Affinage

DISC1

Disrupted in schizophrenia 1 protein · UniProt Q9NRI5

Length
854 aa
Mass
93.6 kDa
Annotated
2026-06-09
100 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DISC1 is a multifunctional neurodevelopmental scaffold protein that nucleates distinct molecular complexes governing cytoskeletal organization, intracellular signaling, organelle transport, and gene expression in the developing and mature brain (PMID:16299498, PMID:18983980). At the centrosome it anchors a dynein motor complex and assembles NDE1/NDEL1/LIS1/dynein together with the cAMP phosphodiesterases PDE4B/PDE4D, coupling cytoskeletal organization to PKA-dependent phosphorylation of NDE1 at threonine-131 that tunes NDE1–LIS1/NDEL1 interactions and neurite outgrowth (PMID:18983980, PMID:21677187); a crystal structure of the DISC1 C-terminal tail bound to Ndel1 established that this interaction controls Ndel1 kinetochore attachment and mitotic progression in radial glia (PMID:29103808). DISC1 directs neuronal transport machinery, recruiting Grb2/KIF5A for NT-3–driven ERK signaling at axon tips (PMID:17202467), assembling FEZ1–Synaptotagmin-1 kinesin cargo complexes for synaptic vesicle transport (PMID:21664390), and acting as a Miro1/Miro2–TRAK1/TRAK2 adaptor that promotes anterograde axonal mitochondrial transport and ER–mitochondria coupling, with mitochondrial directionality gated by the Miro1 GTPase state (PMID:24092329, PMID:26553875, PMID:32637409). It controls neural progenitor proliferation and cortical fate through Wnt–GSK3β/β-catenin signaling via direct GSK3 and Dixdc1 binding (PMID:20624590, PMID:22099458, PMID:26299970), and in the nucleus binds ATF4/CREB2 and N-CoR to modulate CRE-dependent transcription, an interaction defined at atomic resolution (PMID:18762802, PMID:31444471). DISC1 additionally stabilizes serine racemase against ubiquitin-proteasomal degradation to sustain astrocytic D-serine production and NMDA receptor signaling (PMID:22801410), regulates synaptic composition via TNIK (PMID:20838393), and modulates dopamine D2 receptor signaling and trafficking (PMID:25433637). DISC1 levels are themselves regulated by FBXW7-mediated phosphodegron-dependent degradation (PMID:28727686) and transcriptionally by FOXP2 (PMID:22434823). Disease-associated truncations and missense variants act dominant-negatively or via nonsense-mediated decay to disrupt these complexes, and patient frameshift mutations cause synaptic and transcriptional deficits rescuable by PDE4 inhibition or ATF4 reduction, linking DISC1 dysfunction to neurodevelopmental and psychiatric pathology (PMID:16299498, PMID:31444471, PMID:33658519).

Mechanistic history

Synthesis pass · year-by-year structured walk · 40 steps
  1. 2004 Medium

    Established a physical basis for DISC1 centrosomal localization, addressing how a psychiatric-risk protein engages the cytoskeletal machinery.

    Evidence Yeast two-hybrid, Co-IP and colocalization mapping the kendrin/pericentrin-B interaction to DISC1 residues 446–533

    PMID:15094396

    Open questions at the time
    • No direct functional mutagenesis of the interface
    • Did not establish consequences for microtubule nucleation in neurons
  2. 2005 High

    Showed DISC1 is a required component of the centrosomal dynein complex, and that truncating mutations act dominant-negatively, providing a mechanistic link between DISC1 disruption and impaired cortical development.

    Evidence Reciprocal Co-IP, dominant-negative overexpression and RNAi in PC12 cells plus in vivo mouse cortical electroporation

    PMID:16299498

    Open questions at the time
    • Did not resolve the structural basis of dynein anchoring
    • Self-association domain not atomically mapped
  3. 2005 Medium

    Defined the domain architecture of DISC1 targeting, separating mitochondrial/nuclear from centrosomal localization signals.

    Evidence Truncation construct expression and live-cell imaging in COS-7 cells

    PMID:16209927

    Open questions at the time
    • Mitochondrial 'ring' reorganization not mechanistically linked to fusion/fission proteins
    • Overexpression artifact not excluded
  4. 2006 High

    Mapped a discrete DISC1–NDEL1 interaction domain required for neurite outgrowth, connecting disease-associated variants to a defined molecular contact.

    Evidence Co-IP, deletion mapping to aa 802–835, and PC12 neurite outgrowth assays with disease variants

    PMID:17035248

    Open questions at the time
    • Structural detail of the interface awaited later crystallography
    • In vivo consequences not yet tested
  5. 2007 High

    Linked DISC1 to cAMP signaling by showing missense mutations disrupt PDE4B binding and alter enzyme activity, establishing a signaling axis relevant to mood and psychosis.

    Evidence ENU mutant mice (Q31L, L100P), Co-IP, PDE4 activity assay, behavioral pharmacology

    PMID:17481393

    Open questions at the time
    • Did not resolve how DISC1 binding modulates PDE4 catalysis
    • Downstream PKA substrates not yet identified
  6. 2007 Medium

    Identified DISC1 as a kinesin adaptor for growth-factor signaling, showing it recruits Grb2/KIF5A to enable distal-axon ERK activation.

    Evidence Co-IP, RNAi in hippocampal neurons, ERK phosphorylation and immunofluorescence

    PMID:17202467

    Open questions at the time
    • Single lab
    • Direct versus indirect Grb2 binding not fully resolved
  7. 2008 Medium

    Consolidated DISC1 as a scaffold integrating cytoskeletal and cAMP machinery by demonstrating co-assembly of NDE1/NDEL1/LIS1/dynein with PDE4 at the centrosome and synapse.

    Evidence Co-IP, immunofluorescence and subcellular fractionation in cultured neurons

    PMID:18983980

    Open questions at the time
    • Stoichiometry and assembly order not determined
    • Single lab
  8. 2008 Medium

    Demonstrated a nuclear transcriptional function for DISC1 through ATF4/CREB2 and N-CoR, with mapped nuclear-localization elements and an in vivo behavioral readout.

    Evidence Drosophila transgenics, mammalian Co-IP, CRE luciferase reporter, NLS deletion mapping

    PMID:18762802

    Open questions at the time
    • Direct DNA-binding versus co-factor role not separated
    • Mammalian behavioral relevance not tested here
  9. 2008 Medium

    Confirmed the C-terminal kendrin interaction is required for centrosomal targeting and microtubule organization.

    Evidence Directed yeast two-hybrid, deletion mutagenesis, Co-IP and microtubule organization assay

    PMID:18955030

    Open questions at the time
    • No structural interface
    • Effect on gamma-tubulin recruitment inferred indirectly
  10. 2009 Medium

    Extended DISC1 function to neural crest by showing it represses foxd3/sox10 to permit cranial neural crest migration, indicating a transcriptional/developmental role beyond the CNS.

    Evidence Morpholino knockdown, time-lapse imaging and in situ hybridization in zebrafish

    PMID:19570850

    Open questions at the time
    • Mechanism of transcriptional repression unknown
    • Morpholino specificity caveats
  11. 2010 High

    Established a Wnt-dependent and -independent developmental dual function via Dixdc1, linking DISC1 to both progenitor proliferation and neuronal migration.

    Evidence Co-IP, in utero electroporation, Cdk5 phospho-mutant Dixdc1, Wnt reporter

    PMID:20624590

    Open questions at the time
    • Direct GSK3 binding not yet mapped here
    • Phosphoswitch kinetics undefined
  12. 2010 Medium

    Identified TNIK as a synaptic DISC1 partner that stabilizes postsynaptic density proteins, tying DISC1 to synaptic composition and activity.

    Evidence Reciprocal Co-IP, synaptic fractionation, RNAi and electrophysiology

    PMID:20838393

    Open questions at the time
    • Single lab
    • TNIK substrates within the complex not defined
  13. 2010 Medium

    Connected DISC1 to ciliogenesis and dopamine receptor compartmentalization, broadening its role to primary cilium biology.

    Evidence GFP-DISC1 localization, RNAi knockdown and cilia marker immunofluorescence in NIH3T3 and striatal neurons

    PMID:20531939

    Open questions at the time
    • Mechanism of cilia maintenance unresolved
    • Functional link to receptor signaling not tested
  14. 2011 Medium

    Demonstrated direct DISC1–GSK3 binding and that the L100P mutation dysregulates GSK3, with rescue by GSK3 inhibition establishing a therapeutic node.

    Evidence Co-IP mapping to aa 1–220, genetic and pharmacological GSK3 inactivation, behavioral assays in L100P mice

    PMID:20687110

    Open questions at the time
    • Structural interface undefined
    • Single lab
  15. 2011 High

    Defined the biochemical mechanism by which the DISC1–PDE4 module controls cytoskeletal assembly: PKA phosphorylation of NDE1 at T131 modulates NDE1–LIS1/NDEL1 binding and neurite outgrowth.

    Evidence In vitro PKA assay, phospho-specific antibody, homology modeling, Co-IP and phospho-mutant neurite assay

    PMID:21677187

    Open questions at the time
    • In vivo relevance of T131 phosphorylation not tested
    • Other PKA sites not excluded
  16. 2011 Medium

    Showed DISC1 drives synaptic vesicle transport by assembling the FEZ1–Syt-1 kinesin cargo complex, with lithium restoring transport.

    Evidence RNAi, dominant-negative DISC1, live vesicle imaging and Co-IP in cortical neurons

    PMID:21664390

    Open questions at the time
    • Lithium mechanism of rescue undefined
    • Single lab
  17. 2011 Medium

    Separated parallel DISC1 pathways in adult neurogenesis, distinguishing FEZ1-dependent dendritic growth from NDEL1-dependent cell positioning.

    Evidence Retroviral RNAi in adult hippocampus, Co-IP and genetic epistasis in schizophrenia cohorts

    PMID:22099459

    Open questions at the time
    • Molecular branch point not identified
    • Single lab
  18. 2011 High

    Dissected variant-specific loss of DISC1 Wnt signaling activity, assigning A83V/R264Q/L607F to proliferation defects and S704C to migration defects across model systems.

    Evidence Wnt reporter, zebrafish rescue, mouse progenitor assays, human lymphoblasts, TALEN/CRISPR mutants

    PMID:22099458

    Open questions at the time
    • Direct molecular consequence of each variant on GSK3 binding not all resolved
  19. 2012 High

    Placed DISC1-regulated dendritic development of newborn neurons downstream of GABA/NKCC1 depolarization converging on AKT–mTOR, with human genetic epistasis support.

    Evidence Retroviral RNAi, pharmacological NKCC1 and mTOR manipulation, epistasis in two case-control cohorts

    PMID:22385968

    Open questions at the time
    • Direct DISC1–mTOR molecular link not defined
    • Mechanism of NKCC1 convergence indirect
  20. 2012 High

    Revealed a neurochemical function: DISC1 stabilizes serine racemase to sustain D-serine and NMDA receptor signaling, with mutant DISC1 promoting SR degradation.

    Evidence Co-IP, astrocyte-selective dominant-negative mouse, ubiquitination assay, D-serine measurement, behavioral rescue

    PMID:22801410

    Open questions at the time
    • E3 ligase for SR not identified here
    • Interface mapping incomplete
  21. 2012 Medium

    Characterized DISC1 transcriptional regulation, identifying FOXP2 as a repressor whose dyspraxia mutations relieve repression.

    Evidence Dual luciferase promoter assays, deletion constructs, FOXP2 mutant analysis, Western blot

    PMID:22434823

    Open questions at the time
    • Direct FOXP2 promoter occupancy not shown
    • Single lab
  22. 2013 Medium

    Identified DISC1 as a TRAK1/Miro1 mitochondrial transport adaptor specifically promoting anterograde movement, with a rare variant impairing this function.

    Evidence Co-IP and live axonal mitochondria imaging with variant-specific analysis

    PMID:24092329

    Open questions at the time
    • Single lab
    • Directionality mechanism not yet defined
  23. 2014 High

    Demonstrated a DISC1–D2R complex controlling D2R-mediated GSK3 signaling and internalization, with disease relevance shown in postmortem brain and rescue by an interfering peptide.

    Evidence Reciprocal Co-IP, postmortem biochemistry, in vivo interfering peptide, behavioral assays

    PMID:25433637

    Open questions at the time
    • Interface not structurally defined
    • Cell-type specificity of complex not resolved
  24. 2014 Medium

    Connected DISC1 to APP processing and trafficking, showing knockdown shifts APP toward non-amyloidogenic processing and surface retention.

    Evidence RNAi in cortical neurons, Aβ/sAPP ELISA, surface biotinylation, interaction-deficient mutant rescue

    PMID:25224257

    Open questions at the time
    • Direct binding interface not mapped
    • Single lab
  25. 2014 Medium

    Defined a DISC1 role in oligodendrocyte differentiation, showing it negatively regulates myelin marker expression.

    Evidence Bidirectional overexpression/RNAi in oligodendrocyte precursors with myelin marker immunocytochemistry

    PMID:24516667

    Open questions at the time
    • Molecular pathway unidentified
    • Single lab
  26. 2014 Medium

    Characterized the DISC1-Boymaw fusion as inhibiting NADH oxidoreductase activity and protein translation, reducing synaptic protein levels in knock-in mice.

    Evidence Humanized knock-in mice, translation and NADH oxidoreductase assays, Western blot

    PMID:24908665

    Open questions at the time
    • Mechanism linking fusion to translation block unclear
    • Relevance to non-fusion DISC1 limited
  27. 2015 High

    Expanded the mitochondrial transport/fusion role by showing DISC1 binds Miro1/Miro2/TRAK1/TRAK2/mitofusins and that the Boymaw fusion disrupts ER–mitochondria contacts and dendritic development.

    Evidence Multiple Co-IPs, live transport imaging, super-resolution microscopy, dominant-negative expression, dendritic analysis

    PMID:26553875

    Open questions at the time
    • Direct versus indirect mitofusin binding not resolved
    • Quantitative complex stoichiometry undefined
  28. 2015 Medium

    Identified an interneuron-specific DISC1 function inhibiting NRG1–ErbB4 signaling, implicating DISC1 in excitatory–inhibitory circuit balance.

    Evidence Cell-type-specific viral manipulation, mutant mouse, ErbB4 phosphorylation assay and Co-IP

    PMID:26656849

    Open questions at the time
    • Competitive PSD95 mechanism shown as likely but not proven
    • Single lab
  29. 2015 Medium

    Linked DISC1 to ER calcium dynamics via EXOC1-mediated recruitment to IP3R1, with antipsychotic-reversible calcium dysregulation upon knockdown.

    Evidence Subcellular fractionation, Co-IP, calcium imaging, RNAi and KO mouse neurons

    PMID:25732993

    Open questions at the time
    • Direct IP3R1 binding versus EXOC1-bridged recruitment unresolved
    • Single lab
  30. 2016 Medium

    Showed DISC1 promotes astrogenesis via RASSF7-dependent RAS/MEK/ERK activation and pERK nuclear translocation.

    Evidence Co-IP, in utero electroporation, in vitro astrogenesis assay, pERK translocation analysis

    PMID:27287808

    Open questions at the time
    • Direct RASSF7 binding interface undefined
    • Single lab
  31. 2016 Medium

    Placed DISC1 downstream of TLR3–MYD88 innate immune signaling regulating dendritic arborization.

    Evidence TLR3 agonist, MYD88 knockout, DISC1 overexpression rescue, dendritic morphology

    PMID:27979975

    Open questions at the time
    • Transcriptional mechanism of Disc1 repression undefined
    • Single lab
  32. 2017 High

    Provided the first crystal structure of the DISC1 C-terminal tail–Ndel1 complex and showed DISC1 controls Ndel1 kinetochore attachment and mitotic progression in radial glia and human organoids.

    Evidence X-ray crystallography, interface mutagenesis, mitosis/cell-cycle imaging, in utero electroporation, patient iPSC organoids

    PMID:29103808

    Open questions at the time
    • Kinetochore-recruitment partners of the complex not fully defined
  33. 2017 High

    Connected DISC1 to Huntington's disease, showing mutant HTT cross-seeds DISC1 to deplete soluble DISC1 and aberrantly activate PDE4.

    Evidence Co-IP, aggregation assays, PDE4 activity assay, modified DISC1 rescue in R6/2 mice, HD brain validation

    PMID:28263187

    Open questions at the time
    • Structural basis of cross-seeding undefined
    • Generality across HD models untested
  34. 2017 High

    Defined DISC1 protein turnover by identifying the FBXW7 phosphodegron and solving the complex structure, establishing how DISC1 levels are post-translationally controlled.

    Evidence Structural biology of FBXW7–DISC1, ubiquitination assay, Co-IP, proteasome inhibition, patient iPSC NPCs

    PMID:28727686

    Open questions at the time
    • Kinase generating the phosphodegron not identified
    • Physiological triggers of degradation unknown
  35. 2018 Medium

    Showed DISC1 supports astrocyte energy metabolism, with knockdown reducing glucose uptake and lactate production and lactate rescuing behavior.

    Evidence Astrocyte-selective dominant-negative mouse, metabolic flux and lactate assays, behavioral rescue

    PMID:29643356

    Open questions at the time
    • Molecular link from DISC1 to GLUT4 expression undefined
    • Single lab
  36. 2018 Medium

    Showed convergent DISC1 mutations reduce protein via NMD and dysregulate UNC5D netrin signaling to impair neurite outgrowth.

    Evidence Isogenic iPSC NGN2 neurons, RNA-seq, UNC5D knockdown/rescue, longitudinal neurite imaging

    PMID:30410030

    Open questions at the time
    • Direct transcriptional control of UNC5D by DISC1 not shown
    • Single lab
  37. 2019 High

    Solved the DISC1–ATF4 atomic structure and showed a patient frameshift mutation causes nuclear ATF4 accumulation and transcriptional/synaptic deficits rescuable by ATF4 reduction.

    Evidence X-ray crystallography, Co-IP, nuclear fractionation, ChIP, CRISPR ATF4 knockout rescue, iPSC neurons

    PMID:31444471

    Open questions at the time
    • Genome-wide ATF4 target dysregulation incompletely mapped
  38. 2020 Medium

    Established that DISC1-dependent mitochondrial transport directionality is gated by the Miro1 GTPase state, with a psychiatric mutation impairing transport and synaptic positioning.

    Evidence Live transport imaging, Miro1 GTPase domain mutants, mutant DISC1 expression

    PMID:32637409

    Open questions at the time
    • Molecular sensing of GTPase state by DISC1 undefined
    • Single lab
  39. 2021 High

    Demonstrated a patient frameshift mutation elevates PDE4 levels and causes synaptic deficits rescuable by PDE4 inhibition across iPSC neurons and knock-in mice, validating the DISC1–cAMP axis therapeutically.

    Evidence Isogenic iPSC neurons, transcriptome/kinome analysis, PDE4 inhibitor, knock-in mouse, electrophysiology and behavior

    PMID:33658519

    Open questions at the time
    • Mechanism by which mutant DISC1 elevates PDE4 transcript not defined
  40. 2022 High

    Provided in vivo therapeutic proof-of-concept that DISC1 sustains anterograde mitochondrial transport and axonal ATP, with gene delivery rescuing neurons in ocular hypertension.

    Evidence Multiphoton live transport imaging, AAV Disc1 delivery, genetically encoded ATP sensor, visual electrophysiology

    PMID:36103832

    Open questions at the time
    • Translation to CNS disease contexts untested
    • Adaptor stoichiometry in vivo undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DISC1's many spatially distinct complexes are coordinately regulated in a single neuron, and which interactions are direct versus scaffold-bridged, remains unresolved.
  • No integrated model of how DISC1 partitions between centrosome, mitochondria, ER, synapse and nucleus
  • Full-length DISC1 structure and conformational regulation undefined
  • Relative contribution of each pathway to disease phenotypes not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0098772 molecular function regulator activity 5 GO:0008092 cytoskeletal protein binding 4 GO:0140110 transcription regulator activity 3 GO:0140313 molecular sequestering activity 2
Localization
GO:0005739 mitochondrion 4 GO:0005815 microtubule organizing center 4 GO:0005634 nucleus 2 GO:0005783 endoplasmic reticulum 2 GO:0005694 chromosome 1 GO:0005929 cilium 1
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 5 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1640170 Cell Cycle 1
Partners
ATF4FBXW7FEZ1GSK3BMIRO1NDEL1PDE4BTRAK1
Complex memberships
DISC1–Miro1/Miro2–TRAK1/TRAK2 mitochondrial transport complexGrb2–KIF5A kinesin complexNDE1/NDEL1/LIS1/dynein complexSCF(FBXW7) ubiquitin ligase substrate complex

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 DISC1 is a component of the microtubule-associated dynein motor complex and is essential for maintaining this complex at the centrosome. C-terminally truncated mutant DISC1 acts in a dominant-negative manner by redistributing wild-type DISC1 through self-association and dissociating the DISC1-dynein complex from the centrosome, impairing neurite outgrowth in vitro and cerebral cortex development in vivo. Co-immunoprecipitation, dominant-negative overexpression, RNA interference knockdown in PC12 cells and in vivo mouse cortical electroporation Nature cell biology High 16299498
2006 A specific interaction between DISC1 and NDEL1 (mapped to amino acids 802–835 of DISC1, corresponding to exon 13) is required for neurite outgrowth in differentiating PC12 cells. Genetic variants of DISC1 proximal to this binding site alter the DISC1–NDEL1 interaction. Co-immunoprecipitation, deletion mapping, PC12 cell neurite outgrowth assay, analysis of disease-associated DISC1 variants Human molecular genetics High 17035248
2007 DISC1 missense mutations Q31L and L100P both exhibit reduced binding to PDE4B. Q31L mutants show lower PDE4B activity consistent with reduced PDE4 engagement. The DISC1–PDE4B interaction is thus required for normal cAMP signaling relevant to mood and psychosis-related behaviors. ENU mutagenesis in mice, co-immunoprecipitation, PDE4 enzymatic activity assay, behavioral pharmacology Neuron High 17481393
2004 DISC1 localizes to the centrosome by binding to kendrin/pericentrin-B. The interaction domain was mapped to residues 446–533 of DISC1. Kendrin anchors gamma-tubulin to the centrosome, implicating DISC1 in centrosomal microtubule nucleation. Yeast two-hybrid screen, co-immunoprecipitation, immunocytochemistry colocalization Biochemical and biophysical research communications Medium 15094396
2008 DISC1 acts as a scaffold assembling a complex containing NDE1, NDEL1, LIS1, dynein, PDE4B, and PDE4D at the centrosome and synapse. NDE1 is phosphorylated by PKA, whose activity is regulated by PDE4; DISC1 scaffolds both PDE4 and NDE1/NDEL1/LIS1/dynein at the centrosome and synapse. Co-immunoprecipitation, immunofluorescence in cultured neurons, subcellular fractionation Biochemical and biophysical research communications Medium 18983980
2008 DISC1 in the nucleus co-localizes with PML bodies and interacts with ATF4/CREB2 and the co-repressor N-CoR, modulating CRE-mediated gene transcription. Three functional cis-elements regulating nuclear localization of DISC1 were identified. In Drosophila, nuclear DISC1 accumulation disturbs sleep homeostasis linked to CRE-mediated transcription. Drosophila transgenic model, mammalian cell immunofluorescence, co-immunoprecipitation, luciferase CRE reporter assay, deletion mapping of nuclear localization signals Molecular psychiatry Medium 18762802
2007 DISC1 interacts with Grb2 and forms a ternary complex with Grb2 and kinesin heavy chain KIF5A. DISC1 is required for NT-3-induced axon elongation by recruiting Grb2 to axonal tips, enabling ERK-1/2 phosphorylation at the distal axon. Knockdown of DISC1 or kinesin light chains inhibits Grb2 accumulation at axon tips and NT-3-induced ERK activation. Co-immunoprecipitation, RNA interference in hippocampal neurons, immunofluorescence, ERK phosphorylation assay The Journal of neuroscience Medium 17202467
2005 The N-terminal head domain of DISC1 is sufficient for mitochondrial and nuclear targeting, while C-terminal sequence facilitates centrosomal association. DISC1 overexpression produces striking mitochondrial ring-like reorganization, indicating a role in mitochondrial fusion and/or fission. Truncation construct expression in COS-7 cells, immunofluorescence, live-cell imaging of mitochondria Molecular and cellular neurosciences Medium 16209927
2010 Dixdc1 interacts with DISC1 to regulate neural progenitor proliferation via Wnt–GSK3β/β-catenin signaling, and regulates neuronal migration through a distinct pathway requiring Cdk5-mediated phosphorylation of Dixdc1, which then facilitates interaction with the DISC1-binding partner Ndel1. DISC1 and Dixdc1 thus integrate Wnt-dependent and -independent signaling during cortical development. Co-immunoprecipitation, in utero electroporation (mouse cortex), phosphorylation-defective/mimetic Dixdc1 mutants, Wnt reporter assay Neuron High 20624590
2011 DISC1 binds directly to GSK3α/β via its N-terminal region (aa 1–220). The L100P mutation reduces DISC1–GSK3 interaction, leading to dysregulated GSK3 activity. Pharmacological or genetic inactivation of GSK3 reverses schizophrenia-related behavioral deficits in Disc1-L100P mice. Co-immunoprecipitation, genetic GSK3 inactivation, pharmacological GSK3 inhibition, prepulse/latent inhibition behavioral assays Synapse Medium 20687110
2011 DISC1 and PDE4 modulate phosphorylation of NDE1 by PKA at a novel substrate site threonine-131 (T131). Phosphorylation at T131 modulates NDE1–LIS1 and NDE1–NDEL1 interactions; mimicking PKA phosphorylation at T131 inhibits neurite outgrowth. Thus DISC1–PDE4 interaction regulates organization of the NDE1/NDEL1/LIS1 complex. In vitro PKA phosphorylation assay, phospho-specific antibody, homology modeling, Co-immunoprecipitation, neurite outgrowth assay with phospho-mutants The Journal of neuroscience High 21677187
2011 DISC1 regulates synaptic vesicle transport along microtubules via FEZ1. Knockdown or dominant-negative DISC1 disrupts assembly of the kinesin-1 adaptor FEZ1 with the cargo protein Synaptotagmin-1 (Syt-1), attenuating vesicle transport. Lithium restores FEZ1–Syt-1 assembly and normalizes defective transport. RNAi knockdown, dominant-negative DISC1 expression, live vesicle transport imaging in cortical neurons, co-immunoprecipitation Neuroscience research Medium 21664390
2011 DISC1 interacts with FEZ1 to regulate dendritic growth of newborn neurons in the adult hippocampus, functioning in a pathway parallel to and distinct from the DISC1–NDEL1 interaction that regulates cell positioning and morphogenesis. RNAi in adult mouse hippocampus (retroviral), co-immunoprecipitation, genetic epistasis analysis in schizophrenia cohorts Neuron Medium 22099459
2011 DISC1 regulates neural progenitor proliferation through Wnt–GSK3β/β-catenin signaling. Common DISC1 variants A83V, R264Q, and L607F are loss-of-function for Wnt signaling and reduce neural progenitor proliferation, whereas S704C inhibits neuronal migration. These variants fail to rescue DISC1 knockdown-mediated brain development defects in zebrafish. Wnt reporter assay, zebrafish knockdown rescue, mouse cortical progenitor proliferation assay, human lymphoblast Wnt signaling, TALEN/CRISPR mutants Neuron High 22099458
2012 DISC1 regulation of dendritic development of newborn neurons during adult hippocampal neurogenesis requires GABA-induced, NKCC1-dependent depolarization converging on the AKT–mTOR pathway. Genetic epistasis between DISC1 and NKCC1 (SLC12A2) affects schizophrenia risk. Retroviral RNAi in adult mouse hippocampus, pharmacological NKCC1 inhibition, mTOR pathway inhibitor/activator, genetic epistasis in two human case-control cohorts Cell High 22385968
2012 DISC1 binds to and stabilizes serine racemase (SR), the enzyme that generates D-serine. Mutant DISC1 fails to bind SR, facilitating its ubiquitination and proteasomal degradation, decreasing D-serine production and impairing NMDA receptor signaling. Co-immunoprecipitation, dominant-negative DISC1 mouse model (astrocyte-selective), ubiquitination assay, D-serine measurement, NMDA antagonist behavioral tests Molecular psychiatry High 22801410
2010 DISC1 interacts with TNIK (Traf2 and Nck-interacting kinase) at synapses. The DISC1–TNIK interaction stabilizes key postsynaptic density proteins, regulating synaptic composition and activity. Co-immunoprecipitation, synaptic fractionation, RNAi knockdown, electrophysiology Molecular psychiatry Medium 20838393
2010 DISC1 localizes near the base of primary cilia and is required for primary cilia formation/maintenance. RNAi-mediated knockdown of DISC1 markedly reduces the number of cells bearing primary cilia in NIH3T3 cells and striatal neurons. Specific dopamine receptor subtypes (D1, D2, D5 but not D3/D4) are concentrated on the ciliary surface. GFP-DISC1 localization imaging, RNAi knockdown, immunofluorescence for primary cilia markers PloS one Medium 20531939
2013 DISC1 associates with TRAK1 (trafficking-protein kinesin-binding 1) and Miro1, forming a functional mitochondrial transport complex. In neuronal axons, DISC1 specifically promotes anterograde mitochondrial transport. A rare human DISC1 sequence variant (37W) impairs this anterograde transport function. Co-immunoprecipitation, live axonal mitochondria transport imaging, variant-specific functional analysis Human molecular genetics Medium 24092329
2015 DISC1 couples to mitochondrial transport and fusion machinery via interactions with Miro1, Miro2, TRAK1, TRAK2, and mitofusins. Disruption of the DISC1–Miro–TRAK complex inhibits mitochondrial transport in neurons. DISC1–Boymaw fusion protein localizes to mitochondria, disrupts mitochondrial dynamics, decreases ER–mitochondria contact area (shown by super-resolution microscopy), and impairs neuronal dendritic development. Co-immunoprecipitation, live-cell mitochondria transport imaging, super-resolution microscopy, dominant-negative expression, dendritic morphology analysis The Journal of biological chemistry High 26553875
2014 DISC1 forms a protein complex with the dopamine D2 receptor (D2R), facilitating D2R-mediated GSK-3 signaling and inhibiting agonist-induced D2R internalization. D2R–DISC1 complex levels are increased and GSK-3 phospho-inhibition is decreased in schizophrenia postmortem brain and in Disc1-L100P mice. An interfering peptide disrupting this complex reverses schizophrenia-relevant behaviors without inducing catalepsy. Co-immunoprecipitation, postmortem brain biochemistry, interfering peptide in vivo, behavioral assays Neuron High 25433637
2014 DISC1 interaction with APP (amyloid precursor protein) regulates APP proteolytic processing: DISC1 knockdown increases APP-CTFα and sAPPα while decreasing Aβ42 and Aβ40 levels. DISC1 knockdown increases APP at the cell surface and decreases its internalization. Rescue with wild-type but not APP-interaction-deficient DISC1 confirms the interaction is required. RNAi knockdown in cortical neurons, ELISA for Aβ and sAPP fragments, surface biotinylation, rescue with DISC1 interaction-deficient mutant Molecular psychiatry Medium 25224257
2015 DISC1 disruption near the translocation site results in decreased DISC1 protein due to nonsense-mediated decay of long splice variants, causing increased canonical Wnt signaling in neural progenitor cells and altered expression of cortical fate markers (Foxg1, Tbr2). WNT antagonism during a critical developmental window rescues these gene expression changes. TALEN/CRISPR-Cas9 DISC1 targeting in hiPSCs, Wnt reporter assay, RT-qPCR, pharmacological Wnt antagonism rescue Cell reports High 26299970
2015 DISC1 inhibits NRG1-induced ErbB4 activation and downstream signaling in mature cortical interneurons. This is likely mediated by competitive inhibition of ErbB4 binding to PSD95. Interneuronal DISC1 thus affects the fast-spiking interneuron–pyramidal neuron excitatory–inhibitory circuit. Cell type-specific viral gene knockdown/overexpression in vitro and in vivo, mutant DISC1 mouse model, ErbB4 phosphorylation assay, co-immunoprecipitation Nature communications Medium 26656849
2015 DISC1 localizes to the outer surface of the endoplasmic reticulum (ER). EXOC1 (a subunit of the exocyst complex) interacts with DISC1 and affects its recruitment to IP3R1. DISC1 knockdown elicits exaggerated ER calcium responses upon IP3R agonist stimulation, an effect reversed by antipsychotic drugs. Subcellular fractionation, co-immunoprecipitation, calcium imaging, RNAi knockdown, DISC1-deficient mutant mouse neurons Scientific reports Medium 25732993
2016 DISC1 regulates astrogenesis through direct association with RASSF7, activating the RAS/MEK/ERK signaling pathway. The pERK complex undergoes nuclear translocation and influences expression of astrogenesis-related genes. DISC1 knockdown represses astrogenesis; overexpression enhances it. Co-immunoprecipitation, in utero electroporation (knockdown and overexpression), in vitro astrogenesis assay, phospho-ERK nuclear translocation analysis Development Medium 27287808
2016 TLR3 signaling acts through MYD88 to negatively regulate Disc1 expression in neurons, impairing dendritic arborization. DISC1 overexpression rescues TLR3-induced dendritic defects, placing DISC1 downstream of TLR3-MYD88 in this innate immune signaling pathway regulating neuronal morphology. TLR3 agonist treatment of cultured neurons and in vivo mouse brain, MYD88 knockout, DISC1 overexpression rescue, dendritic morphology analysis EMBO reports Medium 27979975
2017 The high-resolution crystal structure of the DISC1 C-terminal tail in complex with the binding domain of Ndel1 was solved. Mechanistically, DISC1 regulates Ndel1's kinetochore attachment (but not centrosome localization) during mitosis. Disrupting the DISC1/Ndel1 complex prolongs mitotic length, interferes with cell-cycle progression in human cells, and causes cell-cycle deficits in radial glial cells in embryonic mouse cortex and human forebrain organoids. X-ray crystallography, DISC1/Ndel1 interface mutagenesis, mitosis imaging, cell-cycle analysis, in utero electroporation, human forebrain organoids including schizophrenia patient iPSC-derived organoids Neuron High 29103808
2017 HTT forms a ternary protein complex with DISC1 and PDE4. In Huntington's disease, pathological cross-seeding between mutant HTT aggregates and DISC1 reduces soluble DISC1, dysregulating the DISC1–PDE4 complex and aberrantly increasing PDE4 activity. Expression of a modified DISC1 that binds PDE4 but not mutant HTT normalizes PDE4 activity and ameliorates anhedonia in R6/2 mice. Co-immunoprecipitation, protein aggregation assays, DISC1/PDE4 activity assay, modified DISC1 rescue in R6/2 mice, behavioral assay The Journal of clinical investigation High 28263187
2017 FBXW7, an F-box protein of the SCF ubiquitin ligase complex, binds a DISC1 phosphodegron motif and mediates DISC1 proteasomal degradation. The structure of FBXW7 bound to the DISC1 phosphodegron was solved, and disruption of the FBXW7–DISC1 complex stabilizes DISC1 protein. Structural biology (FBXW7–DISC1 complex structure), ubiquitination assay, co-immunoprecipitation, pharmacological proteasome inhibition, iPSC-derived neural progenitors from schizophrenia patients Molecular psychiatry High 28727686
2018 DISC1 regulates lactate production in astrocytes: knockdown or dominant-negative DISC1 decreases expression of glucose transporter 4, glucose uptake, oxidative phosphorylation, glycolysis, and lactate production in vitro and in vivo. Lactate treatment rescues abnormal behaviors in DN-DISC1 astrocyte-selective mice. RNAi knockdown, dominant-negative DISC1 astrocyte-selective mouse model, glucose uptake assay, metabolic flux analysis, lactate measurement, behavioral rescue Translational psychiatry Medium 29643356
2019 DISC1 binds to ATF4 (Activating Transcription Factor 4), and the high-resolution atomic structure of the DISC1–ATF4 complex was solved. A patient DISC1 frameshift mutation disrupts DISC1–ATF4 interaction, causing nuclear ATF4 accumulation and excessive ATF4–DNA binding, leading to transcriptional and synaptic dysregulation. CRISPR-mediated heterozygous ATF4 knockout rescues transcriptional and synaptic deficits in DISC1 mutant neurons. X-ray crystallography of DISC1–ATF4 complex, Co-IP, nuclear fractionation, ChIP, CRISPR ATF4 knockout rescue, iPSC-derived neurons Molecular psychiatry High 31444471
2020 DISC1 regulation of mitochondrial trafficking depends on the GTPase state of Miro1. A psychiatric disease-associated DISC1 mutation impairs Miro1-dependent mitochondrial transport. The first Miro1 GTPase domain determines direction of mitochondrial transport, and DISC1 is involved in this directionality determination. Mutant DISC1 also alters positioning of mitochondria at synapses. Live mitochondria transport imaging in neurons, Miro1 GTPase domain mutants, mutant DISC1 expression, synaptic mitochondria positioning analysis Frontiers in cell and developmental biology Medium 32637409
2021 A rare patient DISC1 frameshift mutation elevates PDE4 transcript levels in iPSC-derived cortical neurons and causes synaptic deficits. Pharmacological inhibition of PDE4 or activation of the cAMP signaling pathway rescues synaptic deficits. A knock-in mouse with the same mutation exhibits elevated PDE4 levels, synaptic abnormalities, and behavioral deficits, all rescued by PDE4 inhibition. Isogenic iPSC-derived neurons, kinome/transcriptome analysis, PDE4 inhibitor treatment, knock-in mouse model, synaptic electrophysiology, behavioral assays Nature communications High 33658519
2022 DISC1 (Disc1) acts as a mitochondrial transport adaptor promoting anterograde axonal transport. Ocular hypertension causes loss of Disc1 in retinal neurons and disrupts anterograde mitochondrial transport, leading to axonal energy deficit. Disc1 gene delivery rescues anterograde transport, restores axonal ATP production (measured with genetically encoded sensor), promotes neuronal survival, and restores visual responses. Multiphoton live imaging of mitochondrial transport, Disc1 gene delivery (AAV), genetically encoded ATP sensor, longitudinal in vivo imaging, calcium dynamics, visual electrophysiology Cell reports High 36103832
2008 The C-terminus of DISC1 is required for interaction with kendrin and for centrosomal targeting. Overexpression of the DISC1-binding region of kendrin or a DISC1 deletion mutant lacking the kendrin-binding region impairs microtubule organization. Directed yeast two-hybrid, deletion mutagenesis, co-immunoprecipitation, immunocytochemistry, microtubule organization assay Biochemical and biophysical research communications Medium 18955030
2012 The DISC1 promoter region was characterized: a region -300 to -177 bp relative to the TSS contributes positively to DISC1 promoter activity, while -982 to -301 bp confers repression. FOXP2 inhibits DISC1 promoter activity and protein expression; two FOXP2 point mutations associated with verbal dyspraxia diminish this inhibitory effect. Dual luciferase promoter assay, deletion constructs, FOXP2 overexpression and disease mutant analysis, Western blot for DISC1 protein Human molecular genetics Medium 22434823
2014 DISC1 negatively regulates differentiation of oligodendrocyte precursor cells into oligodendrocytes. DISC1 overexpression decreases expression of myelin markers CNPase and MBP and reduces mature oligodendrocyte number; DISC1 knockdown increases both. A truncated DISC1 acting as dominant-negative similarly increases oligodendrocyte differentiation. Overexpression and RNAi knockdown in primary oligodendrocyte precursor cells, immunocytochemistry for myelin markers, morphological analysis PloS one Medium 24516667
2014 Inhibition of intracellular NADH oxidoreductase activity and protein translation by the DISC1-Boymaw (DB7) fusion gene. In humanized DISC1-Boymaw knock-in mice, protein translation activity is decreased in hippocampus and cultured neurons; Gad67, Nmdar1, and Psd95 protein expression are reduced. Humanized knock-in mice (gene targeting), protein translation assay, NADH oxidoreductase assay, Western blot for synaptic proteins Human molecular genetics Medium 24908665
2009 Disc1 is expressed in zebrafish cranial neural crest (CNC) cells and is required for their migration away from the neural rod. Loss of Disc1 perpetuates expression of transcription factors foxd3 and sox10, impairing CNC cell migration and differentiation. Disc1 functions in transcriptional repression of foxd3 and sox10 to mediate CNC cell development. Morpholino knockdown in zebrafish, time-lapse imaging of CNC cells, in situ hybridization for foxd3/sox10 Development Medium 19570850
2018 Two convergent DISC1 mutations (mimicking Scottish translocation consequences and an American pedigree frameshift) both reduce DISC1 protein levels via nonsense-mediated decay. Both mutations decrease expression of UNC5D (a netrin signaling receptor), and UNC5D knockdown phenocopies DISC1-mutant neurite outgrowth deficit. UNC5D overexpression rescues the neurite phenotype, implicating dysregulated netrin signaling downstream of DISC1. iPSC-derived NGN2 neurons (isogenic), RNA-seq, UNC5D knockdown and rescue, longitudinal neurite outgrowth imaging Translational psychiatry Medium 30410030

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A schizophrenia-associated mutation of DISC1 perturbs cerebral cortex development. Nature cell biology 447 16299498
2007 Behavioral phenotypes of Disc1 missense mutations in mice. Neuron 415 17481393
2005 Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia. Proceedings of the National Academy of Sciences of the United States of America 385 15939883
2011 Linking neurodevelopmental and synaptic theories of mental illness through DISC1. Nature reviews. Neuroscience 353 22095064
2007 Inducible expression of mutant human DISC1 in mice is associated with brain and behavioral abnormalities reminiscent of schizophrenia. Molecular psychiatry 272 17848917
2010 Prenatal interaction of mutant DISC1 and immune activation produces adult psychopathology. Biological psychiatry 211 21130225
2012 Interplay between DISC1 and GABA signaling regulates neurogenesis in mice and risk for schizophrenia. Cell 175 22385968
2010 DISC1-binding proteins in neural development, signalling and schizophrenia. Neuropharmacology 156 21195721
2006 A review of Disrupted-In-Schizophrenia-1 (DISC1): neurodevelopment, cognition, and mental conditions. Biological psychiatry 151 16797264
2006 DISC1-NDEL1/NUDEL protein interaction, an essential component for neurite outgrowth, is modulated by genetic variations of DISC1. Human molecular genetics 146 17035248
2007 Association of DISC1 with autism and Asperger syndrome. Molecular psychiatry 144 17579608
2004 Expression of disrupted in schizophrenia 1 (DISC1) protein in the adult and developing mouse brain indicates its role in neurodevelopment. Molecular psychiatry 138 15381924
2006 The genetics and biology of DISC1--an emerging role in psychosis and cognition. Biological psychiatry 136 16843095
2006 Expression of DISC1 binding partners is reduced in schizophrenia and associated with DISC1 SNPs. Human molecular genetics 135 16510495
2012 Pathogenic disruption of DISC1-serine racemase binding elicits schizophrenia-like behavior via D-serine depletion. Molecular psychiatry 127 22801410
2010 Dixdc1 is a critical regulator of DISC1 and embryonic cortical development. Neuron 127 20624590
2010 The psychiatric disease risk factors DISC1 and TNIK interact to regulate synapse composition and function. Molecular psychiatry 124 20838393
2011 DISC1 at 10: connecting psychiatric genetics and neuroscience. Trends in molecular medicine 110 22015021
2011 Common DISC1 polymorphisms disrupt Wnt/GSK3β signaling and brain development. Neuron 104 22099458
2017 DISC1 Regulates Neurogenesis via Modulating Kinetochore Attachment of Ndel1/Nde1 during Mitosis. Neuron 102 29103808
2011 DISC1: Structure, Function, and Therapeutic Potential for Major Mental Illness. ACS chemical neuroscience 101 22116789
2008 Nuclear DISC1 regulates CRE-mediated gene transcription and sleep homeostasis in the fruit fly. Molecular psychiatry 95 18762802
2017 The impact of Disrupted-in-Schizophrenia 1 (DISC1) on the dopaminergic system: a systematic review. Translational psychiatry 93 28140405
2015 Genomic DISC1 Disruption in hiPSCs Alters Wnt Signaling and Neural Cell Fate. Cell reports 92 26299970
2014 A dopamine D2 receptor-DISC1 protein complex may contribute to antipsychotic-like effects. Neuron 90 25433637
2007 DISC1 regulates neurotrophin-induced axon elongation via interaction with Grb2. The Journal of neuroscience : the official journal of the Society for Neuroscience 90 17202467
2004 DISC1 localizes to the centrosome by binding to kendrin. Biochemical and biophysical research communications 90 15094396
2015 DISC1-dependent Regulation of Mitochondrial Dynamics Controls the Morphogenesis of Complex Neuronal Dendrites. The Journal of biological chemistry 89 26553875
2005 Disrupted in schizophrenia 1 (DISC1): subcellular targeting and induction of ring mitochondria. Molecular and cellular neurosciences 89 16209927
2010 DISC1 regulates primary cilia that display specific dopamine receptors. PloS one 87 20531939
2013 DISC1 complexes with TRAK1 and Miro1 to modulate anterograde axonal mitochondrial trafficking. Human molecular genetics 85 24092329
2011 Interaction between FEZ1 and DISC1 in regulation of neuronal development and risk for schizophrenia. Neuron 85 22099459
2010 DISC1 in schizophrenia: genetic mouse models and human genomic imaging. Schizophrenia bulletin 84 21149852
2002 Cloning and characterization of Disc1, the mouse ortholog of DISC1 (Disrupted-in-Schizophrenia 1). Genomics 77 12504857
2007 Role of DISC1 in neural development and schizophrenia. Current opinion in neurobiology 76 17258902
2008 DISC1, PDE4B, and NDE1 at the centrosome and synapse. Biochemical and biophysical research communications 74 18983980
2007 A novel DISC1-interacting partner DISC1-Binding Zinc-finger protein: implication in the modulation of DISC1-dependent neurite outgrowth. Molecular psychiatry 73 17389905
2011 PKA phosphorylation of NDE1 is DISC1/PDE4 dependent and modulates its interaction with LIS1 and NDEL1. The Journal of neuroscience : the official journal of the Society for Neuroscience 72 21677187
2013 Human brain imaging studies of DISC1 in schizophrenia, bipolar disorder and depression: a systematic review. Schizophrenia research 71 23602339
2009 Disc1 regulates foxd3 and sox10 expression, affecting neural crest migration and differentiation. Development (Cambridge, England) 71 19570850
2011 Impact of DISC1 variation on neuroanatomical and neurocognitive phenotypes. Molecular psychiatry 70 21483430
2006 Genes and schizophrenia: beyond schizophrenia: the role of DISC1 in major mental illness. Schizophrenia bulletin 69 16699061
2011 Genetic and pharmacological evidence for schizophrenia-related Disc1 interaction with GSK-3. Synapse (New York, N.Y.) 68 20687111
2004 DISC1 and DISC2: discovering and dissecting molecular mechanisms underlying psychiatric illness. Annals of medicine 66 15478311
2011 Synergistic interactions between PDE4B and GSK-3: DISC1 mutant mice. Neuropharmacology 63 21376063
2009 The DISC1 pathway modulates expression of neurodevelopmental, synaptogenic and sensory perception genes. PloS one 62 19300510
2011 Impaired NMDA receptor transmission alters striatal synapses and DISC1 protein in an age-dependent manner. Proceedings of the National Academy of Sciences of the United States of America 61 21436042
2006 Differential expression of disrupted-in-schizophrenia (DISC1) in bipolar disorder. Biological psychiatry 60 16814263
2016 Utility and validity of DISC1 mouse models in biological psychiatry. Neuroscience 59 26768401
2015 Interneuronal DISC1 regulates NRG1-ErbB4 signalling and excitatory-inhibitory synapse formation in the mature cortex. Nature communications 59 26656849
2009 Gene models of schizophrenia: DISC1 mouse models. Progress in brain research 58 20302820
2018 Shared effects of DISC1 disruption and elevated WNT signaling in human cerebral organoids. Translational psychiatry 56 29643329
2018 Mechanisms underlying the role of DISC1 in synaptic plasticity. The Journal of physiology 56 30008190
2009 Association of DISC1 and TSNAX genes and affective disorders in the depression case-control (DeCC) and bipolar affective case-control (BACCS) studies. Molecular psychiatry 56 19255581
2006 Genetic association between schizophrenia and the DISC1 gene in the Scottish population. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 51 16389590
2004 Clinical phenotypes associated with DISC1, a candidate gene for schizophrenia. Neurotoxicity research 49 15184103
2014 DISC1 (disrupted-in-schizophrenia-1) regulates differentiation of oligodendrocytes. PloS one 48 24516667
2017 DISC1 in Astrocytes Influences Adult Neurogenesis and Hippocampus-Dependent Behaviors in Mice. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 47 28631721
2014 DISC1 regulates trafficking and processing of APP and Aβ generation. Molecular psychiatry 47 25224257
2006 Effect of antipsychotic drugs on DISC1 and dysbindin expression in mouse frontal cortex and hippocampus. Journal of neural transmission (Vienna, Austria : 1996) 45 16463116
2009 Genetic association and post-mortem brain mRNA analysis of DISC1 and related genes in schizophrenia. Schizophrenia research 44 19632097
2018 DISC1 regulates lactate metabolism in astrocytes: implications for psychiatric disorders. Translational psychiatry 41 29643356
2016 TLR3 downregulates expression of schizophrenia gene Disc1 via MYD88 to control neuronal morphology. EMBO reports 41 27979975
2010 DISC1 regulates cell-cell adhesion, cell-matrix adhesion and neurite outgrowth. Molecular psychiatry 41 20479754
2006 Schizophrenia in translation: disrupted in schizophrenia (DISC1): integrating clinical and basic findings. Schizophrenia bulletin 41 17138582
2012 DISC1 as a therapeutic target for mental illnesses. Expert opinion on therapeutic targets 40 23130881
2011 DISC1 regulates synaptic vesicle transport via a lithium-sensitive pathway. Neuroscience research 40 21664390
2013 DISC1-related signaling pathways in adult neurogenesis of the hippocampus. Gene 39 23353011
2022 Restoration of mitochondria axonal transport by adaptor Disc1 supplementation prevents neurodegeneration and rescues visual function. Cell reports 38 36103832
2011 Mutant DISC1 affects methamphetamine-induced sensitization and conditioned place preference: a comorbidity model. Neuropharmacology 38 21315744
2015 Disrupted-in-schizophrenia-1 (DISC1) Regulates Endoplasmic Reticulum Calcium Dynamics. Scientific reports 37 25732993
2017 Aggregation of scaffolding protein DISC1 dysregulates phosphodiesterase 4 in Huntington's disease. The Journal of clinical investigation 36 28263187
2013 DISC1: a key lead in studying cortical development and associated brain disorders. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry 36 23300216
2013 DISC1 mouse models as a tool to decipher gene-environment interactions in psychiatric disorders. Frontiers in behavioral neuroscience 35 24027503
2019 Kinase network dysregulation in a human induced pluripotent stem cell model of DISC1 schizophrenia. Molecular omics 33 31106784
2012 The DISC1 promoter: characterization and regulation by FOXP2. Human molecular genetics 32 22434823
2021 Pharmacological rescue in patient iPSC and mouse models with a rare DISC1 mutation. Nature communications 31 33658519
2007 How has DISC1 enabled drug discovery? Molecular and cellular neurosciences 31 18055216
2006 Disrupted-in-schizophrenia-1 (DISC1): a key susceptibility factor for major mental illnesses. Annals of the New York Academy of Sciences 31 17185511
2008 DISC1-kendrin interaction is involved in centrosomal microtubule network formation. Biochemical and biophysical research communications 30 18955030
2019 Structural interaction between DISC1 and ATF4 underlying transcriptional and synaptic dysregulation in an iPSC model of mental disorders. Molecular psychiatry 29 31444471
2017 FBXW7 regulates DISC1 stability via the ubiquitin-proteosome system. Molecular psychiatry 29 28727686
2017 Gene polymorphisms of DISC1 is associated with schizophrenia: Evidence from a meta-analysis. Progress in neuro-psychopharmacology & biological psychiatry 29 29031911
2014 Inhibition of protein translation by the DISC1-Boymaw fusion gene from a Scottish family with major psychiatric disorders. Human molecular genetics 29 24908665
2011 Regulation of the cytoskeleton by Disrupted-in-schizophrenia 1 (DISC1). Molecular and cellular neurosciences 29 21757008
2007 PC12 cell model of inducible expression of mutant DISC1: new evidence for a dominant-negative mechanism of abnormal neuronal differentiation. Neuroscience research 29 17418909
2008 Immunohistochemical analysis of Disc1 expression in the developing and adult hippocampus. Gene expression patterns : GEP 28 18620078
2007 Dissecting DISC1 function through protein-protein interactions. Biochemical Society transactions 28 17956330
2013 DISC1 and SLC12A2 interaction affects human hippocampal function and connectivity. The Journal of clinical investigation 26 23921125
2017 Mitochondrial roles of the psychiatric disease risk factor DISC1. Schizophrenia research 24 28087269
2007 Molecular mechanism of schizophrenia with reference to disrupted-in-schizophrenia 1 (DISC1). Neurochemistry international 24 17664024
2020 DISC1 Regulates Mitochondrial Trafficking in a Miro1-GTP-Dependent Manner. Frontiers in cell and developmental biology 23 32637409
2018 Repetitive and compulsive-like behaviors lead to cognitive dysfunction in Disc1Δ2-3/Δ2-3 mice. Genes, brain, and behavior 23 29635888
2018 The TRAX, DISC1, and GSK3 complex in mental disorders and therapeutic interventions. Journal of biomedical science 23 30285728
2016 Missense mutation in DISC1 C-terminal coiled-coil has GSK3β signaling and sex-dependent behavioral effects in mice. Scientific reports 23 26728762
2016 DISC1 regulates astrogenesis in the embryonic brain via modulation of RAS/MEK/ERK signaling through RASSF7. Development (Cambridge, England) 23 27287808
2014 DBZ, a CNS-specific DISC1 binding protein, positively regulates oligodendrocyte differentiation. Glia 23 24481677
2013 A Disc1 mutation differentially affects neurites and spines in hippocampal and cortical neurons. Molecular and cellular neurosciences 23 23396153
2018 Convergence of independent DISC1 mutations on impaired neurite growth via decreased UNC5D expression. Translational psychiatry 22 30410030
2009 Role of the PACAP-PAC1-DISC1 and PACAP-PAC1-stathmin1 systems in schizophrenia and bipolar disorder: novel treatment mechanisms? Pharmacogenomics 22 19958095

Missed literature

Know a paper Affinage missed for DISC1? Flag it for the maintainers and the community.

No submissions yet.