Affinage

DPP6

A-type potassium channel modulatory protein DPP6 · UniProt P42658

Length
865 aa
Mass
97.6 kDa
Annotated
2026-06-09
78 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DPP6 (DPPX) is a single-pass type II transmembrane glycoprotein that serves as an obligatory auxiliary subunit of neuronal Kv4 voltage-gated K+ channels, assembling with Kv4 pore-forming subunits in a 4:4 stoichiometry to reconstitute native somatodendritic A-type K+ currents (PMID:12575952, PMID:18364354). Although its extracellular domain is structurally homologous to the dipeptidyl aminopeptidase DPP-IV, DPP6 lacks the catalytic serine and has no aminopeptidase activity, even after engineering the consensus protease active site (PMID:15476821, PMID:11173531). Functionally, DPP6 partitions its actions across distinct domains: its intracellular and transmembrane regions associate with Kv4.2 and accelerate recovery from inactivation, while disulfide bridges within the cysteine-rich extracellular domain drive ER export and cell-surface stabilization of the channel without being required for the physical Kv4 interaction (PMID:19441798, PMID:25190807). DPP6 shifts Kv4 voltage dependence, accelerates gating kinetics, and raises unitary conductance through electrostatic contributions from N-terminal acidic residues, with alternatively spliced isoforms tuning these properties to match native currents in specific neuron types (PMID:16764835, PMID:19007856, PMID:19279261). In CA1 pyramidal neurons DPP6 establishes the soma-to-distal-dendrite gradient of A-type current that constrains dendritic excitability, back-propagating action potentials, and LTP induction (PMID:18667548, PMID:21943606). Independently of Kv4, DPP6 promotes dendritic filopodia, branching, and synapse formation through interactions with a filopodia-associated myosin and extracellular fibronectin (PMID:23912628). DPP6 expression is epigenetically silenced by Dnmt3b-mediated promoter methylation (PMID:23409053). Human relevance spans multiple disorders: patient autoantibodies against DPPX downregulate surface DPPX and Kv4.2 and cause neuronal hyperexcitability (PMID:28258082, PMID:26291285); missense variants destabilize the protein and reduce membrane expression in early-onset dementia (PMID:30874922); and gain-of-function cardiac variants augment transient outward current (Ito) in familial early repolarization syndrome (PMID:31476289, PMID:38272106).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2001 High

    Established that the DPPX isoforms are surface glycoproteins lacking the enzymatic activity implied by their DPP-IV homology, redirecting attention from catalysis toward a structural/regulatory role.

    Evidence Cell-free translation, COS-1 transfection, immunoblot and mutagenesis introducing a consensus serine protease site

    PMID:11173531

    Open questions at the time
    • Did not identify the functional partner conferring biological role
    • No structural basis for catalytic loss yet
  2. 2003 High

    Identified DPP6 as a native component of neuronal A-type K+ channel complexes, answering what protein partners reconstitute authentic Kv4 currents.

    Evidence Biochemical purification from rat brain, co-IP, heterologous reconstitution, colocalization

    PMID:12575952

    Open questions at the time
    • Stoichiometry of the complex not defined
    • Domains responsible for trafficking vs gating not mapped
  3. 2004 High

    Provided the structural explanation for catalytic inactivity by showing the extracellular domain mirrors DPP-IV but lacks the catalytic serine.

    Evidence X-ray crystallography at 3.0 Å with active-site comparison to DPP-IV

    PMID:15476821

    Open questions at the time
    • Structure of full-length protein and the Kv4 complex not resolved
    • Functional role of the extracellular dimer not addressed
  4. 2008 High

    Defined the channel architecture and the in vivo and biophysical scope of DPP6 action, from 4:4 stoichiometry to dendritic coexpression, isoform-specific kinetics, and a role in oxygen-sensing currents.

    Evidence Tandem-linked stoichiometry constructs with amino acid analysis, immunohistochemistry, oocyte electrophysiology, and siRNA in carotid body chemoreceptors

    PMID:18364354 PMID:18411327 PMID:18978958 PMID:19007856

    Open questions at the time
    • Mechanism of Kv4-independent axonal labeling unexplained
    • Residues mediating kinetic modulation not yet localized
  5. 2009 High

    Mapped specific molecular determinants of DPP6 function: N-terminal acidic residues set unitary conductance electrostatically, and DPP6 drives Kv4.2 surface redistribution and biosynthetic maturation within a ternary KChIP complex.

    Evidence Single-channel recordings in DPP6-KO CGNs, charge-neutralization mutagenesis, heterologous coexpression with imaging, detergent solubility, and MS phosphorylation analysis

    PMID:19279261 PMID:19441798

    Open questions at the time
    • Structural mechanism of the N-terminal electrostatic contact unresolved
    • Order of assembly of the ternary complex inferred indirectly
  6. 2011 High

    Demonstrated the physiological role of DPP6 in vivo: it builds the dendritic A-current gradient that limits excitability and synaptic plasticity.

    Evidence Dendritic patch-clamp, two-photon calcium imaging, and LTP assays in DPP6-KO mice

    PMID:21943606

    Open questions at the time
    • Behavioral consequences of altered plasticity not addressed
    • Whether gradient depends on isoform-specific expression unknown
  7. 2013 High

    Revealed a Kv4-independent developmental role in dendritic morphogenesis and identified non-channel binding partners, and separately showed DPP6 expression is epigenetically controlled.

    Evidence shRNA/KO with live imaging, mEPSC recording, pulldown with myosin and fibronectin; ChIP, bisulfite sequencing, and Dnmt3b knockdown

    PMID:23409053 PMID:23912628

    Open questions at the time
    • Molecular pathway linking DPP6-myosin/fibronectin to spine formation undefined
    • Upstream signals controlling Dnmt3b targeting of Dpp6 unknown
  8. 2014 High

    Dissected the structure-function division of labor by showing the cysteine-rich extracellular domain (disulfide bonds C349/C356, C465/C468) governs ER export while intracellular/transmembrane regions mediate Kv4 binding and gating.

    Evidence Cysteine and domain-deletion mutagenesis with co-IP, surface biotinylation, and immunofluorescence

    PMID:25190807

    Open questions at the time
    • Exact ER-export trafficking machinery not identified
    • How extracellular disulfides communicate to the channel structurally unresolved
  9. 2017 Medium

    Established an autoimmune disease mechanism whereby patient DPPX antibodies reversibly downregulate surface DPPX and Kv4.2, complementing earlier evidence of antibody-induced neuronal hyperexcitability.

    Evidence Patient antibody incubation of cultured neurons with surface cluster quantification and reversal experiments; enteric neuron excitability imaging

    PMID:26291285 PMID:28258082

    Open questions at the time
    • Antibody epitope on DPPX not mapped
    • Whether internalization or trafficking block underlies cluster loss unresolved
  10. 2020 Medium

    Connected DPP6 dosage to human disease across neurological and cardiac systems: variants destabilize the protein in dementia, altered expression changes neuronal excitability in schizophrenia models, and cardiac variants produce Ito gain-of-function in early repolarization syndrome.

    Evidence In vitro variant expression with tissue immunostaining; iPSC-derived cortical neurons with shRNA/pharmacological rescue; HEK293 and iPSC-cardiomyocyte electrophysiology with CRISPR correction

    PMID:30874922 PMID:31476289 PMID:33143549 PMID:38272106

    Open questions at the time
    • Causal contribution of DPP6 variants to disease vs association not fully established
    • Tissue-specific differences in variant consequence not mechanistically reconciled
  11. 2022 Medium

    Showed that chronic DPP6 loss in vivo produces neurodegeneration-like pathology and circadian/sleep phenotypes, extending its role beyond acute channel modulation to long-term brain homeostasis.

    Evidence DPP6-KO and overexpression mice with immunofluorescence, electron microscopy, MRI, cytokine assays, and EEG/EMG sleep telemetry

    PMID:36209950 PMID:41977406

    Open questions at the time
    • Mechanistic link between A-current loss and amyloid/tau accumulation undefined
    • Whether sleep phenotypes derive from channel or Kv4-independent functions unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DPP6 mechanistically couples its non-channel partners (myosin, fibronectin) to synaptic development, and how loss of A-type current drives the downstream neurodegenerative cascade, remain unresolved.
  • No structural model of the full-length DPP6/Kv4 complex
  • Pathway from DPP6 deficiency to amyloid/tau pathology not defined
  • Trafficking machinery recognizing the cysteine-rich domain unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0060089 molecular transducer activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-112316 Neuronal System 2 R-HSA-5653656 Vesicle-mediated transport 2
Partners
FIBRONECTINKCND2KCND3KCNIP2KCNIP4MYOSIN
Complex memberships
Kv4 (Kv4.2/DPP6) A-type K+ channel complexKv4.2/DPP6/KChIP ternary channel complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 DPPX (DPP6) was identified as a component of neuronal A-type K+ channel complexes purified from rat brain membranes. DPPX associates with Kv4 pore-forming subunits, facilitates their trafficking and membrane targeting, and reconstitutes native A-type K+ channel properties in heterologous expression systems. DPPX is coexpressed with Kv4 subunits in the somatodendritic compartment of CNS neurons. Biochemical purification of A-type K+ channel complexes from rat brain membranes, co-immunoprecipitation, heterologous expression reconstitution, immunofluorescence colocalization Neuron High 12575952
2004 X-ray crystal structure of the extracellular domain of human DPPX at 3.0 Å resolution revealed a dimeric architecture highly homologous to DPP-IV. The active-site comparison showed loss of the catalytic serine residue, with an arrangement of residues inconsistent with canonical serine protease activity, establishing that DPPX does not function as a dipeptidyl aminopeptidase. X-ray crystallography at 3.0 Å resolution; active-site structural comparison with DPP-IV Journal of molecular biology High 15476821
2001 DPPX-S and DPPX-L are synthesized as glycoproteins that undergo N-glycosylation maturation (high-mannose to complex-type sugar chains) and are expressed on the cell surface. Neither isoform exhibited DPPIV enzyme activity, even when mutated to contain the consensus Gly-X-Ser-X-Gly serine protease active site sequence. Cell-free translation, transfection in COS-1 cells, immunofluorescence microscopy, immunoblot, mutagenesis to introduce consensus serine protease active site 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. A deletion mutant lacking the variable N-terminus retained the ability to modulate Kv4 channels, establishing that the N-terminus is not required for channel modulation. Xenopus oocyte expression, electrophysiology, deletion mutagenesis, in situ hybridization Brain research High 16764835
2008 DPP6 and Kv4.2 proteins are coexpressed and co-enriched in dendrites of neurons expressing Kv4.2 in the brain, supporting their in vivo association as auxiliary and pore-forming subunits of somatodendritic A-type K+ channels. Additionally, DPP6 antibodies labeled hippocampal mossy fiber axons that lack Kv4 proteins, suggesting a Kv4-independent function. Immunohistochemistry with DPP6-specific antibodies generated in-house, comparison of cellular and subcellular distribution patterns in rat brain Frontiers in molecular neuroscience Medium 18978958
2008 ISA channel complexes contain four subunits each of Kv4.2 and DPP6, establishing a 4:4 stoichiometry. This was determined by biophysical experiments comparing wild-type channels with tandem-linked constructs enforcing defined stoichiometries, and by direct amino acid analysis of purified channel complexes. Tandem-linked subunit constructs (enforced stoichiometry), electrophysiology, amino acid analysis of purified channel complexes The Journal of biological chemistry High 18364354
2008 DPPX downregulation in CA1 pyramidal neurons via siRNA caused depolarizing shifts in steady-state inactivation and activation curves, a shallower conductance-voltage slope, slowed inactivation, and delayed recovery from inactivation of A-type currents. At the physiological level, DPPX knockdown decreased subthreshold excitability (reduced input resistance, delayed AP onset, increased AP threshold) while slowing AP rise and repolarization suprathreshold. siRNA knockdown in hippocampal CA1 neurons, voltage-clamp and current-clamp patch recordings, computer simulations Journal of neurophysiology High 18667548
2008 A novel DPP6 splice isoform (DPP6-E) produces ternary Kv4 channels with very fast inactivation kinetics when expressed in heterologous systems. DPP6-E is selectively expressed in cerebellar granule neurons, hippocampal pyramidal cells, and neurons in intermediate layers of the superior colliculus, accounting for discrepancies between reconstituted and native fast-inactivating A-type currents in these cells. Heterologous expression in Xenopus oocytes/HEK cells, electrophysiology, in situ hybridization Neuroscience letters Medium 19007856
2009 DPP6-S determines the unitary conductance (gamma) of native neuronal Kv4.2 channels. Coexpression of Kv4.2 with DPP6-S was sufficient to match the ~7.5 pS gamma of native cerebellar granule neuron channels (vs ~4 pS for Kv4.2 alone). DPP6-KO mouse CGN channels showed gamma indistinguishable from Kv4.2 alone. Charge-neutralization mutations of two N-terminal acidic residues in DPP6-S eliminated the increase in gamma, implicating electrostatic interactions. Single-channel recordings in cerebellar granule neurons from dpp6 KO mice and reconstituted systems, charge-neutralization mutagenesis of N-terminal acidic residues The Journal of neuroscience High 19279261
2009 DPPX-S coexpression with Kv4.2 in heterologous cells causes dramatic redistribution of Kv4.2 from intracellular retention to plasma membrane expression, and alters Kv4.2 phosphorylation pattern, detergent solubility, and stability. KChIP4a, which inhibits other KChIPs, also inhibits the effects of DPPX-S, consistent with formation of a ternary Kv4.2/DPPX-S/KChIP complex early in biosynthesis. Coexpression with DPPX-S or KChIP2 leads to a pattern of Kv4.2 phosphorylation similar to that in brain. Heterologous coexpression, immunofluorescence, detergent solubility assay, tandem MS phosphorylation analysis, co-immunoprecipitation Biochemistry High 19441798
2011 DPP6 is required to generate the increasing gradient of A-type K+ current density from soma to distal dendrites in CA1 hippocampal pyramidal neurons. DPP6-KO mice showed decreased A-type current specifically in distal dendrites, accompanied by a depolarizing shift in voltage dependence of activation. Loss of DPP6 led to hyperexcitable dendrites with enhanced back-propagating APs, calcium electrogenesis, and increased LTP induction, while somatic firing was largely unaffected. Dendritic patch-clamp recordings in DPP6-KO mice, current-clamp recordings, two-photon calcium imaging, LTP induction assays Neuron High 21943606
2013 DPP6 has a Kv4.2-independent role in dendritic morphogenesis. Knockdown or genetic deletion of DPP6 in hippocampal neurons led to sparser dendritic branching, fewer dendritic spines throughout development and adulthood, and fewer functional synapses. 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 (mEPSC recording), co-immunoprecipitation/pulldown with myosin and fibronectin Nature communications High 23912628
2014 The cysteine-rich domain of DPP6 is required for ER export and cell-surface expression. Disulfide bridges at C349/C356 and C465/C468 in the cysteine-rich domain are necessary for enhancement of Kv4.2 channel surface expression but not for physical interaction with Kv4.2. The intracellular N-terminal and transmembrane domains of DPP6 associate with Kv4.2 and accelerate its recovery from inactivation, while the full extracellular domain is required for enhancing Kv4.2 surface expression and stabilization. Cysteine mutagenesis, domain deletion constructs, co-immunoprecipitation, surface biotinylation, immunofluorescence in heterologous cells The Journal of biological chemistry High 25190807
2013 Dnmt3b epigenetically silences Dpp6 expression by promoter methylation. ChIP analysis showed Dnmt3b recruitment to the Dpp6 promoter; bisulfite sequencing confirmed heavy methylation. Dnmt3b knockdown increased Dpp6 mRNA and protein expression and reduced promoter methylation. Ectopic DPP6 expression inhibited retinoic acid-induced neuronal differentiation of P19 cells. ChIP, bisulfite genomic sequencing, COBRA, methylation-specific PCR, siRNA knockdown of Dnmt3b, ectopic overexpression of DPP6 in P19 cells PloS one Medium 23409053
2008 DPPX association with Kv4 channels confers increased sensitivity to external tetraethylammonium (TEA) in heterologous expression systems and in native rabbit carotid body chemoreceptor cells. DPPX knockdown by siRNA in chemoreceptor cells reduced the anomalous TEA sensitivity, establishing DPPX as an integral component of the oxygen-sensitive K+ current in these cells. siRNA knockdown of DPPX in carotid body chemoreceptor cells, electrophysiology, heterologous coexpression with pharmacological TEA block 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, establishing an antibody-mediated mechanism of channel downregulation. The effect was reversed upon antibody removal. Incubation of cultured neurons with patient antibodies, immunofluorescence quantification of DPPX and Kv4.2 surface clusters, antibody removal/reversal experiment Neurology Medium 28258082
2015 Anti-DPPX patient IgG caused hyperexcitability of enteric nervous system neurons (guinea pig and human) and reduced surface expression of DPPX and Kv4.2 in hippocampal neuron membranes. Patient sera showed somatodendritic and perisynaptic staining in neurons that colocalized with DPPX and Kv4.2. Voltage-sensitive dye imaging of enteric neurons, immunoblot of membrane fractions from hippocampal neurons after patient IgG incubation, immunocytochemistry with patient sera Neurology Medium 26291285
2019 DPP6 missense variants found in early-onset Alzheimer's disease and frontotemporal dementia patients destabilize the DPP6 protein and reduce its membrane expression in vitro. Reduced DPP6 and Kv4.2 expression was also detected in brain tissue of missense variant carriers. In vitro expression of patient missense variants, surface expression quantification (immunofluorescence/western blot), brain tissue immunostaining from variant carriers Acta neuropathologica Medium 30874922
2020 DPP6 overexpression in cortical neurons derived from schizophrenia patient iPSCs increased Kv4.2-mediated K+ current and caused neuronal hypoexcitability. Knockdown of DPP6 by shRNA or blockade of Kv4.2 with AmmTx3 reversed neuronal hypoexcitability in these cells, establishing a causal link between elevated DPP6 expression and reduced neuronal activity. iPSC-derived cortical neurons, multielectrode array recordings, calcium imaging, lentiviral shRNA knockdown of DPP6, Kv4.2 pharmacological block with AmmTx3 Stem cells and development Medium 33143549
2019 A DPP6 missense variant (L747P) identified in familial early repolarization syndrome caused a gain of function of Ito when co-expressed with Kv4.3 and KChIP2 in HEK293 cells: increased current density, decreased inactivation slope, increased activation slope, and accelerated recovery from inactivation, without affecting membrane localization. Heterologous expression in HEK293 cells, whole-cell patch clamp, western blot, immunofluorescence Experimental cell research Medium 31476289
2024 A DPP6 variant (L854P) identified in familial early repolarization syndrome increased transient outward potassium current (Ito) in iPSC-derived cardiomyocytes. CRISPR/Cas9 correction of the L854P variant normalized Ito but did not restore action potential duration prolongation, indicating Ito gain-of-function as the primary electrophysiological consequence of this mutation. iPSC-derived cardiomyocytes, CRISPR/Cas9 gene editing, patch clamp electrophysiology Experimental cell research Medium 38272106
2022 Aging DPP6-KO mice exhibit accumulation of amyloid β, APP, and hyperphosphorylated tau in hippocampus, neuroinflammation (increased microglia, astrocytes, and pro-inflammatory cytokines), reduced hippocampal neuron number, and circadian dysfunction. Novel enlarged presynaptic structures colocalized with neurodegeneration markers were more prevalent in DPP6-KO mice and appeared earlier in development. DPP6-KO mice, immunofluorescence, electron microscopy, in vivo MRI, neuronal counting, cytokine assays, circadian/behavioral monitoring Neurobiology of disease Medium 36209950
2026 DPP6-KO mice display age-dependent sleep phenotypes: young adult KO mice showed increased REM sleep, while aged KO mice developed fragmented sleep and insomnia with decreased REM latency (depression biomarker). DPP6 overexpression in aged wild-type mice increased NREM duration and reduced sleep fragmentation. DPP6-KO mice also showed dysregulated locomotor activity and body temperature rhythms. Wireless EEG/EMG telemetry, behavioral monitoring, body temperature recordings in DPP6-KO and DPP6-overexpressing mice across ages International journal of molecular sciences Medium 41977406

Source papers

Stage 0 corpus · 78 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 301 12575952
2014 DPPX potassium channel antibody: frequency, clinical accompaniments, and outcomes in 20 patients. Neurology 210 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 160 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 151 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 129 19285295
2015 Anti-DPPX encephalitis: pathogenic effects of antibodies on gut and brain neurons. Neurology 97 26291285
2011 DPP6 establishes the A-type K(+) current gradient critical for the regulation of dendritic excitability in CA1 hippocampal neurons. Neuron 92 21943606
2004 Structure of a human A-type potassium channel interacting protein DPPX, a member of the dipeptidyl aminopeptidase family. Journal of molecular biology 82 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 48 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 45 19279261
2019 Loss of DPP6 in neurodegenerative dementia: a genetic player in the dysfunction of neuronal excitability. Acta neuropathologica 44 30874922
2015 Detailed characterization of familial idiopathic ventricular fibrillation linked to the DPP6 locus. Heart rhythm 44 26681609
2006 Differential characterization of three alternative spliced isoforms of DPPX. Brain research 43 16764835
2017 A nanobody-based tracer targeting DPP6 for non-invasive imaging of human pancreatic endocrine cells. Scientific reports 41 29123178
2016 Implication of LRRC4C and DPP6 in neurodevelopmental disorders. American journal of medical genetics. Part A 39 27759917
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
2013 DPP6 regulation of dendritic morphogenesis impacts hippocampal synaptic development. Nature communications 38 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 36 25190807
2013 Loss-of-function variation in the DPP6 gene is associated with autosomal dominant microcephaly and mental retardation. European journal of medical genetics 33 23832105
2008 I SA channel complexes include four subunits each of DPP6 and Kv4.2. The Journal of biological chemistry 32 18364354
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 20 35382765
2009 Association between DPP6 polymorphism and the risk of sporadic amyotrophic lateral sclerosis in Chinese patients. Chinese medical journal 19 20137488
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 17 33143549
2008 A novel DPP6 isoform (DPP6-E) can account for differences between neuronal and reconstituted A-type K(+) channels. Neuroscience letters 17 19007856
2022 Neuronal Roles of the Multifunctional Protein Dipeptidyl Peptidase-like 6 (DPP6). International journal of molecular sciences 16 36012450
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
2022 Alzheimer's disease/dementia-associated brain pathology in aging DPP6-KO mice. Neurobiology of disease 15 36209950
2009 DPL-1 (DP) acts in the germ line to coordinate ovulation and fertilization in C. elegans. Mechanisms of development 14 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 13 19153714
2023 Sleep disturbances associated with DPPX autoantibodies: a case series. Journal of neurology 10 37024733
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 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 9 33225987
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 9 29378180
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
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 6 38875006
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
2024 Expanding the clinical spectrum of anti-DPPX encephalitis: a multicenter retrospective study. Frontiers in neuroscience 5 38756408
2022 Case report: Pain in anti-DPPX encephalitis. Frontiers in neurology 5 36588910
2024 Case report: Ofatumumab treatment in anti-DPPX autoimmune encephalitis. Frontiers in immunology 4 39007139
2022 Modulation of KV4.3-KChIP2 Channels by IQM-266: Role of DPP6 and KCNE2. International journal of molecular sciences 4 36012438
2019 A novel DPP6 variant in Chinese families causes early repolarization syndrome. Experimental cell research 4 31476289
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
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
2025 The role of DPP6 dysregulation in neuropathology: from synaptic regulation to disease mechanisms. Frontiers in cellular neuroscience 2 40109277
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
2025 Changes in DPPX autoantibody levels in autoimmune encephalitis: a case report and brief review. Brain disorders (Amsterdam, Netherlands) 1 40937361
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
2026 What Determines the Clinical Course and Outcome of DPPX Encephalitis? A Systematic Review. Movement disorders clinical practice 0 42210711
2025 DPPX antibody-mediated disease mimicking Wernicke's encephalopathy. BMJ case reports 0 39753277
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
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

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