DOCK3 Gene

Name	dedicator of cytokinesis 3
Description	This gene is specifically expressed in the central nervous system (CNS). It encodes a member of the DOCK (dedicator of cytokinesis) family of guanine nucleotide exchange factors (GEFs). This protein, dedicator of cytokinesis 3 (DOCK3), is also known as modifier of cell adhesion (MOCA) and presenilin-binding protein (PBP). The DOCK3 and DOCK1, -2 and -4 share several conserved amino acids in their DHR-2 (DOCK homology region 2) domains that are required for GEF activity, and bind directly to WAVE proteins [Wiskott-Aldrich syndrome protein (WASP) family Verprolin-homologous proteins] via their DHR-1 domains. The DOCK3 induces axonal outgrowth in CNS by stimulating membrane recruitment of the WAVE complex and activating the small G protein Rac1. This gene is associated with an attention deficit hyperactivity disorder-like phenotype by a complex chromosomal rearrangement. [provided by RefSeq, Aug 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DOCK3 is an atypical guanine nucleotide exchange factor that selectively activates Rac1 to modulate cytoskeletal dynamics in diverse cellular contexts. In tumor cells, DOCK3 functions as a key mediator of mesenchymal‐type movement by forming complexes with scaffolding proteins such as NEDD9, thereby promoting Rac1 activation, remodeling of the actin cytoskeleton, and enhanced cell motility and invasion."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " In neural tissues, where DOCK3 (also known as MOCA) is almost exclusively expressed, it plays dual roles that are essential for maintaining neuronal integrity. DOCK3 facilitates BDNF‐mediated axonal outgrowth and branching by activating Rac1 and inactivating downstream effectors such as glycogen synthase kinase‐3β, which in turn promotes microtubule assembly and proper axon guidance. In addition, DOCK3 protects retinal ganglion cells from excitotoxicity by interacting with NMDA receptor subunits and reducing their surface expression, thereby contributing to neuroprotection and optic nerve regeneration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": " Moreover, human genetic studies have revealed that loss‐of‐function variants or structural disruptions in DOCK3 are associated with neurodevelopmental disorders characterized by developmental delay, hypotonia, and ataxia, thereby underscoring its indispensable role in proper central nervous system development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies highlight DOCK3 as a central regulator of Rac1 signaling that not only drives aberrant cell motility and metastasis in cancer but also supports axonal remodeling, neuroprotection, and normal neurodevelopment. Its dual roles in tumor progression and neural function render DOCK3 an attractive therapeutic target in both oncology and neurodegenerative or neurodevelopmental disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Victoria Sanz-Moreno, Gilles Gadea, Jessica Ahn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rac activation and inactivation control plasticity of tumor cell movement."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2008.09.043"}], "href": "https://doi.org/10.1016/j.cell.2008.09.043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18984162"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18984162"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Wen-Hao Yang, Hsin-Yi Lan, Chi-Hung Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RAC1 activation mediates Twist1-induced cancer cell migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb2455"}], "href": "https://doi.org/10.1038/ncb2455"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22407364"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22407364"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jessica Ahn, Victoria Sanz-Moreno, Christopher J Marshall "}, {"type": "b", "children": [{"type": "t", "text": "The metastasis gene NEDD9 product acts through integrin β3 and Src to promote mesenchymal motility and inhibit amoeboid motility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.101444"}], "href": "https://doi.org/10.1242/jcs.101444"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22328516"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22328516"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xingli Zhu, Guanghui Gao, Kaili Chu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of RAC1-GEF DOCK3 by miR-512-3p contributes to suppression of metastasis in non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biochem Cell Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biocel.2015.02.005"}], "href": "https://doi.org/10.1016/j.biocel.2015.02.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25687035"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25687035"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kazuhiko Namekata, Yasushi Enokido, Kazu Iwasawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MOCA induces membrane spreading by activating Rac1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M311275200"}], "href": "https://doi.org/10.1074/jbc.M311275200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14718541"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14718541"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kazuhiko Namekata, Chikako Harada, Xiaoli Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dock3 stimulates axonal outgrowth via GSK-3β-mediated microtubule assembly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.4884-11.2012"}], "href": "https://doi.org/10.1523/JNEUROSCI.4884-11.2012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22219288"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22219288"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "K Namekata, A Kimura, K Kawamura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dock3 attenuates neural cell death due to NMDA neurotoxicity and oxidative stress in a mouse model of normal tension glaucoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cdd.2013.91"}], "href": "https://doi.org/10.1038/cdd.2013.91"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23852370"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23852370"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Kentaro Semba, Kazuhiko Namekata, Atsuko Kimura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dock3 overexpression and p38 MAPK inhibition synergistically stimulate neuroprotection and axon regeneration after optic nerve injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Lett (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neulet.2014.08.034"}], "href": "https://doi.org/10.1016/j.neulet.2014.08.034"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25172145"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25172145"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Christina A Markunas, Kaia S Quinn, Ann L Collins, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variants in SLC9A9 are associated with measures of attention-deficit/hyperactivity disorder symptoms in families."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Psychiatr Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/YPG.0b013e3283351209"}], "href": "https://doi.org/10.1097/YPG.0b013e3283351209"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20032819"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20032819"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Kimberly Wiltrout, Alejandro Ferrer, Ingrid van de Laar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variants in DOCK3 cause developmental delay and hypotonia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41431-019-0397-2"}], "href": "https://doi.org/10.1038/s41431-019-0397-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30976111"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30976111"}]}]}]}
Synonyms	PBP, MOCA
Proteins	DOCK3_HUMAN
NCBI Gene ID	1795
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DOCK3 has 5,276 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 119 datasets.

Click the + buttons to view associations for DOCK3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

DOCK3 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 DOCK3 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 DOCK3 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 DOCK3 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 DOCK3 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 DOCK3 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 DOCK3 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 DOCK3 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 DOCK3 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 DOCK3 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 DOCK3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of DOCK3 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 DOCK3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with DOCK3 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with DOCK3 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 DOCK3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DOCK3 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 DOCK3 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 DOCK3 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 DOCK3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DOCK3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing DOCK3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing DOCK3 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 DOCK3 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 DOCK3 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 DOCK3 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 DOCK3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DOCK3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with DOCK3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of DOCK3 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 DOCK3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with DOCK3 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 DOCK3 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 DOCK3 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 DOCK3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DOCK3 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 DOCK3 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 DOCK3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DOCK3 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 DOCK3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with DOCK3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.