WDR45 Gene

HGNC Family	WD repeat domain containing (WDR)
Name	WD repeat domain 45
Description	This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene has a pseudogene at chromosome 4q31.3. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the biological validity and full-length nature of some variants have not been determined. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nWDR45, also known as WIPI4, encodes a beta‐propeller scaffold protein that is homologous to yeast Atg18 and plays a pivotal role in the canonical autophagy pathway. It serves as a platform for assembling the autophagic machinery—promoting autophagosome biogenesis and proper cargo recruitment—and ensuring effective autophagic flux. Loss‐of‐function mutations in this gene severely impair protein expression and disrupt normal autophagic processes, establishing its fundamental role in neuronal homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, WDR45/WIPI4 acts as an essential regulator of autophagy signal transduction by interfacing with key pathways—including those mediated by AMPK, mTOR, and ULK1—and by coordinating the recruitment of lipids and autophagy‐related proteins at sites of autophagosome initiation. Experimental studies in patient‐derived cells and model systems have demonstrated that WDR45 deficiency leads to the accumulation of aberrant early autophagic structures, impaired lysosomal function (including defective ferritinophagy), and subsequent cellular iron overload, mitochondrial dysfunction, oxidative stress, and even disturbances in cell cycle regulation. These findings underscore how proper WDR45 function is central to maintaining intracellular iron homeostasis through its regulation of autophagy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, deleterious mutations in WDR45 are causative for neurodegenerative disorders—most notably beta‐propeller protein‐associated neurodegeneration (BPAN), a form of neurodegeneration with brain iron accumulation (NBIA). Patients with BPAN typically present with early developmental delays and epileptic encephalopathies followed by progressive motor deterioration, parkinsonism, and cognitive decline later in life, often accompanied by distinctive brain iron deposition in regions such as the basal ganglia. In addition to these core neurodegenerative features, emerging evidence also links WDR45 dysfunction to other neurodevelopmental and even ocular phenotypes. Collectively, these observations highlight the dual significance of WDR45 in orchestrating autophagic and intracellular iron regulatory mechanisms while its disruption drives the pathogenesis of severe neurologic disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hirotomo Saitsu, Taki Nishimura, Kazuhiro Muramatsu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "De novo mutations in the autophagy gene WDR45 cause static encephalopathy of childhood with neurodegeneration in adulthood."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.2562"}], "href": "https://doi.org/10.1038/ng.2562"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23435086"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23435086"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tobias B Haack, Penelope Hogarth, Michael C Kruer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exome sequencing reveals de novo WDR45 mutations causing a phenotypically distinct, X-linked dominant form of NBIA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2012.10.019"}], "href": "https://doi.org/10.1016/j.ajhg.2012.10.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23176820"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23176820"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Susan J Hayflick, Michael C Kruer, Allison Gregory, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "WDR45 mutation dysregulates iron homeostasis by promoting the chaperone-mediated autophagic degradation of ferritin heavy chain in an ER stress/p38 dependent mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Free Radic Biol Med (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.freeradbiomed.2023.03.012"}], "href": "https://doi.org/10.1016/j.freeradbiomed.2023.03.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36940732"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36940732"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Barbara Garavaglia, Alessia Nasca, Stefania Mitola, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Phenotypic and Imaging Spectrum Associated With WDR45."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatr Neurol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.pediatrneurol.2020.03.005"}], "href": "https://doi.org/10.1016/j.pediatrneurol.2020.03.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32387008"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32387008"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Yuri A Zarate, Julie R Jones, Melanie A Jones, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lessons from a pair of siblings with BPAN."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2015.242"}], "href": "https://doi.org/10.1038/ejhg.2015.242"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26577041"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26577041"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Xiaojun Tang, Xiaoping Lan, Xiaozhen Song, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "[A woman with beta-propeller protein-associated neurodegeneration identified by the WDR45 mutation presenting as Rett-like syndrome in childhood]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "No To Hattatsu (2016)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27349085"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27349085"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Kanako Kano, Gaku Yamanaka, Kazuhiro Muramatsu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Beta-propeller protein-associated neurodegeneration presenting Rett-like features: A case report and literature review."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.61993"}], "href": "https://doi.org/10.1002/ajmg.a.61993"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33251766"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33251766"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Inbal Gazit, Idan Hecht, Chen Weiner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variants in the WDR45 Gene Within the OPA-2 Locus Associate With Isolated X-Linked Optic Atrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Invest Ophthalmol Vis Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1167/iovs.64.13.17"}], "href": "https://doi.org/10.1167/iovs.64.13.17"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37819743"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37819743"}]}]}]}
Synonyms	WDRX1, WIPI4, JM5, WIPI-4, NBIA5, NBIA4
Proteins	WIPI4_HUMAN
NCBI Gene ID	11152
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

WDR45 has 7,716 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 109 datasets.

Click the + buttons to view associations for WDR45 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

WDR45 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of WDR45 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of WDR45 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of WDR45 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of WDR45 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of WDR45 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of WDR45 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of WDR45 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of WDR45 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of WDR45 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of WDR45 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with WDR45 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with WDR45 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of WDR45 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of WDR45 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of WDR45 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with WDR45 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with WDR45 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of WDR45 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing WDR45 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with WDR45 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with WDR45 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of WDR45 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with WDR45 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with WDR45 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of WDR45 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by WDR45 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving WDR45 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving WDR45 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with WDR45 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with WDR45 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with WDR45 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with WDR45 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at WDR45 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of WDR45 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of WDR45 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing WDR45 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of WDR45 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with WDR45 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing WDR45 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of WDR45 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.