DOCK4 Gene

Name	dedicator of cytokinesis 4
Description	This gene is a member of the dedicator of cytokinesis (DOCK) family and encodes a protein with a DHR-1 (CZH-1) domain, a DHR-2 (CZH-2) domain and an SH3 domain. This membrane-associated, cytoplasmic protein functions as a guanine nucleotide exchange factor and is involved in regulation of adherens junctions between cells. Mutations in this gene have been associated with ovarian, prostate, glioma, and colorectal cancers. Alternatively spliced variants which encode different protein isoforms have been described, but only one has been fully characterized. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DOCK4 is an atypical guanine nucleotide exchange factor that plays multifaceted roles in regulating cytoskeletal dynamics, cell migration, and differentiation across diverse biological systems. In cancer settings, DOCK4 modulates cell motility by activating Rac1. For instance, in lung adenocarcinoma cells the TGF‐β/Smad pathway induces DOCK4 expression, which in turn promotes Rac1‐dependent cell protrusion, motility, and extravasation, thereby enhancing metastatic dissemination."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In ovarian serous carcinoma, recurrent homozygous deletions involving DOCK4 suggest that loss of its normal function may contribute to tumor suppressive failure."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In breast cancer, DOCK4’s interaction—mediated through its C‐terminal proline‐rich region—with the phosphoinositide-binding protein SH3YL1 facilitates Rac1 activation and promotes cell migration"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "; moreover, its expression can be indirectly modulated by noncoding RNAs to affect epithelial–mesenchymal transition and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In myelodysplastic syndromes, decreased DOCK4 expression associates with disrupted actin filament organization in erythroblasts, leading to dysplastic red blood cell development and correlating with poor clinical outcome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Outside of oncology and hematologic disease, DOCK4 is critical for proper neuronal development. It regulates neurite differentiation, axon–dendrite polarity, and dendritic spine morphogenesis through Rac1-mediated cytoskeletal remodeling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Disruptions of DOCK4 function—whether via microdeletions or rare missense mutations—have been linked to neurodevelopmental disorders such as autism, dyslexia"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", and are further supported by genetic associations with schizophrenia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Furthermore, upstream regulators including RhoG and its effector ELMO facilitate the plasma membrane recruitment of DOCK4, thereby ensuring its efficient activation of Rac1 to drive directional migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight DOCK4 as a critical modulator whose precise regulation of Rac1 activity influences both cancer cell invasion and metastasis, as well as neural differentiation and synaptic function. Its dysfunction—be it through down‐regulation, deletion, or mutation—can thus contribute to tumor progression, hematologic dysplasia, and neurodevelopmental disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jia-Ray Yu, Yilin Tai, Ying Jin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TGF-β/Smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.248963.114"}], "href": "https://doi.org/10.1101/gad.248963.114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25644601"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25644601"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kuan-Ting Kuo, Bin Guan, Yuanjian Feng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of DNA copy number alterations in ovarian serous tumors identifies new molecular genetic changes in low-grade and high-grade carcinomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-08-3913"}], "href": "https://doi.org/10.1158/0008-5472.CAN-08-3913"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19383911"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19383911"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Masakazu Kobayashi, Kohei Harada, Manabu Negishi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dock4 forms a complex with SH3YL1 and regulates cancer cell migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2014.01.027"}], "href": "https://doi.org/10.1016/j.cellsig.2014.01.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24508479"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24508479"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yue-Yue Wang, Lei Yan, Shuo Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNA AC073284.4 suppresses epithelial-mesenchymal transition by sponging miR-18b-5p in paclitaxel-resistant breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.28887"}], "href": "https://doi.org/10.1002/jcp.28887"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31215650"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31215650"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sriram Sundaravel, Ryan Duggan, Tushar Bhagat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reduced DOCK4 expression leads to erythroid dysplasia in myelodysplastic syndromes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1516394112"}], "href": "https://doi.org/10.1073/pnas.1516394112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26578796"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26578796"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yangui Xiao, Yinghui Peng, Jun Wan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The atypical guanine nucleotide exchange factor Dock4 regulates neurite differentiation through modulation of Rac1 GTPase and actin dynamics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.458612"}], "href": "https://doi.org/10.1074/jbc.M113.458612"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23720743"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23720743"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Alistair T Pagnamenta, Elena Bacchelli, Maretha V de Jonge, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of a family with rare deletions in CNTNAP5 and DOCK4 suggests novel risk loci for autism and dyslexia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Psychiatry (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopsych.2010.02.002"}], "href": "https://doi.org/10.1016/j.biopsych.2010.02.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20346443"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20346443"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Shuang Liang, Xue-lai Wang, Ming-yang Zou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Family-based association study of ZNF533, DOCK4 and IMMP2L gene polymorphisms linked to autism in a northeastern Chinese Han population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Zhejiang Univ Sci B (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1631/jzus.B1300133"}], "href": "https://doi.org/10.1631/jzus.B1300133"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24599690"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24599690"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Anna Alkelai, Sara Lupoli, Lior Greenbaum, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DOCK4 and CEACAM21 as novel schizophrenia candidate genes in the Jewish population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Neuropsychopharmacol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1017/S1461145711000903"}], "href": "https://doi.org/10.1017/S1461145711000903"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21682944"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21682944"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Kiyo Hiramoto, Manabu Negishi, Hironori Katoh "}, {"type": "b", "children": [{"type": "t", "text": "Dock4 is regulated by RhoG and promotes Rac-dependent cell migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2006.09.006"}], "href": "https://doi.org/10.1016/j.yexcr.2006.09.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17027967"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17027967"}]}]}]}
Proteins	DOCK4_HUMAN
NCBI Gene ID	9732
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DOCK4 has 9,096 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 127 datasets.

Click the + buttons to view associations for DOCK4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

DOCK4 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 DOCK4 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 DOCK4 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 DOCK4 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 DOCK4 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 DOCK4 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 DOCK4 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 DOCK4 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 DOCK4 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 DOCK4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of DOCK4 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 DOCK4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with DOCK4 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with DOCK4 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 DOCK4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DOCK4 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 DOCK4 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 DOCK4 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of DOCK4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DOCK4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing DOCK4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with DOCK4 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 DOCK4 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 DOCK4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DOCK4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with DOCK4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with DOCK4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with DOCK4 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of DOCK4 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 DOCK4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving DOCK4 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving DOCK4 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with DOCK4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with DOCK4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with DOCK4 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 DOCK4 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 DOCK4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DOCK4 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 DOCK4 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 DOCK4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DOCK4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.