WDR4 Gene

HGNC Family	WD repeat domain containing (WDR)
Name	WD repeat domain 4
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 is excluded as a candidate for a form of nonsyndromic deafness (DFNB10), but is still a candidate for other disorders mapped to 21q22.3 as well as for the development of Down syndrome phenotypes. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, May 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nWDR4 is emerging as a critical factor in tumorigenesis through its role as an integral component of the METTL1/WDR4 methyltransferase complex that catalyzes N7‐methylguanosine (m7G) modifications on tRNAs. This RNA modification reprograms the translation of mRNAs, selectively boosting the synthesis of oncogenic proteins—including cell‐cycle regulators, growth factor receptors (such as EGFR and c‐MET), and extracellular matrix remodeling factors—to promote cancer cell survival, proliferation, invasion, chemoresistance, and metastasis. In intrahepatic cholangiocarcinoma, lung cancer, osteosarcoma, hepatocellular carcinoma, and non‐small cell lung cancer, WDR4 overexpression is strongly associated with adverse prognosis, in part by also modulating ubiquitin‐mediated degradation of key regulators that further sustain oncogenic signaling and establish an immunosuppressive tumor microenvironment."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural and biochemical investigations have revealed that WDR4 functions as a vital scaffold within the METTL1/WDR4 complex. This architectural role is essential for proper recognition of the tRNA T‐arm and the variable loop during m7G modification, as WDR4 supports conformational changes and stabilizes catalytic elements within METTL1. These insights not only illuminate the molecular basis of tRNA substrate binding and enzymatic activation but also suggest how post‐translational modifications might further regulate this process."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its oncogenic roles, aberrations in WDR4 have been implicated in several developmental disorders. Mutations in WDR4 contribute to conditions such as Galloway–Mowat syndrome—with features of growth deficiency, microcephaly, and renal anomalies—and microcephalic primordial dwarfism. In addition, studies in cerebellar development have shown that loss of WDR4 impairs the proliferation of granule neuron progenitors, leading to cerebellar hypoplasia and gait abnormalities. Defective WDR4 function is also linked to compromised ciliogenesis, which further disrupts protein and ubiquitin homeostasis and contributes to microcephaly. Moreover, genetic polymorphisms in WDR4 have been associated with altered glioma susceptibility, underscoring its multifaceted role in human pathophysiology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zihao Dai, Haining Liu, Junbin Liao, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitination of tumor suppressor PML regulates prometastatic and immunosuppressive tumor microenvironment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI89957"}], "href": "https://doi.org/10.1172/JCI89957"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28691927"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28691927"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hanqian Zeng, Shiwen Xu, Erjie Xia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aberrant expression of WDR4 affects the clinical significance of cancer immunity in pan-cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.203284"}], "href": "https://doi.org/10.18632/aging.203284"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34282052"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34282052"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Zhaoyu Wang, Peng Yu, Yutong Zou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "METTL1/WDR4-mediated tRNA m"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "7"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "G modification and mRNA translation control promote oncogenesis and doxorubicin resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-023-02695-6"}], "href": "https://doi.org/10.1038/s41388-023-02695-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37185458"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37185458"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Wei-Yu Han, Jie Wang, Jing Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "WDR4/TRIM28 is a novel molecular target linked to lenvatinib resistance that helps retain the stem characteristics in hepatocellular carcinomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2023.216259"}], "href": "https://doi.org/10.1016/j.canlet.2023.216259"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37279851"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37279851"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Shaifali Singh, Nai Yang Yeat, Ya-Ting Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PTPN23 ubiquitination by WDR4 suppresses EGFR and c-MET degradation to define a lung cancer therapeutic target."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-023-06201-4"}], "href": "https://doi.org/10.1038/s41419-023-06201-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37821451"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37821451"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Rui Dong, Chuanxu Wang, Bo Tang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "WDR4 promotes HCC pathogenesis through N"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "7"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "-methylguanosine by regulating and interacting with METTL1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2024.111145"}], "href": "https://doi.org/10.1016/j.cellsig.2024.111145"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38493882"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38493882"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jiazhi Li, Longfei Wang, Quentin Hahn, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Mutations in WDR4 as a new cause of Galloway-Mowat syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.40489"}], "href": "https://doi.org/10.1002/ajmg.a.40489"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30079490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30079490"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "A Trimouille, E Lasseaux, P Barat, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Cilia defects upon loss of WDR4 are linked to proteasomal hyperactivity and ubiquitin shortage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-024-07042-5"}], "href": "https://doi.org/10.1038/s41419-024-07042-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39251572"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39251572"}]}]}]}
Synonyms	TRM82, TRMT82
Proteins	WDR4_HUMAN
NCBI Gene ID	10785
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

WDR4 has 6,149 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 113 datasets.

Click the + buttons to view associations for WDR4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

WDR4 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 WDR4 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 WDR4 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 WDR4 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 WDR4 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 WDR4 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 WDR4 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 WDR4 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 WDR4 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of WDR4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of WDR4 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of WDR4 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 WDR4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with WDR4 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with WDR4 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 WDR4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of WDR4 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 WDR4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with WDR4 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 WDR4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing WDR4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing WDR4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing WDR4 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with WDR4 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 WDR4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with WDR4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with WDR4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with WDR4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with WDR4 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by WDR4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving WDR4 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with WDR4 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 WDR4 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 WDR4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with WDR4 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 WDR4 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 WDR4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of WDR4 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 WDR4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with WDR4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with WDR4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.