Affinage

DPP6

A-type potassium channel modulatory protein DPP6 · UniProt P42658

Length
865 aa
Mass
97.6 kDa
Annotated
2026-04-28
77 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DPP6 is a catalytically inactive single-pass transmembrane auxiliary subunit of neuronal Kv4-family voltage-gated potassium channels that shapes A-type K+ current properties and regulates dendritic development. DPP6 assembles with Kv4 pore-forming subunits in a 4:4 stoichiometry, promotes their ER export and plasma membrane trafficking via disulfide-bonded cysteine-rich extracellular domains, shifts channel voltage dependence, accelerates inactivation and recovery kinetics through its transmembrane/intracellular domains, and increases unitary conductance through electrostatic interactions of N-terminal acidic residues (PMID:12575952, PMID:18364354, PMID:25190807, PMID:19279261). Loss of DPP6 in knockout mice produces dendritic hyperexcitability with enhanced back-propagating action potentials and augmented LTP in hippocampal CA1 neurons (PMID:21943606), and independently of Kv4.2, DPP6 promotes dendritic filopodia formation and synaptogenesis through interactions with myosin and fibronectin (PMID:23912628). Missense variants in DPP6 that destabilize the protein and reduce its membrane expression have been identified in early-onset Alzheimer's disease and frontotemporal dementia patients, while a gain-of-function variant (L747P) causes early repolarization syndrome through enhanced transient outward K+ current (PMID:30874922, PMID:31476289).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2001 High

    Establishing that DPP6, despite structural homology to DPP-IV, is catalytically inactive resolved a key question about whether this protein functions as a peptidase or has a non-enzymatic role.

    Evidence Mutagenesis introducing the canonical active-site motif failed to confer dipeptidyl aminopeptidase activity in COS-1 cells

    PMID:11173531

    Open questions at the time
    • Biological function remained unknown at this point
    • Mechanism of glycosylation processing and its functional significance not explored
  2. 2003 High

    Identifying DPP6 as a native component of neuronal Kv4 A-type K+ channel complexes established its primary physiological role and explained how native ISA channel properties differ from reconstituted Kv4 alone.

    Evidence Biochemical purification from rat brain, co-immunoprecipitation with Kv4, heterologous reconstitution of native-like A-type currents, and somatodendritic co-localization

    PMID:12575952

    Open questions at the time
    • Stoichiometry of the complex unknown
    • Which DPP6 domains mediate Kv4 interaction and modulation unresolved
  3. 2004 High

    The crystal structure of the DPP6 extracellular domain confirmed the structural basis for its catalytic incompetence and suggested pH-dependent electrostatic modulation of Kv4 interaction.

    Evidence X-ray crystallography at 3.0 Å resolution of human DPPX extracellular domain

    PMID:15476821

    Open questions at the time
    • No structure of the DPP6–Kv4 complex to reveal interaction interface
    • Histidine protonation-dependent modulation not functionally tested
  4. 2006 High

    Demonstrating that all three splice isoforms modulate Kv4.2 and that the variable N-terminus is dispensable for channel modulation localized the core modulatory function to the transmembrane/extracellular region.

    Evidence Deletion mutagenesis and electrophysiology of DPPX-S, -L, -K isoforms in Xenopus oocytes

    PMID:16764835

    Open questions at the time
    • Specific transmembrane or extracellular residues mediating gating modulation not identified
    • Isoform-specific functional differences in native neurons unclear
  5. 2008 High

    Determining the 4:4 stoichiometry of DPP6:Kv4.2 in ISA complexes defined the quaternary architecture and constrained models of auxiliary subunit–pore interaction.

    Evidence Tandem-linked subunit constructs and amino acid analysis of purified complexes

    PMID:18364354

    Open questions at the time
    • Arrangement of DPP6 subunits around the Kv4 tetramer not resolved
    • Whether KChIPs simultaneously associate in the same 4:4 complex not quantified
  6. 2008 High

    Knockdown of DPP6 in native CA1 neurons demonstrated its necessity for normal A-type current gating and revealed compartment-specific effects on neuronal excitability, while DPP6 localization in Kv4-lacking mossy fiber axons suggested Kv4-independent roles.

    Evidence siRNA knockdown with dendritic and somatic patch-clamp in hippocampal neurons; immunohistochemistry showing DPP6 in mossy fibers

    PMID:18667548 PMID:18978958

    Open questions at the time
    • Nature of Kv4-independent function in axons unknown
    • Whether DPP6 loss affects synaptic transmission not tested
  7. 2008 Medium

    Discovery of the DPP6-E splice isoform explained discrepancies between reconstituted and native channel kinetics in cerebellar granule neurons and hippocampal pyramidal cells, establishing isoform-specific tuning of Kv4 gating.

    Evidence Heterologous expression electrophysiology with DPP6-E/Kv4.2/KChIP1, matched to in situ hybridization expression pattern

    PMID:19007856

    Open questions at the time
    • Structural basis for DPP6-E's faster inactivation not determined
    • Whether DPP6-E and other isoforms co-assemble in native complexes unknown
  8. 2009 High

    Identifying that DPP6-S increases Kv4.2 unitary conductance via two N-terminal acidic residues revealed a distinct electrostatic mechanism of channel modulation separate from gating effects.

    Evidence Single-channel recording in heterologous cells and DPP6-KO mouse cerebellar granule neurons, charge-neutralization mutagenesis

    PMID:19279261

    Open questions at the time
    • How intracellular acidic residues influence the extracellular conduction pathway not structurally explained
    • Whether other isoforms share this conductance effect untested
  9. 2009 High

    Demonstrating that DPP6 promotes Kv4.2 ER-to-surface trafficking, alters its phosphorylation to brain-like patterns, and converges with KChIP action revealed the biosynthetic mechanism underlying auxiliary subunit regulation of channel density.

    Evidence Co-expression in heterologous cells with immunofluorescence, tandem MS phosphorylation, detergent solubility, and KChIP4a epistasis

    PMID:19441798

    Open questions at the time
    • Identity of kinases/phosphatases responsible for DPP6-dependent Kv4.2 phosphorylation changes unknown
    • Whether ternary complex forms co-translationally or post-translationally unresolved
  10. 2011 High

    DPP6 knockout mice revealed that DPP6 is the dominant determinant of distal dendritic A-type current, and its loss causes dendritic hyperexcitability and enhanced LTP without affecting somatic firing, establishing compartment-specific physiology.

    Evidence Dendritic and somatic patch-clamp recordings, calcium imaging, and LTP induction protocols in DPP6-KO mice

    PMID:21943606

    Open questions at the time
    • Whether behavioral or cognitive phenotypes accompany dendritic hyperexcitability not assessed
    • Compensatory changes in other auxiliary subunits not examined
  11. 2013 High

    Demonstrating that DPP6 promotes dendritic filopodia formation and synaptogenesis independently of Kv4.2, via interactions with myosin and fibronectin, established a second, non-channel function in neural development.

    Evidence shRNA knockdown and DPP6-KO mice with live imaging, electrophysiology, co-immunoprecipitation with myosin and fibronectin

    PMID:23912628

    Open questions at the time
    • Which myosin isoform mediates the interaction not specified
    • How DPP6–fibronectin interaction signals to the cytoskeleton mechanistically unclear
    • Whether this developmental role extends to non-hippocampal brain regions untested
  12. 2014 High

    Systematic domain dissection separated DPP6's binding, gating, and trafficking functions: the transmembrane/N-terminal domains bind Kv4.2 and accelerate recovery, while the extracellular cysteine-rich domain with specific disulfide bonds drives ER export and surface expression.

    Evidence Domain deletions, cysteine mutagenesis, co-immunoprecipitation, surface biotinylation, electrophysiology

    PMID:25190807

    Open questions at the time
    • Atomic-resolution structure of DPP6–Kv4 interface still lacking
    • Whether additional extracellular domain functions exist beyond trafficking unresolved
  13. 2015 Medium

    Pathogenic anti-DPPX autoantibodies from patients directly reduce surface DPP6 and Kv4.2, increasing neuronal excitability in both brain and enteric neurons, establishing a molecular mechanism for autoimmune DPPX encephalitis.

    Evidence Purified patient IgG applied to hippocampal neurons and enteric nervous system preparations with membrane immunoblot and voltage-sensitive dye recording

    PMID:26291285 PMID:28258082

    Open questions at the time
    • Whether antibody-mediated internalization or cross-linking is the primary mechanism of surface loss unclear
    • Long-term in vivo pathogenic effects not modeled
  14. 2019 Medium

    DPP6 missense variants identified in early-onset Alzheimer's disease and frontotemporal dementia patients destabilize the protein and reduce membrane expression, linking DPP6 loss-of-function to neurodegeneration, while a gain-of-function variant (L747P) in early repolarization syndrome enhances Ito current, linking DPP6 to cardiac arrhythmia.

    Evidence In vitro expression assays of patient variants, brain tissue immunoblot; whole-cell patch clamp of L747P with Kv4.3/KChIP2 in HEK293 cells

    PMID:30874922 PMID:31476289

    Open questions at the time
    • Causal role of DPP6 variants in neurodegeneration not proven by rescue or animal models
    • Mechanism by which L747P enhances current (trafficking vs gating) not distinguished
    • Whether cardiac DPP6 functions with Kv4.3 in native cardiomyocytes not directly shown
  15. 2020 Medium

    Elevated DPP6 expression in schizophrenia patient iPSC-derived neurons causally drives hypoexcitability, reversible by DPP6 knockdown or Kv4 block, linking DPP6 dosage to disease-relevant excitability changes.

    Evidence iPSC cortical neurons, RNA-seq, MEA recordings, calcium imaging, lentiviral shRNA rescue, AmmTx3 pharmacology

    PMID:33143549

    Open questions at the time
    • Whether DPP6 upregulation is a primary genetic effect or secondary in schizophrenia not resolved
    • Circuit-level consequences of neuronal hypoexcitability not modeled

Open questions

Synthesis pass · forward-looking unresolved questions
  • No high-resolution structure of the DPP6–Kv4 complex exists, the molecular basis of how the transmembrane domain accelerates gating transitions remains unresolved, and the signaling pathway linking DPP6's extracellular fibronectin interaction to cytoskeletal remodeling during synaptogenesis is unknown.
  • Cryo-EM or crystal structure of the full DPP6–Kv4–KChIP ternary complex needed
  • Mechanism of DPP6-mediated filopodia signaling uncharacterized
  • In vivo validation of DPP6 variants as causative for neurodegeneration lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6 GO:0005198 structural molecule activity 3
Localization
GO:0005886 plasma membrane 5 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-112316 Neuronal System 5 R-HSA-382551 Transport of small molecules 3 R-HSA-1266738 Developmental Biology 2
Partners
FN1KCND2KCND3KCNIP1KCNIP2KCNIP4
Complex memberships
Kv4.2/DPP6/KChIP ternary channel complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 DPPX (DPP6) was purified as a novel component of neuronal A-type K+ channel complexes from rat brain membranes. It associates with Kv4 pore-forming subunits, facilitates their trafficking and membrane targeting, and reconstitutes native A-type K+ channel properties in heterologous expression systems. It co-localizes with Kv4 subunits in the somatodendritic compartment of CNS neurons. Biochemical purification of K+ channel complexes from rat brain membranes, co-immunoprecipitation, heterologous expression reconstitution, immunolocalization Neuron High 12575952
2004 X-ray crystal structure of the extracellular domain of human DPPX at 3.0 Å resolution revealed a dimeric structure homologous to DPP-IV. The active-site serine is absent and the residue arrangement is inconsistent with canonical serine proteases, establishing that DPPX lacks dipeptidyl aminopeptidase catalytic activity. The structure suggests surface electrostatic changes based on histidine protonation state that could modulate Kv4.2 interaction. X-ray crystallography, active-site structural analysis Journal of molecular biology High 15476821
2001 DPPX-S and DPPX-L are brain-specific glycoproteins that are synthesized with high-mannose oligosaccharides and processed to complex-type sugar chains before reaching the cell surface. Despite structural homology to DPP-IV, mutagenesis to introduce the canonical Gly-X-Ser-X-Gly active-site motif failed to confer dipeptidyl aminopeptidase activity, confirming catalytic incompetence. Cell-free translation, COS-1 cell transfection, immunofluorescence, enzymatic activity assay, site-directed mutagenesis, immunoblot Journal of biochemistry High 11173531
2006 Three alternatively spliced DPPX isoforms (DPPX-S, DPPX-L, DPPX-K) all modify the voltage dependence and kinetic properties of Kv4.2 channels expressed in Xenopus oocytes. Deletion of the variable N-terminus showed the N-terminus is not required for Kv4 channel modulation, placing the functional domain in the transmembrane or extracellular region. Xenopus oocyte expression, electrophysiology, deletion mutagenesis, in situ hybridization Brain research High 16764835
2008 ISA channel complexes contain four subunits each of Kv4.2 and DPP6 (4:4 stoichiometry), established by both biophysical methods using tandem-linked subunits and direct biochemical amino acid analysis of purified complexes. Tandem-linked subunit constructs (functional), amino acid analysis of purified channel complexes (biochemical) The Journal of biological chemistry High 18364354
2008 DPP6 (DPPX) localization in brain closely mirrors that of Kv4.2, with both enriched in dendrites of neurons that co-express them. Additionally, DPP6 was found in hippocampal mossy fiber axons that lack Kv4 proteins, suggesting a Kv4-independent function in axons. Immunohistochemistry with DPP6 and Kv4.2 antibodies, subcellular fractionation, immunofluorescence Frontiers in molecular neuroscience Medium 18978958
2008 siRNA knockdown of DPPX in hippocampal CA1 pyramidal neurons caused depolarizing shifts in steady-state inactivation and activation curves, slowed inactivation, and delayed recovery from inactivation of A-type currents. This resulted in decreased subthreshold excitability (reduced input resistance, delayed AP onset, increased AP threshold) and slowed AP rise and repolarization suprathreshold. siRNA knockdown in neurons, voltage-clamp and current-clamp electrophysiology, computer simulations Journal of neurophysiology High 18667548
2009 DPP6-S is necessary and sufficient to increase the unitary conductance (gamma) of Kv4.2 channels from ~4 pS to ~7.5 pS (matching native cerebellar granule neuron channels). Charge neutralization of two N-terminal acidic residues in DPP6-S eliminated this conductance increase, implicating electrostatic interactions. DPP6 knockout mouse CGN channels had conductance indistinguishable from Kv4.2 expressed alone. Single-channel patch clamp in heterologous cells and DPP6-KO mouse neurons, site-directed mutagenesis The Journal of neuroscience High 19279261
2009 Co-expression of DPPX-S with Kv4.2 dramatically redistributes Kv4.2 from intracellular retention to plasma membrane expression, alters Kv4.2 phosphorylation pattern (to resemble that in brain), changes detergent solubility and stability. These effects are similar to those of KChIP auxiliary subunits. KChIP4a, which inhibits other KChIPs, also inhibits DPPX-S effects, consistent with formation of a ternary Kv4.2/DPPX-S/KChIP complex early in biosynthesis. Co-expression in heterologous cells, immunofluorescence, tandem MS phosphorylation analysis, detergent solubility assay Biochemistry High 19441798
2011 DPP6 knockout mice lacking the Kv4 transmembrane auxiliary subunit DPP6 show a specific loss of A-type K+ current in distal dendrites of CA1 hippocampal pyramidal neurons, accompanied by a depolarizing shift in activation voltage dependence. This results in hyperexcitable dendrites with enhanced dendritic AP back-propagation, calcium electrogenesis, and enhanced LTP induction, without major effects on somatic firing. Dendritic patch-clamp recordings from DPP6-KO mice, calcium imaging, LTP induction Neuron High 21943606
2013 DPP6 knockdown or genetic deletion reduces dendritic filopodia formation and stability during early hippocampal neuronal development, leading to sparser dendritic branching, fewer spines, and fewer functional synapses in adult neurons. This role in dendritic morphogenesis is independent of Kv4.2. DPP6 was found to interact with a filopodia-associated myosin and with fibronectin in the extracellular matrix. shRNA knockdown, DPP6-KO mice, live imaging, electrophysiology, co-immunoprecipitation with myosin and fibronectin Nature communications High 23912628
2014 The cysteine-rich domain of DPP6 extracellular region is required for ER export and cell surface expression. Disulfide bridges at C349/C356 and C465/C468 are necessary for enhancement of Kv4.2 surface expression but not for physical interaction with Kv4.2. The short intracellular N-terminal and transmembrane domains of DPP6 associate with Kv4.2 and accelerate recovery from inactivation, while the entire extracellular domain is required for Kv4.2 surface expression enhancement and stabilization. Domain deletion/mutagenesis, disulfide bridge mutagenesis, co-immunoprecipitation, surface biotinylation, electrophysiology The Journal of biological chemistry High 25190807
2008 A novel DPP6 splice isoform, DPP6-E, produces ternary Kv4 channels with very fast inactivation kinetics when expressed with Kv4.2 and KChIP1. DPP6-E is selectively expressed in cerebellar granule neurons, hippocampal pyramidal cells, and superior colliculus neurons, accounting for past discrepancies between reconstituted and native Kv4 channel kinetics in these cells. Heterologous expression, electrophysiology, in situ hybridization Neuroscience letters Medium 19007856
2008 DPPX association with Kv4 channels in rabbit carotid body chemoreceptor cells confers TEA sensitivity (increased block by external TEA) to natively TEA-insensitive Kv4 channels. siRNA knockdown of DPPX reduced K(O2) currents and altered TEA sensitivity, establishing DPPX as an integral component of oxygen-sensitive K+ currents in these cells. siRNA knockdown in native cells, pharmacological TEA block, heterologous co-expression electrophysiology The Journal of general physiology Medium 18411327
2017 Patient DPPX antibodies (predominantly IgG1 and IgG4) caused a reversible decrease of DPPX clusters and Kv4.2 protein at the surface of cultured neurons when applied, with recovery upon antibody removal. In hippocampal neurons, anti-DPPX-IgG decreased membrane expression of both DPPX and Kv4.2, and increased enteric nervous system neuron excitability. Immunocytochemistry on cultured neurons, immunoblot of neuronal membrane fractions, voltage-sensitive dye imaging of enteric neurons Neurology Medium 28258082
2013 Dnmt3b epigenetically silences Dpp6 expression through promoter DNA methylation. Depletion of Dnmt3b increases Dpp6 mRNA and protein. Ectopic DPP6 overexpression in P19 cells inhibits retinoic acid-induced neuronal differentiation, indicating DPP6 functions as a negative regulator of this differentiation process. ChIP, bisulfite sequencing, COBRA, methylation-specific PCR, Dnmt3b knockdown, DPP6 overexpression differentiation assay PloS one Medium 23409053
2019 A missense variant DPP6-L747P identified in families with early repolarization syndrome causes gain-of-function of transient outward K+ current (Ito) when co-expressed with Kv4.3 and KChIP2 in HEK293 cells: increased macroscopic current density, altered activation and inactivation slopes, and reduced recovery time constant. Whole-cell patch clamp, western blot, immunofluorescence in HEK293 cells Experimental cell research Medium 31476289
2020 Increased DPP6 expression in iPSC-derived cortical neurons from schizophrenia patients causes neuronal hypoexcitability. Lentiviral shRNA knockdown of DPP6 or pharmacological block of Kv4.2 with AmmTx3 both reversed the hypoexcitability, establishing a causal link between elevated DPP6/Kv4.2 activity and decreased neuronal firing in this model. iPSC differentiation, RNA sequencing, multielectrode array recordings, calcium imaging, lentiviral shRNA, pharmacological block Stem cells and development Medium 33143549
2019 Missense variants in DPP6 found in early-onset Alzheimer's disease and frontotemporal dementia patients destabilize DPP6 protein and reduce its membrane expression in vitro, and reduced DPP6 and Kv4.2 expression was confirmed in brain tissue of missense variant carriers. In vitro expression assay of patient variants, western blot, immunofluorescence, brain tissue immunoblot Acta neuropathologica Medium 30874922
2015 Patient anti-DPPX IgG applied to hippocampal neurons decreased membrane expression of both DPPX and Kv4.2, as measured by immunoblot of purified neuronal membranes. Application to enteric nervous system preparations increased neuronal action potential frequency, demonstrating direct pathogenic antibody effects on both brain and gut neurons. Purified patient IgG application, immunoblot of neuronal membranes, voltage-sensitive dye imaging of enteric neurons Neurology Medium 26291285
2009 DPP6 overexpression in the myocardium of familial idiopathic ventricular fibrillation risk-haplotype carriers shows ~20-fold increased DPP6 mRNA compared to controls, implicating increased DPP6 expression as the pathogenetic mechanism in this cardiac arrhythmia syndrome. DPP6 was proposed as a component of the transient outward current in the heart. Haplotype-sharing genome-wide analysis, qRT-PCR of myocardial DPP6 mRNA American journal of human genetics Low 19285295

Source papers

Stage 0 corpus · 77 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 The CD26-related dipeptidyl aminopeptidase-like protein DPPX is a critical component of neuronal A-type K+ channels. Neuron 300 12575952
2014 DPPX potassium channel antibody: frequency, clinical accompaniments, and outcomes in 20 patients. Neurology 209 25320100
2007 Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis. Nature genetics 183 18084291
2017 DPPX antibody-associated encephalitis: Main syndrome and antibody effects. Neurology 157 28258082
2001 dpl-1 DP and efl-1 E2F act with lin-35 Rb to antagonize Ras signaling in C. elegans vulval development. Molecular cell 150 11463372
2014 Progressive encephalomyelitis with rigidity and myoclonus: a new variant with DPPX antibodies. Neurology 138 24696508
2009 Haplotype-sharing analysis implicates chromosome 7q36 harboring DPP6 in familial idiopathic ventricular fibrillation. American journal of human genetics 128 19285295
2015 Anti-DPPX encephalitis: pathogenic effects of antibodies on gut and brain neurons. Neurology 95 26291285
2011 DPP6 establishes the A-type K(+) current gradient critical for the regulation of dendritic excitability in CA1 hippocampal neurons. Neuron 91 21943606
2004 Structure of a human A-type potassium channel interacting protein DPPX, a member of the dipeptidyl aminopeptidase family. Journal of molecular biology 81 15476821
2008 Kv4 accessory protein DPPX (DPP6) is a critical regulator of membrane excitability in hippocampal CA1 pyramidal neurons. Journal of neurophysiology 62 18667548
1999 The DPL1 gene is involved in mediating the response to nutrient deprivation in Saccharomyces cerevisiae. Molecular cell biology research communications : MCBRC 58 10329480
2008 DPP6 Localization in Brain Supports Function as a Kv4 Channel Associated Protein. Frontiers in molecular neuroscience 57 18978958
2001 Biosynthesis and characterization of the brain-specific membrane protein DPPX, a dipeptidyl peptidase IV-related protein. Journal of biochemistry 47 11173531
2009 The dipeptidyl-peptidase-like protein DPP6 determines the unitary conductance of neuronal Kv4.2 channels. The Journal of neuroscience : the official journal of the Society for Neuroscience 44 19279261
2015 Detailed characterization of familial idiopathic ventricular fibrillation linked to the DPP6 locus. Heart rhythm 43 26681609
2006 Differential characterization of three alternative spliced isoforms of DPPX. Brain research 43 16764835
2019 Loss of DPP6 in neurodegenerative dementia: a genetic player in the dysfunction of neuronal excitability. Acta neuropathologica 41 30874922
2017 A nanobody-based tracer targeting DPP6 for non-invasive imaging of human pancreatic endocrine cells. Scientific reports 41 29123178
2011 Founder mutations in the Netherlands: familial idiopathic ventricular fibrillation and DPP6. Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 39 21512816
2016 Implication of LRRC4C and DPP6 in neurodevelopmental disorders. American journal of medical genetics. Part A 38 27759917
2013 DPP6 regulation of dendritic morphogenesis impacts hippocampal synaptic development. Nature communications 37 23912628
2007 DPL-1 DP, LIN-35 Rb and EFL-1 E2F act with the MCD-1 zinc-finger protein to promote programmed cell death in Caenorhabditis elegans. Genetics 37 17237514
2014 DPP6 domains responsible for its localization and function. The Journal of biological chemistry 34 25190807
2008 I SA channel complexes include four subunits each of DPP6 and Kv4.2. The Journal of biological chemistry 32 18364354
2013 Loss-of-function variation in the DPP6 gene is associated with autosomal dominant microcephaly and mental retardation. European journal of medical genetics 31 23832105
2011 DPP6 as a candidate gene for neuroleptic-induced tardive dyskinesia. The pharmacogenomics journal 31 21826085
2009 No association of DPP6 with amyotrophic lateral sclerosis in an Italian population. Neurobiology of aging 26 19525032
2009 Convergent modulation of Kv4.2 channel alpha subunits by structurally distinct DPPX and KChIP auxiliary subunits. Biochemistry 24 19441798
2008 Effects of MiRP1 and DPP6 beta-subunits on the blockade induced by flecainide of Kv4.3/KChIP2 channels. British journal of pharmacology 23 18536731
2014 DPP6 gene disruption in a family with Gilles de la Tourette syndrome. Neurogenetics 22 25129042
2022 Clinical and imaging analysis to evaluate the response of patients with anti-DPPX encephalitis to immunotherapy. BMC neurology 19 35382765
2009 Association between DPP6 polymorphism and the risk of sporadic amyotrophic lateral sclerosis in Chinese patients. Chinese medical journal 19 20137488
2008 A novel DPP6 isoform (DPP6-E) can account for differences between neuronal and reconstituted A-type K(+) channels. Neuroscience letters 17 19007856
2014 Mapping breakpoints of a familial chromosome insertion (18,7) (q22.1; q36.2q21.11) to DPP6 and CACNA2D1 genes in an azoospermic male. Gene 16 24937803
2013 Epigenetic regulation of Dpp6 expression by Dnmt3b and its novel role in the inhibition of RA induced neuronal differentiation of P19 cells. PloS one 16 23409053
2012 Association between DPP6 polymorphism and the risk of progressive multiple sclerosis in Northern and Southern Europeans. Neuroscience letters 16 23069673
2020 Neuronal Differentiation of Induced Pluripotent Stem Cells from Schizophrenia Patients in Two-Dimensional and in Three-Dimensional Cultures Reveals Increased Expression of the Kv4.2 Subunit DPP6 That Contributes to Decreased Neuronal Activity. Stem cells and development 15 33143549
2022 Alzheimer's disease/dementia-associated brain pathology in aging DPP6-KO mice. Neurobiology of disease 14 36209950
2022 Neuronal Roles of the Multifunctional Protein Dipeptidyl Peptidase-like 6 (DPP6). International journal of molecular sciences 13 36012450
2009 DPL-1 (DP) acts in the germ line to coordinate ovulation and fertilization in C. elegans. Mechanisms of development 13 19368797
2009 The transmembrane beta-subunits KCNE1, KCNE2, and DPP6 modify pharmacological effects of the antiarrhythmic agent tedisamil on the transient outward current Ito. Naunyn-Schmiedeberg's archives of pharmacology 12 19153714
2008 The candidate MAP kinase phosphorylation substrate DPL-1 (DP) promotes expression of the MAP kinase phosphatase LIP-1 in C. elegans germ cells. Developmental biology 10 18304523
2023 Sleep disturbances associated with DPPX autoantibodies: a case series. Journal of neurology 9 37024733
2023 Long term outcomes in patients with anti-DPPX autoimmunity. Journal of neuroimmunology 9 37806046
2020 A novel structure associated with aging is augmented in the DPP6-KO mouse brain. Acta neuropathologica communications 8 33225987
2020 Ratiometric Fluorescence Detection of DNA Based on the Inner Filter Effect of Ru(bpy)2(dppx)2+ toward Silicon Nanodots. ACS omega 8 33458536
2018 Regulation of Kv4.3 and hERG potassium channels by KChIP2 isoforms and DPP6 and response to the dual K+ channel activator NS3623. Biochemical pharmacology 8 29378180
2010 Expression of Dpp6 in mouse embryonic craniofacial development. Acta histochemica 6 20817268
2008 A role for DPPX modulating external TEA sensitivity of Kv4 channels. The Journal of general physiology 6 18411327
1999 Spectral studies on the interaction of DNA and Ru(bipy)2(dppx)2+. Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy 6 10384734
2024 DPPX antibody-mediated autoimmune encephalitis：the first case with breast cancer and review of the literature. Heliyon 5 38449607
2022 Case report: Pain in anti-DPPX encephalitis. Frontiers in neurology 5 36588910
2024 Expanding the clinical spectrum of anti-DPPX encephalitis: a multicenter retrospective study. Frontiers in neuroscience 4 38756408
2024 GWAS Identifies DPP6 as Risk Gene of Cognitive Decline in Parkinson's Disease. The journals of gerontology. Series A, Biological sciences and medical sciences 4 38875006
2024 Case report: Ofatumumab treatment in anti-DPPX autoimmune encephalitis. Frontiers in immunology 4 39007139
2024 Case report: Successful treatment of an anti-D2R and DPPX antibody-associated autoimmune encephalitis patient with high-dose methylprednisolone and intravenous immunoglobulin. Frontiers in immunology 3 38469308
2023 A Devastating Neurological Disorder: Anti-Dipeptidyl-Peptidase-Like Protein 6 (DPPX) Encephalitis Causing Rapidly Progressive Dementia. Cureus 3 38274926
2019 A novel DPP6 variant in Chinese families causes early repolarization syndrome. Experimental cell research 3 31476289
2013 Expression of DPP6 in Meckel's cartilage and tooth germs during mouse facial development. Biotechnic & histochemistry : official publication of the Biological Stain Commission 3 23750656
2024 A rare case of anti-DPPX encephalitis combined with neuroleptospirosis. BMC neurology 2 38243162
2023 Polymorphism of ADAM12, DPP6 and PRKN genes and their associations with milk production traits in Holstein. Reproduction in domestic animals = Zuchthygiene 2 37917556
2022 Modulation of KV4.3-KChIP2 Channels by IQM-266: Role of DPP6 and KCNE2. International journal of molecular sciences 2 36012438
2024 Diffusely Enhancing Lesions on MRI in DPPX Antibody-Associated Encephalitis. JAMA neurology 1 38252428
2024 Correction of Ito in human induced pluripotent stem Cell-derived cardiomyocyte carrying DPP6 mutation in early repolarization syndrome by CRISPR/Cas9 genome editing. Experimental cell research 1 38272106
2023 Binding and stabilizating effect of RNA triplex poly(U)⋅poly(A)*poly(U) by enantiomers of ruthenium(II) polypyridyl complex [Ru(bpy)2(dppx)]2. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 1 37452869
2021 The Mediation Effects of Aluminum in Plasma and Dipeptidyl Peptidase Like Protein 6 (DPP6) Polymorphism on Renal Function via Genome-Wide Typing Association. International journal of environmental research and public health 1 34639784
2026 Dpp6 knockout mice exhibit increased ethanol conditioned place preference and acute ethanol-induced anxiolytic behavior. Alcohol, clinical & experimental research 0 41935344
2026 DPP6 Loss Causes Age-Dependent Sleep Dysregulation and Depression-like Phenotypes Linked to Neurodegeneration. International journal of molecular sciences 0 41977406
2025 DPPX antibody-mediated disease mimicking Wernicke's encephalopathy. BMJ case reports 0 39753277
2025 The role of DPP6 dysregulation in neuropathology: from synaptic regulation to disease mechanisms. Frontiers in cellular neuroscience 0 40109277
2025 Anti-dipeptidyl-peptidase-like protein-6 (DPPX) autoimmune encephalitis associated with severe multifocal dystonia. Clinical parkinsonism & related disorders 0 40241920
2025 Case Report: Treatment of delayed tremor episodes in a patient with DPPX antibody encephalitis. Frontiers in immunology 0 40808961
2025 Dpp6 Homozygous Knockout Mice Exhibit Increased Ethanol Conditioned Place Preference and Acute Ethanol-Induced Anxiolytic Behavior. bioRxiv : the preprint server for biology 0 40894538
2025 Changes in DPPX autoantibody levels in autoimmune encephalitis: a case report and brief review. Brain disorders (Amsterdam, Netherlands) 0 40937361
2024 Association between DPP6 gene rs10260404 polymorphism and increased risk of sporadic amyotrophic lateral sclerosis (sALS): a meta-analysis. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 0 38381392
2009 DPPX modifies TEA sensitivity of the Kv4 channels in rabbit carotid body chemoreceptor cells. Advances in experimental medicine and biology 0 19536467