). Rinsho shinkeigaku = Clinical neurology 3 39401925
2017 A Case of Beta-propeller Protein-associated Neurodegeneration due to a Heterozygous Deletion of WDR45. Tremor and other hyperkinetic movements (New York, N.Y.) 3 29082105
2025 β-propeller protein-associated neurodegeneration protein WDR45 regulates stress granule disassembly via phase separation with Caprin-1. Nature communications 2 40473629
2024 Cardiac glycosides restore autophagy flux in an iPSC-derived neuronal model of WDR45 deficiency. bioRxiv : the preprint server for biology 2 37745522
2023 Targeted resequencing reveals high-level mosaicism for a novel frameshift variant in WDR45 associated with beta-propeller protein-associated neurodegeneration. The International journal of neuroscience 2 37099669
2023 Pathological characteristics of axons and proteome patterns in midbrain dopaminergic neurodegeneration induced by WDR45-deficiency. Research square 2 37292937
2023 Variants in the WDR45 Gene Within the OPA-2 Locus Associate With Isolated X-Linked Optic Atrophy. Investigative ophthalmology & visual science 2 37819743
2020 [A case of novel WDR45 mutation with beta-propeller protein-associated neurodegeneration (BPAN) presenting asymmetrical extrapyramidal signs]. Rinsho shinkeigaku = Clinical neurology 2 32307390
2025 Generation and characterization of a pluripotent stem cell line CIPi005-A derived from a female patient carrying non-canonical splice site c.827 + 1G > A in WDR45. Stem cell research 1 39970510
2025 AAV-Mediated Gene Transfer of WDR45 Corrects Neurological Deficits in the Mouse Model of Beta-Propeller Protein-Associated Neurodegeneration. Human gene therapy 1 39978419
2025 Mutation in Wdr45 leads to early motor dysfunction and widespread aberrant axon terminals in a beta-propeller protein associated neurodegeneration (BPAN) patient-inspired mouse model. Frontiers in neuroscience 1 40092065
2025 WDR45 deficiency shortens axon length in dopaminergic neurons from patient-derived iPSCs. Human molecular genetics 1 40984649
2025 Generation of two human iPSC lines from fibroblasts of BPAN patients carrying pathogenic variants in the WDR45 gene. Stem cell research 1 41496281
2024 A Case of Beta-Propeller Protein-Associated Neurodegeneration With a Unique Truncating Variant in the WDR45 Gene and Uncommon Clinical and Radiologic Findings. Cureus 1 38741870
2024 WDR45-dependent impairment of cell cycle in fibroblasts of patients with beta propeller protein-associated neurodegeneration (BPAN). Biochimica et biophysica acta. Molecular cell research 1 39265886
2024 WDR45 variants as a major cause for a clinically variable intellectual disability syndrome from early infancy in females. Journal of medical genetics 1 39467646
2022 Generation of an induced pluripotent stem cell line FDHPIi001-A derived from a female patient with WDR45-related neurodegeneration disease carrying non-canonical splice site c.344 + 5G > T. Stem cell research 1 36502619
2026 Elevated iron levels in tears of patients diagnosed with WDR45 X-linked optic atrophy. Orphanet journal of rare diseases 0 41943080
2026 Generation of six hiPSC lines from patients with WDR45-related neurodegenerative disease (Beta-propeller Protein-Associated Neurodegeneration, BPAN). Stem cell research 0 41962456
2026 Generation of hiPSCs (JUCGRMi008-A) from a β-propeller protein-associated neurodegeneration patient with WDR45 mutation. Stem cell research 0 42119323
2025 Significant relief of parkinsonism and dystonia with levodopa in beta-propeller protein-associated neurodegeneration: a video case report and insights into the WDR45 c.400C>T mutation. Clinical parkinsonism & related disorders 0 40470481
2025 Generation of two induced pluripotent stem cell lines (FDCHi011-A and FDCHi016-A) from different patients with NBIA5 syndrome carrying WDR45 m.700C > T and m.888G > A mutation. Stem cell research 0 41429710
2024 A unique case of neurodevelopmental disorders and epilepsy linked to WDR45 variant inheritance and maternal mosaicism. Gene 0 39500384
2024 WDR45-related encephalopathy mimicking Leigh syndrome associated with complex I deficiency: a case report. European journal of human genetics : EJHG 0 39578614
2024 Mutation in Wdr45 leads to early motor dysfunction and widespread aberrant axon terminals in a beta-propeller protein associated neurodegeneration (BPAN) patient-inspired mouse model. bioRxiv : the preprint server for biology 0 39763973

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