Affinage

DOCK4

Dedicator of cytokinesis protein 4 · UniProt Q8N1I0

Length
1966 aa
Mass
225.2 kDa
Annotated
2026-04-28
48 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DOCK4 is an atypical guanine nucleotide exchange factor (GEF) that activates Rac1 and Rap1 GTPases to regulate cytoskeletal dynamics, cell adhesion, and migration across diverse tissues. Its DHR-2 domain catalyzes nucleotide exchange on Rac1 and Rap1, while the DHR-1 domain binds PIP3 for membrane targeting; upstream activation is mediated by RhoG/ELMO-dependent translocation to the plasma membrane, GSK3β phosphorylation in the Wnt/β-catenin pathway, and TBK1-mediated phosphorylation at S1787 that enables CRKII engagement and Rap1 signaling (PMID:12628187, PMID:17027967, PMID:18459162, PMID:18641688, PMID:40227532). In neurons, DOCK4 localizes to dendritic spines where it promotes spine formation and excitatory synaptic transmission through Rac1-dependent cortactin interaction and regulation of NMDA/AMPA receptor subunit expression; it also functions as a scaffold forming a Dynein/DOCK4/Nav1.7 complex in DRG neurons to control Nav1.7 membrane trafficking and heat nociception (PMID:23536706, PMID:31388105, PMID:40759894). Beyond the nervous system, DOCK4 maintains endothelial adherens junction integrity by balancing Rac1 and RhoA activities, couples SR-B1 to LDL transcytosis via Rac1 activation in endothelial cells, supports erythropoiesis through RAC1-dependent F-actin organization, and mediates TGF-β/Smad-driven tumor cell extravasation (PMID:35477279, PMID:31019307, PMID:26578796, PMID:25644601).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2003 High

    Establishing DOCK4 as a GEF for Rap1 that promotes adherens junctions and functions as a tumor suppressor resolved its basic enzymatic identity and linked it to cell adhesion and cancer.

    Evidence GTPase activation assays, C. elegans ced-5 rescue, and soft agar/invasion assays with cancer-associated mutant in human cell lines

    PMID:12628187

    Open questions at the time
    • Rac1 GEF activity not yet demonstrated
    • structural basis for Rap1 specificity unknown
    • in vivo tumor suppressor role not validated in mammalian models
  2. 2006 High

    Identifying RhoG/ELMO as upstream activators that translocate DOCK4 to the membrane for Rac1 activation established DOCK4 as a dual Rac1/Rap1 GEF regulated by a GTPase cascade, answering how its membrane recruitment and activation are controlled.

    Evidence Co-immunoprecipitation, subcellular fractionation, Rac1-GTP pulldown, and siRNA knockdown with migration assay in NIH3T3 cells; parallel identification of a brain-specific isoform binding Rac and harmonin

    PMID:16464467 PMID:17027967

    Open questions at the time
    • ELMO isoform specificity not resolved
    • harmonin interaction confirmed only by Y2H
    • structural basis of RhoG-ELMO-DOCK4 complex unknown
  3. 2008 High

    Demonstrating that DOCK4 integrates into the Wnt/β-catenin destruction complex (APC/Axin/GSK3β) and is phosphorylated by GSK3β to enhance Rac activation revealed a non-canonical role as a scaffold linking Wnt signaling to cytoskeletal remodeling, while PIP3 binding via DHR-1 established a lipid-dependent regulatory mechanism.

    Evidence Co-IP of DOCK4 with APC/Axin/GSK3β, in vitro kinase assay, TCF reporter in zebrafish; PIP3-analog bead binding with deletion mapping; neurite outgrowth assays in hippocampal neurons with ELMO2/CrkII complex

    PMID:18459162 PMID:18615735 PMID:18641688

    Open questions at the time
    • Phosphorylation site on DOCK4 by GSK3β not mapped
    • relative contribution of PIP3 vs. ELMO to membrane targeting unclear
    • in vivo Wnt phenotype not tested in mammalian models at this stage
  4. 2013 High

    Showing that DOCK4 concentrates in dendritic spines and requires both GEF activity and cortactin binding to promote spine formation established the molecular mechanism by which DOCK4 controls synaptic structure.

    Evidence shRNA knockdown and rescue with GEF-dead and cortactin-binding-deficient mutants, Co-IP, confocal spine density quantification in hippocampal neurons

    PMID:23536706

    Open questions at the time
    • Whether cortactin interaction is direct or bridged unknown
    • electrophysiological consequences not assessed
    • upstream signals activating DOCK4 at spines not identified
  5. 2015 High

    Identifying DOCK4 as a TGF-β/Smad transcriptional target that drives tumor extravasation via Rac1, and demonstrating its requirement for erythropoiesis via RAC1-dependent actin organization, expanded DOCK4 function beyond neurons to cancer metastasis and hematopoiesis.

    Evidence Smad pathway epistasis and in vivo extravasation assays in lung adenocarcinoma; siRNA in CD34+ cells with erythroid colony assay, F-actin/ADDUCIN phosphorylation readouts, and rescue in MDS erythroblasts

    PMID:25644601 PMID:26578796

    Open questions at the time
    • Direct transcriptional regulation by Smad not confirmed by ChIP
    • specific DOCK4 domains required for erythroid function not mapped
    • relationship between Rap1 vs. Rac1 activation in erythropoiesis unclear
  6. 2019 High

    Discovering that SR-B1 recruits DOCK4 via its cytoplasmic tail to drive LDL transcytosis through Rac1 activation revealed a receptor-coupled GEF mechanism in endothelial lipid transport, while conditional Dock4 KO in hippocampal CA1 neurons established that DOCK4 controls global protein synthesis, glutamate receptor expression, and social behavior via Rac1.

    Evidence Co-IP with SR-B1 tail mutants, LDL transcytosis assay, in vivo colocalization; Dock4 conditional KO mice with electrophysiology, spine analysis, Rac1 viral rescue, NMDA pharmacological rescue; phosphoproteomics in hematopoietic cells showing LYN/SHP1/SHIP1 perturbation

    PMID:31019307 PMID:31308061 PMID:31388105

    Open questions at the time
    • Whether DOCK4 GEF activity is required for SR-B1 coupling not tested with GEF-dead mutant
    • how DOCK4 controls global translation machinery not resolved
    • LYN/SHP1 pathway connection to Rac1 unclear
  7. 2022 High

    Demonstrating that DOCK4 maintains endothelial barrier integrity by balancing Rac1 and RhoA upon S1P stimulation, with DOCK4-deficient mice exhibiting pulmonary hemorrhage, established its vascular homeostatic function and the RhoA-counterbalancing mechanism.

    Evidence DOCK4-deficient mice with hemorrhage/permeability phenotypes, DOCK4 silencing and reconstitution in HPAEC, Rac1/RhoA activation assays, subcellular fractionation upon S1P treatment

    PMID:35477279

    Open questions at the time
    • Whether DOCK4 directly inhibits RhoA or acts indirectly via Rac1 not resolved
    • S1P receptor isoform specificity for DOCK4 recruitment unknown
    • role in other vascular beds not tested
  8. 2024 High

    Identifying DOCK4 as a scaffold in a Dynein/DOCK4/Nav1.7 ternary complex that mediates Nav1.7 membrane trafficking in DRG neurons, regulated by histone H4K8 lactylation, revealed a GEF-independent adaptor function and an epigenetic control layer for DOCK4 expression in pain signaling.

    Evidence Co-IP and proximity ligation assay for ternary complex, Nav1.7 trafficking assay, Dock4 KD in mice and nonhuman primates, histone lactylation ChIP, nociception behavioral assays

    PMID:40759894

    Open questions at the time
    • Whether GEF activity contributes to Nav1.7 trafficking not tested
    • lactylation writers/erasers controlling DOCK4 locus not identified
    • applicability to other ion channels unknown
  9. 2025 Medium

    Revealing that TBK1 phosphorylates DOCK4 at S1787 (scaffolded by THEMIS2) to enable CRKII engagement and Rap1 activation in ovarian cancer metastasis provided the first mapped phospho-regulatory switch controlling DOCK4's Rap1 GEF output.

    Evidence IP-mass spectrometry, phospho-site mapping, GST-Rap1 pulldown, Co-IP, in vivo metastasis model

    PMID:40227532

    Open questions at the time
    • Whether S1787 phosphorylation also regulates Rac1 activation unknown
    • structural basis for phospho-dependent CRKII binding not resolved
    • single lab finding awaiting independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for DOCK4's dual Rac1/Rap1 specificity, the relative contributions of GEF-dependent versus GEF-independent (scaffolding) functions across tissues, and how tissue-specific isoforms and post-translational modifications partition DOCK4 among its diverse signaling outputs.
  • No crystal or cryo-EM structure of DOCK4 DHR-2 with Rac1 or Rap1
  • GEF-independent adaptor functions not systematically separated from GEF activity
  • isoform-specific functions in inner ear and brain not fully delineated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 8 GO:0060090 molecular adaptor activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005856 cytoskeleton 2 GO:0005829 cytosol 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-112316 Neuronal System 4 R-HSA-1500931 Cell-Cell communication 3 R-HSA-1643685 Disease 3
Partners
CORTCRKIIELMO2SCARB1SH3YL1TBK1THEMIS2USP36
Complex memberships
APC/Axin/GSK3β destruction complexDOCK4/ELMO/CrkIIDynein/DOCK4/Nav1.7

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 DOCK4 specifically activates Rap1 GTPase, enhancing formation of adherens junctions; a recurrent missense mutant found in human prostate and ovarian cancers is defective in Rap1 activation; wild-type DOCK4 rescues the engulfment defect of C. elegans ced-5 mutants but the cancer-associated mutant does not GTPase activation assays, C. elegans genetic rescue, soft agar/invasion assays with wild-type vs. mutant DOCK4 Cell High 12628187
2006 Dock4 is regulated upstream by the small GTPase RhoG and its effector ELMO; active RhoG induces translocation of the Dock4-ELMO complex from the cytoplasm to the plasma membrane and enhances Dock4/ELMO-dependent Rac1 activation and cell migration; Dock4 knockdown in NIH3T3 cells reduces cell migration Co-immunoprecipitation, subcellular fractionation/imaging, Rac1 activation assay (GST-PAK pulldown), siRNA knockdown with migration assay Experimental cell research High 17027967
2008 DOCK4 mediates Wnt-induced Rac activation in the canonical Wnt/β-catenin pathway by interacting with the β-catenin degradation complex (APC, Axin, GSK3β); this interaction enhances β-catenin stability and Axin degradation; GSK3β phosphorylates DOCK4, which enhances Wnt-induced Rac activation; DOCK4 is required for Wnt/β-catenin activity in vivo in zebrafish Co-immunoprecipitation, in vitro kinase assay, TCF reporter assay, zebrafish Wnt reporter model, β-catenin stability assays Oncogene High 18641688
2008 Dock4 promotes dendritic growth and branching in hippocampal neurons via Rac activation; Dock4 forms a complex with ELMO2 and CrkII in hippocampal neurons; the C-terminal Crk-binding region of Dock4 is required for morphological effects; knockdown reduces dendritic growth and branching while overexpression with ELMO2 enhances it shRNA knockdown, overexpression, Co-immunoprecipitation, Rac activation assay, morphometric analysis of cultured hippocampal neurons Journal of neuroscience research High 18615735
2006 A novel DOCK4 isoform (DOCK4-Ex49) is expressed in brain, eye, and inner ear; it localizes to stereocilia hair bundles in the inner ear; it binds nucleotide-free Rac and activates Rac as effectively as DOCK2; it interacts with the PDZ-domain protein harmonin (USH1C) identified by yeast two-hybrid Yeast two-hybrid, immunostaining with isoform-specific antibody, Rac binding/activation assay Journal of molecular biology Medium 16464467
2008 DOCK4 and its splicing variant bind PIP3 through the DHR-1 domain, suggesting regulation of DOCK4 by phosphoinositides PIP3-analog bead binding assay, deletion mutant mapping IUBMB life Medium 18459162
2013 Dock4 is concentrated in dendritic spines and promotes spine formation via interaction with the actin-binding protein cortactin; a GEF-deficient mutant and a mutant lacking the cortactin-binding region both fail to rescue spine density upon Dock4 knockdown; cortactin knockdown suppresses Dock4-mediated spine formation shRNA knockdown and rescue with domain mutants, Co-immunoprecipitation, confocal imaging, dendritic spine density quantification Molecular biology of the cell High 23536706
2014 Dock4 forms a complex with SH3YL1 (a phosphoinositide-binding protein) via the C-terminal proline-rich region of Dock4; SH3YL1 interaction promotes Dock4-mediated Rac1 activation and cell migration; phosphoinositide-binding domain mutations in SH3YL1 disrupt its ability to promote Dock4-mediated migration; SH3YL1 depletion suppresses cell migration Co-immunoprecipitation, Rac1 activation assay, domain-mapping, siRNA knockdown, cell migration assay Cellular signalling Medium 24508479
2015 TGF-β induces DOCK4 expression via the Smad pathway in lung adenocarcinoma cells; DOCK4 induction mediates TGF-β's pro-metastatic effects by enhancing tumor cell extravasation through Rac1 activation, without affecting EMT Smad pathway inhibition/activation, DOCK4 knockdown/overexpression, Rac1 activation assay, in vivo extravasation assays, cell motility/invasion assays Genes & development High 25644601
2015 DOCK4 knockdown in primary marrow CD34+ stem cells leads to decreased erythroid colony formation and increased apoptosis; reduced DOCK4 leads to disruption of F-actin filament network in erythroblasts via decreased RAC1 GTPase activation, leading to increased phosphorylation of the actin-stabilizing protein ADDUCIN siRNA knockdown in primary CD34+ cells, erythroid colony assay, F-actin quantification, RAC1 activation assay, ADDUCIN phosphorylation western blot, DOCK4 re-expression in MDS patient erythroblasts Proceedings of the National Academy of Sciences of the United States of America High 26578796
2017 DOCK4 promotes nuclear β-catenin accumulation in GBM progenitor cells via increased GSK3β activity in a feed-forward mechanism; nuclear β-catenin then induces miR-302 expression, which represses cyclin D1 and stemness features, resulting in anti-proliferative effects; DOCK4 overexpression suppresses self-renewal and tumorigenicity of GBM stem-like cells DOCK4 overexpression, GSK3β activity assay, β-catenin nuclear fractionation, miR-302 reporter, cyclin D1 western blot, neurosphere assay Oncogene Medium 28925399
2019 SR-B1 recruits DOCK4 via an eight-amino-acid cytoplasmic domain of the receptor; DOCK4 promotes internalization of SR-B1 and LDL transcytosis across endothelial monolayers by coupling LDL binding to SR-B1 with activation of RAC1 Co-immunoprecipitation, domain mapping (SR-B1 cytoplasmic tail mutants), Rac1 activation assay, LDL transcytosis assay across endothelial monolayers, SR-B1/DOCK4 colocalization in vesicles in vivo Nature High 31019307
2019 Dock4 deficiency in mice reduces Rac1 activity in hippocampus, causing downregulation of global protein synthesis and diminished AMPA and NMDA receptor subunit expression; conditional Dock4 deletion in CA1 neurons attenuates excitatory synaptic transmission and decreases spine density; Rac1 replenishment in CA1 restores synaptic transmission and corrects social deficits; NMDA receptor pharmacological activation also restores social novelty preference Dock4 KO and conditional KO mice, Rac1 activation assay, electrophysiology, spine density analysis, western blot for receptor subunits, viral Rac1 rescue, pharmacological NMDA activation Molecular psychiatry High 31388105
2019 Reduced DOCK4 expression in hematopoietic stem cells leads to increased tyrosine phosphorylation of LYN kinase and phosphatases SHIP1 (INPP5D) and SHP1 (PTPN6); LYN kinase targets SHIP1 and SHP1 as substrates; these signaling alterations increase migration and impede HSC differentiation; pharmacological SHP1 inhibition reverses erythroid differentiation block in DOCK4-low/-7q MDS cells Phosphoproteomics, siRNA knockdown, kinase substrate assay, migration assay, erythroid differentiation assay, pharmacological inhibition Clinical cancer research Medium 31308061
2020 Two DOCK4 variants (Exon27-52 deletion producing Dock4-945VS, and missense R853H) show decreased ability to activate both Rac1 and Rap1, are dysfunctional for cell morphology/cytoskeleton regulation, and have compromised function in promoting neurite outgrowth and dendritic spine formation; R853H partially loses ability to promote excitatory synaptic transmission while 945VS totally loses it GTPase activation assay (Rac1, Rap1), cell morphology analysis, neurite outgrowth assay in Neuro-2a cells and hippocampal neurons, spine density quantification, electrophysiological recordings Frontiers in cellular neuroscience High 32009906
2020 DOCK4 overexpression increases cytotrophoblast (CTB) invasiveness, consistent with the placenta accreta spectrum (PAS) over-invasion phenotype; DOCK4 mRNA is the most highly upregulated molecule in PAS CTBs compared to normal depth-invading CTBs Global gene expression comparison, DOCK4 overexpression with invasion assay Proceedings of the National Academy of Sciences of the United States of America Medium 32576693
2022 DOCK4 deficiency in mice causes pulmonary hemorrhage, incomplete smooth muscle coverage in pulmonary vessels, increased basal microvascular permeability, and impaired S1P-induced reversal of thrombin-induced permeability; DOCK4 rapidly translocates to the cell periphery (detergent-insoluble fraction) upon S1P treatment; DOCK4 absence prevents S1P-induced Rac1 activation; DOCK4-silenced cells exhibit enhanced RhoA activation; DOCK4 maintains AJs by balancing RhoA and Rac1 activity DOCK4-deficient mice (in vivo hemorrhage, permeability), DOCK4 silencing and reconstitution in HPAEC, subcellular fractionation, Rac1/RhoA activation assays, endothelial permeability assay Arteriosclerosis, thrombosis, and vascular biology High 35477279
2022 Dock4 knockdown in cochlear hair cells causes hair bundle deficits, increased oxidative stress, and progressive HC apoptosis; mechanistically, Rac1/β-catenin signaling is downregulated in Dock4 KD cochleae, causing disorganized stereocilia and increased oxidative stress piggyBac transposon-mediated Dock4 KD mice, ABR/DPOAE hearing tests, hair bundle morphology, Rac1 and β-catenin western blot/immunofluorescence, oxidative stress markers, HC apoptosis assay Fundamental research Medium 38933554
2024 Brain endothelial cells activate EGFR signaling in triple-negative breast cancer cells via soluble factors, and this activation occurs via DOCK4 (RAC1 GEF); DOCK4 is required for breast cancer cell extravasation to the brain in vivo; DOCK4 knockdown inhibits elongated morphology preceding intercalation into brain endothelium; DOCK4 and DOCK9 together mediate paracrine stimulation of mesenchymal-like morphology via RAC1 and CDC42 DOCK4 knockdown, in vivo brain extravasation assay, cell morphology analysis, EGFR inhibitor (Afatinib) experiments, RAC1/CDC42 activation assays Communications biology Medium 38762624
2024 HIF2α functions in normoxia in kidney epithelial cells to induce Dock4/Rac1/Pak1 signaling, which mediates stability and compaction of E-cadherin at nascent adherens junctions; HIF2α- or Dock4-deficient cells show aberrant cyst morphogenesis in 3D cultures HIF2α and Dock4 siRNA knockdown, Rac1/Pak1 activation assays, E-cadherin localization imaging, 3D cyst morphogenesis assay Scientific reports Medium 38802496
2024 Dock4 in dorsal root ganglion neurons interacts with Nav1.7 and mediates its trafficking from the membrane to the cytoplasm; Dock4 acts as an adaptor binding the motor protein Dynein to form a Dynein/DOCK4/Nav1.7 complex, where Dynein provides mechanical force for Nav1.7 trafficking; DOCK4 expression in DRG neurons is regulated by histone H4K8 lactylation; DOCK4 deficiency increases heat nociception Co-immunoprecipitation, proximity ligation assay, Nav1.7 trafficking assay, Dock4 KD in DRG (mice and nonhuman primates), histone lactylation ChIP, nociception behavioral assays Nature communications High 40759894
2024 Heterozygous loss-of-function missense variants in DOCK4 impair neurite outgrowth in Neuro-2A cells; Dock4 knockout Neuro-2A cells also exhibit defects in neurite outgrowth; molecular modeling suggests missense variants affect the globular structure of DOCK4 In vitro functional expression of DOCK4 variants in Neuro-2A cells (neurite outgrowth assay), Dock4 KO cells, molecular modeling Human genetics Medium 38526744
2025 THEMIS2 acts as a molecular scaffold that recruits TBK1 to DOCK4, facilitating phosphorylation of DOCK4 at serine 1787 (S1787); this post-translational modification enables DOCK4 to engage with CRKII, subsequently triggering Rap1 signaling activation and promoting ovarian cancer metastasis Immunoprecipitation-mass spectrometry, GST pull-down assay for active Rap1 (Rap1-GTP), co-immunoprecipitation, phospho-site mapping, wound healing and invasion assays, in vivo metastasis model Cellular oncology Medium 40227532
2024 Dock4 facilitates excitatory synaptic transmission in spinal dorsal horn neurons by promoting GluN2B expression at the synaptic site and synaptogenesis; Dock4 knockdown prevents dendritic growth, synaptogenesis, and increased excitatory postsynaptic currents in a spinal nerve ligation neuropathic pain model Dock4 RNAi knockdown, whole-cell patch clamp electrophysiology in spinal cord slices, GluN2B immunofluorescence/western blot, Rac1 activation assay, dendritic spine analysis in cultured dorsal spinal neurons Frontiers in molecular neuroscience Medium 39282658
2021 USP36 directly binds DOCK4 and mediates its deubiquitination, thereby stabilizing DOCK4; stabilized DOCK4 activates Wnt/β-catenin signaling and promotes EMT in diabetic renal tubular epithelial cells Co-immunoprecipitation, ubiquitination assay, USP36 overexpression/knockdown with DOCK4 stability readout, EMT marker western blot Frontiers in cell and developmental biology Medium 33968925

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 SR-B1 drives endothelial cell LDL transcytosis via DOCK4 to promote atherosclerosis. Nature 261 31019307
2003 DOCK4, a GTPase activator, is disrupted during tumorigenesis. Cell 196 12628187
2010 Characterization of a family with rare deletions in CNTNAP5 and DOCK4 suggests novel risk loci for autism and dyslexia. Biological psychiatry 115 20346443
2009 High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism susceptibility. Molecular psychiatry 112 19401682
2019 Autism-like social deficit generated by Dock4 deficiency is rescued by restoration of Rac1 activity and NMDA receptor function. Molecular psychiatry 82 31388105
2006 Dock4 is regulated by RhoG and promotes Rac-dependent cell migration. Experimental cell research 75 17027967
2015 TGF-β/Smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis. Genes & development 63 25644601
2020 Long Noncoding RNA EBLN3P Promotes the Progression of Liver Cancer via Alteration of microRNA-144-3p/DOCK4 Signal. Cancer management and research 55 33061623
2008 Dock4 regulates dendritic development in hippocampal neurons. Journal of neuroscience research 52 18615735
2008 Molecular association between beta-catenin degradation complex and Rac guanine exchange factor DOCK4 is essential for Wnt/beta-catenin signaling. Oncogene 49 18641688
2011 DOCK4 and CEACAM21 as novel schizophrenia candidate genes in the Jewish population. The international journal of neuropsychopharmacology 45 21682944
2004 Examination of NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate genes. BMC medical genetics 43 15128462
2013 Rac GEF Dock4 interacts with cortactin to regulate dendritic spine formation. Molecular biology of the cell 41 23536706
2011 Aberrant epigenetic and genetic marks are seen in myelodysplastic leukocytes and reveal Dock4 as a candidate pathogenic gene on chromosome 7q. The Journal of biological chemistry 40 21532034
2019 Identification and validation of DOCK4 as a potential biomarker for risk of bone metastasis development in patients with early breast cancer. The Journal of pathology 37 30426503
2014 Dock4 forms a complex with SH3YL1 and regulates cancer cell migration. Cellular signalling 36 24508479
2020 Up-regulated cytotrophoblast DOCK4 contributes to over-invasion in placenta accreta spectrum. Proceedings of the National Academy of Sciences of the United States of America 34 32576693
2015 Reduced DOCK4 expression leads to erythroid dysplasia in myelodysplastic syndromes. Proceedings of the National Academy of Sciences of the United States of America 31 26578796
2017 DOCK4 promotes loss of proliferation in glioblastoma progenitor cells through nuclear beta-catenin accumulation and subsequent miR-302-367 cluster expression. Oncogene 29 28925399
2014 Family-based association study of ZNF533, DOCK4 and IMMP2L gene polymorphisms linked to autism in a northeastern Chinese Han population. Journal of Zhejiang University. Science. B 28 24599690
2020 Two Autism/Dyslexia Linked Variations of DOCK4 Disrupt the Gene Function on Rac1/Rap1 Activation, Neurite Outgrowth, and Synapse Development. Frontiers in cellular neuroscience 27 32009906
2006 An isoform of GTPase regulator DOCK4 localizes to the stereocilia in the inner ear and binds to harmonin (USH1C). Journal of molecular biology 26 16464467
2021 DOCK4 stimulates MUC2 production through its effect on goblet cell differentiation. Journal of cellular physiology 20 33559155
2021 USP36-Mediated Deubiquitination of DOCK4 Contributes to the Diabetic Renal Tubular Epithelial Cell Injury via Wnt/β-Catenin Signaling Pathway. Frontiers in cell and developmental biology 18 33968925
2024 Brain endothelial cells promote breast cancer cell extravasation to the brain via EGFR-DOCK4-RAC1 signalling. Communications biology 12 38762624
2015 A novel KCNQ4 mutation and a private IMMP2L-DOCK4 duplication segregating with nonsyndromic hearing loss in a Brazilian family. Human genome variation 12 27081546
2008 Identification of DOCK4 and its splicing variant as PIP3 binding proteins. IUBMB life 12 18459162
2021 miR-33b-3p Acts as a Tumor Suppressor by Targeting DOCK4 in Prostate Cancer. Frontiers in oncology 10 34804930
2019 Loss of Function of DOCK4 in Myelodysplastic Syndromes Stem Cells is Restored by Inhibitors of DOCK4 Signaling Networks. Clinical cancer research : an official journal of the American Association for Cancer Research 9 31308061
2013 DOCK4 deletion at 7q31.1 in a de novo acute myeloid leukemia with a normal karyotype. Cellular oncology (Dordrecht, Netherlands) 8 23979775
2022 Dock4 is required for the maintenance of cochlear hair cells and hearing function. Fundamental research 7 38933554
2024 Integration analysis of lncRNA and mRNA expression data identifies DOCK4 as a potential biomarker for elderly osteoporosis. BMC medical genomics 6 38443923
2022 DOCK4 Regulation of Rho GTPases Mediates Pulmonary Vascular Barrier Function. Arteriosclerosis, thrombosis, and vascular biology 5 35477279
2025 THEMIS2 contributes to ovarian cancer metastasis via DOCK4-mediated activation of Rap1 signaling. Cellular oncology (Dordrecht, Netherlands) 4 40227532
2024 Heterozygous loss-of-function variants in DOCK4 cause neurodevelopmental delay and microcephaly. Human genetics 4 38526744
2022 Deficiency of Autism-Related Gene Dock4 Leads to Impaired Spatial Memory and Hippocampal Function in Mice at Late Middle Age. Cellular and molecular neurobiology 4 35635601
2025 LncRNA OIP5-AS1 suppresses lung adenocarcinoma progression and modulates macrophage polarization through the miR-429/DOCK4 regulatory axis. Frontiers in pharmacology 3 40529490
2025 Histone lactylation regulates DOCK4 to control heat nociception and supports Dynein-mediated Nav1.7 trafficking. Nature communications 3 40759894
2023 Direct targeting of DOCK4 by miRNA-181d in oxygen-glucose deprivation/reoxygenation-mediated neuronal injury. Lipids in health and disease 3 36882763
2025 A potential therapeutic molecule target: lncRNA AK023507 inhibits the metastasis of breast cancer by regulating the WNT/DOCK4/β-catenin axis. Breast cancer research and treatment 2 40205246
2009 New Variations in the Promoter Regions of Human DOCK4 and RAP1A Genes, and Coding Regions of RAP1A in Sporadic Breast Tumors. Avicenna journal of medical biotechnology 2 23407849
2025 APOE+ Tumor-Associated Macrophages and CD4-DOCK4 T Cells Reveal Distinct Microenvironmental Features in HER2-Low and HER2-0 Hormone Receptor-Positive Breast Cancer. bioRxiv : the preprint server for biology 1 40964334
2024 HIF2α-dependent Dock4/Rac1-signaling regulates formation of adherens junctions and cell polarity in normoxia. Scientific reports 1 38802496
2022 DOCK4 regulates ghrelin production in gastric X/A-like cells. Journal of endocrinological investigation 1 35302184
2025 Could the Polymorphisms of DOCK4 (rs147636134), SYNGAP1 (rs199759879), and FOXP1 (rs767001715) be the Primary Risk Factors for Bipolar Disorder and Autism Spectrum Disorder? Developmental neurobiology 0 40790933
2025 TMOD2 and DOCK4 as Novel Gut Microbiota-Associated Biomarkers for Colorectal Adenoma: Integrated Transcriptomic Analysis and Therapeutic Target Identification. Mediators of inflammation 0 41378121
2024 Dock4 contributes to neuropathic pain by regulating spinal synaptic plasticity in mice. Frontiers in molecular neuroscience 0 39282658
2023 Genetic variations in DOCK4 contribute to schizophrenia susceptibility in a Chinese cohort: A genetic neuroimaging study. Behavioural brain research 0 36822513