Affinage

DOK7

Protein Dok-7 · UniProt Q18PE1

Length
504 aa
Mass
53.1 kDa
Annotated
2026-06-09
77 papers in source corpus 18 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DOK7 encodes a muscle-intrinsic cytoplasmic adaptor that is the obligate activator of the receptor tyrosine kinase MuSK and is essential for acetylcholine receptor (AChR) clustering and neuromuscular junction (NMJ) formation (PMID:16794080, PMID:19244212). Dok-7 binds the cytoplasmic domain of MuSK through its phosphotyrosine-binding (PTB) domain, and a dimeric arrangement of its PH-PTB module bound to a MuSK phosphopeptide drives trans-autophosphorylation of the MuSK activation loop, providing the structural basis for kinase activation (PMID:16794080, PMID:20603078); agrin-dependent MuSK activation requires Dok-7, and Dok-7 also directs MuSK to the central region of muscle (PMID:19244212). Both the PH and PTB domains are strictly required for MuSK activation, whereas the C-terminal region is important but not absolutely essential, contributing to full activation and normal NMJ size (PMID:18165682, PMID:28069867). Downstream, agrin-induced phosphorylation of two C-terminal tyrosines recruits the Crk and Crk-L adaptors, which are required in muscle for synapse formation (PMID:21041412), and Dok-7-dependent signaling further engages effectors including Anxa3 in postsynaptic development (PMID:32043676). Dok-7 abundance and activity are tuned by post-translational and gene-regulatory inputs: CK2 binds and phosphorylates Dok-7 on serines to enhance AChR clustering (PMID:26198629), APC2/APC/C-mediated ubiquitination at K243 (dependent on MuSK activity and Dok-7 Y106 phosphorylation) promotes its degradation (PMID:32687671), the splicing factor SRSF1 ensures production of full-length functional Dok-7 mRNA (PMID:28874828), and the coactivator PGC1α with ERRα drives DOK7 transcription in muscle (PMID:38245592). DOK7 mutations cause congenital myasthenic syndrome: the common 1124_1127dup allele produces neonatal lethality through severe loss of MuSK activation that is rescued by MuSK agonist antibodies (PMID:34163073), and the PH-domain p.G64R mutation destabilizes Dok-7 into juxtanuclear aggresomes with reduced MuSK phosphorylation (PMID:36579833).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2006 High

    Established that Dok-7 is the essential muscle-intrinsic activator of MuSK, answering how MuSK is switched on to build the neuromuscular synapse.

    Evidence Dok-7-null mice and PTB-domain/MuSK-site mutagenesis in cultured myotubes

    PMID:16794080

    Open questions at the time
    • Did not resolve the structural mechanism of activation
    • C-terminal tyrosine signaling not yet defined
  2. 2009 High

    Showed Dok-7 directly binds and activates the MuSK cytoplasmic kinase and is required for agrin-driven activation and central MuSK localization, placing Dok-7 mechanistically within the agrin pathway.

    Evidence In vitro MuSK kinase activation assays, in vivo muscle overexpression, immunofluorescence localization

    PMID:19244212

    Open questions at the time
    • Mechanism of dimerization-driven activation not shown
    • Downstream effectors of activated MuSK not mapped
  3. 2010 High

    Defined the molecular basis of MuSK activation: a dimeric Dok-7 PH-PTB arrangement positions two MuSK molecules for trans-autophosphorylation of the activation loop.

    Evidence X-ray crystallography of PH-PTB bound to MuSK phosphopeptide with biochemical dimerization and structure-guided mutagenesis

    PMID:20603078

    Open questions at the time
    • Membrane recruitment step not structurally resolved
    • Role of C-terminal region in activation not addressed
  4. 2010 High

    Identified the C-terminal signaling output of Dok-7, showing agrin-induced tyrosine phosphorylation recruits Crk/Crk-L adaptors essential for synapse formation.

    Evidence Mass spectrometry of Dok-7 phosphotyrosines, Crk/Crk-L Co-IP, muscle-specific Crk/Crk-L conditional knockout mice

    PMID:21041412

    Open questions at the time
    • Effectors downstream of Crk/Crk-L not defined
    • Relative contribution of activation vs. C-terminal signaling unresolved
  5. 2007 High

    Established Dok-7 subcellular trafficking, showing a CRM1-dependent NES maintains cytoplasmic localization required for productive MuSK interaction while the PH domain mediates nuclear import.

    Evidence Fluorescence localization, leptomycin B treatment, domain mutagenesis in myotube AChR clustering assays

    PMID:18165682

    Open questions at the time
    • Functional significance of nuclear Dok-7 unknown
    • Regulation of shuttling not defined
  6. 2010 Medium

    Established conservation of Dok-7 function in vivo, showing it drives the earliest aneural AChR clustering and influences muscle fiber arrangement in a partly MuSK-independent manner.

    Evidence Zebrafish morpholino knockdown with AChR/NMJ imaging and muscle fiber live imaging

    PMID:20147321

    Open questions at the time
    • Mechanism of MuSK-independent muscle fiber role unknown
    • Morpholino specificity not genetically confirmed
  7. 2010 Medium

    Connected MuSK CMS pathogenesis to the Dok-7 interface by showing specific MuSK mutations selectively disrupt MuSK-Dok-7 binding.

    Evidence Co-IP of MuSK mutants with Dok-7/LRP4/Tid1 in MuSK-deficient myotubes with AChR clustering assays

    PMID:20371544

    Open questions at the time
    • Quantitative binding affinities not measured
    • Single-lab Co-IP without structural confirmation
  8. 2015 Medium

    Revealed kinase regulation of Dok-7, showing CK2 binds and phosphorylates Dok-7 serines to enhance its AChR-clustering activity.

    Evidence Co-IP, in vitro CK2 kinase assay, phosphomimetic mutagenesis with C2C12 AChR clustering

    PMID:26198629

    Open questions at the time
    • In vivo relevance of CK2 phosphorylation not established
    • Specific serine sites and their individual contributions unclear
  9. 2016 Low

    Provided a structural model of membrane engagement, predicting the Dok-7 PH domain binds PIP-containing membranes via charged loops and clusters PIP lipids.

    Evidence Multiscale molecular dynamics simulations and density landscape calculation

    PMID:27459095

    Open questions at the time
    • Computational prediction only, no experimental validation
    • Physiological PIP species and binding affinity not tested
  10. 2016 Medium

    Demonstrated that Dok-7 dosage determines NMJ robustness, showing reduced Dok-7 lowers synaptic AChR and sensitizes to antibody-mediated attack.

    Evidence In vivo shRNA electroporation in rat muscle, passive-transfer MG model, electrophysiology and AChR immunostaining

    PMID:27658713

    Open questions at the time
    • Single-lab study
    • Mechanism linking Dok-7 level to AChR stability not defined
  11. 2017 High

    Dissected domain requirements, showing PH and PTB are obligatory for MuSK activation while the C-terminal region contributes a significant but non-essential boost to activation and NMJ size.

    Evidence Quantitative in vitro MuSK kinase assays with recombinant Dok-7-ΔC, myotube transfection, transgenic rescue of Dok-7 knockout mice

    PMID:28069867

    Open questions at the time
    • Molecular reason for residual ΔC activity unclear
    • Single lab
  12. 2017 High

    Identified a splicing checkpoint, showing SRSF1 promotes intron-proximal 5' splice site use to generate full-length functional Dok-7 mRNA.

    Evidence Block-scanning mutagenesis, RNA affinity purification-MS, SRSF1 knockdown and MS2 tethering, early spliceosome complex analysis

    PMID:28874828

    Open questions at the time
    • In vivo muscle relevance of this splicing control not shown
    • Other splicing regulators of DOK7 not surveyed
  13. 2020 Medium

    Revealed negative feedback on Dok-7 abundance, showing APC2/APC/C ubiquitinates Dok-7 at K243 for degradation in a MuSK-activity and Y106-phosphorylation dependent manner.

    Evidence Fractionation/immunostaining, ubiquitination assays, K243/Y106 mutagenesis, AChR clustering assays

    PMID:32687671

    Open questions at the time
    • In vivo physiological role of this degradation not tested
    • Single lab
  14. 2020 Medium

    Expanded the agrin/Dok-7 phosphosignaling network, identifying Anxa3 as a Dok-7-dependent effector required for postsynaptic development.

    Evidence CRISPR Dok-7 mutant myotubes with iTRAQ phosphoproteomics, AChR clustering assays, in vivo muscle knockdown

    PMID:32043676

    Open questions at the time
    • Direct kinase acting on Anxa3 not identified
    • Mechanism of Anxa3 action on clustering unknown
  15. 2021 High

    Defined the pathogenic mechanism of the most common DOK7 CMS mutation and a therapeutic route, showing 1124_1127dup causes lethality via loss of MuSK activation rescuable by MuSK agonist antibodies.

    Evidence Dok7CM and Dok72YF knock-in mice, MuSK phosphorylation assays, agonist antibody rescue

    PMID:34163073

    Open questions at the time
    • Long-term efficacy of antibody therapy not assessed
    • Mechanism by which the duplication impairs activation not structurally resolved
  16. 2023 Medium

    Defined a destabilizing CMS mechanism, showing the PH-domain p.G64R mutation reduces Dok-7 to ~10% and forms juxtanuclear aggresomes with impaired MuSK phosphorylation.

    Evidence Cell-line transfection, patient iPS cells with isogenic CRISPR correction, immunofluorescence, Western blot, MG132 treatment

    PMID:36579833

    Open questions at the time
    • In vivo confirmation lacking
    • Pathway clearing the aggregates not fully defined
  17. 2024 Medium

    Identified transcriptional control of DOK7, showing PGC1α with ERRα drives Dok-7 expression required for NMJ formation.

    Evidence Muscle-specific PGC1α knockout/overexpression mice, luciferase promoter assay, RT-qPCR, NMJ morphology

    PMID:38245592

    Open questions at the time
    • Direct ERRα binding sites on DOK7 promoter not mapped
    • Single lab
  18. 2025 Low

    Extended the Dok-7-dependent phosphosignaling network to serine/threonine targets, implicating JPH2 in AChR clustering.

    Evidence Phosphorylated iTRAQ proteomics with AChR clustering assays in muscle cells

    PMID:40290048

    Open questions at the time
    • Single downstream validation, abstract-level detail only
    • Kinase acting on JPH2 not identified
    • In vivo role not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the upstream regulatory layers (CK2 phosphorylation, APC2 degradation, SRSF1 splicing, PGC1α transcription) are coordinated in vivo to set Dok-7 levels and tune NMJ maintenance remains unresolved.
  • No integrated in vivo model linking the regulatory inputs
  • Temporal dynamics of Dok-7 turnover during synapse maturation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 1
Localization
GO:0005886 plasma membrane 2 GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3
Partners
ANC2CRKCRKLCSNK2A1MUSKSRSF1

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Dok-7 is essential for MuSK activation and neuromuscular synaptogenesis; the Dok-7 phosphotyrosine-binding (PTB) domain and its target site on MuSK are indispensable for MuSK activation in cultured myotubes, and mice lacking Dok-7 form neither acetylcholine receptor clusters nor neuromuscular synapses. Genetic knockout (Dok-7-null mice), in vitro myotube assays, domain mutagenesis Science High 16794080
2010 The crystal structure of the Dok7 PH-PTB domains in complex with a phosphopeptide from MuSK's Dok7-binding site revealed a dimeric arrangement of Dok7 PH-PTB that facilitates trans-autophosphorylation of the MuSK kinase activation loop, providing the molecular basis for MuSK activation by Dok7. X-ray crystallography, biochemical dimerization assays, structure-guided mutagenesis Molecular Cell High 20603078
2009 Dok-7 directly interacts with the cytoplasmic portion of MuSK and activates its kinase activity; neural agrin requires Dok-7 to activate MuSK. In vivo overexpression of Dok-7 increased MuSK activation and promoted NMJ formation. Dok-7 is also required for the correct localization of MuSK to the central region of muscle. In vitro MuSK kinase activation assays, in vivo overexpression in muscle, immunofluorescence localization Science Signaling High 19244212
2010 Agrin stimulates phosphorylation of two tyrosine residues in the C-terminal domain of Dok-7, which recruits the adaptor proteins Crk and Crk-L. Selective inactivation of Crk and Crk-L in skeletal muscle causes severe defects in neuromuscular synapse formation in vivo, placing Crk/Crk-L downstream of Dok-7 in NMJ signaling. Mass spectrometry identification of Dok-7 phosphotyrosines, Co-IP/pulldown of Crk/Crk-L, conditional muscle-specific Crk/Crk-L knockout mice with NMJ phenotyping Genes & Development High 21041412
2007 A chromosome region maintenance 1 (CRM1)-dependent nuclear export signal (NES) in the C-terminal region of Dok-7 is essential for its cytoplasmic localization; disruption of the NES causes nuclear accumulation and impairs Dok-7/MuSK interaction in myotubes. The N-terminal PH domain mediates nuclear import of Dok-7. Src homology 2 (SH2) target motifs in the C-terminal region are also active and crucial for MuSK activation. Subcellular localization by fluorescence microscopy, CRM1 inhibitor (leptomycin B) treatment, domain mutagenesis in myotube AChR clustering assays Journal of Biological Chemistry High 18165682
2021 The most common disease-causing DOK7 mutation (1124_1127dup) causes neonatal lethality in mice primarily due to severe deficiency in MuSK phosphorylation/activation rather than loss of DOK7 C-terminal tyrosine phosphorylation. Agonist antibodies against MuSK restored neuromuscular synapse formation and prevented lethality in Dok7CM mice. Mouse knock-in model (Dok7CM and Dok72YF), MuSK phosphorylation assays, agonist antibody rescue experiments Nature High 34163073
2015 Protein kinase CK2 physically interacts with Dok-7 at the neuromuscular junction and phosphorylates Dok-7 at several serine residues. Phosphomimetic Dok-7 mutants cluster nicotinic AChRs in C2C12 myotubes at significantly higher frequency than wild-type Dok-7. Co-immunoprecipitation, in vitro CK2 kinase assay, phosphomimetic mutagenesis with AChR clustering assay in C2C12 myotubes Journal of Biological Chemistry Medium 26198629
2017 The C-terminal region of Dok-7 plays a key but not fully essential role in MuSK activation: purified recombinant Dok-7 lacking the C-terminal region (Dok-7-ΔC) showed marginal but significant MuSK kinase activation in vitro and in myotubes, in contrast to PH- or PTB-domain mutants which showed none. Forced expression of Dok-7-ΔC partially rescued Dok-7-deficient mice, but resulted in only marginal MuSK activation and abnormally small NMJs. Quantitative in vitro MuSK kinase assays with purified recombinant proteins, myotube transfection assays, rescue of Dok-7 knockout mice by transgenic expression Journal of Biochemistry High 28069867
2020 APC2 (core subunit of APC/C E3 ligase) is enriched at the post-synapse of NMJs and negatively regulates agrin signaling by promoting ubiquitination of DOK7 at lysine 243 for its proteolytic degradation; this degradation requires MuSK kinase activity and phosphorylation of tyrosine 106 in DOK7. Subcellular fractionation/immunostaining, ubiquitination assays, site-directed mutagenesis (K243, Y106), AChR clustering assays FASEB Journal Medium 32687671
2020 Quantitative phosphoproteomic analysis (CRISPR/Cas9 Dok-7 mutant myotubes + iTRAQ) identified 13 Dok-7-dependent tyrosine-phosphorylated proteins downstream of agrin/Dok-7 signaling, including Anxa3; knockdown of Anxa3 inhibited agrin-induced AChR clustering in myotubes, and reduction of Anxa3 in mouse muscles caused abnormal postsynaptic development. CRISPR/Cas9 knockout, quantitative phosphoproteomics (iTRAQ), in vitro AChR clustering assay, in vivo mouse muscle knockdown FASEB Journal Medium 32043676
2017 The splicing factor SRSF1 binds a cis-element near the 3' end of DOK7 exon 4 and suppresses selection of an intron-distal 5' splice site in intron 4, thereby promoting production of full-length functional Dok-7 mRNA. SRSF1 acts by inhibiting U1 snRNP association with the intron-distal 5' SS and enhancing U1 snRNP association with the intron-proximal 5' SS. Block-scanning mutagenesis, RNA affinity purification with mass spectrometry, SRSF1 knockdown/artificial tethering (MS2 system), early spliceosome complex isolation Scientific Reports High 28874828
2023 The missense mutation p.G64R in the PH domain of Dok-7 reduces protein expression to ~10% of wild-type and causes formation of insoluble aggresomes at the juxtanuclear region in myoblasts, co-localizing with autophagosome markers. Patient-derived iPS cells show juxtanuclear DOK7 aggregates, reduced endogenous DOK7 expression, and reduced MuSK phosphorylation. Transfection of C2C12 myotubes/myoblasts and COS7 cells, patient-derived iPS cells with CRISPR/Cas9 isogenic correction, immunofluorescence, Western blot (MuSK phosphorylation), proteasome inhibitor (MG132) treatment Human Molecular Genetics Medium 36579833
2016 Molecular dynamics simulations indicate that the Dok7 PH domain associates with PIP-containing membranes through positively charged loops (β1/β2, β3/β4, β5/β6) that interact with negatively charged PIP headgroups, and that this membrane association involves both canonical and atypical PIP-binding sites, leading to local clustering of PIP molecules. Multiscale molecular dynamics simulations (coarse-grained and atomistic), density landscape calculation PLoS Computational Biology Low 27459095
2010 In zebrafish, Dok-7 is crucial for the earliest step of NMJ development (AChR cluster formation in the middle of the muscle fiber prior to motor neuron contact). At later stages, Dok-7 is not absolutely essential for synapse formation, but its absence results in smaller synaptic contacts. Dok-7 also has a role in slow muscle fiber arrangement that appears independent of MuSK. Zebrafish morpholino knockdown, immunofluorescence of AChR clusters and NMJ structure, live imaging of muscle fiber arrangement Human Molecular Genetics Medium 20147321
2016 Silencing of Dok-7 in adult rat tibialis anterior muscle by shRNA electroporation reduced AChR protein levels at the NMJ by ~25% and significantly impaired neuromuscular transmission when a subclinical dose of anti-AChR antibody was applied, demonstrating that Dok-7 levels influence AChR cluster resistance to antibody-mediated attack. In vivo shRNA electroporation in rat muscle, passive transfer myasthenia gravis model, electrophysiology (neuromuscular transmission recording), AChR quantification by immunostaining American Journal of Pathology Medium 27658713
2010 MuSK mutations A727V (catalytic loop) and M605I (kinase domain) in CMS patients severely or moderately impair interaction between MuSK and Dok-7, while not impairing interaction with LRP4 or Tid1, demonstrating that impaired MuSK-Dok-7 interaction is a major determinant of pathogenesis in MuSK-mutation CMS. Expression studies in MuSK-deficient myotubes, co-immunoprecipitation of MuSK mutants with Dok-7/LRP4/Tid1, AChR clustering assays Human Molecular Genetics Medium 20371544
2024 Dok-7 expression in skeletal muscle is regulated by the transcriptional coactivator PGC1α; luciferase reporter assays show that the Dok-7 promoter activity is greatly increased by co-expression of PGC1α and estrogen receptor-related receptor α (ERRα), and skeletal muscle-specific PGC1α knockout mice have reduced Dok-7 expression and impaired NMJ formation. Skeletal muscle-specific PGC1α knockout and overexpression mice, luciferase promoter assay, RT-qPCR, NMJ morphological analysis Scientific Reports Medium 38245592
2025 Phosphoproteomic analysis (phosphorylated iTRAQ) identified JPH2 as a Dok-7-dependent serine/threonine phosphorylated protein downstream of agrin/Dok-7 signaling; knockdown or functional perturbation of JPH2 impaired AChR clustering in muscle cells. Phosphorylated iTRAQ proteomics, AChR clustering assays in muscle cells FEBS Letters Low 40290048

Source papers

Stage 0 corpus · 77 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 The muscle protein Dok-7 is essential for neuromuscular synaptogenesis. Science (New York, N.Y.) 345 16794080
2006 Dok-7 mutations underlie a neuromuscular junction synaptopathy. Science (New York, N.Y.) 219 16917026
2012 DNA methylation profiling in breast cancer discordant identical twins identifies DOK7 as novel epigenetic biomarker. Carcinogenesis 114 23054610
2007 Phenotypical spectrum of DOK7 mutations in congenital myasthenic syndromes. Brain : a journal of neurology 114 17439981
2010 The cytoplasmic adaptor protein Dok7 activates the receptor tyrosine kinase MuSK via dimerization. Molecular cell 108 20603078
2010 Ephedrine treatment in congenital myasthenic syndrome due to mutations in DOK7. Neurology 96 20458068
2007 Clinical features of the DOK7 neuromuscular junction synaptopathy. Brain : a journal of neurology 96 17452375
2011 Beneficial effects of albuterol in congenital endplate acetylcholinesterase deficiency and Dok-7 myasthenia. Muscle & nerve 95 21952943
2010 Dok-7 regulates neuromuscular synapse formation by recruiting Crk and Crk-L. Genes & development 94 21041412
2008 Dok-7 myasthenia: phenotypic and molecular genetic studies in 16 patients. Annals of neurology 93 18626973
2009 Dok-7 activates the muscle receptor kinase MuSK and shapes synapse formation. Science signaling 85 19244212
2010 Mutations in MUSK causing congenital myasthenic syndrome impair MuSK-Dok-7 interaction. Human molecular genetics 81 20371544
2014 Neuromuscular disease. DOK7 gene therapy benefits mouse models of diseases characterized by defects in the neuromuscular junction. Science (New York, N.Y.) 79 25237101
2017 DOK7 gene therapy enhances motor activity and life span in ALS model mice. EMBO molecular medicine 66 28490573
2009 Phenotype genotype analysis in 15 patients presenting a congenital myasthenic syndrome due to mutations in DOK7. Journal of neurology 65 20012313
2012 Salbutamol benefits children with congenital myasthenic syndrome due to DOK7 mutations. Neuromuscular disorders : NMD 62 23219351
2007 Mutations causing DOK7 congenital myasthenia ablate functional motifs in Dok-7. The Journal of biological chemistry 59 18165682
2021 Mechanism of disease and therapeutic rescue of Dok7 congenital myasthenia. Nature 55 34163073
2009 Germline mutation in DOK7 associated with fetal akinesia deformation sequence. Journal of medical genetics 49 19261599
2012 The spectrum of mutations that underlie the neuromuscular junction synaptopathy in DOK7 congenital myasthenic syndrome. Human molecular genetics 48 22661499
2013 Salbutamol therapy in congenital myasthenic syndrome due to DOK7 mutation. Journal of the neurological sciences 44 23790237
2008 Variable phenotypes associated with mutations in DOK7. Muscle & nerve 42 18161030
2013 DOK7 congenital myasthenic syndrome in childhood: early diagnostic clues in 23 children. Neuromuscular disorders : NMD 37 23831158
2020 DOK7 Gene Therapy Enhances Neuromuscular Junction Innervation and Motor Function in Aged Mice. iScience 33 32758427
2010 Congenital stridor with feeding difficulty as a presenting symptom of Dok7 congenital myasthenic syndrome. International journal of pediatric otorhinolaryngology 32 20554332
2020 Effect of salbutamol on neuromuscular junction function and structure in a mouse model of DOK7 congenital myasthenia. Human molecular genetics 31 32543656
2012 DOK7 limb-girdle myasthenic syndrome mimicking congenital muscular dystrophy. Neuromuscular disorders : NMD 26 22884442
2020 AAV9-DOK7 gene therapy reduces disease severity in Smn2B/- SMA model mice. Biochemical and biophysical research communications 22 32828271
2016 Multiscale Simulations Suggest a Mechanism for the Association of the Dok7 PH Domain with PIP-Containing Membranes. PLoS computational biology 22 27459095
2012 DOK7 congenital myasthenic syndrome. Annals of the New York Academy of Sciences 22 23278577
2010 Dok-7 promotes slow muscle integrity as well as neuromuscular junction formation in a zebrafish model of congenital myasthenic syndromes. Human molecular genetics 22 20147321
2008 Dok-7/MuSK signaling and a congenital myasthenic syndrome. Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology 22 19108574
2010 DOK7 mutations presenting as a proximal myopathy in French Canadians. Neuromuscular disorders : NMD 20 20610155
2015 Effective Treatment With Albuterol in DOK7 Congenital Myasthenic Syndrome in Children. Pediatric neurology 18 26552645
2021 DOK7 Inhibits Cell Proliferation, Migration, and Invasion of Breast Cancer via the PI3K/PTEN/AKT Pathway. Journal of oncology 16 33552156
2015 Protein kinase CK2 interacts at the neuromuscular synapse with Rapsyn, Rac1, 14-3-3γ, and Dok-7 proteins and phosphorylates the latter two. The Journal of biological chemistry 16 26198629
2017 Congenital Myasthenic Syndrome due to DOK7 mutations in a family from Chile. European journal of translational myology 15 29118959
2018 Examination of methylation changes of VIM, CXCR4, DOK7, and SPDEF genes in peripheral blood DNA in breast cancer patients. Indian journal of cancer 13 30829272
2016 Silencing of Dok-7 in Adult Rat Muscle Increases Susceptibility to Passive Transfer Myasthenia Gravis. The American journal of pathology 13 27658713
2011 Investigation for RAPSN and DOK-7 mutations in a cohort of seronegative myasthenia gravis patients. Muscle & nerve 13 21305573
2017 The carboxyl-terminal region of Dok-7 plays a key, but not essential, role in activation of muscle-specific receptor kinase MuSK and neuromuscular synapse formation. Journal of biochemistry 11 28069867
2017 DOK7 myasthenic syndrome with subacute adult onset during pregnancy and partial response to fluoxetine. Neuromuscular disorders : NMD 11 29395672
2023 IgG1-3 MuSK Antibodies Inhibit AChR Cluster Formation, Restored by SHP2 Inhibitor, Despite Normal MuSK, DOK7, or AChR Subunit Phosphorylation. Neurology(R) neuroimmunology & neuroinflammation 10 37582613
2021 A novel DOK7 mutation causing congenital myasthenic syndrome with limb-girdle weakness: case series of three family members. Heliyon 10 34027146
2019 Overexpression of Dok-7 in skeletal muscle enhances neuromuscular transmission with structural alterations of neuromuscular junctions: Implications in robustness of neuromuscular transmission. Biochemical and biophysical research communications 10 31848047
2023 A mutation in DOK7 in congenital myasthenic syndrome forms aggresome in cultured cells, and reduces DOK7 expression and MuSK phosphorylation in patient-derived iPS cells. Human molecular genetics 9 36579833
2022 DOK7 Promotes NMJ Regeneration After Nerve Injury. Molecular neurobiology 9 36464749
2020 APC2CDH1 negatively regulates agrin signaling by promoting the ubiquitination and proteolytic degradation of DOK7. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 9 32687671
2018 Repression of Dok7 expression mediated by DNMT1 promotes glioma cells proliferation. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 9 29990858
2021 Hsa_Circ_0001947/MiR-661/DOK7 Axis Restrains Non-Small Cell Lung Cancer Development. Journal of microbiology and biotechnology 8 34528912
2020 A late-onset congenital myasthenic syndrome due to a heterozygous DOK7 mutation. Neuromuscular disorders : NMD 7 32360404
2017 Repression of DOK7 mediated by DNMT3A promotes the proliferation and invasion of KYSE410 and TE-12 ESCC cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 7 28343076
2022 DOK7 CpG hypermethylation in blood leukocytes as an epigenetic biomarker for acquired tamoxifen resistant in breast cancer. Journal of human genetics 6 36372800
2020 Identification of the downstream molecules of agrin/Dok-7 signaling in muscle. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 6 32043676
2015 Anticholinesterase Therapy Worsening Head Drop and Limb Weakness Due to a Novel DOK7 Mutation. Journal of clinical neuromuscular disease 6 26583494
2014 [Beneficial effects of 3,4-diaminopyridine in a 26-year-old woman with DOK7 congenital myasthenic syndrome who was originally diagnosed with facioscapulohumeral dystrophy]. Rinsho shinkeigaku = Clinical neurology 6 25087557
2024 DOK7 congenital myasthenic syndrome: case series and review of literature. BMC neurology 5 38907197
2023 Long-term muscle-specific overexpression of DOK7 in mice using AAV9-tMCK-DOK7. Molecular therapy. Nucleic acids 5 37637210
2017 Intragenic DOK7 deletion detected by whole-genome sequencing in congenital myasthenic syndromes. Neurology. Genetics 5 28508085
2015 Limb girdle weakness responding to salbutamol: an Indian family with DOK7 mutation. Indian pediatrics 5 25849006
2016 ELF5 and DOK7 regulation in anti-estrogen treated cells and tumors. Cancer cell international 4 26884724
2024 Peroxisome proliferator-activated receptor γ coactivator 1α regulates downstream of tyrosine kinase-7 (Dok-7) expression important for neuromuscular junction formation. Scientific reports 3 38245592
2023 DOK7, a target of miR-299-5p, suppresses the progression of bladder cancer. Aging 3 38095644
2020 Congenital myasthenic syndrome due to DOK7 mutation in a cohort of patients with 'unexplained' limb-girdle muscular weakness. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 3 32238315
2017 SRSF1 suppresses selection of intron-distal 5' splice site of DOK7 intron 4 to generate functional full-length Dok-7 protein. Scientific reports 3 28874828
2024 Dose escalation pre-clinical trial of novel DOK7-AAV in mouse model of DOK7 congenital myasthenia. bioRxiv : the preprint server for biology 2 38405691
2025 Dose escalation pre-clinical trial of novel DOK7-AAV in mouse model of DOK7 congenital myasthenia. Brain communications 1 39944742
2024 Effective treatment with oral Salbutamol on late onset respiratory impairment in a DOK7 Congenital Myasthenia Syndrome: a case report. Multidisciplinary respiratory medicine 1 38756045
2023 When Breathing Becomes a Challenge: A Case of Congenital Myasthenia Gravis in an Indian Neonate With a DOK-7 Gene Mutation. Cureus 1 37303354
2023 Congenital Myasthenic Syndrome Caused by DOK7 Mutation in a Quinquagenarian Male with Calf Hypertrophy. Journal of clinical neuromuscular disease 1 37611271
2021 Diagnosis of DOK7 congenital myasthenic syndrome during pregnancy: A case report and literature review. Clinical neurology and neurosurgery 1 33714798
2019 Phenotypic Differences in 2 Unrelated Cases Carrying Identical DOK7 Mutations. Journal of clinical neuromuscular disease 1 31453852
2008 [Overview: MuSK/Dok-7]. Nihon rinsho. Japanese journal of clinical medicine 1 18540360
2025 Agrin/Dok-7-induced JPH2 phosphorylation in muscle cells is involved in AChR clustering. FEBS letters 0 40290048
2025 Congenital Myasthenic Syndrome With Adult Onset Due to the Novel Heterozygous c.1399_1404del Variant in the Downstream of Tyrosine Kinase-7 (DOK7): A Case Report. Cureus 0 40330390
2023 DOK7 Gene Novel Homozygous Mutation is Related to Fetal Akinesia Deformation Sequence 3. Journal of obstetrics and gynaecology of India 0 40390963
2022 Epigenteic Alteration of DOK7 Gene CpG Island in Blood Leukocyte of Patients with Gastric Cancer and Intestinal Methaplasia. Iranian journal of biotechnology 0 36337064

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