Affinage

DOCK4

Dedicator of cytokinesis protein 4 · UniProt Q8N1I0

Length
1966 aa
Mass
225.2 kDa
Annotated
2026-06-09
48 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DOCK4 is an unconventional guanine nucleotide exchange factor of the DOCK180/CDM family that activates the small GTPases Rac1 and Rap1 to drive actin cytoskeletal remodeling across diverse cellular contexts, from adherens junction assembly to neuronal morphogenesis (PMID:12628187, PMID:17027967, PMID:31388105). It was first defined as a Rap1 activator that promotes adherens junction formation and behaves as a tumor suppressor, with a cancer-derived missense mutant defective in Rap1 activation and unable to rescue the engulfment defect of C. elegans ced-5 mutants (PMID:12628187). Membrane recruitment and activity are governed by multiple upstream inputs: active RhoG drives translocation of the DOCK4–ELMO complex to the plasma membrane to enhance Rac1 activation and migration (PMID:17027967), the DHR-1 domain binds PIP3 (PMID:18459162), and accessory partners SH3YL1 and CrkII potentiate GEF output (PMID:24508479, PMID:18615735). In endothelial cells, DOCK4 is recruited by the cytoplasmic tail of the LDL receptor SR-B1 to couple LDL binding to Rac1 activation and LDL transcytosis (PMID:31019307), and it maintains the endothelial barrier by balancing RhoA and Rac1 activity downstream of S1P (PMID:35477279). Beyond GEF activity, DOCK4 acts as a scaffold within the β-catenin degradation complex (APC/Axin/GSK3β), where GSK3β-mediated phosphorylation links DOCK4 to Wnt-induced Rac activation and β-catenin signaling (PMID:18641688), and it serves as a Dynein adaptor that binds the Nav1.7 sodium channel to traffic it from the membrane in sensory neurons, thereby restraining heat nociception (PMID:40759894). In the nervous system, DOCK4 promotes dendritic growth, spine formation via cortactin, and excitatory synaptic transmission through Rac1-dependent control of glutamate receptor expression, and its conditional loss produces social deficits reversible by Rac1 or NMDA receptor restoration (PMID:18615735, PMID:23536706, PMID:31388105). DOCK4 protein levels are further controlled by USP36-mediated deubiquitination (PMID:33968925), and site-specific phosphorylation at S1787 by TBK1 (scaffolded by THEMIS2) enables CrkII engagement and Rap1 activation (PMID:40227532). Disease-associated DOCK4 variants linked to autism spectrum disorder and dyslexia are deficient in Rac1/Rap1 activation and impair neurite outgrowth, spine formation, and synaptic transmission (PMID:32009906).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2003 High

    Established DOCK4 as a functional GEF, identifying Rap1 as its target and linking its activity to adherens junction formation and tumor suppression.

    Evidence GTPase activation assays, C. elegans ced-5 genetic rescue, soft agar and in vivo tumor invasion assays with a cancer-derived missense mutant

    PMID:12628187

    Open questions at the time
    • Structural basis of nucleotide exchange not resolved
    • Relationship between Rap1 and Rac1 specificity left open
  2. 2006 Medium

    Defined the upstream activation logic, showing RhoG/ELMO recruits DOCK4 to the membrane to drive Rac1-dependent migration, and identified a tissue-specific isoform and a candidate inner-ear partner.

    Evidence Co-IP, fluorescence localization, GST-PAK Rac1 pull-down, RNAi migration assay; yeast two-hybrid and isoform-specific immunostaining

    PMID:16464467 PMID:17027967

    Open questions at the time
    • Harmonin interaction by Y2H only, not validated in cells
    • How RhoG engagement is itself triggered unaddressed
  3. 2008 High

    Revealed dual roles beyond GEF activity: DOCK4 is a phosphorylated scaffold in the β-catenin degradation complex linking Wnt to Rac, binds PIP3 through its DHR-1 domain, and shapes dendritic morphology via ELMO2/CrkII.

    Evidence Co-IP, in vitro GSK3β kinase assay, zebrafish TCF reporter; PIP3-bead pull-down with deletion mutants; neuronal shRNA and morphometry

    PMID:18459162 PMID:18615735 PMID:18641688

    Open questions at the time
    • Sites of GSK3β phosphorylation not mapped
    • How scaffold versus GEF functions are coordinated unclear
  4. 2013 Medium

    Connected DOCK4 GEF activity to a specific actin effector, showing cortactin binding is required for dendritic spine formation.

    Evidence shRNA, Co-IP, domain-deletion rescue, spine density quantification in cultured neurons

    PMID:23536706

    Open questions at the time
    • Whether cortactin is a direct Rac1 effector downstream of DOCK4 not resolved
  5. 2014 Medium

    Identified SH3YL1 as a phosphoinositide-binding cofactor that potentiates DOCK4-mediated Rac1 activation and migration.

    Evidence Co-IP, Rac1 activation assay, domain mutagenesis, shRNA migration assay in MDA-MB-231

    PMID:24508479

    Open questions at the time
    • Single cell line; in vivo relevance of SH3YL1 cofactor role untested
  6. 2015 High

    Extended DOCK4 function to cancer metastasis and hematopoiesis, placing it downstream of TGF-β/Smad to drive invasion and showing it sustains erythroid differentiation through a RAC1→ADDUCIN→F-actin axis.

    Evidence Smad inhibitor epistasis, knockdown/overexpression, Rac1 assays, invasion and in vivo extravasation; siRNA, F-actin assay, RAC1 assay, rescue in MDS patient erythroblasts

    PMID:25644601 PMID:26578796

    Open questions at the time
    • Mechanism of TGF-β/Smad-specific DOCK4 induction not detailed
    • Direct kinase responsible for ADDUCIN phosphorylation not identified
  7. 2017 Medium

    Showed a context-dependent tumor-suppressive output in glioblastoma, where DOCK4 drives a β-catenin/miR-302/cyclin D1 cascade to limit stem-like self-renewal.

    Evidence Overexpression, luciferase reporter, sphere-formation and tumorigenicity assays

    PMID:28925399

    Open questions at the time
    • Reconciliation with pro-metastatic roles in other tumors unaddressed
    • Whether GEF activity is required not tested
  8. 2019 High

    Demonstrated receptor-coupled and circuit-level functions: SR-B1 recruits DOCK4 to drive LDL transcytosis, DOCK4 sustains CA1 excitatory transmission and social behavior via Rac1, and its loss in MDS HSCs perturbs LYN/SHIP1/SHP1 signaling.

    Evidence Co-IP and domain mapping with transcytosis and atherosclerosis models; conditional KO, electrophysiology, Rac1 and genetic/pharmacological rescue; phosphoproteomics and pharmacological rescue in MDS samples

    PMID:31019307 PMID:31308061 PMID:31388105

    Open questions at the time
    • Direct vs indirect link between DOCK4 loss and LYN activation not fully resolved
    • How Rac1 controls global protein synthesis mechanistically unclear
  9. 2020 Medium

    Tied disease-associated DOCK4 variants to functional deficits, showing ASD/dyslexia alleles fail to activate Rac1/Rap1 and impair neuronal morphology and synaptic transmission.

    Evidence Rac1/Rap1 activation assays, cell morphology, neurite outgrowth, electrophysiology with disease variants

    PMID:32009906

    Open questions at the time
    • No animal model carrying the patient variants
    • Penetrance and genetic context of variants not established
  10. 2021 Medium

    Identified DOCK4 protein stability and tissue-specific differentiation roles, with USP36 deubiquitinating DOCK4 to activate Wnt/β-catenin and DOCK4 controlling goblet cell differentiation via Gfi1/Spdef/MUC2.

    Evidence Co-IP and ubiquitination assays; Dock4 KO mice, siRNA, overexpression with qPCR/Western

    PMID:33559155 PMID:33968925

    Open questions at the time
    • E3 ligase opposing USP36 not identified
    • Whether goblet cell role requires GEF activity untested
  11. 2022 High

    Established DOCK4 as a balancer of RhoA/Rac1 activity maintaining the endothelial barrier downstream of S1P and as a driver of cochlear hair cell maintenance via Rac1/β-catenin.

    Evidence DOCK4-deficient mice and reconstitution in endothelial cells, permeability, GTPase, fractionation, S1P assays; piggyBac knockdown mice with ABR and histology

    PMID:35477279 PMID:38933554

    Open questions at the time
    • How S1P signaling triggers DOCK4 translocation mechanistically unclear
    • Hair cell findings rely on knockdown only
  12. 2024 High

    Expanded the mechanistic repertoire with epithelial morphogenesis (HIF2α→Dock4→Rac1/Pak1→E-cadherin), brain metastasis via EGFR/DOCK4/Rac1-CDC42, and a non-GEF adaptor role bridging Dynein and Nav1.7 to control nociception.

    Evidence Knockdown and 3D cyst assays with Rac1/Pak1 readouts; shRNA brain extravasation with EGFR inhibitor; Co-IP, Nav1.7 trafficking assay, DRG knockdown in mice and primates, ChIP for H4K8 lactylation

    PMID:38762624 PMID:38802496 PMID:40759894

    Open questions at the time
    • Structural basis of the Dynein/DOCK4/Nav1.7 complex undefined
    • How lactylation-driven DOCK4 repression integrates with GEF signaling unclear
  13. 2025 Medium

    Defined a phospho-switch controlling DOCK4 Rap1 output, with THEMIS2 scaffolding TBK1 to phosphorylate S1787 and enable CrkII binding and Rap1 activation in cancer metastasis.

    Evidence IP-MS, site-specific mutagenesis, active Rap1 GST pull-down, in vitro/in vivo metastasis assays

    PMID:40227532

    Open questions at the time
    • Whether S1787 phosphorylation also affects Rac1 activity untested
    • Phosphatase reversing S1787 not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DOCK4 selects between Rac1 and Rap1 outputs, and how its scaffold, GEF, and Dynein-adaptor functions are integrated across cell types, remains unresolved.
  • No structural model of DOCK4 GEF or adaptor complexes
  • Determinants of Rac1- versus Rap1-directed activity not defined
  • Context-dependent tumor-suppressive versus pro-metastatic switch unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 2 GO:0060090 molecular adaptor activity 2 GO:0008289 lipid binding 1
Localization
GO:0005886 plasma membrane 3 GO:0005856 cytoskeleton 2 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 5 R-HSA-112316 Neuronal System 4 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-9609507 Protein localization 2
Partners
CRKIIELMO2GSK3BNAV1.7SH3YL1SR-B1TBK1USP36
Complex memberships
DOCK4-ELMO complexDynein/DOCK4/Nav1.7 complexβ-catenin degradation complex (APC/Axin/GSK3β)

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 DOCK4 specifically activates Rap GTPase (Rap1), enhancing the 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 mutant allele does not. GTPase activation assays, C. elegans genetic rescue, soft agar colony formation and in vivo tumor invasion assays 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 cytoplasm to the plasma membrane, enhancing DOCK4/ELMO-dependent Rac1 activation and cell migration. DOCK4 knockdown in NIH3T3 cells reduces cell migration. Co-immunoprecipitation, fluorescence localization, Rac1 GTPase activation assay (GST-PAK pull-down), RNAi knockdown with migration assay Experimental cell research Medium 17027967
2006 A novel DOCK4 isoform (DOCK4-Ex49) is expressed in brain, eye, and inner ear tissues, localizes to stereocilia hair bundles in the inner ear, binds nucleotide-free Rac as effectively as DOCK2, and is a potent Rac activator. DOCK4-Ex49 interacts with harmonin (USH1C) via yeast two-hybrid. Yeast two-hybrid, immunostaining with isoform-specific antibody, Rac nucleotide-free binding assay Journal of molecular biology Medium 16464467
2008 DOCK4 mediates Wnt-induced Rac activation in the canonical Wnt/β-catenin pathway. DOCK4 interacts biochemically 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, β-catenin stability assay, TCF reporter assay in zebrafish Oncogene High 18641688
2008 DOCK4 (a Rac GEF) regulates dendritic growth and branching in hippocampal neurons. Knockdown reduces dendritic growth and branching; overexpression with ELMO2 enhances dendrite number and branching. These effects require Rac activation and the C-terminal Crk-binding region. DOCK4 forms a complex with ELMO2 and CrkII in hippocampal neurons. shRNA knockdown, overexpression, co-immunoprecipitation in neurons, dendritic morphometry Journal of neuroscience research Medium 18615735
2008 DOCK4 DHR-1 domain binds PIP3 (phosphatidylinositol 3,4,5-trisphosphate), as determined by PIP3-analog bead binding assay using deletion mutants. A novel splicing variant of DOCK4 also binds PIP3 via the DHR-1 domain. PIP3-analog bead pull-down assay with deletion mutants IUBMB life Medium 18459162
2013 DOCK4 is concentrated in dendritic spines and promotes spine formation via interaction with the actin-binding protein cortactin. shRNA knockdown of DOCK4 reduces spine density; rescue requires GEF activity and the cortactin-binding C-terminal region. Cortactin knockdown suppresses DOCK4-mediated spine formation. shRNA knockdown, co-immunoprecipitation, domain-deletion rescue experiments, spine density quantification in cultured neurons Molecular biology of the cell Medium 23536706
2014 DOCK4 forms a complex with SH3YL1 (a phosphoinositide-binding protein) through its C-terminal proline-rich region. SH3YL1 promotes DOCK4-mediated Rac1 activation and cell migration; mutations in the SH3YL1 phosphoinositide-binding domain abolish this promotion. Depletion of SH3YL1 suppresses cell migration in MDA-MB-231 cells. Co-immunoprecipitation, Rac1 GTPase activation assay, domain mutant analysis, shRNA knockdown with migration assay Cellular signalling Medium 24508479
2015 TGF-β induces DOCK4 expression via the Smad pathway (but not other DOCK family members) in lung adenocarcinoma cells, and DOCK4 mediates TGF-β pro-metastatic effects by activating Rac1 to enhance tumor cell protrusion, motility, invasion, and extravasation without affecting EMT. Smad pathway inhibitor experiments, DOCK4 knockdown/overexpression, Rac1 GTPase activation assay, invasion/migration assays, in vivo extravasation model Genes & development Medium 25644601
2015 DOCK4 knockdown in primary bone marrow CD34+ stem cells leads to decreased erythroid colony formation and increased apoptosis. Mechanistically, reduced DOCK4 expression decreases RAC1 GTPase activation, leading to increased phosphorylation of the actin-stabilizing protein ADDUCIN, disrupting the F-actin filament network in erythroblasts and causing erythroid dysplasia. siRNA knockdown, F-actin single-cell assay, RAC1 GTPase activation assay, re-expression rescue in MDS patient erythroblasts Proceedings of the National Academy of Sciences of the United States of America High 26578796
2017 In glioblastoma, DOCK4 drives nuclear β-catenin accumulation through a feed-forward mechanism with β-catenin enabled by increased GSK3β activity; this results in miR-302 expression that represses cyclin D1, suppressing self-renewal and tumorigenicity of GBM stem-like cells. Overexpression, luciferase reporter, Western blot, sphere-formation and tumorigenicity assays Oncogene Medium 28925399
2019 SR-B1 in endothelial cells recruits DOCK4 via an eight-amino-acid cytoplasmic domain of the receptor upon LDL binding. DOCK4 promotes SR-B1 internalization and LDL transcytosis across endothelial monolayers by coupling LDL-SR-B1 binding with RAC1 activation. Co-immunoprecipitation, domain deletion mutagenesis, transcytosis assay across endothelial monolayers, in vivo mouse atherosclerosis model with SR-B1/DOCK4 manipulation Nature High 31019307
2019 Dock4 deficiency in hippocampal CA1 neurons reduces Rac1 activity, leading to downregulation of global protein synthesis and diminished AMPA and NMDA receptor subunit expression, decreased spine density, and attenuated excitatory synaptic transmission. Rac1 replenishment in CA1 of Dock4 KO mice restores excitatory synaptic transmission and corrects social deficits. Pharmacological NMDA receptor activation also restores social novelty preference. Conditional Dock4 knockout, Rac1 activity assay, electrophysiology, Western blot for receptor subunits, viral Rac1 rescue, pharmacological rescue Molecular psychiatry High 31388105
2019 Reduced DOCK4 expression in -7q MDS HSCs leads to increased tyrosine phosphorylation of LYN kinase and phosphatases SHIP1 and SHP1. Increased SHIP1/SHP1 phosphorylation is caused by LYN kinase targeting these as substrates. These signaling alterations increase migration and impede HSC differentiation. Pharmacologic inhibition of SHP1 reverses these functional aberrations. Phosphoproteomics, siRNA knockdown, kinase-substrate assay, pharmacological rescue in primary human HSCs and MDS patient samples Clinical cancer research Medium 31308061
2020 Two DOCK4 variants associated with ASD/dyslexia (Exon27-52 deletion producing Dock4-945VS and missense R853H) show decreased ability to activate both Rac1 and Rap1, are dysfunctional for regulation of cell morphology and cytoskeleton, and have compromised ability to promote neurite outgrowth, dendritic spine formation, and excitatory synaptic transmission. GTPase activation assay (Rac1 and Rap1), cell morphology analysis, neurite outgrowth assay in Neuro-2a and hippocampal neurons, electrophysiology Frontiers in cellular neuroscience Medium 32009906
2020 DOCK4 overexpression in cytotrophoblasts increases invasiveness consistent with placenta accreta spectrum phenotype; DOCK4 was the most highly up-regulated gene in PAS cytotrophoblasts compared to controls. DOCK4 overexpression in CTB cells with invasion assay Proceedings of the National Academy of Sciences of the United States of America Low 32576693
2021 USP36 (a deubiquitinating enzyme) directly binds DOCK4 and mediates its deubiquitination, thereby stabilizing DOCK4 protein levels, which activates Wnt/β-catenin signaling and induces EMT in diabetic renal tubular epithelial cells. Co-immunoprecipitation, ubiquitination assay, overexpression/knockdown with Western blot and EMT marker analysis Frontiers in cell and developmental biology Medium 33968925
2021 DOCK4 regulates goblet cell differentiation and MUC2 production in the intestine. DOCK4 knockout mice show disordered intestinal epithelium, shortage of goblet cells, and reduced expression of MUC2 and differentiation factors Gfi1 and Spdef. DOCK4 overexpression increases these factors, while siRNA knockdown decreases them in HT-29 cells. Dock4 knockout mice, siRNA knockdown, overexpression in HT-29 cells, qPCR and Western blot Journal of cellular physiology Medium 33559155
2022 DOCK4 deficiency in pulmonary endothelial cells leads to increased basal vascular permeability, hemorrhage in lung, and impaired S1P-induced barrier restoration. DOCK4 rapidly translocates to the cell periphery and associates with detergent-insoluble fraction following S1P treatment; its absence prevents S1P-induced Rac1 activation. DOCK4-silenced cells show enhanced basal permeability associated with enhanced RhoA activation, indicating DOCK4 maintains adherens junctions by balancing RhoA and Rac1 activity. DOCK4-deficient mice, DOCK4 silencing/reconstitution in human pulmonary artery endothelial cells, permeability assay, GTPase activation assays, subcellular fractionation, S1P treatment Arteriosclerosis, thrombosis, and vascular biology High 35477279
2022 Dock4/Rac1/β-catenin signaling is required for maintenance of cochlear hair cell stereocilia organization and hearing function. Dock4 knockdown in mice causes hair bundle deficits, increased oxidative stress, HC apoptosis, and progressive hearing loss; Rac1/β-catenin signaling is significantly downregulated in Dock4 KD cochleae. piggyBac transposon knockdown mice, auditory brainstem response, immunofluorescence, Western blot Fundamental research Medium 38933554
2024 HIF2α regulates Dock4 expression in normoxia in kidney epithelial cells; Dock4/Rac1/Pak1 signaling mediates stability and compaction of E-cadherin at nascent adherens junctions. HIF2α- or Dock4-deficient cells show aberrant cyst morphogenesis in 3D kidney epithelial cultures. HIF2α and Dock4 knockdown/depletion, E-cadherin localization assay, 3D cyst morphogenesis assay, Rac1/Pak1 activity assays Scientific reports Medium 38802496
2024 Brain endothelial cell-secreted soluble factors activate EGFR signaling in triple-negative breast cancer cells via DOCK4, which is required for breast cancer cell extravasation to the brain in vivo. DOCK4 knockdown inhibits breast cancer cell entry to the brain and loss of elongated morphology preceding intercalation into brain endothelium. Brain endothelial cells promote mesenchymal-like morphology via DOCK4, DOCK9, RAC1, and CDC42. DOCK4 shRNA knockdown, in vivo brain extravasation assay, EGFR inhibitor (Afatinib), cell morphology analysis Communications biology Medium 38762624
2024 Dock4 deficiency in sensory neurons (DRG) increases heat nociception. Mechanistically, DOCK4 interacts with Nav1.7 sodium channel and acts as an adaptor that binds Dynein to form a Dynein/DOCK4/Nav1.7 complex, mediating trafficking of Nav1.7 from the membrane to the cytoplasm. DOCK4 expression in DRG neurons is decreased by histone H4K8 lactylation across pain models. Co-immunoprecipitation, Nav1.7 trafficking assay, DRG-specific Dock4 knockdown in mice and non-human primates, heat nociception behavioral tests, ChIP for H4K8 lactylation Nature communications High 40759894
2025 THEMIS2 acts as a molecular scaffold that recruits TBK1 to DOCK4, facilitating site-specific phosphorylation of DOCK4 at serine 1787 (S1787). This post-translational modification enables DOCK4 to engage with CRKII, subsequently triggering Rap1 signaling activation, which promotes ovarian cancer cell metastasis. Immunoprecipitation-mass spectrometry, GST pull-down for active Rap1, site-specific mutagenesis, in vitro and in vivo metastasis assays Cellular oncology Medium 40227532
2024 Dock4 promotes excitatory synaptic transmission in spinal cord neurons by promoting GluN2B expression at synaptic sites and synaptogenesis. Dock4 knockdown prevents dendritic growth, synaptogenesis, and the increase in GTP-Rac1 and GluN2B induced by spinal nerve ligation. Rac1 GTPase activation assay, Western blot, immunofluorescence, electrophysiology (patch-clamp), RNAi knockdown in dorsal spinal neurons Frontiers in molecular neuroscience Medium 39282658
2024 Loss-of-function variants in DOCK4 (missense and null) impair neurite outgrowth in Neuro-2A cells. Dock4 knockout Neuro-2A cells also exhibit defects in neurite outgrowth. Molecular modeling of missense variants suggests disruption of globular DOCK4 structure. In vitro functional expression in Neuro-2A cells, DOCK4 knockout Neuro-2A cells, molecular modeling Human genetics Low 38526744

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 267 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 116 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 83 31388105
2006 Dock4 is regulated by RhoG and promotes Rac-dependent cell migration. Experimental cell research 77 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 44 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 35 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 21 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 19 33968925
2024 Brain endothelial cells promote breast cancer cell extravasation to the brain via EGFR-DOCK4-RAC1 signalling. Communications biology 15 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
2025 Histone lactylation regulates DOCK4 to control heat nociception and supports Dynein-mediated Nav1.7 trafficking. Nature communications 7 40759894
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 6 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
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

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