DOCK8 Gene

Name	dedicator of cytokinesis 8
Description	This gene encodes a member of the DOCK180 family of guanine nucleotide exchange factors. Guanine nucleotide exchange factors interact with Rho GTPases and are components of intracellular signaling networks. Mutations in this gene result in the autosomal recessive form of the hyper-IgE syndrome. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Jun 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DOCK8 is a multifaceted guanine nucleotide exchange factor whose functions span several key aspects of immune cell biology. In T cells, DOCK8 is essential for maintaining normal lymphocyte survival and memory formation; its deficiency disrupts immunological synapse formation and impairs CD8⁺ T‐cell survival and long‐term antiviral immunity (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In dendritic cells, DOCK8 acts as a Cdc42‐specific activator at the leading edge, ensuring efficient migration through three‐dimensional extracellular matrices necessary for T‐cell priming."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In B cells, DOCK8 functions as an adaptor that links Toll‐like receptor 9 (TLR9) signaling via MyD88 to downstream kinases (including Lyn, Syk, and STAT3), thereby facilitating B‐cell proliferation, differentiation, and the generation of high‐affinity antibody responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In natural killer cells, DOCK8 is critical for proper F‐actin accumulation at the lytic synapse, which underpins effective target cell conjugation and cytotoxicity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Furthermore, associations of DOCK8 with actin regulators such as WIP and WASp integrate receptor signaling with cytoskeletal reorganization in lymphocytes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " DOCK8 also plays a protective role during cellular migration through confined, collagen-dense environments by preserving cell shape integrity and preventing a form of catastrophic cell death termed “cytothripsis”."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Clinically, autosomal recessive mutations in DOCK8 result in a form of combined immunodeficiency characterized by recurrent viral and bacterial infections, elevated serum IgE, atopy, and increased risk of malignancy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_fs", "start_ref": "11", "end_ref": "13"}]}, {"type": "t", "text": " Additionally, emerging evidence even suggests that DOCK8 may be expressed outside the immune system—in the brain—hinting at a broader role in normal neurodevelopment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies illustrate that DOCK8 is indispensable for orchestrating immune responses through its regulation of cytoskeletal architecture, cell migration, receptor-mediated signaling pathways, and the maintenance of lymphocyte function and viability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "10"}, {"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " \n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Qian Zhang, Jeremiah C Davis, Ian T Lamborn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Combined immunodeficiency associated with DOCK8 mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "N Engl J Med (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1056/NEJMoa0905506"}], "href": "https://doi.org/10.1056/NEJMoa0905506"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19776401"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19776401"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Teresa Lambe, Greg Crawford, Andy L Johnson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DOCK8 is essential for T-cell survival and the maintenance of CD8+ T-cell memory."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Immunol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/eji.201141759"}], "href": "https://doi.org/10.1002/eji.201141759"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21969276"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21969276"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yosuke Harada, Yoshihiko Tanaka, Masao Terasawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migration during immune responses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2012-01-407098"}], "href": "https://doi.org/10.1182/blood-2012-01-407098"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22461490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22461490"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Katrina L Randall, Teresa Lambe, Andy L Johnson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dock8 mutations cripple B cell immunological synapses, germinal centers and long-lived antibody production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.1820"}], "href": "https://doi.org/10.1038/ni.1820"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19898472"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19898472"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Matthew Collin, Rachel Dickinson, Venetia Bigley "}, {"type": "b", "children": [{"type": "t", "text": "Haematopoietic and immune defects associated with GATA2 mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Haematol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/bjh.13317"}], "href": "https://doi.org/10.1111/bjh.13317"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25707267"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25707267"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Melissa C Mizesko, Pinaki P Banerjee, Linda Monaco-Shawver, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Defective actin accumulation impairs human natural killer cell function in patients with dedicator of cytokinesis 8 deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Allergy Clin Immunol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jaci.2012.12.1568"}], "href": "https://doi.org/10.1016/j.jaci.2012.12.1568"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23380217"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23380217"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hyoungjun Ham, Sabrice Guerrier, JungJin Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dedicator of cytokinesis 8 interacts with talin and Wiskott-Aldrich syndrome protein to regulate NK cell cytotoxicity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1202792"}], "href": "https://doi.org/10.4049/jimmunol.1202792"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23455509"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23455509"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Aino Ruusala, Pontus Aspenström "}, {"type": "b", "children": [{"type": "t", "text": "Isolation and characterisation of DOCK8, a member of the DOCK180-related regulators of cell morphology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2004.06.095"}], "href": "https://doi.org/10.1016/j.febslet.2004.06.095"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15304341"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15304341"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Erin Janssen, Mira Tohme, Mona Hedayat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A DOCK8-WIP-WASp complex links T cell receptors to the actin cytoskeleton."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI85774"}], "href": "https://doi.org/10.1172/JCI85774"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27599296"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27599296"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Qian Zhang, Christopher G Dove, Jyh Liang Hor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20141307"}], "href": "https://doi.org/10.1084/jem.20141307"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25422492"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25422492"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Vincent Plagnol, James Curtis, Michael Epstein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A robust model for read count data in exome sequencing experiments and implications for copy number variant calling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioinformatics (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/bioinformatics/bts526"}], "href": "https://doi.org/10.1093/bioinformatics/bts526"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22942019"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22942019"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Karin R Engelhardt, Sean McGhee, Sabine Winkler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Large deletions and point mutations involving the dedicator of cytokinesis 8 (DOCK8) in the autosomal-recessive form of hyper-IgE syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Allergy Clin Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jaci.2009.10.038"}], "href": "https://doi.org/10.1016/j.jaci.2009.10.038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20004785"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20004785"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Karin R Engelhardt, Michael E Gertz, Sevgi Keles, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The extended clinical phenotype of 64 patients with dedicator of cytokinesis 8 deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Allergy Clin Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jaci.2014.12.1945"}], "href": "https://doi.org/10.1016/j.jaci.2014.12.1945"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25724123"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25724123"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Bradley L Griggs, Sydney Ladd, Robert A Saul, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dedicator of cytokinesis 8 is disrupted in two patients with mental retardation and developmental disabilities."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genomics (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ygeno.2007.10.011"}], "href": "https://doi.org/10.1016/j.ygeno.2007.10.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18060736"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18060736"}]}]}]}
Synonyms	MRD2, ZIR8, HEL-205
Proteins	DOCK8_HUMAN
NCBI Gene ID	81704
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DOCK8 has 8,189 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, 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 DOCK8 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

DOCK8 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 DOCK8 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 DOCK8 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 DOCK8 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 DOCK8 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 DOCK8 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 DOCK8 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 DOCK8 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 DOCK8 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 DOCK8 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with DOCK8 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with DOCK8 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 DOCK8 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DOCK8 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 DOCK8 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 DOCK8 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with DOCK8 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of DOCK8 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing DOCK8 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 DOCK8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing DOCK8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with DOCK8 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 DOCK8 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 DOCK8 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DOCK8 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with DOCK8 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with DOCK8 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 DOCK8 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for DOCK8 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving DOCK8 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with DOCK8 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 DOCK8 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 DOCK8 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 DOCK8 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DOCK8 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 DOCK8 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 DOCK8 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DOCK8 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 DOCK8 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with DOCK8 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with DOCK8 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.