Affinage

DOK7

Protein Dok-7 · UniProt Q18PE1

Length
504 aa
Mass
53.1 kDa
Annotated
2026-04-28
77 papers in source corpus 18 papers cited in narrative 18 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DOK7 is a cytoplasmic adaptor protein essential for the formation and maintenance of neuromuscular junctions (NMJs), functioning as the obligate activator of the MuSK receptor tyrosine kinase in skeletal muscle. Its dimeric PH-PTB domain architecture binds the MuSK juxtamembrane region and promotes trans-autophosphorylation of the MuSK activation loop; the PH domain mediates membrane association, while a CRM1-dependent nuclear export signal in the C-terminal region ensures cytoplasmic retention required for MuSK interaction (PMID:16794080, PMID:20603078, PMID:18165682). Agrin-stimulated phosphorylation of two C-terminal tyrosines on Dok-7 recruits Crk/Crk-L adaptors to drive pre- and postsynaptic differentiation, and Dok-7 protein levels are negatively regulated by APC2-mediated ubiquitination at K243, which depends on MuSK-phosphorylated Y106 (PMID:21041412, PMID:32687671). Loss-of-function mutations in DOK7—including the common 1124_1127dup frameshift—cause congenital myasthenic syndrome through impaired MuSK kinase activation, a defect that can be rescued by MuSK agonist antibodies in mouse models (PMID:34163073, PMID:36579833).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2006 High

    The identity of the intracellular activator of MuSK was unknown; Dok-7 was identified as the essential PTB-domain adaptor that activates MuSK and is absolutely required for AChR clustering and NMJ formation in vivo.

    Evidence Dok-7 knockout mice lack NMJ synapses; PTB domain mutagenesis and Co-IP in cultured myotubes

    PMID:16794080

    Open questions at the time
    • Mechanism by which Dok-7 activates MuSK kinase at the structural level was unknown
    • Downstream signaling from Dok-7 uncharacterized
    • Role of the C-terminal domain undefined
  2. 2007 High

    How Dok-7 maintains cytoplasmic localization and which domains beyond the PTB contribute to function was unclear; a CRM1-dependent NES was identified in the C-terminus, while the PH domain mediates nuclear import, and C-terminal SH2-target motifs were shown to be crucial for MuSK activation.

    Evidence Domain mutagenesis, subcellular fractionation, CRM1 inhibitor treatment, myotube MuSK activation assays

    PMID:18165682

    Open questions at the time
    • PH domain lipid-binding specificity unresolved experimentally
    • CMS mutations mapped but rescue not attempted
  3. 2009 High

    Whether Dok-7 could promote NMJ formation when overexpressed in vivo and whether agrin signaling required Dok-7 were open; Dok-7 overexpression was shown to increase MuSK activation and NMJ formation, and agrin was shown to require Dok-7 for MuSK activation.

    Evidence In vivo overexpression, myotube co-activation assays, MuSK localization studies

    PMID:19244212

    Open questions at the time
    • Structural basis of Dok-7-mediated MuSK activation not yet determined
    • Downstream effectors of Dok-7 phosphorylation unknown
  4. 2010 High

    The structural mechanism of MuSK activation and the identity of downstream effectors recruited by Dok-7 were simultaneously resolved: crystal structure revealed Dok-7 PH-PTB dimerization drives MuSK trans-autophosphorylation, agrin-stimulated C-terminal tyrosine phosphorylation recruits Crk/Crk-L, and zebrafish studies confirmed conserved roles in AChR pre-patterning.

    Evidence X-ray crystallography with mutagenesis (Molecular Cell); phosphotyrosine mapping, Co-IP, and Crk/Crk-L muscle-specific KO (Genes & Development); zebrafish morpholino knockdown (Human Molecular Genetics); MuSK CMS mutation Co-IP studies

    PMID:20147321 PMID:20371544 PMID:20603078 PMID:21041412

    Open questions at the time
    • Signaling events downstream of Crk/Crk-L at NMJ undefined
    • Dok-7 regulation by post-translational modifications other than tyrosine phosphorylation unexplored
    • Potential MuSK-independent roles suggested in zebrafish slow muscle not followed up
  5. 2015 Medium

    Whether serine/threonine kinases regulate Dok-7 activity was unknown; CK2 was identified as a kinase that phosphorylates Dok-7 on serine residues, and phosphomimetic mutants enhanced AChR clustering.

    Evidence Co-IP, in vitro kinase assay, phosphomimetic mutant expression in C2C12 myotubes

    PMID:26198629

    Open questions at the time
    • In vivo relevance of CK2-mediated Dok-7 phosphorylation not tested
    • Specific serine sites and their individual contributions not fully dissected
  6. 2016 Medium

    Whether Dok-7 is required for NMJ maintenance in adult muscle (beyond developmental formation) was unresolved; in vivo silencing in adult rat muscle reduced AChR density and impaired neuromuscular transmission.

    Evidence In vivo electroporation of shRNA in adult rat tibialis anterior, electrophysiology, immunofluorescence

    PMID:27658713

    Open questions at the time
    • Long-term consequences and reversibility not assessed
    • Mechanism of Dok-7 maintenance function versus developmental function not distinguished
  7. 2017 High

    The functional necessity of the C-terminal domain versus the PH-PTB core was quantified: truncated Dok-7 lacking the C-terminus partially activated MuSK and rescued neonatal lethality of Dok-7 KO mice but produced small NMJs and early death, and SRSF1-dependent splicing was shown to control production of full-length functional Dok-7 mRNA.

    Evidence In vitro kinase assay with purified recombinant proteins, transgenic rescue of Dok-7 KO mice (J Biochem); block-scanning mutagenesis, RNA affinity purification, spliceosome complex analysis (Scientific Reports)

    PMID:28069867 PMID:28874828

    Open questions at the time
    • Whether SRSF1 regulation of Dok-7 splicing is disrupted in CMS patients unknown
    • Quantitative contribution of C-terminal tyrosine phosphorylation versus C-terminal scaffolding not separated
  8. 2020 Medium

    Negative regulation of Dok-7 protein levels and broader downstream signaling were characterized: APC2-mediated ubiquitination at K243 (dependent on MuSK-phosphorylated Y106) targets Dok-7 for proteolysis, and phosphoproteomics identified 13 agrin/Dok-7-dependent phosphoproteins including Anxa3 as a functional downstream effector.

    Evidence Ubiquitination assay with site-directed mutagenesis (FASEB J); CRISPR/Cas9 Dok-7 KO phosphoproteomics with Anxa3 validation in vivo (FASEB J)

    PMID:32043676 PMID:32687671

    Open questions at the time
    • Whether APC2 regulation is altered in disease not tested
    • Most of the 13 Dok-7-dependent phosphoproteins not functionally validated
    • Relationship between ubiquitination and CK2-mediated serine phosphorylation unexplored
  9. 2021 High

    The pathogenic mechanism of the most common DOK7 CMS mutation (1124_1127dup) was clarified as deficient MuSK phosphorylation/activation rather than loss of Dok-7 tyrosine phosphorylation, and MuSK agonist antibodies rescued NMJ formation and neonatal lethality in knock-in mice.

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

    PMID:34163073

    Open questions at the time
    • Whether agonist antibodies can reverse established disease in adult animals not shown
    • Pharmacokinetics and long-term safety of MuSK agonist antibodies unknown
  10. 2023 Medium

    How PH domain missense mutations cause disease at the protein level was unknown; the G64R mutation was shown to cause Dok-7 misfolding into insoluble aggresomes, reducing soluble protein to ~10% and impairing AChR clustering, confirmed in patient-derived iPSC myotubes.

    Evidence Transfection in C2C12/COS7 cells, patient-derived iPSCs with CRISPR isogenic controls, immunofluorescence, proteasome inhibitor treatment

    PMID:36579833

    Open questions at the time
    • Whether aggresome formation is a general mechanism for PH domain CMS mutations not tested
    • Therapeutic strategies to restore Dok-7 solubility not explored
  11. 2024 Medium

    Transcriptional regulation of DOK7 in adult muscle was poorly understood; PGC1α and ERRα were identified as transcriptional activators of the DOK7 promoter, linking exercise-responsive signaling to NMJ maintenance.

    Evidence Skeletal muscle-specific PGC1α KO and overexpression mice, luciferase promoter assay, NMJ morphology

    PMID:38245592

    Open questions at the time
    • Direct binding of ERRα to DOK7 promoter not demonstrated by ChIP
    • Whether PGC1α-DOK7 axis is relevant to CMS or aging-related NMJ decline unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full downstream signaling network through which Dok-7/Crk/Crk-L remodel the postsynaptic membrane, whether the MuSK-independent role in slow muscle fiber patterning is real and conserved, and whether pharmacological stabilization of Dok-7 protein (preventing APC2-mediated degradation or aggresome formation) is therapeutically viable for CMS.
  • Full Crk/Crk-L effector pathway at NMJ not mapped
  • MuSK-independent functions remain unvalidated beyond zebrafish
  • No structural model of full-length Dok-7 including C-terminal domain exists

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-112316 Neuronal System 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1643685 Disease 2
Partners
APC2CRKCRKLCSNK2A1LRP4MUSKSRSF1

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 in cultured myotubes; the Dok-7 phosphotyrosine-binding (PTB) domain and its target site on MuSK are indispensable for this activation. Mice lacking Dok-7 form neither acetylcholine receptor clusters nor neuromuscular synapses, demonstrating Dok-7 is essential for neuromuscular synaptogenesis through its interaction with MuSK. Knockout mouse model, cultured myotube assays, domain mutagenesis, Co-IP Science High 16794080
2010 Crystal structure of the Dok-7 PH-PTB domains in complex with a phosphopeptide from the Dok-7-binding site on MuSK reveals a dimeric arrangement of Dok-7 PH-PTB that facilitates trans-autophosphorylation of the MuSK kinase activation loop, providing the molecular basis for MuSK activation by Dok-7. X-ray crystallography, biochemical dimerization assays, mutagenesis Molecular Cell High 20603078
2009 Dok-7 directly interacts with the cytoplasmic portion of MuSK and activates its receptor tyrosine kinase activity; neural agrin requires Dok-7 to activate MuSK. In vivo overexpression of Dok-7 increases MuSK activation and promotes NMJ formation. Dok-7 is required for correct localization of MuSK to the central region of muscle. In vivo overexpression, myotube co-activation assays, localization studies 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 leads to severe defects in neuromuscular synapses in vivo, placing Crk/Crk-L downstream of Dok-7 in synaptic differentiation. Phosphotyrosine mapping, Co-IP/pulldown, muscle-specific genetic inactivation (Crk/Crk-L KO), NMJ morphology analysis Genes & Development High 21041412
2007 A chromosome region maintenance 1 (CRM1)-dependent nuclear export signal (NES) in the C-terminal moiety of Dok-7 is essential for its cytoplasmic localization and interaction with MuSK in myotubes. The N-terminal PH domain mediates nuclear import of Dok-7. The C-terminal Src homology 2 (SH2) target motifs are active and crucial for MuSK activation. CMS-associated missense mutations in the PH or PTB domain inactivate Dok-7. Domain mutagenesis, subcellular fractionation/localization, myotube MuSK activation assays, CRM1 inhibitor treatment Journal of Biological Chemistry High 18165682
2021 The common disease-causing mutation DOK7 1124_1127dup causes severe deficiency in MuSK phosphorylation and activation (rather than a deficiency in DOK7 tyrosine phosphorylation itself). Agonist antibodies against MuSK restore neuromuscular synapse formation and prevent neonatal lethality in Dok7CM mice, demonstrating that the pathogenic mechanism is principally through impaired MuSK kinase activation. Knock-in mouse model (Dok7CM and Dok72YF point-mutant mice), biochemical phosphorylation assays, agonist antibody rescue experiments Nature High 34163073
2015 Protein kinase CK2 interacts with Dok-7 at the neuromuscular junction and phosphorylates Dok-7 at multiple serine residues. Phosphomimetic Dok-7 mutants aggregate nicotinic acetylcholine receptors in C2C12 myotubes with significantly higher frequency than wild-type Dok-7. Co-immunoprecipitation, in vitro kinase assay, phosphomimetic mutant expression in C2C12 myotubes, AChR clustering assay Journal of Biological Chemistry Medium 26198629
2020 APC2 (core subunit of APC/C E3 ligase complex), enriched at the post-synapse of NMJs in postmitotic myotubes, negatively regulates AChR clustering by promoting ubiquitination of DOK7 at lysine 243 for its proteolytic degradation. This ubiquitination relies on MuSK kinase activity and phosphorylation of tyrosine 106 in DOK7. Ubiquitination assay, site-directed mutagenesis (K243, Y106), agrin stimulation, Co-IP, AChR clustering assay FASEB Journal Medium 32687671
2016 Computational multiscale molecular dynamics simulations indicate that the Dok-7 PH domain associates with membranes containing phosphatidylinositol phosphates (PIPs) via positively charged loops (β1/β2, β3/β4, β5/β6), identifying both canonical and atypical PIP-binding sites and showing that PH domain-membrane binding leads to local PIP clustering—a key step for Dok-7 membrane localization and MuSK complex formation. Multiscale molecular dynamics simulations (coarse-grained and atomistic) PLoS Computational Biology Low 27459095
2017 The C-terminal region of Dok-7 plays a key but not fully essential role in MuSK activation: Dok-7 lacking the C-terminal region (Dok-7-ΔC) shows marginal but significant MuSK activation in myotubes and in a cell-free kinase assay with purified recombinant protein. Forced expression of Dok-7-ΔC rescues Dok-7-deficient mice from neonatal lethality but NMJs remain abnormally small and mice die by 3 weeks, confirming the C-terminal domain is important but not absolutely required for kinase activation. Quantitative MuSK activation assay in myotubes, in vitro kinase assay with purified recombinant proteins, rescue of Dok-7 KO mice by transgenic expression Journal of Biochemistry High 28069867
2017 SRSF1 binds a cis-element near the 3' end of DOK7 exon 4 and suppresses selection of an intron-distal 5' splice site, thereby promoting canonical full-length Dok-7 mRNA production. SRSF1 achieves this by inhibiting association of U1 snRNP with the intron-distal 5' SS and enhancing U1 snRNP binding to the intron-proximal 5' SS. Full-length Dok-7 enhances AChR clustering whereas the truncated isoform does not. Block-scanning mutagenesis, RNA affinity purification/mass spectrometry, SRSF1 knockdown and MS2-tethering assays, early spliceosomal complex isolation, AChR clustering assay Scientific Reports Medium 28874828
2020 Quantitative phosphoproteomics using CRISPR/Cas9-generated Dok-7 mutant myotubes identified 13 proteins whose agrin-stimulated tyrosine phosphorylation depends on Dok-7, including Anxa3. Knockdown of Anxa3 in cultured myotubes inhibited agrin-induced AChR clustering, and reduction of Anxa3 in mouse muscle induced abnormal postsynaptic development, placing Anxa3 downstream of agrin/Dok-7 signaling. CRISPR/Cas9 KO, quantitative phosphoproteomics, Anxa3 knockdown, AChR clustering assay, in vivo muscle injection FASEB Journal Medium 32043676
2010 Dok-7 deficiency in zebrafish leads to motility defects and impairs the earliest step of NMJ formation (AChR pre-patterning clusters in the middle of the muscle fiber prior to motor neuron contact). At later stages, focal and non-focal synapses do form but are smaller. Additionally, Dok-7 influences slow muscle fiber arrangement in a manner apparently independent of MuSK. Zebrafish morpholino knockdown, live imaging of AChR clusters, fluorescence microscopy of NMJs Human Molecular Genetics Medium 20147321
2010 MUSK missense mutations (A727V and M605I) impair agrin-dependent MuSK phosphorylation and interaction of MuSK with Dok-7 but not with LRP4 or Tid1, indicating that inability of MuSK mutants to interact with Dok-7 is a major determinant of CMS pathogenesis caused by MUSK mutations. Expression studies in MuSK-deficient myotubes, Co-immunoprecipitation, AChR aggregation assay Human Molecular Genetics Medium 20371544
2016 Silencing Dok-7 in adult rat tibialis anterior muscle by in vivo electroporation of shRNA reduces AChR protein levels at the NMJ by ~25% and significantly impairs neuromuscular transmission, demonstrating that Dok-7 is required for maintaining AChR cluster density and NMJ transmission in adult muscle. In vivo electroporation of shRNA, passive transfer myasthenia gravis model, electrophysiology, immunofluorescence quantification of AChR American Journal of Pathology Medium 27658713
2023 A pathogenic DOK7 missense mutation p.G64R in the PH domain causes Dok-7 to form insoluble aggresomes at the juxtanuclear region (co-localizing with autophagosome markers) in C2C12 myoblasts and COS7 cells, reducing soluble Dok-7 expression to ~10% of wild-type and markedly impairing AChR clustering. Patient-derived iPS cell-differentiated myotubes confirmed reduced endogenous DOK7 expression and reduced MuSK phosphorylation. Transfection of mutant DOK7 in C2C12/COS7 cells, patient-derived iPS cells with CRISPR/Cas9 isogenic correction, immunofluorescence, proteasome inhibitor (MG132) treatment, AChR clustering assay Human Molecular Genetics Medium 36579833
2024 PGC1α regulates Dok-7 expression in skeletal muscle; luciferase reporter assays show that co-expression of PGC1α and estrogen receptor-related receptor α (ERRα) greatly increases Dok-7 promoter activity, linking exercise-induced PGC1α upregulation to transcriptional control of DOK7 and NMJ formation. Skeletal muscle-specific PGC1α knockout and overexpression mice, luciferase promoter assay, NMJ morphology analysis Scientific Reports Medium 38245592
2025 Phosphoproteomics using phosphorylated iTRAQ identified 16 Agrin/Dok-7-mediated serine/threonine phosphorylated proteins downstream of Dok-7 in muscle cells. One validated target, JPH2, when manipulated, regulates AChR clustering, extending understanding of the signaling network downstream of Dok-7. Phosphorylated iTRAQ phosphoproteomics, functional validation of JPH2 in AChR clustering assay 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.) 344 16794080
2006 Dok-7 mutations underlie a neuromuscular junction synaptopathy. Science (New York, N.Y.) 218 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 113 17439981
2010 The cytoplasmic adaptor protein Dok7 activates the receptor tyrosine kinase MuSK via dimerization. Molecular cell 107 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
2008 Dok-7 myasthenia: phenotypic and molecular genetic studies in 16 patients. Annals of neurology 93 18626973
2010 Dok-7 regulates neuromuscular synapse formation by recruiting Crk and Crk-L. Genes & development 92 21041412
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 80 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 64 20012313
2012 Salbutamol benefits children with congenital myasthenic syndrome due to DOK7 mutations. Neuromuscular disorders : NMD 61 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 52 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 43 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 29 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
2016 Silencing of Dok-7 in Adult Rat Muscle Increases Susceptibility to Passive Transfer Myasthenia Gravis. The American journal of pathology 13 27658713
2018 Examination of methylation changes of VIM, CXCR4, DOK7, and SPDEF genes in peripheral blood DNA in breast cancer patients. Indian journal of cancer 12 30829272
2011 Investigation for RAPSN and DOK-7 mutations in a cohort of seronegative myasthenia gravis patients. Muscle & nerve 12 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
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
2023 Long-term muscle-specific overexpression of DOK7 in mice using AAV9-tMCK-DOK7. Molecular therapy. Nucleic acids 4 37637210
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
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 Dose escalation pre-clinical trial of novel DOK7-AAV in mouse model of DOK7 congenital myasthenia. Brain communications 0 39944742
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