HOOK3 Gene

Name	hook microtubule-tethering protein 3
Description	Hook proteins are cytosolic coiled-coil proteins that contain conserved N-terminal domains, which attach to microtubules, and more divergent C-terminal domains, which mediate binding to organelles. The Drosophila Hook protein is a component of the endocytic compartment.[supplied by OMIM, Apr 2004]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HOOK3 is a multifunctional adaptor protein that plays pivotal roles in intracellular trafficking, cytoskeletal motor regulation, and oncogenic signaling. In the context of cancer, gene fusions involving HOOK3—such as FGFR1–HOOK3 in gastrointestinal stromal tumors"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "and HOOK3–RET in papillary thyroid carcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "—promote constitutive tyrosine kinase activation and malignant transformation. HOOK3 also functions as a cargo adaptor that links cytoplasmic dynein–dynactin and kinesin motors to their cargoes. Structural analyses have shown that its conserved Hook domain directly interacts with the dynein light intermediate chain 1 (LIC1), thereby facilitating formation of a motile dynein–dynactin complex."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, HOOK3 participates in the assembly of multiprotein complexes such as the FTS/Hook/FHIP complex, which regulates vesicle trafficking and fusion via the HOPS complex."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": " In addition, HOOK3 enhances the microtubule engagement of the kinesin‐3 motor KIF1C, thereby promoting cargo transport."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Dysregulation of HOOK3 is implicated in several pathological conditions. In Alzheimer’s disease, reduced HOOK3 expression is associated with impaired endosomal transport and increased β‐amyloid production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In hypoxia–reoxygenation injury of cardiomyocytes, targeting of HOOK3 by miR-496 modulates PI3K/Akt/mTOR signaling, leading to enhanced cell survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Elevated HOOK3 expression has also been linked to advanced tumor stage and compromised genomic integrity in prostate cancer, likely through its role in centrosome assembly"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", while copy number alterations of HOOK3 in endometrial serous carcinoma further underscore its clinical relevance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Finally, direct interactions between HOOK3 and receptors such as the scavenger receptor SR-A help regulate receptor turnover and endocytosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Collectively, these studies highlight HOOK3 as a central regulator of intracellular transport and signaling, with significant implications for cell homeostasis and disease.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Eileen Shi, Juliann Chmielecki, Chih-Min Tang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FGFR1 and NTRK3 actionable alterations in \"Wild-Type\" gastrointestinal stromal tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Transl Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12967-016-1075-6"}], "href": "https://doi.org/10.1186/s12967-016-1075-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27974047"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27974047"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Raffaele Ciampi, Thomas J Giordano, Kathryn Wikenheiser-Brokamp, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HOOK3-RET: a novel type of RET/PTC rearrangement in papillary thyroid carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocr Relat Cancer (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1677/ERC-07-0039"}], "href": "https://doi.org/10.1677/ERC-07-0039"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17639057"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17639057"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Courtney M Schroeder, Ronald D Vale "}, {"type": "b", "children": [{"type": "t", "text": "Assembly and activation of dynein-dynactin by the cargo adaptor protein Hook3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201604002"}], "href": "https://doi.org/10.1083/jcb.201604002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27482052"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27482052"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "In-Gyun Lee, Mara A Olenick, Malgorzata Boczkowska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A conserved interaction of the dynein light intermediate chain with dynein-dynactin effectors necessary for processivity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-03412-8"}], "href": "https://doi.org/10.1038/s41467-018-03412-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29515126"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29515126"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lai Xu, Mathew E Sowa, Jing Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An FTS/Hook/p107(FHIP) complex interacts with and promotes endosomal clustering by the homotypic vacuolar protein sorting complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e08-05-0473"}], "href": "https://doi.org/10.1091/mbc.e08-05-0473"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18799622"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18799622"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yoram Shotland, Helmut Krämer, Eduardo A Groisman "}, {"type": "b", "children": [{"type": "t", "text": "The Salmonella SpiC protein targets the mammalian Hook3 protein function to alter cellular trafficking."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Microbiol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1046/j.1365-2958.2003.03668.x"}], "href": "https://doi.org/10.1046/j.1365-2958.2003.03668.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12950921"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12950921"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Frank Kaiser, Stefan H E Kaufmann, Jens Zerrahn "}, {"type": "b", "children": [{"type": "t", "text": "IIGP, a member of the IFN inducible and microbial defense mediating 47 kDa GTPase family, interacts with the microtubule binding protein hook3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.01039"}], "href": "https://doi.org/10.1242/jcs.01039"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15075236"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15075236"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Nida Siddiqui, Alexander James Zwetsloot, Alice Bachmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-10644-9"}], "href": "https://doi.org/10.1038/s41467-019-10644-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31217419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31217419"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Lydia Herrmann, Caspar Wiegmann, Annika Arsalan-Werner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hook proteins: association with Alzheimer pathology and regulatory role of hook3 in amyloid beta generation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0119423"}], "href": "https://doi.org/10.1371/journal.pone.0119423"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25799409"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25799409"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Yongping Jin, Shimao Ni "}, {"type": "b", "children": [{"type": "t", "text": "miR-496 remedies hypoxia reoxygenation-induced H9c2 cardiomyocyte apoptosis via Hook3-targeted PI3k/Akt/mTOR signaling pathway activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.29316"}], "href": "https://doi.org/10.1002/jcb.29316"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31436348"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31436348"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Nathaniel Melling, Levon Harutyunyan, Claudia Hube-Magg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High-Level HOOK3 Expression Is an Independent Predictor of Poor Prognosis Associated with Genomic Instability in Prostate Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0134614"}], "href": "https://doi.org/10.1371/journal.pone.0134614"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26230842"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26230842"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Ozlen Saglam, Zhenya Tang, Guilin Tang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KAT6A amplifications are associated with shorter progression-free survival and overall survival in patients with endometrial serous carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0238477"}], "href": "https://doi.org/10.1371/journal.pone.0238477"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32877461"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32877461"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Hitomi Sano, Masaho Ishino, Helmut Krämer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The microtubule-binding protein Hook3 interacts with a cytoplasmic domain of scavenger receptor A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M611537200"}], "href": "https://doi.org/10.1074/jbc.M611537200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17237231"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17237231"}]}]}]}
Synonyms	HK3
Proteins	HOOK3_HUMAN
NCBI Gene ID	84376
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HOOK3 has 6,119 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 105 datasets.

Click the + buttons to view associations for HOOK3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

HOOK3 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 HOOK3 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 HOOK3 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 HOOK3 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 HOOK3 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 HOOK3 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 HOOK3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of HOOK3 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 HOOK3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of HOOK3 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 HOOK3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with HOOK3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with HOOK3 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 HOOK3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HOOK3 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 HOOK3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing HOOK3 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HOOK3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HOOK3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing HOOK3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing HOOK3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with HOOK3 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 HOOK3 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 HOOK3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HOOK3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with HOOK3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by HOOK3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with HOOK3 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 HOOK3 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 HOOK3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with HOOK3 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 HOOK3 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 HOOK3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of HOOK3 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 HOOK3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with HOOK3 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 HOOK3 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of HOOK3 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of HOOK3 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of HOOK3 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of HOOK3 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.